What causes von Willebrand's disease?

It has now been established that von Willebrand's disease is not one disease but a group of related hemorrhagic diathesis caused by a violation of synthesis or qualitative anomalies of the von Willebrand factor.

Hereditary disease of von Willebrand

The cause of hereditary von Willebrand disease is the polymorphism of the gene coding for the synthesis of von Willebrand factor. Hereditary disease of von Willebrand is the most common hemorrhagic disease. The frequency of carriage of the defective gene of von Willebrand factor in the population reaches 1 per 100 people, but only 10-30% of them have clinical manifestations. Transmitted by autosomal dominant or recessive type and occurs in both girls and boys.

The von Willebrand factor is expressed in endotheliocytes and megakaryocytes. It is contained in alpha-granules of platelets, endotheliocytes, in plasma and subendothelial matrix. The von Willebrand factor consists of polymers of progressively increasing molecular weight. Light, medium, heavy and super-heavy multimers with a molecular mass of about 540 kDa are divided into dimers to several thousand kilo daltons in the largest multimers. The greater the molecular weight of the von Willebrand factor, the greater their thrombogenic potential.

In hemostasis, the von Willebrand factor plays a dual role: it mediates the adhesion of platelets to the subendothelial structures and the mutual adhesion of platelets during the formation of the thrombus, serves as a "bearer" of factor VIII in the plasma, significantly prolonging its circulation time.

Acquired von Willebrand disease

Acquired von Willebrand's disease is a hemorrhagic condition, laboratory and clinically similar to the disorders characteristic of congenital Willebrand disease. A total of about 300 cases of acquired von Willebrand disease have been described. In children, the development of acquired von Willebrand disease occurs against a background of heart disease, blood vessels, connective tissue, systemic and oncological processes.

Pathogenetic mechanisms for the formation of a deficiency of von Willebrand factor:

• specific antibodies to factor VIII / von Willebrand factor;
• nonspecific antibodies, forming immune complexes and activating the clearance of von Willebrand factor;
• absorption of von Willebrand factor by malignant tumor cells;
• increased proteolytic degradation of von Willebrand factor;
• loss of heavy molecules of von Willebrand factor under stress with high shear stress under conditions of active blood flow;
• reduction in the synthesis or release of von Willebrand factor.

Classification and pathogenesis of von Willebrand disease

There are three types of von Willebrand disease:

1. Type 1 - characterized by a quantitative decrease in the content of von Willebrand factor in the blood of varying severity;
2. Type 2 - characterized by qualitative changes in von Willebrand factor. Four subtypes are distinguished: 2A, 2B, 2M, 2N;
3. Type 3 - almost complete absence of von Willebrand factor in the blood.

Pseudology of von Willebrand (platelet type) occurs due to the increased binding of von Willebrand factor to the glycoprotein Ib-IX-V, which is associated with changes in the structure of the latter. This leads to an accelerated elimination, in the first place, of the most high-molecular complexes of von Willebrand factor from the plasma and a disproportionate decrease in its activity in comparison with the antigen. With the disease, moderate thrombocytopenia is possible. Pseudo-valebrand disease is phenotypically similar to type 2B of von Willebrand disease, but differs from it by localization of the disorder. For a differential diagnosis, RIPA with low concentrations of ristomycin should be performed. In this test, with healthy donor plasma and platelet patients, aggregation will be observed in a patient with pseudo-Villebrand disease, and in a study with platelets of a healthy donor and patient plasma, aggregation will be observed in a patient with Willebrand disease (type 2B).