Von Willebrand's disease What we need to know

10.11.2023

about the disease

Table of Contents

Von Willebrand factor is a protein involved in blood coagulation, which ensures the primary adhesion (sticking) of platelets to the surface of the damaged endothelium of the blood vessel and subsequent aggregation (grouping) of platelets to form a thrombus. It interacts with other coagulation factors, particularly coagulation factor VIII, and activates the next steps in clotting.

Von Willebrand's disease is a blood clotting disorder. The cause of the disease is the deficiency of the Willebrand factor involved in the clotting process. The condition is mostly congenital (genetic), although there are also acquired forms. Bleeding episode usually occurs on the background of trauma, surgery or dental intervention.

Willebrand's disease cannot be cured, but with symptomatic treatment of coagulopathy, it is possible for a person with this diagnostics to live an active life.

reasons

The cause of the disease is a defect in the Willebrand factor synthesizing gene, which a person inherits from one or both parents.

Low concentration of Willebrand factor (protein) in plasma leads to disruption of its function, in particular, decrease in the ability of platelet adhesion (sticking to each other and to the wall of the damaged blood vessel), this disrupts the process of thrombus formation and causes bleeding.

Many people with Willebrand disease also have coagulation factor VIII deficiency.

coagulation factor VIII (Antihemophilic factor AND), non-enzymatic is a cofactor, which is synthesized in the liver და of Willebrand with the factor Together circulates in plasma. I-8 factor და of Willebrand factor of molecules is a ratio 1: 50-with.

The coagulation factor VIII protein is called the FVIII antigen. Von Willebrand factor regulates plasma concentration of factor VIII and stabilizes it by prolonging its half-life to 8-12 hours. Through the cleavage of procofactor FVIII, activated factor VIII is obtained, which in turn interacts with serine protease with the participation of calcium ions and forms a prothrombinase-like complex. This complex is involved in the next step of the coagulation process and is an activator of coagulation factor X.

Coagulation factor VIII deficiency is the cause of another genetic coagulopathy - hemophilia. However, unlike hemophilia, Willebrand's disease is not linked to the X chromosome and occurs in both women and men, and is characterized by an average course compared to hemophilia.

Symptoms

Most people with von Willebrand disease are not even aware of their disease, as symptoms are mild or moderate. The most characteristic symptom of the condition is bleeding.

There are three main types of the disease, according to which the intensity of bleeding is different.

Von Willebrand's disease is characterized by:

Bleeding after trauma, surgery or dental intervention
Frequent bleeding from the nose, the duration of which exceeds 10 minutes
Prolonged and intense menstrual bleeding
Bloody urine and stool
Propensity to subcutaneous hemorrhages
Anemia symptoms: weakness and fatigue, shortness of breath, sometimes tachycardia

Risk factors

The main risk factor for von Willebrand disease is family history. The disease is inherited in an autosomal dominant manner, which means that one copy of the defective gene (from one parent) is enough to develop the disease. When a person has only one defective copy of the gene, 50% of the offspring will be affected, 50% will be healthy.

When a person receives a defective copy of the gene from both parents, this is called a homozygous condition, and the disease manifests in a more severe clinical form. All offspring of a homozygous sufferer will inherit a copy of the defective gene.

Complications

Rarely, von Willebrand disease is accompanied by uncontrolled bleeding, which can be life-threatening. Other complications include:

Iron deficiency anemia - especially in women, with heavy menstrual bleeding
Hemarthrosis – bleeding and pain in the joint

Diagnosis

Mild forms of Willebrand's disease are not easy to diagnose because the bleeding is not active. However, when the disease is suspected, it becomes necessary to involve a hematologist in the process.

To diagnose Willebrand's disease, a number of laboratory studies are provided:

Willebrand factor antigen – measures the amount of Willebrand factor (protein) in the blood
Willebrand factor activity – to determine the intensity of involvement in the coagulation process.
Coagulation factor VIII activity - determines the amount of factor in plasma and its participation in coagulation
Willebrand factor-degrading protease ADAMTS-13

Willebrand's disease is the most common congenital (genetic) coagulopathy. The disease is divided into 3 main groups:

Type 1 – Willebrand factor production is deficient, although its function is preserved. This form accounts for 75% of Willebrand's disease. It is characterized by mild or moderate symptoms.

Type 2 – The amount of the Willebrand factor is within the normal range, but its function is disturbed. Symptoms are much more intense than in type 1. Its 2A, 2B, 2M and 2N subtypes are distinguished.

Type 3 – It is associated with a very low rate of the Willebrand factor and a profound disruption of the coagulation function. Bleeding episodes are severe and begin in early childhood.

Under the influence of various factors, the mentioned data may change (stress, physical exertion, pregnancy, various medications). Therefore, repeated studies in dynamics are recommended.