Normocitic Anemia: Classification, Causes, Risk Factors, Symptoms, Diagnosis and Treatment

It is a type of anemia, and it is a common problem that occurs in men and women who are generally over 85 years old.

Its prevalence increases with age, reaching 44 percent in men older than 85 years.

Normocytic anemia has many causes, the most common being anemia due to sudden loss of blood, long-term diseases (chronic diseases), kidney failure, aplastic anemia, artificial heart valves, or drug therapy.

Anemia is a condition where there is a low level of a substance called hemoglobin in the blood. This hemoglobin is responsible for oxygen transport around the blood inside the red blood cells.

Chronic disease anemia is the second most common type of anemia, behind iron deficiency anemia, and maybe the most common cause of anemia in hospitalized patients.

The normocytic anemia rates for some conditions are the following:

  • Up to 95% of patients with an acute (short-term) or chronic infection (ongoing for more than six months).
  • Up to 77% of patients with cancer.
  • Up to 81% of people with autoimmune diseases.
  • Up to 70% of patients have rejection after an organ transplant.
  • Up to 50% of patients with chronic kidney disease and inflammation.
  • Up to 40% of patients with cardiovascular disease.
  • Approximately 46% of patients with infection by the Human Immunodeficiency Virus ( HIV ).
  • One-third of patients with inflammatory bowel disease.
  • 67% of patients with hepatitis C.
  • 5% of the elderly population.

The anemia of the chronic disease appears gradually during the underlying condition that causes the disease. It can be improved with the effective management of chronic illness.


It should be noted that almost all anemias are normocytic in the initial stage.


Normocytic anemia is anemia with a mean corpuscular volume (MCV) of 80-100, which is the normal range. However, the hematocrit and hemoglobin decrease.

Prognosis of Normocytic Anemia of chronic diseases

The outcome of this disease will depend mainly on the severity, what the underlying cause is, and how well it responds to treatment.

In general, when anemia occurs with an underlying condition, it is associated with:

  • A less favorable result of the underlying condition.
  • Longer hospital stays.
  • Worst quality of life.
  • Cognitive impairment (cerebral).
  • Heart failure.
  • Increase in morbidity

It can cause an increase in the symptoms of the underlying condition and even accelerate the progression of the disease.

The surgeon and the anesthetist must know any coexisting anemia in the surgical context. It may increase the need for blood transfusions and contribute to delirium, bleeding, and fatigue after the operation.

When anemia is corrected within certain levels, quality of life and energy levels can be improved.


In patients with cancer, anemia is associated with poor survival, so the relative risk of death increased by 65% ​​in cancer patients with anemia.

It is also associated with increased fatigue, which can lead to a reduced ability to work and perform activities of daily living and contribute to social isolation.

Chronic kidney disease

Patients with chronic kidney disease with experience of coexisting anemia:

  • Reduced quality of life
  • Cognitive impairment
  • Sleep disturbance.
  • Progressive disease
  • Increase in cardiovascular morbidity and mortality.
  • Reduction of tolerance to exercise, angina, and worsening heart failure (when this already exists).
  • Worse functioning of the organ after kidney transplant surgery.
  • Increase in mortality


Anemia in patients with HIV / AIDS is associated with:

  • Faster progression from HIV disease to AIDS.
  • Decreased survival, so the risk of death in up to 70% higher.
  • Greater need for transfusions.
  • Increase in fatigue.
  • Worst quality of life.

Cardiovascular diseases

In patients with heart failure, anemia is associated with reduced quality of life scores, a predictor of patients requiring rehospitalization, and increased mortality.

In patients following a myocardial infarction ( heart attack ), the presence of anemia is a risk factor for death. Similarly, anemia is associated with increased adverse events in patients undergoing coronary artery bypass surgery.

Old people

In the elderly, anemia is associated with a more rapid decrease in physical function. It is associated with:

  • Greater risk of falls.
  • Weakness, muscle wasting, and immobility.
  • Cardiovascular and neurological deterioration.
  • Depression and dementia
  • Hospitalization.
  • Dependence on long-term care or institutionalization.
  • Mortality.


The problem is considered to be any of the following:

  • There is a decreased production of normal-sized red blood cells (e.g., chronic disease anemia, aplastic anemia).
  • Increased production of sickle hemoglobin as seen in sickle cell disease (not in the sickle cell trait).
  • More significant destruction or loss of red blood cells (e.g., hemolysis, posthemorrhagic anemia).
  • There is an unbalanced increase in plasma volume (e.g., pregnancy, fluid overload).
  • A deficiency of B2 (riboflavin).
  • A lack of B6 (pyridoxine).
  • A mixture of conditions that produce microcytic and macrocytic anemia.

The loss of blood, the repressed production of red blood cells, or hemolysis represent the majority of cases of normocytic anemia. In blood loss, morphological findings are usually not noticeable, except after 12 to 24 hours when polychromasia appears.

Anemia of chronic disease is a condition where anemia is caused by long-term inflammation present in many different types of infections.

When you have inflammation, the body releases many different chemicals (called ‘cytokines’) into the bloodstream, which helps the body heal itself.

However, if the inflammation is present for a long time, these cytokines can affect the production of hemoglobin and cause anemia.

They do it in different ways. First, several chemicals reduce the production of a hormone (a type of signaling chemical) called ‘ erythropoietin. ‘

Erythropoietin tells the body to increase the production of red blood cells and hemoglobin, so because these inflammatory cytokines reduce the amount produced, it can cause anemia.

Another product of inflammation is the production of a chemical called “hepcidin” created by the liver and prevents iron from being absorbed into the intestines. Without iron, hemoglobin can not form.

Some cytokines can also cause the immune system to swallow more iron than it is in the blood and destroy the red blood cells earlier and absorb the iron inside them in the immune cells.

Immune cells also change their structure so that it is harder to get iron from them, which means that it is blocked inside and not accessible to other parts of the body.

Risk factor’s

Some diseases, in particular, can cause anemia due to chronic conditions, such as:

Chronic infections

Immune disorders

Symptoms of Normocytic Anemia in chronic diseases

People with anemia or chronic disease can have symptoms such as:

  • Fatigue.
  • Headaches.
  • Weakness.
  • Breathless.
  • Angina.
  • Intermittent claudication (pain in the muscles of the legs that leads to lameness or lameness).
  • Heart palpitations.
  • Impaired cognitive function (decreased ability to think or concentrate).
  • Depression.

How is Normocytic Anemia diagnosed in chronic diseases?

Physicians are sometimes inefficient in assessing normocytic anemia, either ordering an excessive battery of tests or thoroughly testing in the belief that a cause is not likely to be found.

The first step in evaluating anemia is to correlate the finding of anemia with the information obtained from the patient’s history and physical examination.

This approach allows a working diagnosis and eliminates many disorders in many cases.

Most algorithms published for diagnosing normocytic anemia begin with examining the peripheral blood smear or a corrected reticulocyte index.

When a doctor examines you, you will look for signs of anemia and possible underlying conditions. You can look for some things like:

  • Paleness, although this can only be observed when the anemia is severe.
  • A rapid heartbeat.
  • A sound in the heart.
  • There is evidence of heart failures, such as swelling in the legs and pleural effusions (fluid in the lungs).

A blood test called a complete blood count can be very useful and is required for diagnosis because it provides hemoglobin levels in the blood.

It will also give information about the size of red blood cells and the amount of hemoglobin contained in each cell.

Usually, anemia of chronic disease will have an average size of red blood cells (called normocytes) that have a moderate amount of hemoglobin (called “normochromic” because they are the right color).

The distribution width of red blood cells measures cells’ size variability ( anisocytosis ) and is generally reported as a component of automated CBCs.

Therefore, a practical and valuable first step is to use the distribution width of red blood cells to help categorize normocytic anemia as heterogeneous (e.g., hemolytic anemia) or homogeneous (e.g., chronic disease anemia).

In patients with mild homogenous normocytic anemia (hematocrit of 30 percent or more) and a known chronic disease, anemia due to chronic illness is very likely, and bone marrow biopsy may not be necessary.

Another helpful blood test is to do an “iron study” since this will show the amount of iron in the blood and show other factors, such as how much iron the blood has the potential to bind.

Anemia of chronic diseases

Anemia due to chronic disease is the most common normocytic anemia and the second most common form of anemia globally (after iron deficiency anemia). The average corpuscular volume may be low in some patients with this type of anemia.

The pathogenesis of anemia due to chronic diseases is multifactorial. It is related to the hypoactivity of the bone marrow, with relatively inadequate production of erythropoietin or an insufficient response to erythropoietin, as well as a slightly shortened survival of the red blood cells.

Anemia of chronic diseases is associated with various chronic disorders, including inflammatory conditions, infections, neoplasms, and various systemic diseases.

Diagnosis of anemia due to chronic disease generally does not apply to anemia associated with kidney, liver, or endocrine disorders.

Patients with these disorders may not show the characteristic ferrokinetic profile of anemia due to chronic disease (i.e., decreased serum iron level, decreased transferrin level, or standard or elevated ferritin levels, which makes iron present but inaccessible for use).

Endocrine deficiency

Endocrine deficiency states, which include hypothyroidism, adrenal or pituitary insufficiency, and hypogonadism, may cause secondary bone marrow failure due to reduced stimulation of erythropoietin secretion.

Hyperthyroidism can also cause normocytic anemia.

Renal insufficiency

Anemia occurs in acute and chronic renal failure. The anemia is usually normocytic but may be microcytic.

In kidney failure, anemia occurs in part because uraemic metabolites shorten the life of circulating red blood cells and reduce erythropoiesis.

Anemia secondary to uremia is characterized by inappropriately low levels of erythropoietin, in contrast to normal or high levels that occur with most other causes of anemia.

To further confuse the presentation, serum iron levels and iron saturation percentage are often low, apparently due to adverse acute phase reactions. In addition, the serum creatinine level and the degree of anemia may not correlate well.

Other causes

Other causes of decreased production of red blood cells include bone marrow infiltration, fibrosis, various myeloproliferative diseases, and sideroblastic anemias. These rare disorders are usually diagnosed by bone marrow biopsy.

Treatment of Normocytic Anemia

The best and most important treatment in chronic disease anemia is to keep the underlying condition under control. When the situation is resolved, the anemia must also be determined.

However, in some extreme cases, a blood transfusion may be necessary so that the body still has enough hemoglobin to transport oxygen effectively throughout the body.

Agents that stimulate the body to increase the production of red blood cells called erythropoietin enabling agents are also sometimes used to help treat the anemia of chronic diseases. These medications are commonly used in patients with chronic kidney disease who require dialysis.

Administering iron orally as a tablet or an infusion in the veins may benefit some patients, although it is not the best or most common form of therapy. It is beneficial in patients who have a poor response to treatment with erythropoietin stimulating agents.

New drugs that target the hepcidin protein are also being created and tested. These agents aim to reduce their production or block their action.

When released by the liver, this protein decreases the absorption of iron by the intestines and prevents iron from being removed from body stores.

Therefore, if the production of this protein decreases or can not carry out its function, more iron can be absorbed from the diet, and the iron stored in the body can be released to create an average level of iron in the available bloodstream, for use by the body.

Strategy ‘drainage and retention

Because the diagnosis of normocytic anemia usually progresses step by step and begins with the corrected reticulocyte index and peripheral blood smear examination, a patient-friendly, cost-effective, and time-efficient strategy is to use “drainage and retention” ” “Order for possible subsequent tests.”

Most laboratories do not charge for containing tubes, and analyzes can usually be added up to a week after the samples are obtained. The doctor should consult with the local laboratory to determine the amount and type of pieces to be received.

Peripheral hemorrhage

Peripheral blood smear examination often yields diagnostic clues or confirmatory evidence.

Findings of readily recognizable red blood cells related to normocytic anemias include the following:

  • Large polychromatic “displacement cells” represent reticulocytosis.
  • Target cells can be found in liver disease.
  • Basophil, which may be present in hemolytic anemias.
  • Mixtures of large and small red blood cells may suggest the presence of mixed microcytic and macrocytic processes (a finding that should be indicated by a high distribution width of red blood cells).

Other findings include grapevine cells ( uremia ), spherocytes (hereditary spherocytosis, autoimmune hemolysis, G6PD deficiency), adipocytes (hereditary elliptocytosis), schistocytes (microangiopathic processes), bite or blister cells (where all hemoglobin seems to be pushed aside) of the cell, G6PD deficiency).

These findings may be present in other anemias and other conditions.

The corrected reticulocyte index and white blood cell and platelet counts indicate whether the bone marrow is functioning correctly. The fixed reticulocyte index should be elevated in patients with acute anemia but competent bone marrow.

Hemolytic anemias

Other than alloimmune hemolytic anemias of newborns (e.g., incompatibility with Rh or ABO proteins) can be classified as congenital or acquired.

Congenital hemolytic anemias include:

  • Hemoglobinopathies (homozygous sickle cell disease [hemoglobin SS disease], heterozygous hemoglobin C disease [SC hemoglobin disease]).
  • Red cell membrane disorders.
  • Enzyme deficiencies.

The red blood cells.

Homozygous sickle cell disease is the most common cause of normocytic hemolytic anemia in children. Due to longevity, this disease is also becoming an increasingly prevalent cause of these anemias in adults.

Hereditary spherocytosis is the most common disorder of the red blood cell membrane. It usually occurs in childhood with anemia, jaundice, and splenomegaly.

Pigmented gallstones, growth retardation, and dysmorphic features may occur. Hereditary elliptocytosis ranges from an asymptomatic carrier state to severe hemolytic anemia.

Deficiencies of red blood cell enzymes include glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase deficiencies.

Acquired hemolytic anemias include autoimmune hemolytic anemias, mechanical hemolysis, and paroxysmal nocturnal hemoglobinuria. Autoimmune hemolytic anemias occur mainly in people over 40 years of age.

The most common and typically most severe anemias are those caused by warm-reaction antibodies. Autoimmune hemolytic anemias caused by cold-reactive antibodies are the most commonly followed by mycoplasma pneumonia or infectious mononucleosis.

Drugs that induce autoimmune hemolytic anemias include methyldopa (Aldomet), penicillins, cephalosporins, erythromycin, and acetaminophen (for example, Tylenol), and procainamide (Pronestyl).

Paroxysmal nocturnal hemoglobinuria usually presents as chronic hemolytic anemia. Classic nocturnal hemoglobinuria is rarely seen.

Blood loss without compensation

Acute posthemorrhagic anemia occurs with gastrointestinal bleeding, hemorrhage from an external wound, or, less obviously, retroperitoneal hemorrhage or hemorrhage in a hip fracture.

A young, healthy person would be expected to tolerate the rapid loss of 500 to 1,000 ml of blood (10 to 20 percent of the total blood volume) with few or no symptoms. However, about 5 percent of the general population would react to vasovagal.

At rest, healthy young people can tolerate an acute isovolemic reduction of the hemoglobin volume at 5g per dL (50g per L) without deteriorating the critical oxygen supply.


Hypersplenism leads to anemia only after the spleen reaches three to four times its standard size, as can occur in cirrhosis, chronic infections, and myeloproliferative diseases.

Anemia is mainly caused by removing red blood cells from the circulation, but further destruction of red blood cells is usually a contributing factor.

Normocytic anemia in children

The prevalence of anemia caused by iron deficiency or lead toxicity decreases in the United States. As a result, normocytic anemias constitute a more significant proportion of cases in the pediatric age group.

Iron deficiency, which in its early stages is generally characterized by a normal MCV, remains a common cause of mild normocytic anemia in children beyond the neonatal period.

Other ordinary childhood normocytic anemias result from acute hemorrhage, sickle cell anemia, red blood cell membrane disorders, and current or recent infections (especially in younger children).

Aplastic crises in patients of any age with chronic hemolytic anemias are often precipitated by infection with human parvovirus B19.

Most anemias in children can be diagnosed with a fundamental analysis that includes a complete blood cell count (CBC), a corrected reticulocyte index, a peripheral blood smear, and specific peripheral blood studies (e.g., hemoglobin electrophoresis ).

Although bone marrow tests are usually unnecessary, one study found that when basic laboratory studies and historical and physical tests did not reveal, bone marrow samples yielded a specific diagnosis in 92 percent of children.

The most frequent diagnosis in this study was transient erythroblastopenia of childhood, a common erythrocytic aplasia, usually mild and self-limiting of unknown etiology.

This entity must be distinguished from Blackfan-Diamond syndrome, a rare, usually macrocytic, and probably genetic disorder of babies.

Blackfan-Diamond syndrome is congenital erythroid hypoplasia that usually does not remit spontaneously.