Von Willebrand Disease: Causes, Risk Factors, Symptoms, Treatment and Prognosis

It is the most common of the bleeding disorders.

Von Willebrand disease is characterized by prolonged bleeding and is caused by a deficiency or abnormality in a protein called von Willebrand factor.

The Finnish doctor Erik von Willebrand in 1926, noticed that many men and women members of the same family had an increase in bruising and prolonged bleeding.

The severity of the bleeding ranged from mild to severe and affected the mouth, nose, genital and urinary tracts, and occasionally the intestinal tract.

Some women in the family also experienced excessive menstrual bleeding, which appeared not to be associated with muscle and joint bleeding and affected women and men rather than just men.

Dr. von Willebrand called this disorder hereditary pseudohemophilia.

It is necessary to heal an injury to a blood vessel, that blood clotting takes place.

When a blood vessel is injured, von Willebrand factor allows platelets to adhere to the injured area and form a plug to temporarily seal the hole and stop bleeding.

Von Willebrand factor is secreted by platelets and endothelial cells that line the inner wall of blood vessels to form a permanent clot.

Von Willebrand factor binds and stabilizes factor VIII, one of the factors involved in the formation of the permanent clot.

A deficiency or abnormality in the factor interferes with the formation of the temporary platelet plug and affects the normal function of factor VIII, for the production of the permanent clot.

Therefore, they have a hard time forming blood clots, and as a result, they can bleed longer.

Causes of Von Willebrand disease

People with von Willebrand disease have limited or no von Willebrand factor in their blood.

Von Willebrand disease is transmitted through an abnormal gene that can be inherited from either the mother or the father (or both, in some cases).

The complex genetics of von Willebrand disease involves a gene found on chromosome 12.

Different types of changes in the von Willebrand factor gene can affect its production.

Some changes cause the von Willebrand factor gene to produce reduced amounts of normal von Willebrand factor, while other changes cause the gene to produce abnormal von Willebrand factor.

Most changes in the von Willebrand factor gene are significant enough that a change in just one von Willebrand factor gene is sufficient to cause von Willebrand disease.

However, some types of genetic changes only cause von Willebrand disease if both genes are changed, often leading to more severe symptoms.

Type 1 von Willebrand disease is called an autosomal dominant condition because it is caused by a change in a single von Willebrand factor gene.

Most cases of type 2 von Willebrand disease are autosomal dominant, as a change in just one von Willebrand factor gene results in the production of an abnormal form of von Willebrand factor.

An autosomal dominant form of von Willebrand disease can be inherited from either parent or it can occur as a spontaneous mutation (change) of a gene in the embryo that forms when the cells of the egg and sperm unite during fertilization. .

Some cases of type 2 von Willebrand disease and all cases of type 3 von Willebrand disease are autosomal recessive, as they are caused only by changes in both von Willebrand factor genes.

Many carriers of the autosomal recessive forms of von Willebrand disease type 2 and von Willebrand disease type 3 do not have any symptoms.

Each child born to parents who have a modified gene has a 25 percent chance of having von Willebrand disease, a 50 percent chance of being a carrier, and a 25 percent chance of not being and not having von Willebrand disease. von Willebrand’s disease.

Risk factors for Von Willebrand disease

Since von Willebrand disease is inherited (passed from parent to child), there is usually a family history of bleeding problems.

The symptoms of von Willebrand disease can vary greatly within a family, so there are times when this is unclear.

Like most genetic disorders, there are rare occasions when von Willebrand disease can occur even when there is no family history of the disorder due to a spontaneous change in the von Willebrand gene before the baby is born.

Von Willebrand disease is similar to hemophilia, but people who have it tend to have more external bleeding rather than internal bleeding.

Unlike hemophilia, von Willebrand disease is not gender specific and affects men and women equally.

Symptoms

There is great variability in the severity of symptoms, which can range from clinically insignificant to life threatening.

Even children within the same family who are affected with the same type of von Willebrand disease can have different symptoms.

A child with von Willebrand disease can exhibit a variety of symptoms throughout his life and may experience improvement in symptoms with age.

Type 1

Type 1, the mildest form of von Willebrand disease, is generally associated with easy bruising, recurring nosebleeds, significant trauma, heavy menstrual periods, and prolonged bleeding after invasive work and surgeries.

The amount of von Willebrand factor made by the body increases during pregnancy, so prolonged bleeding during childbirth is rare in people with type 1 von Willebrand disease.

Type 2

Children with type 2 von Willebrand disease usually have symptoms from early childhood, they may even be present at birth.

These children generally experience prolonged bleeding due to cuts, easy bruising, nosebleeds, skin bruising, and prolonged bleeding from the gums after tooth extraction and minor trauma.

Gastrointestinal bleeding and heavy menstrual periods may require a blood transfusion and can be life threatening.

Some women with type 2 von Willebrand disease have prolonged bleeding during childbirth.

Type 3

This type of von Willebrand disease can be associated with bruising and bleeding in the mouth, nose, and in the intestinal, genital, and urinary tracts.

This type is also associated with spontaneous bleeding in the muscles and joints.

Some women with type 3 von Willebrand disease experience prolonged bleeding during childbirth.

Diagnosis of von Willebrand disease

If von Willebrand disease is suspected, a specialist (hematologist) can do tests to determine how long you bleed before the blood clots.

The doctor will also take into account your personal and family medical history.

The diagnosis can sometimes take some time because some people with von Willebrand disease have levels of clotting factors in the blood that are near normal.

Additionally, stress can promote a falsely negative result, as it is known to raise von Willebrand factor levels in the blood.

Many mild symptoms can be mistaken for other bleeding disorders, making it difficult for a doctor to diagnose von Willebrand disease based on clinical symptoms alone.

Von Willebrand disease should be suspected in a patient with a normal number of platelets in the blood and bleeding from the mucous membranes, nose, gums, and gastrointestinal tract.

Tests when von Willebrand disease is suspected often include the following:

  • The clotting time.
  • The amount of von Willebrand factor (measurement of von Willebrand factor antigen).
  • The co-factor activity of ristocetin.
  • The amount of factor VIII (measure of factor VIII antigen) factor VIII
    activity.

Children with type 1 von Willebrand disease generally have a decreased amount of von Willebrand factor and decreased von Willebrand factor activity, and usually have slightly lower factor VIII levels and activity.

Children with type 2 von Willebrand disease have a prolonged bleeding time and decreased activity of von Willebrand factor, they may also have reduced amounts of von Willebrand factor and factor VIII and decreased activity of factor VIII.

Type 3 children have undetectable amounts of von Willebrand factor, negligible von Willebrand factor activity, factor VIII levels of less than 5 to 10 percent, and significantly reduced factor VIII activity.

Von Willebrand factor activity is reduced for all types of von Willebrand disease, making it the most sensitive means of identifying all three types.

Once a person is diagnosed with von Willebrand disease, additional tests such as multimeric analysis for von Willebrand factor and ristocetin-induced platelet aggregation should be performed to determine the subtype.

Multimer analysis evaluates the structure of von Willebrand factor, and ristocetin-induced platelet aggregation measures the amount of ristocetin that is required to cause platelet accumulation in a blood sample.

Multimeric von Willebrand factor analysis can differentiate children with structurally normal von Willebrand factor (Type 1) from children with structurally abnormal von Willebrand factor (Type 2) and can often identify the subtype of patients with the von Willebrand disease type 2.

Children with type 1 von Willebrand disease generally have normal or decreased ristocetin-induced platelet aggregation levels.

Depending on the subtype, patients with type 2 VWD have increased or decreased ristocetin-induced platelet aggregation.

Ristocetin-induced platelet aggregation is generally absent, and multimer analysis shows undetectable von Willebrand factor in children with type 3 von Willebrand disease.

Detection of genetic alterations in DNA tests can confirm a diagnosis and determine the type and subtype of von Willebrand disease, and are a valuable adjunct to biochemical tests and facilitate prenatal testing.

Unfortunately, many people with von Willebrand disease have DNA changes that are not detectable through DNA testing.

If the relative with von Willebrand disease has a detectable genetic change, then DNA testing should be considered.

Treatment

For those who need treatment, there are several options, depending on individual circumstances and the severity of the disorder.

Minor bleeding can be controlled with the PRICE method: protection, rest, ice, compression, and elevation.

Treatments include:

Desmopressin treatment

Von Willebrand disease is most commonly treated by replacement of von Willebrand factor by administration of blood products containing von Willebrand factor or by treatment with desmopressin (desmopressin, 1-deamino-8-D-arginine vasopressin).

Desmopressin works by increasing the amount of factor VIII and von Willebrand factor in the circulating blood.

Treatment with blood products or desmopressin can be given before surgical procedures or dental work.

The type of treatment chosen depends on the type of von Willebrand disease and a patient’s response to a preliminary treatment trial.

About 80 percent of people with type 1 von Willebrand disease respond to desmopressin therapy.

Desmopressin treatment can also be used to treat some people with type 2 von Willebrand disease.

Patients with type 2B von Willebrand disease should not be treated with this drug, as desmopressin can induce dangerous clumping of platelets.

Type 3 von Willebrand disease should not be treated with desmopressin, as this drug does not increase the level of von Willebrand factor in type 3 patients.

Used to treat smaller bleeds and during minor surgical procedures, it is injected into the vein and increases the level of von Willebrand factor in the blood.

Treatment with blood products

Patients who do not respond to drug treatments are treated with concentrated factor VIII obtained from blood products.

Not all factor VIII concentrates can be used, as some do not contain enough von Willebrand factor.

The concentrated von Willebrand factor is used to treat severe forms of the disorder. The missing factor is injected and replaced in the blood so that clotting occurs at a normal rate.

Hormonal treatment

Estrogens, as found in oral contraceptives (birth control pills), increase the synthesis of von Willebrand factor and can sometimes be used in the long-term treatment of women with mild to moderate von Willebrand disease.

Estrogens are also sometimes used before surgery in women with type 1 von Willebrand disease.

Precautions

Antifibrinolytic agents can be very effective in treating heavy menstruation.

Tranexamic acid is often used to treat small but persistent bleeds (such as nosebleeds).

This medication is taken by mouth and works by slowing the breakdown of clots.

Medicines called fibrinolytic inhibitors can be helpful in controlling intestinal, oral, and nasal bleeding.

Aspirin should not be administered in patients with von Willebrand’s disease as it may increase the susceptibility to bleeding.

Patients with severe forms of von Willebrand disease should avoid activities that increase the risk of injury.

Forecast

The prognosis for von Willebrand disease is generally good, and most individuals have a normal lifespan and will depend on an accurate diagnosis and appropriate treatment.