Pulmonary Thromboembolism – PET: Symptoms, Causes, Diagnosis, Formation, Pathophysiology and Treatments

It is the obstruction of a pulmonary artery because of a thrombus (hence its name) that develops in situ.

Summary

Pulmonary emboli usually arise from thrombi that originate in the deep venous system of the lower extremities; however, they rarely also originate in the pelvic, renal, upper extremity, or right heart chambers.

After traveling to the lung, large thrombi can lodge in the bifurcation of the main pulmonary artery or the lobar branches and cause a hemodynamic compromise.

Pulmonary thromboembolism is not a disease in itself. Rather, it is a complication of the underlying venous thrombosis. Under normal conditions, microthrombi (small aggregates of red blood cells, platelets and fibrin) are formed and lysed continuously within the venous circulatory system.

Signs and symptoms

The classic presentation of pulmonary embolism is the abrupt appearance of pleuritic chest pain, difficulty breathing and hypoxia. However, the majority of patients with pulmonary embolism do not present obvious symptoms in the presentation.

Conversely, symptoms may range from sudden catastrophic hemodynamic collapse to gradually progressive dyspnea. The diagnosis of pulmonary embolism should be suspected in patients with respiratory symptoms not explained by an alternative diagnosis.

Patients with pulmonary thromboembolism may present atypical symptoms, such as the following:

• Seizures
• Syncope
• Abdominal pain
• Fever
• Productive cough
• Wheezing
• Decreasing level of consciousness
• New onset of atrial fibrillation
• Hemoptisis
• Pain in the flank
• Delirium (in elderly patients)

Diagnosis

The evidence-based literature supports the practice of using clinical scoring systems to determine the clinical probability of pulmonary embolism before proceeding with the test. The validated clinical prediction rules should be used to estimate the likelihood of pulmonary thromboembolism prior to the test and interpret the results of the test.

The physical signs of pulmonary embolism include the following:

• Tachypnea (respiratory rate> 16 / min): 96%
• Rales: 58%
• Second accented heart sound: 53%
• Tachycardia (heart rate> 100 / min): 44%
• Fiebre (temperatura> 37.8 ° C [100.04 ° F]): 43%
• Diaphoresis: 36%
• Gallop S 3 or S 4: 34%
• Clinical signs and symptoms suggesting thrombophlebitis: 32%
• Edema of the lower extremity: 24%
• Heart murmur: 23%

Tests

Perform diagnostic tests in symptomatic patients with suspected pulmonary thromboembolism to confirm or exclude the diagnosis or until an alternative diagnosis is found. Routine laboratory findings are nonspecific and are not useful in pulmonary embolism, although they may suggest another diagnosis.

A hypercoagulation study should be performed if there is no obvious cause of embolic disease, including the detection of conditions such as the following:

• Antithrombin III deficiency
• Deficiency of protein C or protein S
• Anticoagulant lupus
• Homocystinuria
• Hidden neoplasia
• Connective tissue disorders

Potentially useful laboratory tests in patients with suspected pulmonary thromboembolism include the following:

• D-dimer test
• Level of albumin modified by ischemia
• white blood cell count
• Gasometría arterial:
• Levels of serum troponin
• Brain natriuretic peptide

Image studies

Imaging studies that help in the diagnosis of pulmonary thromboembolism include the following:

• Computed tomography angiography (CTA): Multidetector row ATC (ATCM) is the standard of criteria for diagnosing pulmonary embolism
• Pulmonary angiography: Standard criteria for the diagnosis of pulmonary embolism when ATCM is not available
• Chest x-ray: abnormal in most cases of pulmonary embolism, but non-specific
• V / Q scan: when CT is not available or contraindicated
• ECG: the most common anomalies are tachycardia and nonspecific abnormalities of the ST-T wave
• Magnetic resonance: through the use of standard or controlled spin-echo techniques, pulmonary emboli demonstrate a greater intensity of the signal within the pulmonary artery
• Echocardiography: transesophageal echocardiography can identify central pulmonary embolism
• Venography: Standard criteria for diagnosing PE
• Duplex ultrasound: noninvasive diagnosis of pulmonary embolism by demonstrating the presence of a PET in any place

Control

Anticoagulation and thrombolysis

Immediate complete anticoagulation is mandatory for all patients with suspected pulmonary embolism or PE. Diagnostic investigations should not delay empirical anticoagulant therapy.

Thrombolytic therapy should be used in patients with acute pulmonary embolism who have hypotension (systolic blood pressure <90 mm Hg) who are not at high risk of bleeding and in selected patients with acute pulmonary embolism not associated with hypotension who have a low risk of bleeding and whose initial clinical presentation or clinical course suggests a high risk of developing hypotension.

Long-term anticoagulation is essential for the prevention of recurrence of pulmonary embolism or pulmonary embolism, because even in fully anticoagulated patients, PE and pulmonary embolism can recur and often reoccur.

Anticoagulant medications include the following:

• Unfractionated heparin
• Low molecular weight heparin
• Factor X inhibitors
• Fondaparinux
• Warfarin

Thrombolytic agents used in the management of pulmonary embolism include the following:

Tissue plasminogen activator

• Alteplase
• Reteplase

Surgical options

Surgical management options include the following:

• Embolectomy and fragmentation of the catheter or surgical embolectomy
• Placement of vena cava filters

Training

Pulmonary embolism is a common and life-threatening condition. Most patients who succumb to pulmonary embolism do so within the first hours of the event. Despite diagnostic advances, delays in the diagnosis of pulmonary embolism are common and represent a major problem.

As a cause of sudden death, massive pulmonary embolism is the second after sudden cardiac death.

In patients who survive a pulmonary embolism, recurrent embolism and death can be prevented with rapid diagnosis and therapy. Unfortunately, the diagnosis is often overlooked because patients with pulmonary embolism have nonspecific signs and symptoms.

If left untreated, about one-third of patients who survive an initial pulmonary embolism die from a subsequent embolic episode.

When a pulmonary embolism is identified, it is characterized as acute or chronic. In terms of pathological diagnosis, an embolus is acute if it is centrally located within the vascular lumen or if it occludes a vessel (vessel cut-off sign) (see the first image below).

Acute pulmonary embolism commonly causes distension of the affected vessel. A plunger is chronic if it is eccentric and contiguous to the vessel wall (see the second image below), it reduces the arterial diameter by more than 50%, there is evidence of recanalization within the thrombus and there is an arterial network.

A pulmonary embolism is also characterized as central or peripheral, depending on the location or arterial branch involved.

The central vascular zones include the main pulmonary artery, the left and right main pulmonary arteries, the anterior trunk, the right and left interlobular arteries, the trunk of the left upper lobe, the right middle lobe artery, and the right lower lobe arteries. left.

A pulmonary embolus is characterized by being massive when it affects both pulmonary arteries or when it produces a hemodynamic compromise. Peripheral vascular zones include the segmental and subsegmental arteries of the right upper lobe, the right middle lobe, the right lower lobe, the left upper lobe, the lingula, and the left lower lobe.

The variability of the presentation puts the patient and the clinician in a situation of possible loss of diagnosis. The challenge is that the “classic” presentation with abrupt onset of pleuritic chest pain, shortness of breath and hypoxia is rarely seen.

Studies of patients who unexpectedly died of pulmonary embolism revealed that patients had complained of bothersome symptoms, often for weeks, before dying. Forty percent of these patients had been seen by a doctor in the weeks before their death.

The most important conceptual breakthrough with respect to pulmonary embolism in recent decades has been the finding that pulmonary embolism is not a disease; rather, pulmonary embolism is a complication of venous thromboembolism, most commonly deep vein thrombosis.

Practically all physicians involved in patient care encounter patients at risk of venous thromboembolism and, therefore, at risk of pulmonary embolism.

The clinical signs and symptoms of pulmonary embolism are nonspecific; therefore, patients with suspected pulmonary embolism – due to unexplained dyspnea, tachypnea or chest pain or the presence of risk factors for pulmonary embolism – should undergo diagnostic tests until the diagnosis is determined or eliminated or confirmed an alternative diagnosis

In addition, routine laboratory findings are nonspecific and are not useful in pulmonary embolism, although they may suggest another diagnosis. Historically, pulmonary angiography was the standard criteria for the diagnosis of pulmonary embolism, but with the improvement of the sensitivity and specificity of CT angiography, it is now rarely performed.

Immediate complete anticoagulation is mandatory for all patients with suspected pulmonary embolism or PE. Diagnostic investigations should not delay empirical anticoagulant therapy.

Long-term anticoagulation is essential for the prevention of recurrence of pulmonary embolism or pulmonary embolism. The general consensus is that a significant reduction in recurrence is associated with 3-6 months of anticoagulation.

Anatomy

The knowledge of the bronchovascular anatomy is the key to the accurate interpretation of the computed tomographies obtained for the evaluation of pulmonary embolism. A systematic approach to identify all ships is important.

Bronchovascular anatomy has been described based on the segmental anatomy of the lungs. The segmental arteries are observed near the accompanying branches of the bronchial tree and are found either medially (in the upper lobes) or laterally (in the lower lobes, lingula and right middle lobe).

Pulmonary thromboembolism is not a disease in itself. Rather, it is a complication of the underlying venous thrombosis. Under normal conditions, microthrombi (small aggregates of red blood cells, platelets and fibrin) are formed and lysed continuously within the venous circulatory system.

This dynamic equilibrium ensures local hemostasis in response to an injury without allowing uncontrolled propagation of the clot.

Pathophysiology

There are respiratory and hemodynamic consequences associated with pulmonary embolism.

Respiratory consequences

The acute respiratory consequences of pulmonary embolism include the following:

• Increase in alveolar dead space
• Hypoxemia
• Hyperventilation

Additional consequences that may occur include regional loss of surfactant and pulmonary infarction. Arterial hypoxemia is a common but not universal finding in patients with acute embolism.

The mechanisms of hypoxemia include ventilation-perfusion mismatch, intrapulmonary shunts, reduced cardiac output, and intracardiac shunt through a permeable foramen ovale. Pulmonary infarction is an uncommon consequence due to collateral arterial bronchial circulation.

Hemodynamic consequences

Pulmonary embolism reduces the cross-sectional area of ​​the pulmonary vascular bed, resulting in increased pulmonary vascular resistance, which in turn increases right ventricular afterload. If the afterload is severely increased, right ventricle failure may occur. In addition, the humoral and reflex mechanisms contribute to pulmonary arterial constriction.

After the start of anticoagulant therapy, the resolution of the emboli usually occurs rapidly during the first 2 weeks of treatment; however, it may persist in chest imaging studies for months or years. Chronic pulmonary hypertension can occur when the initial embolus fails to undergo lysis or in the context of a recurrent thromboembolism.

Etiology

Three main influences predispose a patient to thrombus formation; These form the so-called Virchow triad, which consists of the following:

• Endothelial injury
• Stasis or turbulence of blood flow
• Hypercoagulability of blood

Thrombosis usually originates as a platelet nest in the valves in the veins of the lower extremities. Additional growth occurs by accretion of platelets and fibrin and progression to red fibrin thrombus, which can rupture and embolize or result in total occlusion of the vein.

The endogenous thrombolytic system leads to a partial dissolution; then, the thrombus is organized and incorporated into the venous wall.

Pulmonary emboli usually arise from thrombi that originate in the deep venous system of the lower extremities; however, they rarely originate in the pelvic, renal or upper limb veins or in the chambers of the right heart.

After traveling to the lung, large thrombi can lodge in the bifurcation of the main pulmonary artery or the lobar branches and cause a hemodynamic compromise. The smaller thrombi typically travel more distally, occluding smaller vessels in the periphery of the lung.

They are more likely to produce pleuritic chest pain when initiating an inflammatory response adjacent to the parietal pleura. Most pulmonary emboli are multiple and the lower lobes are affected more frequently than the upper lobes.

The causes of pulmonary embolism are multifactorial and are not evident in many cases. The causes described in the literature include the following:

• Estasis venous
• Hypercoagulable states
• Immobilization
• Surgery and trauma
• The pregnancy
• Oral contraceptives and estrogen replacement
• Malignancy
• Hereditary factors
• Acute medical illness

A study by Malek et al confirmed the hypothesis that people with HIV infection are more likely to have clinically detected thromboembolic disease. The risk of developing pulmonary embolism or PE increases by 40% in these individuals.

Estasis venous

Venous stasis leads to the accumulation of platelets and thrombin in the veins. The increase in viscosity can occur due to polycythemia and dehydration, immobility, increased venous pressure in heart failure or compression of a vein by a tumor.

Hypercoagulable states

The complex and delicate balance between coagulation and anticoagulation is altered by many diseases, obesity or trauma. It can also happen after surgery.

Concomitant hypercoagulability may be present in disease states in which prolonged venous stasis or vein injury occurs.

Hypercoagulability states can be acquired or congenital. The factor V variant of Leiden that causes resistance to activated protein C is the most common risk factor. The mutation of factor V Leiden is present in up to 5% of the normal population and is the most common cause of familial thromboembolism.

Primary or acquired deficiencies in protein C, protein S and antithrombin III are other risk factors. The deficiency of these natural anticoagulants is responsible for 10% of venous thrombosis in younger people.

Immobilization

Immobilization leads to local venous stasis due to the accumulation of coagulation factors and fibrin, which results in the formation of thrombi. The risk of pulmonary embolism increases with prolonged bed rest or immobilization of a limb in a cast.

In the prospective Investigation study of the diagnosis of pulmonary embolism II (PIOPED II), immobilization (usually due to surgery) was the most common risk factor in patients with pulmonary embolism.

Surgery and trauma

A prospective study conducted by Geerts and colleagues indicated that major trauma was associated with a 58% incidence of PTSD in the lower limbs and an incidence of 18% in the proximal veins.

Surgical and accidental trauma predispose patients to venous thromboembolism by activating coagulation factors and causing immobility. Pulmonary embolism can represent 15% of all postoperative deaths. Leg amputations and surgery of the hip, pelvis and spine are associated with the greatest risk.

Fractures of the femur and tibia are associated with the increased risk of pulmonary embolism related to the fracture, followed by pelvic, spinal, and other fractures. Severe burns also carry a high risk of PE or pulmonary embolism.

The pregnancy

It has been reported that the incidence of thromboembolic disease in pregnancy varies from 1 case in 200 births to 1 case in 1400 births. Fatal events are rare, with 1-2 cases per 100,000 pregnancies.

Oral contraceptives and estrogen replacement

Birth control pills that contain estrogen have increased the occurrence of venous thromboembolism in healthy women. The risk is proportional to the estrogen content and increases in postmenopausal women with hormone replacement therapy. The relative risk is 3 times, but the absolute risk is 20-30 cases per 100,000 people per year.

Malignancy

Malignancy has been identified in 17% of patients with venous thromboembolism. It has been reported that pulmonary emboli occur in association with solid tumors, leukemias, and lymphomas. This is probably independent of the permanent catheters that are often used in such patients.

The neoplasms most commonly associated with pulmonary embolism, in descending order of frequency, are pancreatic carcinoma; bronchogenic carcinoma; and carcinomas of the genitourinary tract, colon, stomach and breast.

Hereditary factors

Hereditary factors associated with the development of pulmonary embolism include the following:

• Antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency
• Factor V Leiden (most common genetic risk factor for thrombophilia)
• Plasminogen abnormality
• Abnormality of the plasminogen activator
• Abnormality of fibrinogen
• Resistance to activated protein C

Acute medical illness

Acute medical conditions associated with the development of pulmonary embolism include the following:

• AIDS (lupus anticoagulant)
• Behçet’s disease
• Congestive heart failure (CHF)
• Myocardial infarction
• Policitemia
• Systemic lupus erythematosus
• Ulcerative colitis

Additional risk factors

Risk factors for pulmonary embolism also include the following:

• Drug abuse (intravenous drugs [IV])
• Drug-induced lupus anticoagulant
• Hemolytic anemias
• Thrombocytopenia associated with heparin
• Homocysteinemia
• Homocystinuria
• Hyperlipidemias
• Phenothiazines
• Trombocitosis
• Varicose veins
• Venografía
• Venous Pacemakers
• Estasis venous
• Warfarin (first days of therapy)
• Inflammatory bowel disease
• Breathing sleep

In the PIOPED II study, 94% of patients with pulmonary embolism had one or more of the following risk factors:

• Immobilization
• Trip of 4 hours or more in the last month
• Surgery in the last 3 months
• Malignancy, especially lung cancer
• Current or past history of thrombophlebitis
• Trauma in the lower extremities and the pelvis during the last 3 months
• Smoking
• Central venous instrumentation in the last 3 months
• Stroke, paresis or paralysis
• Previous pulmonary embolism
• Heart failure
• Chronic obstructive pulmonary disease

Pulmonary thromboembolism in children

Unlike adults, the majority of children (98%) diagnosed with pulmonary emboli have an identifiable risk factor or a serious underlying disorder (see Epidemiology).

In 1993, David et al reported that 21% of children with PE and / or pulmonary embolism had a permanent central venous catheter. Additional series reported the presence of central lines in up to 36% of patients. A clot can form like a fibrin sleeve that lines the catheter.

When the catheter is removed, the fibrin sleeve often breaks off, releasing a nest for the formation of emboli. In another scenario, a thrombus may adhere to the vessel wall adjacent to the catheter.

David and his colleagues also reported that 5-10% of children with venous thromboembolic disease have inherited coagulation disorders, such as antithrombin III, protein C, or protein S deficiency.

In 1997, Nuss et al. They reported that 70% of children diagnosed with pulmonary embolism had antiphospholipid antibodies or alterations in the coagulation regulatory protein. However, this was a small study in a population with clinically recognized pulmonary emboli; therefore, its applicability to the pediatric population in general is uncertain.

One study reported that major thrombosis or pulmonary embolism was present in more than 33% of children treated with long-term hyperalimentation and that pulmonary embolism was the leading cause of death in 30% of these children. Fat embolization can exacerbate this clinical picture.

Dehydration, especially hyperosmolar dehydration, is typically seen in smaller babies with pulmonary emboli.

Epidemiology

Statistics of the United States

The incidence of pulmonary embolism in the United States is estimated at 1 case per 1000 people per year. The 2008 studies suggest that the increasing use of computed tomography (CT) to evaluate patients with possible pulmonary embolism has led to an increase in the incidence of reported pulmonary embolism.

From 1979 to 1998, the age-adjusted mortality rate for pulmonary embolism in the United States decreased from 191 deaths per million population to 94 deaths per million population. Regional studies covering the years after 1998 found a slight decrease in the incidence of mortality or no change in frequency.

Pulmonary embolism is present in 60-80% of patients with PE, although more than half of these patients are asymptomatic. Pulmonary embolism is the third most common cause of death in hospitalized patients, with at least 650,000 cases occurring annually.

Autopsy studies have shown that approximately 60% of patients who died in the hospital had pulmonary embolism, and the diagnosis was omitted in up to 70% of the cases.

Prospective studies have demonstrated PET in 10-13% of all medical patients in bed rest for 1 week, 29-33% of all patients in medical intensive care units, 20-26% of patients with lung diseases to whom they are given bed rest for 3 or more days, 27-33% of patients admitted to a critical care unit after a myocardial infarction and 48% of patients who are asymptomatic after an artery bypass coronary

Venous thromboembolism is a major health problem. The average annual incidence of venous thromboembolism in the United States is 1 person per 1000 population, with approximately 250,000 incidental cases occurring annually.

A challenge to understand the real disease has been that autopsy studies have found that an equal number of patients diagnosed with pulmonary embolism at autopsy were initially diagnosed by physicians.

This has led to estimates of between 650,000 and 900,000 fatal and nonfatal venous thromboembolic events occurring in the United States annually. The incidence of venous thromboembolism has not changed significantly in the last 25 years.

Capturing the true incidence in the future will be a challenge due to the decrease in the autopsy rate. In a 25-year longitudinal prospective study from 1966 to 1990, autopsy rates decreased from 55% to 30% during the study period. Current trends would suggest a continuous decrease in the autopsy rate.

International statistics

The incidence of pulmonary embolism can differ substantially from one country to another; the variation observed is probably due to differences in the accuracy of the diagnosis rather than in the actual incidence.

Canadian data derived from 15 tertiary care centers showed a frequency of 0.86 events per 10,000 pediatric hospitalizations for patients from 1 month to 1 year. The frequency of pulmonary embolism in developed countries has been increasing in comparison with historical data.

This increase in frequency is related to the increase in the use of central venous lines in the pediatric population. The overall frequency in children is still considerably lower than in adults.

Association between sex and pulmonary embolism

The data are contradictory as to whether the male sex is a risk factor for pulmonary embolism; however, an analysis of national mortality data found that pulmonary embolism mortality rates were 20-30% higher among men than among women.

The incidence of venous thromboembolic events in the elderly population is higher among men than among women. In patients younger than 55 years, the incidence of pulmonary disease is higher in women. It is reported that the annual incidence adjusted for age and sex of venous thromboembolism is 117 cases per 100,000 people (PE, 48 cases per 100,000, pulmonary embolism, 69 cases per 100,000).

A prospective study of nurses’ cohorts found an association between idiopathic pulmonary embolism and the hours spent sitting each week.

Women who reported both in 1988 and in 1990 who were sitting more than 40 hours per week had more than double the risk of pulmonary embolism compared to women who reported both years who took less than 10 hours per week.

Association between race and pulmonary embolism

The incidence of pulmonary embolism appears to be significantly higher in blacks than in whites. Mortality rates for pulmonary embolism in African Americans have been 50% higher than those of whites, and those of whites have been 50% higher than those of other races (eg, Asians, Native Americans). ).

Asian / Pacific Islander / American Indian patients have a markedly lower risk of thromboembolism.

Pulmonary embolism in elderly people

Pulmonary embolism is increasingly prevalent in elderly patients; however, the diagnosis is more frequently missed in these patients than in younger patients because respiratory symptoms are often ruled out as chronic.

Even when the diagnosis is made, appropriate therapy is often withheld inappropriately due to bleeding problems. In this patient population, an appropriate diagnostic study and therapeutic anticoagulation with a careful risk-to-benefit assessment is recommended.

Pulmonary embolism in pediatric patients

PET and pulmonary embolism are uncommon in pediatric practice. In 1993, David et al identified 308 children reported in the 1975-1993 medical literature with PE of a limb and / or pulmonary embolism.

In 1986, Bernstein reported 78 episodes of pulmonary embolism per 100,000 hospitalized adolescents. Autopsy studies not selected in children estimate the incidence of pulmonary embolism of 0.05-3.7%.

However, among pediatric patients in whom pulmonary embolus or pulmonary embolism occurs, these conditions are associated with significant morbidity and mortality. Several authors suggest that pulmonary embolism contributes to the death of affected children in approximately 30% of cases.

(Others, however, have reported pulmonary embolism as the cause of death in less than 5% of affected children.

Thromboembolic disease in pregnancy

A population study covering the years 1966-1995 compiled the cases of pulmonary embolism or pulmonary embolism in women during pregnancy or postpartum.

The relative risk was 4.29, and the overall incidence of venous thromboembolism (absolute risk) was 199.7 incidents per 100,000 women-years. Among postpartum women, the annual incidence was 5 times higher than in pregnant women (511.2 versus 95.8 incidents per 100,000 women, respectively).

The incidence of PE was 3 times higher than that of pulmonary embolism (151.8 versus 47.9 incidents, respectively, per 100,000 women). Pulmonary embolism was relatively less common during pregnancy than in the postpartum period (10.6 vs. 159.7 incidents, respectively, per 100,000 women, respectively).

A national review of severe obstetric complications from 1998-2005 found a significant increase in the rate of pulmonary embolism associated with the increasing rate of cesarean delivery.

Pulmonary embolism and postoperative mortality

Pulmonary embolism can represent 15% of all postoperative deaths. Leg amputations and surgery of the hip, pelvis and spine are associated with the greatest risk.

Forecast

The prognosis of patients with pulmonary embolism depends on two factors: the state of the underlying disease and the appropriate diagnosis and treatment. Approximately 10% of patients who develop pulmonary embolism die within the first hour, and 30% die later from recurrent embolism.

Mortality from acute pulmonary embolism can be divided into 2 categories: massive pulmonary embolism and non-massive pulmonary embolism.

Anticoagulant treatment decreases mortality to less than 5%. After 5 days of anticoagulant therapy, 36% of the lung examination defects are resolved; at 2 weeks, 52% is resolved; and at 3 months, 73% is resolved.

The majority of patients treated with anticoagulants do not develop long-term sequelae after the follow-up evaluation. Mortality in patients with undiagnosed pulmonary embolism is 30%.

In the PIOPED study, the 1-year mortality rate was 24%. The deaths occurred due to heart disease, recurrent pulmonary embolism, infection and cancer.

The risk of recurrent pulmonary embolism is due to the recurrence of proximal venous thrombosis; approximately 17% of patients with recurrent pulmonary embolism had proximal PE. In a small proportion of patients, pulmonary embolism does not resolve; therefore, results of chronic thromboembolic pulmonary arterial hypertension.

Elevated plasma levels of natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) have been associated with increased mortality in patients with pulmonary embolism.

In one study, levels of pro-N brain natriuretic peptide greater than 500 ng / l were independently associated with central pulmonary embolism and were a possible predictor of death from pulmonary embolism.

In a study of 270 adult patients with symptomatic pulmonary embolism objectively confirmed, the researchers found that elevated plasma lactate levels (≥2 mmol / l) were associated with an increased risk of mortality and other adverse outcomes, regardless of shock, hypotension , right lateral ventricular dysfunction or injury markers.

Massive pulmonary embolism

As a cause of sudden death, massive pulmonary embolism is the second after sudden cardiac death. Massive pulmonary embolism is defined as the presentation of a systolic blood pressure less than 90 mm Hg. The mortality of patients with massive pulmonary embolism is between 30% and 60%, according to the study cited.

Autopsy studies of patients who died unexpectedly in a hospital setting have shown that approximately 80% of these patients died of massive pulmonary embolism.

The majority of deaths due to massive pulmonary embolism occur in the first 1-2 hours of care, so it is important that the initial treating physician has a systematic and aggressive evaluation and a treatment plan for patients with pulmonary embolism.

Non-massive pulmonary embolism

Non-massive pulmonary embolism is defined as a systolic blood pressure greater than or equal to 90 mm Hg. This is the most common presentation for pulmonary embolism and represents 95.5-96% of patients.

Hemodynamically stable pulmonary embolism has a much lower mortality rate due to treatment with anticoagulant therapy. In non-massive pulmonary embolism, the mortality rate is less than 5% in the first 3-6 months of anticoagulant treatment.

The rate of recurrent thromboembolism is less than 5% during this time. However, recurrent thromboembolism reaches 30% after 10 years.}

Patient education

The importance of adherence to the treatment regimen should be emphasized repeatedly. The patient should be instructed on what to do in case of hemorrhagic complications. Because most patients are given warfarin or low molecular weight heparin upon discharge from the hospital, they should be informed about the possible interactions between these agents and other medications.

Clinical Presentation of Pulmonary Thromboembolism

History

The challenge in the treatment of pulmonary embolism is that patients rarely show the classic presentation of this problem, that is, the abrupt appearance of pleuritic chest pain, shortness of breath and hypoxia.

Studies of patients who died unexpectedly from pulmonary embolism have revealed that these people often complained of bothersome symptoms for weeks before death. Forty percent of these patients had been seen by a doctor in the weeks before their death.

The following risk factors may be indications of the presence of pulmonary embolism:

• Estasis venous
• Hypercoagulable states
• Immobilization
• Surgery and trauma
• The pregnancy
• Oral contraceptives and estrogen replacement
• Malignancy
• Hereditary factors that result in a state of hypercoagulability
• Acute medical illness
• Drug abuse (intravenous drugs [IV])
• Drug-induced lupus anticoagulant
• Hemolytic anemias
• Thrombocytopenia associated with heparin
• Homocysteinemia
• Homocystinuria
• Hyperlipidemias
• Phenothiazines
• Trombocitosis
• Varicose veins
• Venografía
• Venous Pacemakers
• Warfarin (first days of therapy)
• Inflammatory bowel disease

The PIOPED II study listed the following indicators for pulmonary embolism:

• Trip of 4 hours or more in the last month
• Surgery in the last 3 months
• Malignancy, especially lung cancer
• Current or past history of thrombophlebitis
• Trauma in the lower extremities and the pelvis during the last 3 months
• Smoking
• Central venous instrumentation in the last 3 months
• Stroke, paresis or paralysis
• Previous pulmonary embolism
• Heart failure
• Chronic obstructive pulmonary disease

Physical exam

The findings of the physical examination are quite variable in pulmonary embolism and, for convenience, can be grouped into four categories as follows:

• Massive pulmonary embolism
• Acute pulmonary infarction
• Acute embolism without infarction
• Multiple embolisms or pulmonary thrombi

The presentation of pulmonary embolism can vary from sudden catastrophic hemodynamic collapse to gradually progressive dyspnea. (The patient’s poor prior cardiopulmonary status is an important factor leading to hemodynamic collapse).

The majority of patients with pulmonary embolism do not present obvious symptoms in the presentation. In contrast, patients with symptomatic PE usually have pulmonary embolism confirmed in diagnostic studies in the absence of pulmonary symptoms.

Sickle cell anemia often creates a diagnostic difficulty with respect to pulmonary embolism. Often, the initial symptom is a chest infection.

Patients with pulmonary embolism may present atypical symptoms. In such cases, the strong suspicion of pulmonary embolism based on the presence of risk factors may lead to considering pulmonary embolism in the differential diagnosis. These symptoms include the following:

• Seizures
• Syncope
• Abdominal pain
• Fever
• Productive cough
• Wheezing
• Decreasing level of consciousness
• New onset of atrial fibrillation
• Flank pain
• Delirium (in elderly patients)

The diagnosis of pulmonary embolism should be actively sought in patients with respiratory symptoms not explained by an alternative diagnosis. The symptoms of pulmonary embolism are nonspecific; therefore, a high index of suspicion is required, particularly when a patient has risk factors for the condition.

The acute respiratory consequences of pulmonary embolism include the following:

• Increase in alveolar dead space
• Hypoxemia
• Hyperventilation

In patients with recognized pulmonary embolism, the incidence of physical signs has been reported as follows:

• Tachypnea (respiratory rate> 16 / min): 96%
• Rales – 58%
• Second accented heart sound: 53%
• Tachycardia (heart rate> 100 / min): 44%
• Fiebre (temperatura> 37.8 ° C [100.04ºF]) – 43%
• Diaforesis – 36%
• Gallop S 3 or S 4 – 34%
• Clinical signs and symptoms suggesting thrombophlebitis: 32%
• Edema of the lower extremities: 24%
• Heart murmur – 23%
• Cyanosis – 19%

The PIOPED study reported the following incidence of common symptoms of pulmonary embolism:

• Dyspnea (73%)
• Pleuritic chest pain (66%)
• Tos (37%)
• Hemoptisis (13%)

Fever of less than 39 ° C (102.2 ° F) may be present in 14% of patients; however, the temperature is higher than 39.5 ° C (103.1 ° F) Fis, not pulmonary embolism. Tenderness of the chest wall upon palpation, with no history of trauma, may be the only physical finding in rare cases.

Pleuritic chest pain without other symptoms or risk factors may be a presentation of pulmonary embolism. Pleuritic or respirophasic pelvic pain is a particularly troubling symptom. It is reported that pleuritic pain in the chest occurs in up to 84% of patients with pulmonary emboli. Its presence suggests that the plunger is more peripheral and, therefore, may be smaller.

Pulmonary embolism has been diagnosed in 21% of young and active patients who go to the emergency departments (ED) and only complain of pleuritic pain in the chest. These patients generally lack other signs, symptoms, or known risk factors for pulmonary embolism.

Such patients are often dismissed inappropriately with inadequate treatment and nonspecific diagnosis, such as musculoskeletal chest pain or pleurisy.

Massive pulmonary embolism

Patients with massive pulmonary embolism are in shock. They have systemic hypotension, poor perfusion of the extremities, tachycardia and tachypnea. In addition, patients appear weak, pale, sweaty and oliguric and develop a mental disorder.

Signs of pulmonary hypertension may occur, such as a palpable impulse in the second left intercostal space, strong P2, gallop S3 of the right ventricle, and a stronger systolic murmur in the inspiration at the left sternal border (tricuspid regurgitation).

Massive pulmonary embolism has been defined by hemodynamic parameters and evidence of myocardial injury instead of anatomical findings because the former is associated with adverse outcomes.

Although previous studies of CT scans in the diagnosis of pulmonary emboli suggested that central obstruction was not associated with adverse outcomes, a new multicenter study clarifies this observation. Vedovati et al. They found no association between central obstruction and death or clinical deterioration in 579 patients with pulmonary embolus.

However, when a subset of 516 patients who were hemodynamically stable was evaluated, it was found that the central location of the emboli was a risk factor for independent mortality, whereas the distal location was inversely related to the adverse events.

Therefore, anatomical findings by computed tomography may be important to assess the risk in hemodynamically stable patients with pulmonary embolus.

Acute pulmonary infarction

Approximately 10% of patients have peripheral occlusion of a pulmonary artery, which causes a parenchymal infarction. These patients present an acute onset of pleuritic chest pain, dyspnea and hemoptysis. Although chest pain may be clinically indistinguishable from ischemic myocardial pain, normal ECG findings and lack of response to nitroglycerin exclude myocardial pain.

Patients with acute lung infarction have decreased excursion of the involved hemithorax, palpable or audible pleural friction friction, and even localized sensitivity. There may be signs of pleural effusion, such as lack of brightness to percussion and decreased respiratory sounds.

Acute embolism without infarction

Patients with acute embolism without infarction have nonspecific physical signs that can easily be secondary to another disease process. Tachycardia and tachycardia are often detected, sometimes there may be pleuritic pain, crackles can be heard in the area of ​​embolization, and local wheezing is rarely heard.

Multiple embolisms or pulmonary thrombi

Patients with pulmonary emboli and thrombi have physical signs of pulmonary hypertension and cor pulmonale.

Patients may have elevated jugular venous pressure, right ventricular elevation, palpable impulse in the second left intercostal space, S3 gallop of the right ventricle, systolic murmur on the left sternal border that is stronger during inspiration, hepatomegaly, ascites and edema with fovea dependent.

These findings are not specific for pulmonary embolism and require a high index of suspicion to perform appropriate diagnostic studies.

Pulmonary embolism in children

Many physical findings are typically less marked in children than in adults, presumably because children have a greater hemodynamic reserve and, therefore, are more able to tolerate significant hemodynamic and pulmonary changes.

Due to the rarity of pulmonary emboli in children, these patients are probably underdiagnosed. For the same reason, much of the information regarding the diagnosis and management of pulmonary embolism has been derived from adult practice.

Cough is present in approximately 50% of children with pulmonary embolism; tachypnea occurs with the same frequency. Hemoptysis is a characteristic in a minority of children with pulmonary emboli, which occurs in approximately 30% of cases. Crackles are heard in a minority of cases.

Cyanosis and hypoxemia are not prominent features of pulmonary embolism. If present, cyanosis suggests a massive embolism leading to a marked ventilation-perfusion imbalance (V / Q) and systemic hypoxemia. Some case reports describe a massive pediatric pulmonary embolism with normal saturation.

A pleural friction is often associated with pleuritic pain in the chest and indicates an embolism at a peripheral location in the pulmonary vasculature. Signs indicating pulmonary hypertension and right ventricular failure include a strong pulmonary component of the second heart sound, elevation of the right ventricle, distended neck veins, and hypotension.

It is reported that an increase in pulmonary artery pressure is not evident until at least 60% of the vascular bed has been occluded.

A gallop rhythm means ventricular failure, while peripheral edema is a sign of congestive heart failure. Several heart murmurs can be audible, including a tricuspid regurgitant murmur that means pulmonary hypertension.

Fever is an unusual sign that is not specific, and diaphoresis is a manifestation of sympathetic arousal. Signs of other organ involvement in patients with sickle cell anemia, such as seizure crisis, priapism, anemia and stroke, would be triggered.

Complications

Complications of pulmonary embolism include the following:

• Sudden cardiac death
• Obstructive shock
• Pulse-free electrical activity
• Atrial or ventricular arrhythmias
• Secondary pulmonary arterial hypertension
• Cor pulmonale
• Severe hypoxemia
• Intracardiac shunt from right to left
• Lung infarction
• Pleural effusion
• Paradoxical Embolism
• Heparin-induced thrombocytopenia
• Tromboflebitis

Differential diagnoses of pulmonary thromboembolism

Diagnostic considerationsSick cell surgery

The variability of the presentation for pulmonary embolism puts the patient and the clinician in a situation of possible loss of diagnosis. Such missed diagnoses occur in approximately 400,000 patients in the United States per year; Approximately 100,000 deaths could be prevented with proper diagnosis and treatment.

The diagnostic challenge is that the “classic” presentation of the condition is rarely seen, with abrupt onset of pleuritic chest pain, shortness of breath and hypoxia.

Studies of patients who died unexpectedly from pulmonary embolism revealed that patients complained of persistent symptoms, often for weeks, before dying. Forty percent of these patients had been seen by a doctor in the weeks before their death.

Differential diagnoses are extensive and should be carefully considered with any patient considered to have pulmonary embolism. These patients should also have a confirmed alternative diagnosis, or pulmonary embolism should be excluded, before stopping treatment. Additional problems to consider include the following:

• Musculoskeletal pain
• Pleuritis
• Pericarditis
• Salicylate poisoning
• Hyperventilation
• Lung silicone embolism
• Pulmonary trauma
• Acute mediastinitis

Sickle cell anemia often creates a diagnostic difficulty with respect to pulmonary embolism. Often, the initial symptom is a chest infection. Hypoxemia, dehydration and fever cause the formation of intravascular sludge within the pulmonary vasculature (among others).

This promotes a vicious circle that further aggravates local hypoxemia and, ultimately, causes a local tissue infarction. This process is further aggravated by bone marrow infarction, which can cause the release of fatty emboli that are lodged in the pulmonary circulation.

Differential diagnostics

• Acute coronary syndrome
• Acute pericarditis
• The acute respiratory distress syndrome
• Angina pectoris
• Anxiety disorders
• Aortic stenosis
• Atrial fibrillation
• Shock cardiogénico
• Cor Pulmonale
• Dilated cardiomyopathy
• Emphysema
• Fat embolism
• Hypersensitivity pneumonitis
• Mitral stenosis
• Myocardial infarction
• Pneumothorax images
• Idiopathic Pulmonary Arterial Hypertension
• Pulmonary arteriovenous fistulas
• Restrictive cardiomyopathy
• Non-idiopathic pulmonary hypertension
• Sudden cardiac death
• Vena Cava Superior Syndrome in Emergency Medicine
• Syncope

Treatment of Pulmonary Thromboembolism

Focus considerations

The clinical signs and symptoms of pulmonary embolism are nonspecific; therefore, patients with suspected pulmonary embolism – due to unexplained dyspnea, tachypnea or chest pain or the presence of risk factors for pulmonary embolism – should undergo diagnostic tests until the diagnosis is determined or eliminated or confirmed an alternative diagnosis

In addition, routine laboratory findings are nonspecific and are not useful in pulmonary embolism, although they may suggest another diagnosis.

A hypercoagulation study should be performed if there is no obvious cause for the embolic disease. This may include the evaluation of conditions such as the following:

• Antithrombin III deficiency
• Deficiency of protein C or protein S
• Anticoagulant lupus
• Homocystinuria
• Hidden neoplasia
• Connective tissue disorders

More clinical studies are needed to evaluate the usefulness of new approaches to the diagnosis of the condition. The availability of diagnostic tests, as well as the cost-effectiveness analysis, local traditions and the experience of the radiologists involved in the diagnosis, are considerations in the study of a patient in whom a pulmonary embolism is suspected.

Clinical scoring systems

Evidence-based literature supports the practice of determining the clinical probability of pulmonary embolism before proceeding with the test. One study evaluated the performance of four clinical decision rules in addition to the D-dimer test to exclude acute PE.

The four rules, the Wells rule, the simplified Wells rule, the revised Geneva score and the simplified revised Geneva score, showed similar performance to exclude acute PE when combined with a normal D-dimer result.

D-Dimer Tracking in Probability of low to moderate previous test

When the results of the clinical prediction rule indicate that the patient has a low or moderate likelihood of pulmonary embolism before the test, the D-dimer test may be the next step.

D-Dimer, a degradation product produced by plasmin-mediated proteases of cross-linked fibrin, is measured by a variety of assay types, including rapid quantitative, semiquantitative and qualitative rapid immunoabsorbent (ELISA) assays; quantitative and semiquantitative latex; and complete blood analysis.

A systematic review of prospective studies of high methodological quality concluded that ELISAs, especially rapid quantitative ELISA, dominate the comparative classification between D-dimer assays for sensitivity and negative likelihood ratio.

The rapid quantitative ELISA has a sensitivity of 0.95 and a negative likelihood ratio of 0.13; The latter is similar to a normal or near normal lung examination in patients with suspected pulmonary embolism.

Negative results in a high sensitivity D-dimer test in a patient with a low probability of pulmonary embolism prior to the test indicate a low probability of venous thromboembolism and reliably exclude pulmonary embolism.

A large prospective randomized trial found that in patients with a low probability of pulmonary embolism who had negative D-dimer results, the omission of additional diagnostic tests was not associated with an increased frequency of symptomatic venous thromboembolism during the subsequent 6 months.

In a 2012 prospective cohort study, it was observed that a Wells score of 4 or less combined with a negative qualitative D-dimer test safely excluded pulmonary embolism in primary care patients.

The D-dimer test is more reliable to exclude pulmonary embolism in younger patients who do not have associated comorbidity or a history of venous thromboembolism and whose symptoms are short-lived.

However, it has a questionable value in patients who are over 80 years old, who are hospitalized, who have cancer or who are pregnant, because the non-specific elevation of D-dimer concentrations is common in these patients.

The D-dimer test should not be used when the clinical probability of pulmonary embolism is high, since the test has a low negative predictive value in such cases.

The combination of D-dimer results with the measurement of the end-to-end ratio of carbon dioxide to oxygen (etCO2 / O2) may be useful for the diagnosis of pulmonary embolism.

Kline et al found that, in patients at moderate risk with a positive D-dimer (> 499 ng / mL), an etCO2 / O2 <0.28 significantly increased the probability of finding segmental or larger pulmonary embolism on multidetector pulmonary computed tomography angiography , whereas an etCO2 / O2)> 0.45 predicted the absence of segmental or larger pulmonary embolism.

Due to the low specificity, positive measurements of D-dimer are not useful to confirm the diagnosis of venous thromboembolic disease. However, a positive measurement of D-dimer may lead to considering venous thromboembolic disease in the differential diagnosis in selected patients.

In addition, the use of D-dimers in children is not well studied. A small pediatric series reported that D-dimer measurements are negative in 40% of patients. A retrospective series reported a high D-dimer in 86% of the patients in the presentation.

Levels of albumin modified by ischemia

A possible alternative to D-dimer testing is the evaluation of albumin level modified by ischemia (AMI), which suggests that the data is 93% sensitive and 75% specific for pulmonary embolism.

Notably, in a study that compared the prognostic value of AMI with the D-dimer test, the evaluation of AMI in combination with the Wells and Geneva probability scores seemed to have a positive impact on overall sensitivity and negative predictive value.

The positive predictive value of AMI, in particular, is better than D-Dimer. However, it should not be used alone.

White blood cell count

The white blood cell count (WBC) may be normal or elevated in patients with pulmonary embolism, with a white blood cell count of up to 20,000 is not uncommon in patients with this condition.

Arterial blood gases

Arterial blood gas determinations characteristically reveal hypoxemia, hypocapnia, and respiratory alkalosis; however, the predictive value of hypoxemia is quite low. PaO2 and the calculation of the alveolar-arterial oxygen gradient contribute to the diagnosis in a general population that is believed to have pulmonary embolism.

However, in high-risk environments such as patients in postoperative conditions in which other respiratory conditions can be ruled out, a low PaO2 together with dyspnea can have a strong positive predictive value.

The PO2 in the arterial blood gas analysis (GSA) has a zero or even negative predictive value in a typical population of patients in whom pulmonary embolism is suspected clinically. This is contrary to what has been taught in many textbooks, and although it seems counterintuitive, it is demonstrably true.

This is because other etiologies that are disguised as pulmonary embolism are more likely to decrease PO2 than pulmonary embolism.

In fact, because other diseases that can be disguised as pulmonary embolism (for example, chronic obstructive pulmonary disease [COPD], pneumonia, CHF) affect oxygen exchange more than pulmonary embolism, the level of oxygen in the blood usually has an inverse predictive value for pulmonary embolism.

In most contexts, less than half of all patients with symptoms suggestive of pulmonary embolism actually have pulmonary embolism as a diagnosis.

In this population, if a reasonable level of PaO2 is chosen as a dividing line, the incidence of pulmonary embolism will be higher in the group with PaO2 above the dividing line than in the group whose PaO2 is below the divisor.

This is a specific example of a general truth that can be mathematically demonstrated for any test finding with a Gaussian distribution and a population incidence of less than 50%.

Conversely, in a population of patients with a very high incidence of pulmonary embolism and a lower incidence of other respiratory conditions (eg, postoperative orthopedic patients with sudden onset of shortness of breath), a low PO2 has a predictive value very positive for pulmonary embolism.

The above discussion is valid not only for arterial PO2 but also for the alveolar-arterial oxygen gradient and for the level of oxygen saturation measured by pulse oximetry. In particular, pulse oximetry is extremely insensitive, is normal in most patients with pulmonary embolism and should not be used to conduct a diagnostic study.

Levels of troponin

Serum troponin levels may be elevated in up to 50% of patients with moderate to large pulmonary embolism, presumably due to an acute stretch of the right ventricular myocardium.

Although the evaluation of troponin is not currently recommended as part of the diagnostic study, studies have shown that elevated troponin levels in the context of pulmonary embolism correlate with increased mortality.

However, more studies are needed to identify subsets of patients with pulmonary embolism who could benefit from this test.

A meta-analysis of Jiménez et al. He suggested that in acute symptomatic pulmonary embolism, elevated troponin levels do not distinguish between patients at high risk of death and those at low risk.

The combined results of studies that included 1366 normotensive patients with acute symptomatic pulmonary embolism showed that elevated troponin levels were associated with a 4.26-fold increase in overall mortality probabilities (95% confidence interval [CI]). , 13 to 8.50, heterogeneity chi2 = 12.64, freedom = 8, P = .125).

The analysis of the operating characteristic curve of the summary receiver showed a relationship between the sensitivity and the specificity of the troponin levels to predict the general mortality (correlation coefficient of the Spearman range = 0.68, p = 0.046). The pooled probability ratios (LR) were not extreme (negative LR, 0.59 [95% CI, 0.39-0.88], positive LR, 2.26 [95% CI, 1.66 to 3] , 07]).

Serum troponin, although apparently marginal for the purposes of diagnosing pulmonary embolism, can contribute significantly to the ability to stratify patients because of the risk of short-term death or adverse events when they arrive at the emergency department.

In patients with pulmonary embolism and normal blood pressure specifically, the elevated level of serum troponin has been associated with right ventricular overload.

Leptin is another cardiovascular risk factor that may be associated with the outcome in acute pulmonary embolism. Dellas et al performed a prospective analysis of 264 patients with acute pulmonary embolism and found that serum leptin levels were inversely associated with the risk of adverse outcomes.

More studies will be needed to confirm these findings and determine the clinical utility of measuring leptin.

Brain natriuretic peptide

Although brain natriuretic peptide (PNC) tests are neither sensitive nor specific, patients with pulmonary embolism tend to have higher levels of PNC. The PNC test had a sensitivity and specificity of only 60% and 62%, respectively, in a case-control study of 2,213 hemodynamically stable patients with suspected acute pulmonary embolism.

The elevated levels of PNCo of its precursor, the N-terminal pro-cerebral natriuretic peptide (NT-proPNC), correlate with an increased risk of subsequent complications and mortality in patients with acute pulmonary embolism.

A meta-analysis revealed that patients with a PNC level greater than 100 pg / ml or a NT-proPNC level greater than 600 ng / l had an all-cause in-hospital mortality rate between 6 and 16 times higher than those below of these cut points, respectively.

In a second, smaller observational study, serum PNC levels greater than 90 pg / ml were associated with a higher rate of complications, such as the need for cardiopulmonary resuscitation, the need for mechanical ventilation, the need for vasopressor therapy, and death .

The PNC test is not currently recommended as part of the standard assessment of acute pulmonary embolism, and future studies can help define its role in this context.

Elevated levels of brain-type natriuretic peptides (NPCs) can also provide prognostic information.

A meta-analysis showed a significant association between the elevation of the N-terminal-pro-PNC (NT-pro-PNC) and the right ventricle function in patients with pulmonary embolism (p <0.001), which increases the risk of intrahospital course complications (odds ratio [OR] 6.8, 95% confidence interval [CI], 9.0-13) and 30-day mortality (OR 7.6, 95% CI, 3.4-17).

It is important to note that the increase in NT-pro-PNC alone does not justify a more invasive treatment.

A recent study by Scherz et al analyzed a large sample of patients hospitalized with acute pulmonary embolism. Hyponatremia in the presentation was common and was associated with an increased risk of mortality and readmission at 30 days.

Venografía

Venography is the standard criteria for diagnosing PE. With the advent of noninvasive imaging, it has become less common in pediatric and adult practice.

Angiography

Pulmonary angiography is the standard of historical criteria for the diagnosis of pulmonary embolism. After the injection of iodinated contrast, anteroposterior, lateral and oblique studies are performed in each lung. The positive results consist of a filling defect or acute cut of the affected artery (as shown in the image below).

It is described that the non-occlusive emboli have a tram track appearance. Abnormal findings on V / Q scans performed before angiography guide the operator to focus on abnormal areas. Angiography is usually a safe procedure. The mortality rate for patients undergoing this procedure is less than 0.5% and the morbidity rate is less than 5%.

Patients with prolonged pulmonary arterial hypertension and right ventricular failure are considered high-risk patients. The findings of the negative pulmonary angiogram, even if they are false negative, exclude clinically relevant pulmonary embolism.

If multidetector row computed tomography angiography (CTFM) is not available, perform a pulmonary angiogram.

However, the reference criterion for the diagnosis of pulmonary embolism is pulmonary angiography, which however is more invasive and more difficult to perform than the TCFM, and for these reasons, it is rapidly being replaced. However, pulmonary angiography remains a useful diagnostic modality when TCFM can not be performed.

When pulmonary angiography has been performed carefully and completely, a positive result provides almost 100% certainty that there is an obstruction to pulmonary arterial blood flow. A negative pulmonary angiogram provides a certainty greater than 90% for the exclusion of pulmonary embolism.

A positive angiogram is an acceptable endpoint, no matter how abbreviated the study. However, a complete negative study requires visualization of the entire pulmonary tree bilaterally.

This is achieved through the selective cannulation of each branch of the pulmonary artery and the injection of contrast material into each branch, with multiple views of each area. Even then, no embolisms are seen in vessels smaller than the lobulated or third-order arteries.

Small emboli can not be seen angiographically, however, embolic obstruction of these smaller pulmonary vessels is very common when post mortem examination follows a negative angiogram. These small emboli can produce pleuritic chest pain and a small sterile effusion even though the patient has a normal V / Q scan and a normal pulmonary angiogram.

In the majority of patients, however, pulmonary embolism is a disease of multiple recurrences, with large and small emboli already present at the time the diagnosis is suspected. Under these circumstances, it is likely that the V / Q scan and the angiogram will detect at least some of the emboli.

Pulmonary angiography demonstrates subsegmental vessels in more detail than CT scan, although superposition of small vessels remains a limiting factor. As a result, the interobserver agreement rate for isolated subsegmental pulmonary embolism is only 45%.

The routine use of pulmonary CT angiography for the detection of pulmonary emboli has led to an overdiagnosis of the disease, according to a recent study. The excess diagnosis of pulmonary embolism has resulted in a possible inadequate treatment with anticoagulation, one of the main causes of death related to medication.

Between 1998, when pulmonary angiography was introduced by computed tomography and 2006, there was an 80% increase in the incidence of pulmonary embolism but a subsequent decrease in deaths, suggesting that many of the additional emboli that are detected are not clinically important

During this period, the detection rate increased from 62.1 to 112.3 per 100,000 adults in the US. UU And deaths in the US UU Pulmonary embolism decreased from 12.3 to 11.9 per 100,000.

Computed tomography scan

Technical advances in CT scanning, including the development of multidetector matrix scanners, have led to the appearance of computed tomography as an important diagnostic technique in the suspicion of pulmonary embolism.

Contrast-enhanced CT is increasingly used as the initial radiological study in the diagnosis of pulmonary embolism, especially in patients with abnormal chest radiographs in whom the results of the scintigraphy are more likely to be nondiagnostic.

Computed tomography angiography (CTA) is the initial imaging modality of choice for stable patients with suspected pulmonary embolism. The American College of Radiology (ACR) considers thoracic ATC to be the current standard of care for the detection of pulmonary embolism.

A study by Ward et al determined that a selective strategy in which TCA is used after compression ultrasound is cost-effective for patients with a high probability of pulmonary embolism prior to the test. [70] This strategy can reduce the need for TCAs and help eliminate the adverse effects associated with TCA.

With the aim of reducing unnecessary THA and exposure to associated radiation, Drescher et al studied the effect of implementing a computerized decision support system for the evaluation of pulmonary embolism in the emergency department.

Prior to implementation, the diagnostic rate of positive pulmonary embolism for the TCAs performed was 8.3%; later, the positivity rate increased to 12.7%. The positive performance would have been higher (16.7%) if the emergency physicians had adhered in all cases to the result of the decision support system; in 27% of the cases they did not.

Like pulmonary angiography, computed tomography shows embolisms directly, but is noninvasive, is more economical than pulmonary angiography and is widely available.

Computed tomography is the only test that can provide significant additional information related to alternative diagnoses; The results of spiral CT scan (helical) can suggest an alternative diagnosis in up to 57% of patients. This is a clear advantage of CT over pulmonary angiography or scintigraphy.

A study of multidetector computed tomography (MSCT) for the detection of right ventricular dysfunction in 457 patients with acute pulmonary embolism found a reasonable correlation with echocardiography, the reference standard.

The selected criterion, a right-to-left dimensional relationship of 0.9 or more in MCT, had a 92% sensitivity for right ventricular dysfunction. The combination of quantitative assessment of ventricular dimensions by CT and measurement of biomarkers can provide additional diagnostic accuracy for the presence of right ventricular dysfunction.

Chest x-ray

Chest radiographs are abnormal in most cases of pulmonary embolism, but the findings are nonspecific. Common radiographic abnormalities include atelectasis, pleural effusion, parenchymal opacities, and elevation of a hemidiaphragm.

The classic radiographic findings of a pulmonary infarction include a triangular wedge-shaped opacity and pleura with a vertex pointing towards the hilum (Hampton hump) or a decrease in vascularization (Westermark sign). These findings suggest a pulmonary embolism, but they are observed infrequently.

A prominent central pulmonary artery (knuckle sign), cardiomegaly (especially on the right side of the heart) and pulmonary edema are other findings. In the appropriate clinical setting, these findings may be consistent with acute cor pulmonale.

A chest radiograph of normal appearance in a patient with severe dyspnea and hypoxemia, but without evidence of bronchospasm or cardiac shunt, is very indicative of pulmonary embolism.

The ACR recommends chest radiography as the most appropriate study to rule out other causes of chest pain in patients with suspected pulmonary embolism. Initially, the radiographic findings of the thorax are normal in most cases of pulmonary embolism.

However, in later stages, radiographic signs may include a Westermark sign (dilatation of the pulmonary vessels and an acute cut), atelectasis, a small pleural effusion, and an elevated diaphragm.

In general, chest x-rays can not be used to conclusively demonstrate or exclude pulmonary embolism; however, radiography and electrocardiography may be useful to establish alternative diagnoses.

Ventilation-Perfusion Scan

The V / Q exploration of the lungs is an important modality to establish the diagnosis of pulmonary embolism. The V / Q scan can be used when the CT scan is not available or if the patient has a contraindication for CT scan or intravenous contrast material.

Children usually have a more homogeneous perfusion scan; therefore, deficits in perfusion are more likely to represent actual or significant pulmonary embolism than in adults.

The PIOPED II trial provided high, intermediate, and low probability criteria for the V / Q scan diagnosis of pulmonary embolism

The criteria of high probability are the following:

• Two large segmental perfusion defects (> 75% of a segment) without corresponding ventilation or chest radiographic anomalies
• One large segmental perfusion defect and two moderate segmental perfusion defects (25-75% of a segment) without corresponding ventilation or radiographic abnormalities
• Four moderate segmental perfusion defects without corresponding ventilation or chest radiographic abnormalities

The criteria of intermediate probability are the following:

• From a moderate to less than two major segmental perfusion defects without corresponding ventilation or chest radiographic abnormalities
• Corresponding V / Q defects and radiographic parenchymal opacity in the lower lung zone
• Simple defects of V / Q of moderate coincidence with normal chest radiographic findings
• V / Q correspondence and small chest X-ray pleural effusion
• Difficult to categorize as normal, low or high probability

The criteria of low probability are the following:

• Multiple matching V / Q defects, regardless of size, with normal chest radiographic findings
• Corresponding V / Q defects and radiographic parenchymal opacity in the upper or middle lung zone
• Corresponding V / Q defects and large pleural effusion
• Any perfusion defect with substantially greater radiographic abnormality
• Defects surrounded by normally perfused lung (band sign)
• More than three small segmental perfusion defects (<25% of a segment) with normal chest radiographic findings
• Non-segmental perfusion defects (cardiomegaly, aortic impression, enlarged thread)

The normal finding is the presence of perfusion and perfusion defects that describe the shape of the lung seen on the chest radiograph.

The criterion of very low probability is the presence of three small segmental perfusion defects (<25% of a segment) with normal chest radiographic findings.

In the PIOPED II study, very low probability V / Q scans in patients whose Wells score indicated a low probability of pulmonary embolism prior to the test, reliably excluded pulmonary embolism.

Electrocardiograph

The most common ECG abnormalities in the context of pulmonary embolism are tachycardia and nonspecific ST-T wave abnormalities. The finding of S1 Q3 T3 is nonspecific and insensitive in the absence of clinical suspicion of pulmonary embolism.

The classic findings of right cardiac stress and acute cor pulmonale are high and pointed P waves in lead II (P pulmonale); deviation of the right axis; right branch block; a pattern S1 Q3 T3; or atrial fibrillation.

Unfortunately, only 20% of patients with proven pulmonary embolism have any of these classic electrocardiographic abnormalities. If there are electrocardiographic abnormalities, they may be suggestive of pulmonary embolism, but the absence of such anomalies does not have a significant predictive value.

Magnetic resonance image

With magnetic resonance imaging (MRI), the evidence of pulmonary emboli can be detected by using standard or controlled spin-echo techniques. The pulmonary emboli demonstrate a greater signal intensity within the pulmonary artery.

By obtaining a sequence of images, this signal that originates from the slow blood flow can be distinguished from pulmonary embolism. However, this remains a problem in pulmonary hypertension.

Magnetic resonance angiography is performed after the intravenous administration of gadolinium.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or dermopathy nephrogenic fibrosing (DFN).

The disease has occurred in patients with moderate-to-terminal kidney disease after receiving a gadolinium-based contrast agent to improve magnetic resonance or magnetic resonance imaging.

FSN / DFN is a debilitating and sometimes fatal disease. Features include red or dark patches on the skin; burning, itching, swelling, hardening and hardening of the skin; yellow spots on the whites of the eyes; joint stiffness with problems moving or straightening the arms, hands, legs or feet; deep pain in the bones of the hip or ribs; and muscle weakness

MRI has a sensitivity of 85% and a specificity of 96% for central, lobular and segmental emboli; Magnetic resonance imaging is inadequate for the diagnosis of subsegmental emboli.

Few data are available regarding the use of MRI in children suspected of having a pulmonary embolism. Its use in these patients should be considered research at this time.

Few investigators have reported on the feasibility of MRI in the evaluation of pulmonary embolism. However, the role of MRI is mainly limited to the evaluation of patients with renal insufficiency or other contraindications to the use of iodinated contrast material.

The most recent blood contrast agents and respiratory navigators can improve the role of MRI in the diagnosis of pulmonary embolism.

Echocardiography

This modality generally has limited accuracy in the diagnosis of pulmonary embolism. Transesophageal echocardiography can identify a central pulmonary embolism, and the sensitivity for central pulmonary embolism is reported to be 82%. The overall sensitivity and specificity for central and peripheral pulmonary embolism is 59% and 77%.

Echocardiography (ECHO) provides useful information. It can allow the diagnosis of other conditions that can be confused with a pulmonary embolism, such as a pericardial effusion. ECHO allows visualization of the right ventricle and assessment of pulmonary arterial pressure.

ECHO fulfills a prognostic function; the mortality rate is almost 10% in the presence of right ventricular dysfunction and 0% in the absence of right ventricular dysfunction. (Vanni et al reported that a right ventricular strain pattern is associated with a worse short-term outcome.

ECHO can be used to identify the presence of emboli in the right chamber. Subcostal vision is preferable in the initial screening of mechanical activity and pericardial fluid and for the general evaluation of global and regional anomalies.

To obtain a subcostal view, place the transducer in the left subcostal margin with the beam directed toward the left shoulder. The parasternal view allows the visualization of the aortic valve, the proximal ascending aorta and the posterior pericardium, and allows the determination of the size of the left ventricle.

It is particularly useful when the subcostal view is difficult to obtain. To obtain a parasternal view, place the transducer in the left parasternal area between the second and fourth intercostal spaces. The plane of the beam is parallel to a line drawn from the right shoulder to the left hip.

Several echocardiographic findings have been proposed for the non-invasive diagnosis of right ventricular dysfunction in the patient’s bedside, including right ventricular enlargement and / or hypokinesia of the free wall, septal displacement to the left and evidence of pulmonary hypertension.

If right ventricular dysfunction is observed on cardiac ultrasound, the diagnosis of acute or massive submassive pulmonary embolism is accepted. Although the presence of right ventricular dysfunction can be used to support the clinical suspicion of pulmonary embolism, prognostic information can be obtained by assessing the severity of right ventricular dysfunction.

Duplex ultrasound

The diagnosis of pulmonary embolism can be demonstrated by demonstrating the presence of a PET at any site. This can sometimes be achieved non-invasively through the use of duplex ultrasound.

To search for PET using ultrasound, the ultrasound transducer is placed against the skin and pressed in firmly enough to compress the vein being examined.

In an area of ​​normal veins, the veins are easily compressed completely, while the muscular arteries are extremely resistant to compression. Where there is a PET scan, the veins do not collapse completely when pressure is applied with the ultrasound probe.

A prospective observational study of 146 patients with suspicion or confirmation of pulmonary embolism indicates that the identification of right ventricular dilatation in the bedside echocardiography can aid in the diagnosis of pulmonary embolism.

The bedside echocardiography showed dilatation of the right ventricle in 15 of the 30 patients who had pulmonary emboli, compared with 2 of the 116 patients without pulmonary emboli.

The presence of dilation of the right ventricle in the bedside echocardiography has a sensitivity of 50%, specificity of 98% and positive and negative predictive values ​​of 88% for the diagnosis of pulmonary embolism.

Most of the 15 patients with confirmed pulmonary embolism and right ventricular dilatation had proximal clots, while most of those with confirmed pulmonary emboli and a normal right ventricle / left ventricle had more distal clots.

Note that a negative ultrasound scan does not rule out PE, since many PET scans occur in areas that are inaccessible for ultrasound examination. Before an ultrasound examination can be considered negative, the entire deep venous system should be interrogated by a compression test centimeter by centimeter of each vessel.

In two thirds of patients with pulmonary embolism, the PET site can not be visualized with ultrasonography, so a negative duplex ultrasound does not significantly reduce the likelihood of pulmonary embolism.

Treatment and management of pulmonary thromboembolism

Focus considerations

However, even in patients who are completely anticoagulated, PE and PE can recur, and often do. The new EP in the hospital can occur in the following patients despite therapeutic anticoagulation:

• Patients with non-floating PE without EP at presentation (3%)
• Patients who have a floating thrombus but do not have PE (13%)
• Patients who have PE but do not have a floating thrombus (11%)
• Patients presenting with PE who have a visible thrombus in venography (39%)

Deciding how to treat a venous thrombosis that can lead to PE is difficult. A survey of Canadian pediatric intensivists reported the following four commonly used patient factors to determine if a venous thrombosis is clinically important:

• Clinical suspicion of a PE
• symptom
• Detection of thrombosis in the clinical examination
• Presence of an acute or chronic cardiopulmonary comorbidity that affects the patient’s ability to tolerate PE

Anticoagulants are the treatment of choice in most children with pulmonary emboli. Thrombolytics are rarely used. To date, there is little data available on the use of LMWH in children with thromboembolic disease.

Trombolisis

All patients with PD require a rapid risk stratification. Thrombolytic therapy should be used in patients with acute PE associated with hypotension (systolic BP <90 mm HG) who do not have a high risk of bleeding.

Do not delay thrombolysis in this population because an irreversible cardiogenic shock can develop. Thrombolytic therapy is suggested in selected patients with acute PE not associated with hypotension and with a low risk of bleeding whose initial clinical presentation or clinical course after initiating anticoagulation suggests a high risk of developing hypotension.

The assessment of the severity of pulmonary embolism, the prognosis and the risk of bleeding determine whether thrombolytic therapy should be initiated. Thrombolytic therapy is not recommended for most patients with acute PE not associated with hypotension.

Although most studies demonstrate the superiority of thrombolytic therapy with respect to the resolution of radiographic and hemodynamic abnormalities within the first 24 hours, this advantage disappears 7 days after treatment.

Controlled clinical trials have not shown benefits in terms of reduced mortality rates or earlier resolution of symptoms when compared to heparin.

A large retrospective review suggests that the use of thrombolytic therapy in unstable patients with PD may lead to reduced mortality compared to anticoagulation therapy alone. The concomitant use of thrombolytic therapy and vena cava filters in such patients can reduce mortality even more.

In a meta-analysis of 16 randomized studies comparing thrombolytic therapy with anticoagulant therapy in patients with pulmonary embolism, including patients at intermediate risk, hemodynamically stable with right ventricular dysfunction, Chatterjee et al.

They found that thrombolytic therapy, compared to standard anticoagulant therapy, reduced mortality by 47%, but was associated with a 2.7-fold increase in major bleeding.

The researchers also found, however, that the rate of major bleeding did not increase significantly with thrombolysis in patients younger than 65 years, while it tripled in the subgroup of patients older than 65 years.

Thrombolytic therapy was associated with an increased risk of intracranial hemorrhage and a lower risk of recurrent pulmonary embolism. Until randomized clinical trials demonstrate a clear morbidity or mortality benefit, the role of thrombolytic therapy in the treatment of acute pulmonary embolism will remain controversial (especially in the treatment of intermediate-risk patients).

The currently accepted indications for thrombolytic therapy include hemodynamic instability (systolic BP <90 mm Hg) or an evaluation of the clinical risk factor that suggests that hypotension is likely to develop.

Anticoagulation

Unfractionated heparin therapy

In patients with acute PE, anticoagulation with IV HNF, LMWH or fondaparinux is preferable to anticoagulation. Most patients with acute PE should receive LMWH or fondaparinux instead of HNF IV.

In patients with PD, if doubts arise regarding subcutaneous absorption, there is severe renal insufficiency or if thrombolytic therapy is being considered, IVFNH is the recommended form of initial anticoagulation.

Physicians often choose to use FNH IV instead of LMWH and fondaparinux in specific clinical circumstances where medical or surgical procedures are likely to be performed and the short half-life of FNH IV allows temporary cessation of anticoagulation and presumptive Reduction of bleeding risk during the procedure.

Although this strategy has limited support evidence, it seems to represent a reasonable practice. The effectiveness of heparin therapy depends on reaching a critical therapeutic level of heparin within the first 24 hours of treatment. The critical therapeutic level of heparin is 1.5 times the reference control value or the upper limit of the normal range of activated partial thromboplastin time (aPTT).

It is expected that this level of anticoagulation corresponds to a heparin blood level of 0.2-0.4 U / ml by the protamine sulfate titration assay and 0.3-0.6 by the anti-factor X assay.

Each laboratory should establish the minimum therapeutic level for heparin, as measured by the aPTT, to match a blood level of heparin of at least 0.2 U / ml for each batch of thromboplastin reagent used.

If HNF IV is chosen, an initial bolus of 80 U / kg or 5000 U should be administered followed by an infusion of 18 U / kg / h or 1300 U / h, with the objective of reaching and maintaining the APTT rapidly at levels corresponding to to therapeutic heparin levels. Fixed doses and controlled regimens of subcutaneous UFH are available, which are acceptable alternatives.

Low molecular weight heparin therapy

Current guidelines for patients with acute PE recommend LMWH for IV HNF (grade 2C) and for HNF SC (grade 2B). [5] In patients receiving treatment with LMWH, regimens are preferred once a day instead of twice daily regimens (grade 2C).

The choice between fondaparinux and LMWH should be based on local considerations to include cost, availability and familiarity of use.

LMWH have many advantages over HNF. These agents have a greater bioavailability, can be administered by subcutaneous injections and have a longer anticoagulant effect. A fixed dose of LMWH can be used, and aPTT monitoring in the laboratory is not necessary.

Trials comparing LMWH with UFH have shown that LMWH is at least as effective and as safe as UFH. Studies have not indicated any significant difference in recurrent thromboembolic events, severe bleeding or mortality between the 2 types of heparin.

LMWH can be safely administered in an outpatient setting. This has led to the development of programs in which patients with clinically stable PE are treated at home, with substantial cost savings.

The ACCP guidelines suggest that patients with low risk PE who have acceptable home circumstances were discharged early from the hospital (ie, before the first five days of treatment) (grade 2B).

An open-label, randomized, international trial compared to outpatient treatment and inpatient treatment (both using LMWH enoxaparin as initial therapy) of low-risk PD patients and concluded that outpatient treatment was not inferior to inpatient treatment.

Direct inhibitors of thrombin and factor Xa inhibitors

Apixaban, dabigatran, rivaroxaban and edoxaban are alternatives to warfarin for the prophylaxis and treatment of PE. Apixaban, edoxaban and rivaroxaban inhibit factor Xa, while dabigatran is a direct inhibitor of thrombin.

Rivaroxaban

Rivaroxaban (Xarelto) is an oral factor Xa inhibitor approved by the FDA in November 2012 for the treatment of PE or EP, and to reduce the risk of recurrence of PE and PE after initial treatment.

The approval for this indication was based on studies that totaled 9478 patients with PE or PE. Participants were randomly assigned to receive rivaroxaban, a combination of enoxaparin and a vitamin K antagonist (VKA) (eg, Warfarin) or a placebo.

The endpoints of the study were designed to measure the number of patients who experienced recurrent symptoms of PE, PE or death after receiving treatment. In addition, the results of prolonged treatment demonstrated a reduced risk of recurrence of PE and PE.

Approximately 1.3% in the rivaroxaban group experienced recurrent PE or PE compared to 7.1% in the placebo group.

The results of the Einstein-EP study provide an important advance in the treatment of symptomatic PE. In a prospective, open-label study, 4832 patients were randomized to receive rivaroxaban or enoxaparin followed by a dose-adjusted vitamin K antagonist for 3, 6 or 12 months.

The treatment with a fixed-dose regimen of rivaroxaban was not inferior to the standard treatment and had a satisfactory safety profile.

Data from a pooled analysis of the EINSTEIN-EP and EINSTEIN-TEP studies in the treatment of pulmonary embolism or pulmonary embolism suggest that rivaroxaban is as effective in preventing recurrence of VTE as the administration of enoxaparin followed by a vitamin K antagonist. .

Rivaroxaban may also be associated with less bleeding, particularly in elderly patients and those with moderate renal impairment.

Apixabán

Apixaban was approved for the treatment of PE in August 2014. The approval for the treatment of PE and the prevention of recurrence was based on the result of AMPLIFY (Apixaban for the initial treatment of pulmonary embolism and deep thrombosis as first line treatment).

AMPLIFY-EXT studies, in which treatment with apixaban was compared with treatment with enoxaparin and warfarin.

The AMPLIFY study showed that, compared to the standard anticoagulant regimen, apixaban therapy resulted in a 16% reduction in the risk of a composite endpoint that included recurrent symptomatic venous thromboembolism (VTE) or death associated with VTE.

Therefore, this breakthrough offers the possibility of a safe and effective anticoagulation regimen for patients with the advantages of simplicity and cost effectiveness compared to current treatment strategies.

Dabigatran

Dabigatran (Pradaxa) was approved by the FDA in 2014 for the treatment of PE and PE and to reduce venous thromboembolic recurrence. In the RE-COVER and RE-COVER 2 studies, patients with PE and PE who had received initial parenteral anticoagulation (eg, Heparin IV, LMWH SC) for 5-10 days were randomized to warfarin or dabigatran.

These two trials showed that dabigatran was not inferior to warfarin in reducing PE and PE, and was associated with lower bleeding rates.

They were

Edoxaban (Savaysa) was approved by the FDA in January 2015 for the treatment of PE and PE in patients who have been initially treated with a parenteral anticoagulant for 5-10 days. The approval was based on the Hokusai-TEV study, which included 3,319 patients with PD.

Of these patients, 938 had right ventricle dysfunction, as assessed by measuring N-terminal pro-brain natriuretic peptide levels. The rate of recurrent VTE in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group.

Edoxaban was not inferior to standard high-quality warfarin therapy and caused significantly less bleeding in a broad spectrum of patients with VTE, including those with severe pulmonary embolism.

Betrixabán

Betrixabán, a factor Xa inhibitor, was approved by the FDA in June 2017. It is indicated for the prophylaxis of VTE in adults hospitalized for acute medical illness who are at risk of thromboembolic complications due to moderate or severe restricted mobility and other factors. risk that can cause TEV.

The approval of betrixaban was based on the data from the phase 3 APEX studies. These randomized, double-blind, multinational trials compared the long-lasting betrixaban (35-42 days) with the short-lived enoxaparin (6-14 days) for VTE in 7513 patients hospitalized with acute medical illnesses with VTE risk factors.

Patients in the betrixaban group took an initial dose of 160 mg orally on day 1, followed by 80 mg once daily for 35 to 42 days, and received a placebo injection once a day for 6-14 days . Patients in the enoxaparin group received 40 mg subcutaneously once a day for 6-4 days and took an oral placebo once a day for 35-42 days.

Efficacy was measured in 7441 patients using a composite outcome score composed of the occurrence of asymptomatic or symptomatic proximal deep vein thrombosis, non-fatal pulmonary embolism, cerebrovascular accident or death related to VTE. Betrixaban showed a significant decrease in episodes of VTE compared with enoxaparin.

Fondaparinux

In patients with acute PE, fondaparinux as initial treatment is favored by FNH IV and FNH SC. The choice between fondaparinux and LMWH should be based on local considerations to include cost, availability and familiarity of use.

Fondaparinux is a synthetic polysaccharide derived from the antithrombin binding region of heparin. Fondaparinux catalyzes the inactivation of factor Xa by antithrombin without inhibiting thrombin.

Once daily, fondaparinux was found to have similar rates of recurrent PE, bleeding, and death as UFH IV, according to an open randomized study of 2213 patients with symptomatic pulmonary embolism. In general, the use of LMWH or fondaparinux is recommended over HNF IV and HNF SC.

This is due to a more predictable bioavailability, a faster onset of the complete anticoagulant effect and the benefit of not typically needing to control the anticoagulant effect. However, if uncertainty arises with respect to the precision of the dosage, factor Xa levels can be controlled to determine efficacy.

Warfarin therapy

A vitamin K antagonist such as warfarin should be started on the same day as anticoagulant therapy in patients with acute PE. Parenteral anticoagulation and warfarin should be continued together for a minimum of at least five days and until the RIN is 2.0.

The anticoagulant effect of warfarin is mediated by the inhibition of vitamin K-dependent factors, which are II, VII, IX and X. The maximum effect does not occur until 36-72 hours after administration of the drug, and the dosage It is difficult to assess.

A prothrombin time ratio is expressed as an RIN and is monitored to assess the suitability of warfarin therapy. The recommended therapeutic range for venous thromboembolism is an RIN of 2-3. This level of anticoagulation markedly reduces the risk of hemorrhage without loss of effectiveness.

Initially, RIN measurements are performed daily; Once the patient is stabilized with a specific dose of warfarin, RIN determinations can be performed every 1-2 weeks or at longer intervals.

Duration of anticoagulant therapy

A patient with a first thromboembolic event that occurs in the context of reversible risk factors, such as immobilization, surgery or trauma, should be treated with warfarin for at least 3 months. No differences were observed in the recurrence rate in any of the 2 studies comparing 3 versus 6 months of anticoagulant therapy in patients with first idiopathic (or unprovoked) events.

The current recommendation is anticoagulation for at least 3 months in these patients; the need to extend the duration of anticoagulation should be reevaluated at that time.

The current ACCP guidelines recommend that all patients with unprovoked PE receive three months of anticoagulation therapy for a shorter duration of treatment and have an evaluation of the risk-benefit ratio of prolonged treatment at the end of three months (grade 1B ).

Patients with a first episode of venous thromboembolism and with a low or moderate risk of bleeding should have a prolonged anticoagulant treatment (grade 2B). Patients with a first episode of venous thromboembolism who have a high risk of bleeding should have a treatment limited to three months (grade 1B).

In patients with a second unprovoked episode of venous thromboembolism and risk of low or moderate haemorrhage, prolonged anticoagulant therapy is recommended (grades 1B and 2B, respectively). In patients with a second episode of venous thromboembolism and a high risk of hemorrhage, three months of anticoagulation is preferred over prolonged anticoagulation (grade 2B).

Patients with PD and pre-existing irreversible risk factors, such as deficiency of antithrombin III, protein S and C, mutation of factor V Leiden or the presence of antiphospholipid antibodies, should be subjected to long-term anticoagulation.

Patients with cancer

Patients who have PE in association with an active neoplasm present challenges for long-term treatment due to their increased continual risk of recurrence of VTE and PE.

The ninth edition of the ACCP guidelines recommends that such patients receive a prolonged anticoagulation compared to the three-month therapy if they have a low or moderate risk of hemorrhagic complications (grade 1B).

If patients with active neoplasia have a high risk of bleeding, it is suggested that they receive prolonged therapy, although the supporting evidence is less conclusive (grade 2B). For the treatment of PD in patients with cancer, LMWH is recommended in preference to a vitamin K antagonist such as warfarin (grade 2B).

However, some cancer patients choose not to have long-term treatment with LMWH due to the need for daily injections and treatment costs. If patients with cancer with PD choose not to receive treatment with LMWH, a vitamin K antagonist such as warfarin over dabigatran or rivaroxaban (grade 2C) is preferred.

Heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is a transient prothrombotic disorder initiated by heparin. The main characteristics of HIT are (1) thrombocytopenia resulting from platelet activation mediated by immunoglobulin G and (2) in vivo generation of thrombin and increased risk of venous and arterial thrombosis.

The highest frequency of HIT, 5%, was reported in patients undergoing orthopedic surgery who received up to 2 weeks of unfractionated heparin. HIT occurred in approximately 0.5% of patients undergoing orthopedic surgery who received LMWH for up to 2 weeks.

HIT may manifest clinically as the extension of the thrombus or the formation of a new arterial thrombosis. HIT should be suspected as long as the patient’s platelet count falls below 100,000 / μL or less than 50% of the reference value, usually after 5-15 days of heparin therapy.

For patients receiving heparin where the risk of HIT is believed to be greater than 1%, the guidelines suggest that platelet counts are obtained every two or three days from day 4 through day 14 of treatment or until discontinued. heparin (grade 2C). [5] The definitive diagnosis is made by performing a platelet activation factor assay.

The treatment of patients who develop HIT involves suspending all heparin products, including catheters and heparin-coated catheters, and initiating an alternative non-heparin anticoagulant, even when thrombosis is not clinically evident.

In patients with HIT with or without thrombosis, the use of lepirudin, argatroban or danaparoid is preferred instead of the continued use of heparin, LMWH or the initiation or continuation of a vitamin K antagonist (grade 1C). If a vitamin K antagonist has already been started when HIT is diagnosed, the guidelines recommend discontinuing it and administering vitamin K (grade 2C).

When HIT has been confirmed, vitamin K antagonists should not start until the platelet count has recovered to at least 150 x 109 / L (grade 1C), should be started at low doses (ie, 5 mg warfarin ), and should be administered concomitantly with an anticoagulant that does not contain heparin for a minimum of five days and until the RIN is within the target range (grade 1C).

In patients with renal insufficiency who have HIT and thrombosis, argatroban is preferred over other non-heparin anticoagulants (grade 2C).

Resistance to heparin

Few patients with venous thromboembolism require large doses of heparin to achieve optimal activated partial thromboplastin time (aPTT). Those patients who do need them have increased plasma concentrations of factor VIII and heparin binding proteins.

The increase in the concentration of factor VIII causes the dissociation between the values ​​of aPTT and heparin in plasma. The aPTT is suboptimal, but patients have adequate levels of heparin after the protamine titration. This commonly occurs in patients with concomitant inflammatory disease.

The monitoring of the results of the Xa antifactor assay in this situation is safe and effective and results in a smaller escalation of the heparin dose compared to monitoring with aPTT. When a therapeutic level of aPTT can not be achieved with large doses of UFH, the determination of plasma heparin concentration or LMWH therapy should be instituted.

Embolectomía

Either embolectomy with catheter and fragmentation or surgical embolectomy are reasonable for patients with massive pulmonary embolism who have contraindications to fibrinolysis or who remain unstable after receiving fibrinolysis.

If these procedures are not available locally, it is reasonable to consider transferring the patient to an institution experienced in one of these procedures, provided that the transfer can be done safely.

In patients with acute submassive PE, embolectomy with catheter or surgical embolectomy may be considered if they have clinical evidence of an adverse prognosis (ie, new hemodynamic instability, worsening of respiratory failure, severe right ventricular dysfunction, or increased myocardial necrosis).

These interventions are not recommended for patients with sub-acute or low-risk acute pulmonary embolism who have minor right ventricular dysfunction, minor myocardial necrosis, and clinical worsening.

Vena Cava Filters

Patients with acute PE should not routinely receive vena cava filters in addition to anticoagulants. An ideal VCI filter should be placed easily and safely using a percutaneous, biocompatible and mechanically stable technique, and capable of trapping emboli without causing occlusion of the vena cava.

The interruption of VCI by inserting a VCI filter (Greenfield filter) is only indicated in the following configurations:

• Patients with acute venous thromboembolism who have an absolute contraindication to anticoagulant therapy (eg, recent surgery, hemorrhagic stroke, active or recent significant bleeding)
• Patients with massive PE who survived but in whom the recurrent embolism will invariably be fatal
• Patients who have objectively documented recurrent venous thromboembolism, despite adequate anticoagulant therapy

In patients with a limited time indication for IVC filter placement (eg, a short-term contraindication to anticoagulation), it is reasonable to select a recoverable IVC filter and evaluate the patient periodically for filter recovery.

After the placement of a VCI filter, anticoagulation should be resumed once the contraindications for anticoagulation or active bleeding complications have been resolved.

Support care

Compression socks

For patients who have had a proximal TEP, the use of elastic compression stockings provides a safe and effective adjuvant treatment that can limit postphlebitic syndrome. We recommend the stockings with a pressure of 30-40 mm Hg in the ankle, used during 2 years after diagnosis (grade 2B) to reduce the risk of postphlebitic syndrome.

Compression stockings with a real gradient are very elastic, providing a compression gradient that is higher in the fingers and gradually decreases to the level of the thigh. This reduces the capacitive venous volume by approximately 70% and increases the measured blood flow velocity in the deep veins by a factor of 5 or more.

Compression stockings of this type have been shown to be effective in the prophylaxis of thromboembolism and are also effective in preventing thrombus progression in patients who already have PE and pulmonary embolism.

A 1994 meta-analysis calculated an odds ratio of PE risk of 0.28 for gradient compression means (compared to no prophylaxis) in patients undergoing abdominal surgery, gynecological surgery or neurosurgery.

Other studies found that gradient compression stockings and LMWH were the most effective modalities to reduce the incidence of PE after hip surgery; They were more effective than subcutaneous UFH, oral warfarin, dextran or aspirin.

The ubiquitous white stockings known as antiseptic stockings or “Ted hose” produce a maximum compression of 18 mm Hg. Ted hoses are rarely equipped in such a way as to provide even inadequate gradient compression.

Because they provide such limited compression, they are not effective in the treatment of PE and pulmonary embolism, nor have they proven effective as prophylaxis against recurrence.

Gradient compression pantyhose of 30-40 mm Hg are available in sizes for pregnant women. They are recommended by many specialists for all pregnant women because they not only prevent PTE, but also reduce or prevent the development of varicose veins during pregnancy.

Additional support therapies

The activity is recommended according to tolerance. Early ambulation on bed rest is recommended when possible (grade 2C recommendation).

The pharmacological support of the cardiovascular system may be necessary. Dopamine and dobutamine are the usual inotropic agents. Mechanical ventilation may be necessary to provide respiratory support and as adjuvant therapy for a defective circulatory system.

Children with sickle cell disease who have pulmonary symptoms require treatment with a macrolide antibiotic and cephalosporin. Your clinical status should be monitored closely to anticipate those children who may develop acute chest syndrome.

The transfusion with concentrated red blood cells (either simple or exchange) improves oxygenation immediately, which helps break the vicious circle described above. Intravenous fluids may help or may damage the hypotensive patient due to a pulmonary embolism, depending on which point of the Starling curve describes the patient’s condition.

A prudent trial of a small fluid bolus can be attempted, with careful monitoring of systolic and diastolic blood pressures and immediate cessation if the situation worsens after fluid bolus. The improvement or normalization of blood pressure after fluid loading does not mean that the patient has become hemodynamically stable.

Individuals with acute submassive pulmonary embolisms have low levels of endogenous activated protein C. A study by Dempfle et al determined that the administration of drotrecogin alfa (activated) together with therapeutic doses of enoxaparin improved the inhibition of fibrin formation in these patients.

Drotrecogin alfa was withdrawn from the world market on October 25, 2011 after analysis of the global test of recombinant human-activated protein C in severe sepsis (PROWESS) -SHOCK. Drotrecogin alfa failed to demonstrate a statistically significant reduction in all-cause mortality at 28 days in patients with severe sepsis and septic shock.

The trial results observed a 28-day all-cause mortality rate of 26.4% in patients treated with drotrecogin alfa activated compared with 24.2% in the study placebo group.

Long-term monitoring

PT must be measured on a regular basis; the goal is an RIN of 2-3.

The duration of treatment depends on the presence of risk factors. If there are no underlying risk factors, the therapy can be discontinued in 1-2 months. If there are risk factors present, especially anticardiolipin antibodies, therapy should continue for at least 4-6 months.

Long-term anticoagulation is essential for patients who survive initial PE or pulmonary embolism. The optimal total duration of anticoagulation is controversial, but the general consensus holds that at least 6 months of anticoagulation is associated with a significant reduction in recurrence and a positive net benefit.

Patients can start treatment with concomitant warfarin and unfractionated heparin for 5 days in the hospital, with high with warfarin alone when the international normalized index (NIR) is 2. Alternatively, patients can be discharged with concomitant therapy with LMWH and warfarin for at least 5 days.

At least 5 days Then, LMWH is suspended in the outpatient setting when the RIN reaches 2.

Pulmonary embolism in pregnancy

The risk of venous thromboembolism increases during pregnancy and the postpartum period. Pulmonary embolism is the leading cause of death in pregnancy. PET and pulmonary embolism are common during all the trimesters of pregnancy and for 6-12 weeks after delivery.

Diagnosis

The diagnostic approach for patients with pulmonary embolism should be exactly the same in a pregnant patient as in a non-pregnant patient. A nuclear perfusion lung scan is safe during pregnancy, as is a chest CT scan.

The guidelines of professional societies on the diagnosis of pulmonary embolism make this evaluation easier and reduce the risks of radiation to the fetus.

If the patient has a low probability of pretesting for pulmonary embolism and a normal D-dimer test result, clinical exclusion of future investigations is recommended. When the suspicion is high, patients should undergo a bilateral Doppler evaluation of the leg.

If the results are positive, the patient should receive treatment for pulmonary embolism. If the results are negative, pulmonary angiotomography is the next step. To rule out contrast-induced hypothyroidism, all neonates exposed to iodinated contrast in the uterus should monitor their serum thyrotropin level in the first week of life.

Treatment

Heparin and fibrinolysis are safe during pregnancy. Lack of adequate treatment of the mother is the most common cause of fetal death.

Pregnant patients diagnosed with PE or pulmonary embolism can be treated with LMWH throughout the pregnancy. Warfarin is contraindicated because it crosses the placental barrier and can cause fetal malformations. Unfractionated heparin is category C.

Therefore, LMWH at full anticoagulation doses should be continued until the time of delivery. Women who experience a thromboembolic event during pregnancy should receive therapeutic treatment with unfractionated heparin or LMWH during pregnancy, with anticoagulation for 4 to 6 weeks after delivery and for a total of at least 6 months.

In addition to the thrombotic risks in pregnancy, women of childbearing age who are prescribed warfarin should be informed of the teratogenic effects of this medication. Alteplase is a category C drug, and should only be administered following a judicious assessment of the risk-benefit ratio.

Pregnant women who are in a state of hypercoagulability or who have had prior venous thromboembolism should receive prophylactic anticoagulation during pregnancy.

Queries

Fibrinolytic therapy should not be delayed while seeking consultation. The decision to treat pulmonary embolism by fibrinolysis is made by the responsible emergency physician alone, and fibrinolytic therapy is appropriately administered in the emergency department.

A pulmonologist is often consulted before the actual diagnosis is made due to the non-specific nature of the symptoms, and consultation with a cardiologist is justified to rule out a cardiac etiology for symptoms and signs of presentation and to perform ECHO and angiography pulmonary.

If embolectomy is considered, consultation with a cardiac surgeon is mandatory. Few data are available regarding the use of surgical embolectomy in children. Consider embolectomy in the context of massive heart failure when time is insufficient for natural or pharmacological thrombolysis or if thrombolysis is contraindicated.

Thrombotic endarterectomy is another option for surgical treatment for patients with hemodynamic compromise due to large pulmonary emboli. Thrombotic endarterectomy is only performed in certain centers and has a high mortality rate, but it can be successful in certain populations.

A hematologist may suggest an appropriate treatment for a procoagulant defect and may recommend an anticoagulation regimen. Consultation with a hematologist is essential in children with sickle cell disease.

An interventional radiology consultation may be useful for catheter-directed fibrinolysis in selected patients. In rare cases, it may be appropriate to arrange the placement of a venous filter if the patient is not a candidate for thrombolytic therapy.

Prevention

The prevention of idiopathic outpatient pulmonary embolism is difficult, if not impossible. That said, most pulmonary embolisms occur in hospitalized patients. The incidence in these cases can be reduced by adequate prophylaxis, achieved mechanically or by the administration of heparin, LMWH or warfarin.

The incidence of venous thrombosis, pulmonary embolism and death can be significantly reduced by adopting a prophylactic strategy in high-risk patients. The prevention of PET in the lower extremities inevitably reduces the frequency of pulmonary embolism; therefore, at-risk populations should be identified and safe and effective prophylactic modalities should be used.

The QThrombosis algorithm is intended to identify the currently asymptomatic adults with higher future risk of venous thrombosis depending on the established risk factors. According to the study in which it was developed and validated, QTrombosis estimates the absolute risk of venous thrombosis in 1 year and 5 years in the future, information that can be used to guide prophylaxis and decisions about medications.

Medical-legal concerns

Pulmonary embolism is an extremely common disorder. It presents nonspecific clinical features and requires specialized investigations to confirm the diagnosis. Therefore, many patients die from unrecognized pulmonary embolism. The other common pitfalls are the following:

• Without taking into account the patient’s complaints of unexplained dyspnea such as anxiety or hyperventilation
• Blame complaints of unexplained chest pain in musculoskeletal pain
• Not recognize, diagnose and treat PE
• Do not initiate an appropriate diagnostic study in patients with symptoms compatible with pulmonary embolism
• Do not start therapeutic anticoagulant therapy with heparin in patients with suspected pulmonary embolism, before V / Q screening or other investigations
• Lack of advice on risk factors, such as smoking, pregnancy and the use of the oral contraceptive pill
• Lack of diagnosis of predisposing or associated conditions

Future research

Advances in recent decades have significantly improved the ability of physicians to diagnose pulmonary embolism and have refined the treatment of this disorder. However, several areas need more research and therapeutic trials performed adequately.

The role of LMWH and the optimal duration of anticoagulant therapy in different subgroups of patients with venous thromboembolism require further studies.

Because warfarin treatment causes bleeding, future studies should determine if less intense warfarin therapy is effective in preventing recurrences of pulmonary embolism.

If drugs that inhibit the action of thrombin (eg, hirudin) are useful in the treatment of patients with venous thromboembolic disease they should also be determined in future trials.

Guidelines for pulmonary thromboembolism

The following organizations have published guidelines for the diagnosis and treatment of pulmonary embolism (PE):

• American Academy of Family Physicians (AAFP) / American College of Physicians (ACP)
• American College of Physicians (ACP)
• American College of Emergency Physicians (ACEP)
• American College of Radiology (ACR)
• American College of Chest Physicians
• American Heart Association (AHA)
• American College of Obstetricians and Gynecologists (ACOG)

Clinical rating guidelines

A 2007 clinical practice guide from the American Academy of Family Physicians (AAFP) and the American College of Physicians (ACP) recommends that validated clinical prediction rules be used to estimate the likelihood of pulmonary embolism (PE) before the test and interpret the results of the test.

The guide, Current Diagnosis of Venous Thromboembolism in Primary Care, recommends the use of the Wells prediction rule for this purpose, but notes that the Wells rule works best in younger patients without comorbidities or a history of venous thromboembolism (VTE) that in other patients.

In 2015, the ACP published guidelines for the evaluation of patients with suspected acute PE, which included the following recommendations:

• Plasma D-dimer tests are more appropriate for people at intermediate risk for PE, and testing for some low-risk patients is not necessary.
• Use the Wells or Geneva rules to choose tests based on a patient’s risk of developing PE.
• If the patient has a low risk, physicians should use the eight Exclusion Criteria for pulmonary embolism (PERC); If a patient meets all eight criteria, the risks of the tests are greater than the risk of stroke, and no tests are needed.
• For patients at intermediate risk, or for those at low risk who do not meet all criteria for discarding, use a highly sensitive plasma D-dimer test as an initial test.
• In patients older than 50 years, use an age-adjusted threshold (age × 10 ng / ml, instead of a coverage of 500 ng / ml), because normal D-dimer levels increase with age.
• Patients with a D-dimer level below the age-adjusted limit should not receive any imaging studies.
• Patients with high levels of D-dimer should receive images.
• Patients at high risk should skip the D-dimer test and proceed to pulmonary CT angiography, since a negative D-Dimer test does not eliminate the need for imaging in these patients.
• Physicians should only obtain ventilation-perfusion scans in patients with a contraindication to pulmonary CT angiography or if pulmonary CT angiography is not available.
• Physicians should use validated clinical prediction rules to estimate the likelihood of prior testing in patients in whom acute PE is considered.

In contrast, the 2011 guidelines of the American College of Emergency Physicians (ACEP) find that objective criteria or gestalt clinical assessment can be used to stratify the risk of patients with suspected PE.

There is not enough evidence to support the preferential use of one method over another (level B). For patients with a low probability of pretesting for suspected PE, PERC can be used to exclude the diagnosis based on the data from the physical and historical examination alone (level B). Other key recommendations include the following [108]:

• The results of the quantitative negative D-dimer assay can be used to exclude PE in patients with a low probability of pretesting for PE (level A).
• The results of the quantitative negative D-dimer assay can be used to exclude PE in patients with an intermediate pretest probability for PE (level C).
• For patients with a low pretest probability or PE (Wells score 4) for PE who require additional diagnostic tests (eg, positive D-dimer score or highly sensitive D-dimer test not available), negative multidetector pulmonary CT angiography can only be used to exclude EP (level B).
• For patients with an intermediate or high pretest probability of PE and a negative CT pulmonary angiogram in whom there is still a clinical concern for PE and CT venogram, consider additional diagnostic tests (eg, D-Dimer, limb images) inferior, VQ scan, traditional pulmonary arteriography) before the exclusion of VTE disease (level C).
• Venous ultrasound can be considered as an initial image in patients with obvious signs of deep vein thrombosis (PE) for whom venous ultrasound is readily available, patients with relative contraindications to CT (eg, borderline renal insufficiency, CT contrast agent) and pregnant patients. A positive finding in a patient with symptoms consistent with PE can be considered evidence for the diagnosis of VTE disease and may exclude the need for additional diagnostic images in the emergency department (level B).

Image guidelines

In its 2011 guidelines, the American College of Radiology (ACR) considers

Multislice CT lung angiography is the standard of care for the detection of pulmonary embolism (PE). The additional recommendation includes the following:

• A chest X-ray can not exclude or confirm PD, but it is important (as a complementary study) because it can guide further investigations and suggest alternative diagnoses.
• Any test that can confirm deep vein thrombosis (PE) (ie, the venous duplex of the lower extremities) or PE is sufficient. Only certain studies, however, are accurate enough to exclude PE.
• The ventilation / perfusion (V / Q) scan seems to have a high general accuracy.
• In pregnancy, with radiation as a particular concern, the choice between the perfusion scan and pulmonary CT angiography depends on the local equipment and experience, as well as the patient’s factors (normal chest radiography, breathing capacity) .

Guidelines for antithrombotic and thrombolytic therapy

In 2016, the American College of Chest Physicians (ACCP) updated the recommendations on 12 topics that were in the ninth edition of its Antithrombotic Therapy for ETV Disease: Antithrombotic Therapy and Thrombosis Prevention, and addresses three new topics.

New or revised key recommendations include the following:

• Dabigatran, rivaroxaban, apixaban or edoxaban are preferable to therapy with vitamin K antagonists (VKA) as a long-term anticoagulant treatment (first 3 months) for non-cancer patients (all of grade 2 B).
• Low molecular weight heparin (LMWH) is recommended for AVK, dabigatran, rivaroxaban, apixaban or edoxaban therapy as long-term anticoagulant therapy (first 3 months) for patients with thrombosis associated with cancer (all grades 2C).
• Aspirin is recommended without aspirin to prevent recurrent venous thromboembolism (VTE) in patients who stop anticoagulant therapy and do not have a contraindication to aspirin (grade 2B).
• In the majority of patients with acute pulmonary embolism (PE) not associated with hypotension, thrombolytic therapy administered systemically (grade 1B) is recommended.
• In selected patients with acute PE who deteriorate after starting anticoagulant therapy but who have not yet developed hypotension and who have a low risk of bleeding, thrombolytic therapy administered systemically over any such therapy (grade 2C) is preferred.

In accordance with the guidelines of the ninth edition of ACCP, immediate therapeutic anticoagulation should be initiated for patients with suspected deep vein thrombosis (PE) or PE (grade 1B).

Anticoagulant therapy reduces mortality rates from 30% to less than 10%. Diagnostic investigations should not delay empirical anticoagulant therapy in patients with high or intermediate risk of PE (grade 2C).

For acute PE, the ACCP guidelines recommend starting with LMWH or fondaparinux, preferring unfractionated heparin (FNH) (grade 2C for LMWH, grade 2B for fondaparinux) or subcutaneous heparin (grade 2B for LMWH, grade 2C for fondaparinux). ). [5] If patients should be treated with LMWH, treatment is preferred once a day to twice a day (grade 2C).

Patients considered to be at low risk should be discharged early from the hospital (grade 2B).

Patients should have an oral anticoagulant (warfarin) started at the time of diagnosis, and UFH, LMWH or fondaparinux should be discontinued only after the international standardized rate (RIN) is 2.0 for at least 24 hours, but not before 5 days later therapy with warfarin (grade 1B) was started.

The recommended duration of UFH, LMWH and fondaparinux is based on evidence suggesting that the relatively long half-life of factor II, together with the short half-life of protein C and protein S, can cause a state of paradoxical hypercoagulability if these agents They are discontinued prematurely.

The ACCP guidelines for antithrombotic and thrombolytic therapy are summarized as follows:

• Hrombolytic therapy should be used in patients with acute PE associated with hypotension (systolic BP <90 mm Hg), who are not at high risk of bleeding (grade 2C).
• Thrombolytic therapy is suggested in selected patients with acute PE not associated with hypotension and with a low risk of hemorrhage whose initial clinical presentation or clinical course after initiating anticoagulation suggests a high risk of developing hypotension (grade 2C).
• The evaluation of the severity of PE, the prognosis and the risk of hemorrhage determine whether thrombolytic therapy should be initiated. Thrombolytic therapy is not recommended for most patients with acute PE not associated with hypotension (grade 1C).
• All patients with unprovoked PE receive 3 months of anticoagulation therapy instead of a shorter duration of treatment, and have an evaluation of the risk-benefit ratio of prolonged therapy at the end of 3 months (grade 1B).
• Patients with a first episode of VTE and with a low or moderate risk of bleeding should have a prolonged anticoagulant treatment (grade 2B). Patients with a first episode of VTE who have a high risk of bleeding should have a treatment limited to 3 months (grade 1B). In patients with a second unprovoked episode of VTE and risk of low or moderate bleeding, prolonged anticoagulant therapy is recommended (grades 1B and 2B, respectively). In patients with a second episode of VTE and a high risk of bleeding, 3-month anticoagulation is preferred instead of prolonged anticoagulation (grade 2B).
• Patients with PD and pre-existing irreversible risk factors, such as antithrombin III deficiency, proteins S and C, mutation of factor V Leiden or the presence of antiphospholipid antibodies, should be subjected to long-term anticoagulation.

Guidelines on advanced therapies for acute VTE

In 2011, the American Heart Association (AHA) issued guidelines to help the emergency department and other physicians determine which patients with venous thromboembolism (VTE) should receive advanced therapies instead of simple anticoagulation. [102] The recommendations for the treatment of acute pulmonary embolism (PE) are the following:

• Therapeutic anticoagulation with subcutaneous low molecular weight heparin (LMWH), intravenous or subcutaneous unfractionated heparin (UFH) with monitoring, unmonitoring subcutaneous UFH or subcutaneous fondaparinux should be administered to patients with objectively confirmed PE and without contraindications to anticoagulation (class I ).
• Therapeutic anticoagulation during the diagnostic study should be administered to patients with intermediate or high clinical probability of PD and without contraindications for anticoagulation (class I).
• Fibrinolysis is reasonable in patients with massive acute PE and acceptable risk of haemorrhagic complications (class IIa).
• Fibrinolysis can be considered for patients with acute submassive PE who are considered to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening of respiratory failure, severe right ventricular dysfunction or major myocardial necrosis) and low risk of bleeding complications (class IIb) .
• Fibrinolysis is not recommended for the following patients (class III): (1) low risk PE; (2) Acute sumasive EP with minor right ventricular dysfunction, minor myocardial necrosis and no clinical worsening; and (3) with undifferentiated cardiac arrest.

Recommendations for catheter-based interventions include the following:

• For patients with massive PE and contraindications for fibrinolysis, embolectomy and catheter fragmentation or surgical embolectomy are reasonable, depending on the available experience (class IIa).
• For patients with massive PE who remain unstable after receiving fibrinolysis, embolectomy with catheter and fragmentation or surgical embolectomy are reasonable (class IIa).
• For patients with massive PE who can not receive fibrinolysis or who remain unstable after fibrinolysis, consider transfer to an institution with experience in embolectomy with catheter or surgical embolectomy if these procedures are not available and a safe transfer can be achieved (class IIa ).
• Either embolectomy with catheter or surgical embolectomy may be considered in patients with acute submassive PE who are considered to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening of respiratory failure, severe right ventricular dysfunction, or major myocardial necrosis) (class IIb).
• Embolectomy with catheter and surgical thrombectomy are not recommended for patients with low risk PE or submassive acute PE with minor right ventricular dysfunction, minor myocardial necrosis and no clinical worsening (class III).

The recommendations for the use of vena cava filters include the following:

• Patients with confirmed acute PE (or proximal deep vein thrombosis [EPT]) with contraindications for anticoagulation or with active bleeding complications should receive a lower vena cava filter (class I).
• Anticoagulation should be resumed in patients with an IVC filter once the contraindications for anticoagulation or active haemorrhagic complications (class I) have been resolved.
• Patients receiving retrievable VCI filters should be periodically evaluated for filter recovery within the specific filter recovery window (class I).
• The placement of a VCI filter is reasonable for patients with recurrent acute PE despite therapeutic anticoagulation (class IIa).
• A permanent VCI filter device is reasonable for patients with a long-term contraindication to anticoagulation (class IIa).
• A recoverable IVC filter device is reasonable for patients with a short-term contraindication to anticoagulation therapy (class IIa).
• The placement of a VCI filter can be considered for patients with acute PE and very poor cardiopulmonary reserve, including those with massive PE (class IIb).
• A VCI filter should not be routinely used as an adjunct to anticoagulation and systemic fibrinolysis in the treatment of acute PE (class III).

Guidelines for pregnancy and gynecological surgery

In 2011, the American College of Obstetricians and Gynecologists (ACOG) published a practice bulletin on the diagnosis, treatment and prevention of thromboembolism during pregnancy. The key recommendations included the following:

• Compression ultrasound of the proximal veins is the recommended initial diagnostic test when the signs or symptoms suggest a new onset venous thrombosis (PE) (level A).
• Women with a history of thrombosis who have not been thoroughly evaluated for possible underlying causes should receive antiphospholipid antibody tests, as well as inherited thrombophilias (level C).
• Heparin compounds are preferred for anticoagulation (level B).
• Anticoagulation is recommended for women with acute thromboembolism during current pregnancy or those at high risk of venous thromboembolism (VTE), such as women with mechanical heart valves (level C).
• In the last month of pregnancy, or sooner if delivery seems imminent, women receiving therapeutic or prophylactic anticoagulation can convert from low molecular weight heparin (LMWH) to unfractionated heparin (UFH), which has a shorter half-life ( DO level).
• Neuraxial block should be retained for 10-12 hours after the last prophylactic dose of LMWH or 24 hours after the last therapeutic dose of LMWH (level C).
• For all women who do not yet receive thromboprophylaxis, the placement of pneumatic compression devices before cesarean delivery is recommended. However, an emergency cesarean should not be delayed for placement of compression devices (level C).
• To minimize postpartum hemorrhagic complications, a reasonable strategy is to resume anticoagulant treatment before 4 to 6 hours after vaginal delivery or 6 to 12 hours after cesarean delivery (level B).
• For women planning to restart anticoagulation after delivery, pneumatic compression devices should be left in place until the woman is ambulatory and anticoagulant therapy is resumed (level C).
• Warfarin, LMWH, and UFH are compatible with breastfeeding because they do not accumulate in breast milk and do not cause anticoagulation in the infant (level B).

Medication for pulmonary thromboembolism

Medication summary

Immediate therapeutic anticoagulation is initiated in patients with suspected deep vein thrombosis (PE) or pulmonary embolism (PE). Anticoagulation therapy with heparin reduces mortality rates from 30% to less than 10%.

Anticoagulation is essential, but anticoagulation alone does not guarantee a successful outcome. PET and PE can recur or spread despite anticoagulation with complete and effective heparin.

Chronic anticoagulation is essential to prevent relapse of PE or PE after initial heparinization. Heparin works by activating antithrombin III to slow or prevent the progression of PE and to reduce the size and frequency of PE. Heparin does not dissolve the existing clot.

Anticoagulants

Heparin increases the activity of antithrombin III and prevents the conversion of fibrinogen into fibrin. Full-dose IV heparin or full-dose unfractionated IV heparin should be started at the first suspicion of PE or PE.

With adequate dosing, it has been found that several LMWH products are safer and more effective than unfractionated heparin, both for prophylaxis and for the treatment of PE and PE. APTT control is neither necessary nor useful when LMWH is administered, since the drug is more active in a tissue phase and does not exert most of its effects on coagulation factor IIa.

Many different LMWH products are available worldwide. Due to pharmacokinetic differences, the dosage is highly product specific. Several LMWH products are approved for use in the United States: enoxaparin (Lovenox), dalteparin (Fragmin) and tinzaparin (Innohep).

Enoxaparin and tinzaparin are currently approved by the FDA for the treatment of PE. Dalteparin is approved by the FDA for prophylaxis and has approval for cancer patients. Each of the other agents has been approved by the FDA at a lower dose for prophylaxis, but all appear to be safe and effective at some therapeutic dose in patients with active PE or PE.

Fractionated LMWH administered subcutaneously is now the preferred option for initial anticoagulant therapy. Unfractionated IV heparin can be almost as effective, but it is more difficult to assess for the therapeutic effect. Maintenance therapy with warfarin can be started after 1-3 days of effective heparinization.

The weight-adjusted heparin dosing regimens that are appropriate for the prophylaxis and treatment of coronary artery thrombosis are too low to be used without modification in the treatment of active PE and PE.

Thrombosis of the coronary artery is not the result of hypercoagulability, but rather the adhesion of platelets to plaque rupture. In contrast, patients with PE and PE are in the midst of a hypercoagulable crisis, and aggressive countermeasures are essential to reduce mortality and morbidity rates.

Enoxaparina (Lovenox)

Exonaparin was the first low molecular weight heparin (LMWH) released in the United States. It was approved by the FDA for the treatment and prophylaxis of PE and PE. Enoxaparin increases the inhibition of factor Xa and thrombin by increasing the activity of antithrombin III.

In addition, inhibition of factor Xa increases preferentially. LMWH has been widely used during pregnancy, although clinical trials are not yet available to show that it is as safe as unfractionated heparin.

Except in overdoses, PT or aPTT control is not useful, since aPTT does not correlate with the anticoagulant effect of fractionated LMWHs. Factor Xa levels can be controlled if the concern arises as to whether the dose is adequate.

Dalteparina (Fragmin)

Dalteparin is a LMWH with many similarities to enoxaparin but with a different dosing schedule. It is approved for the prophylaxis of PET in patients undergoing abdominal surgery.

Except in overdoses, PT or aPTT control is not useful, since aPTT does not correlate with the anticoagulant effect of fractionated LMWHs. LMWH Factor Xa levels can be controlled if the concern arises as to whether the dose is adequate.

Tinzaparin (Innohep)

Tinzaparin is approved for the treatment of PE in hospitalized patients. It improves the inhibition of factor Xa and thrombin by increasing the activity of antithrombin III. In addition, inhibition of factor Xa increases preferentially.

Heparina (Hep-Lock U / P, Hep-Lock, Hep-Flush-10)

Heparin increases the activity of antithrombin III and prevents the conversion of fibrinogen into fibrin. It is not actively lysed but is capable of inhibiting greater thrombogenesis. Heparin prevents re-accumulation of a clot after spontaneous fibrinolysis.

When using HNF, the aPTT should not be checked until 6 hours after the initial heparin bolus, because an extremely high or low value during this time should not cause any action.

Warfarina (Coumadin, Jantoven)

Warfarin (Coumadin) interferes with the hepatic synthesis of coagulation factors dependent on vitamin K. It is used for the prophylaxis and treatment of venous thrombosis, pulmonary embolism and thromboembolic disorders.

Never give warfarin to patients with thrombosis until after they have been fully anticoagulated with heparin (the first few days of warfarin treatment produce a state of hypercoagulability).

The lack of anticoagulation with heparin before initiating warfarin causes clot expansion and recurrent thromboembolism in approximately 40% of patients, compared with 8% of those receiving full-dose heparin before starting warfarin.

Heparin should be continued for the first 5-7 days of oral warfarin therapy, regardless of PT time, to allow the depletion time of procoagulant vitamin K-dependent proteins.

Adapt the dose of warfarin to maintain an RIN in the range of 2.5-3.5. The risk of major bleeding (including hemorrhagic stroke) is approximately constant when the RIN is 2.5-4.5 but increases dramatically when the RIN is greater than 5. In the UK, an RIN target greater than 3-4 is recommended. .

Evidence suggests that 6 months of anticoagulation reduce the recurrence rate to half the recurrence rate observed when only 6 weeks of anticoagulation are administered. Long-term anticoagulation is indicated for patients with an irreversible underlying risk factor and recurrent PE or recurrent pulmonary embolism.

Vitamin K-dependent procoagulant proteins are responsible for a transient state of hypercoagulability when warfarin is started and stopped for the first time. This is the phenomenon that occasionally causes warfarin-induced necrosis in large areas of the skin or distal appendages.

Heparin is always used to protect against this hypercoagulability when warfarin is started; however, when warfarin is stopped, the problem reappears, which causes an abrupt and temporary increase in the rate of recurrent venous thromboembolism.

At least 186 different foods and drugs reportedly interact with warfarin. Clinically significant interactions have been verified for a total of 26 medications and common foods, including 6 antibiotics and 5 cardiac medications.

Every effort should be made to keep the patient adequately anticoagulated at all times, since the procoagulant factors are first recovered when warfarin therapy is inadequate.

Patients who have difficulty maintaining adequate anticoagulation while taking warfarin may be asked to limit the intake of foods containing vitamin K.

Foods that have moderate to high amounts of vitamin K include Brussels sprouts, kale, green tea, asparagus, avocado, broccoli, cabbage, cauliflower, kale, liver, soybean oil, soy, certain beans, mustard greens, peas (black eyes peas, peas, chickpeas), turnip greens, parsley, chives, spinach and lettuce.

Fondaparinux sodium (Arixtra)

Fondaparinux sodium is a synthetic anticoagulant that works by inhibiting factor Xa, a key component involved in the coagulation of blood. It provides a highly predictable response and has a 100% bioavailability.

The drug has a rapid onset of action and a half-life of 14-16 hours, which allows sustained antithrombotic activity for a period of 24 hours. Fondaparinux sodium does not affect prothrombin time or activated partial thromboplastin time, nor does it affect platelet aggregation or function.

Trombolisis

Thrombolysis is indicated for patients with hemodynamically unstable pulmonary embolism. Thrombolysis drastically improves acute cor pulmonale. Thrombolytic therapy has replaced surgical embolectomy as the treatment for hemodynamically unstable patients with massive pulmonary embolism.

Fibrinolytic regimens currently in common use for pulmonary embolism include two forms of recombinant tPA, alteplase and reteplase. Alteplase is usually administered as a frontal loading infusion for 90 or 120 minutes.

Reteplase is a new generation thrombolytic with a longer half-life; it is administered in the form of a single bolus or as 2 boluses administered 30 minutes apart.

The fast-acting reteplase and alteplase agents are preferred for patients with pulmonary embolism, because the condition of patients with pulmonary embolism can deteriorate extremely rapidly.

Many comparative clinical studies have shown that administration of a 2-hour infusion of alteplase is more effective (and more quickly effective) than urokinase or streptokinase (both suspended by the FDA) for a period of 12 hours.

A prospective, randomized study comparing reteplase and alteplase found that total lung resistance (together with pulmonary artery pressure and cardiac index) improved significantly after only half an hour in the reteplase group compared to 2 hours in the group of alteplase. The fibrinolytic agents do not appear to differ significantly with respect to safety or general efficacy.

Empiric thrombolysis may be indicated in selected hemodynamically unstable patients, particularly when the clinical probability of pulmonary embolism is overwhelming and the patient’s condition is deteriorating. The overall risk of serious complications from thrombolysis is low and the potential benefit in a patient with deteriorating pulmonary embolism is high.

Empirical therapy is especially indicated when a patient is so compromised that he or she will not survive long enough to get a confirmatory study.

Empiric thrombolysis should be reserved, however, for cases that truly comply with these definitions, since many other clinical entities (including aortic dissection) may be masked as pulmonary embolism, although they may not benefit from thrombolysis in any way.

Newborns may be relatively resistant to thrombolytics due to their lack of fibrinogen activity.

Reteplasa (Retavase)

Reteplase is a second-generation recombinant tissue plasminogen activator (recombinant tPA) that forms plasmin after facilitating the cleavage of endogenous plasminogen.

In clinical trials, it has been shown that reteplase is comparable to alteplase of recombinant tPA to achieve TIMI, permeability of 2 or 3, at 90 minutes. Reteplase is administered in the form of a single bolus or as 2 boluses administered 30 minutes apart.

As a fibrinolytic agent, reteplase seems to work faster than its predecessor, alteplase, and may be more effective in patients with large loads of clots. It has also been reported to be more effective than other agents in the lysis of older clots.

Two important differences help explain these improvements. Because reteplase does not bind fibrin as strongly as alteplase does, this allows the reteplase drug to diffuse more freely through the clot.

Another advantage seems to be that reteplase does not compete with plasminogen for fibrin binding sites, which allows the plasminogen at the clot site to transform into plasmin that dissolves the clots.

The FDA has not approved reteplase for administration to patients with pulmonary embolism. Studies on the use of the drug for pulmonary embolism have used the same dose approved by the FDA for fibrinolysis of the coronary artery.

Alteplase (Activasa, Activated by Cathflo)

Alteplase, a recombinant tPA, is used in the treatment of acute myocardial infarction (AMI), acute ischemic stroke and pulmonary embolism. Alteplase is most often used to treat patients with pulmonary embolism in the emergency department. It is usually administered as a frontal loading infusion for 90-120 minutes.

It is approved by the FDA for this indication. Most emergency personnel are familiar with the use of alteplase, since it is widely used in the treatment of patients with AMI. An accelerated 90-minute regimen is widely used, and most believe it is safer and more effective than the approved 2-hour infusion. A dose of accelerated regimen is based on the weight of the patient.

Heparin therapy should be instituted or reinstituted near the end or immediately after the infusion, when the time of aPTT or thrombin returns to twice normal or less.

Direct inhibitors of thrombin and factor Xa inhibitors

Factor Xa inhibitors inhibit platelet activation by selectively blocking the active site of factor Xa without requiring a cofactor (eg, antithrombin III) for activity. Direct inhibitors of thrombin prevent the development of thrombi through the direct and competitive inhibition of thrombin, thus blocking the conversion of fibrinogen to fibrin during the coagulation cascade.

Rivaroxaban (Xarelto)

Indicated for the treatment of PD and for the prevention of recurrence (after the first 6 months of treatment).

Apixabán (Eliquis)

Indicated for the treatment of PD and for the prevention of recurrence (after the first 6 months of treatment).

Dabigatran (Pradaxa)

Dabigatran is indicated for the treatment of PE and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days. It is also indicated to reduce the risk of recurrence of PE and EP in patients who have been previously treated.

Edoxaban (Savaysa)

Edoxaban is a factor Xa inhibitor indicated for the treatment of PE and PE in patients who have been initially treated with a parenteral anticoagulant for 5-10 days.

Betrixabán (Bevyxxa)

Betrixaban is indicated for the prophylaxis of venous thromboembolism (VTE) in adults hospitalized for acute medical conditions who are at risk of thromboembolic complications due to moderate or severe restricted mobility and other risk factors that can cause VTE.