Willebrand-Jürgens syndrome (Von Willebrand syndrome)

Willebrand-Jürgens syndrome (also known as Von Willebrand syndrome or angiohaemophilia) is the most common congenital disorder of blood coagulation, which leads to an increased tendency to bleed. Several types of Willebrand-Jürgens syndrome are distinguished, the common feature of which is a qualitative or disturbance deviation of the Von Willebrand factor in the blood. The Von Willebrand factor plays a major role in blood clotting. In many cases, affected individuals live without any significant health impairments and without being aware of their disease.

Willebrand-Jürgens syndrome is the most common congenital bleeding disorder. It is estimated that about 800 per 100,000 people have the disease, with only about 12 per 100,000 suffering from significant symptoms. A severe course of Willebrand-Jürgens syndrome is extremely rare, affecting less than 0.3 per 100,000 people on average. The disease is inherited in an autosomal dominant manner, but the severe variants of the disease are inherited in an autosomal recessive manner. Women and men are affected by angiohaemophilia at about the same rate.

The blood clotting disorder is named after the Finnish physician Erik Adolf von Willebrand (1870 to 1949) and the German physician Rudolf Jürgens (1898 to 1961).

The cause of Willebrand-Jürgens syndrome is a qualitative or quantitative disorder of the Von Willebrand factor in the blood. The Von Willebrand factor is an important carrier and protective protein of the blood clotting factor VIII. A deficiency of the Von Willebrand factor thus causes a disturbance of normal blood clotting, which leads to symptoms similar to those of haemophilia A (deficiency of clotting factor VIII) and thus to an increased tendency to bleed.

In addition to inherited forms of the disease, acquired variants also exist, but are extremely rare. Acquired forms occur mostly in the context of certain autoimmune diseases (for example, Purpura Schönlein-Henoch), in heart valve defects (mainly in aortic stenosis) or in therapy with valproate (antiepileptic drug).

Three forms of hereditary Willebrand-Jürgens syndrome are distinguished:

• Type 1: In this form, affected individuals have a quantitative deficiency of Von Willebrand factor in the blood. About 60 to 80 percent of cases are classified as type 1. Most of those affected suffer only mild symptoms, so that an almost normal life is possible. However, patients may have a tendency to bleed for longer than average periods of time and to bleed after operations, for example. Type 1 is inherited in an autosomal dominant manner.
• Type 2: Patients suffer from a qualitative defect of the Von Willebrand factor. About 15 percent of all cases of Willebrand-Jürgens syndrome are type 2. Five different subtypes of type 2 (A, B, C, M, N) are distinguished. The mode of inheritance is autosomal dominant.
• Type 3: This is the rarest, but also the most severe variant of Willebrand-Jürgens syndrome, in which the Von Willebrand factor in the blood is either completely absent or reduced to less than five percent of its normal concentration. The mode of inheritance in type 3 is autosomal recessive.

The clinical presentation varies from patient to patient. The following symptoms may indicate the presence of Willebrand-Jürgens syndrome:

• increased bleeding tendency
• recurrent, severe nosebleeds
• prolonged bleeding after minor injuries or surgical procedures
• prolonged menstruation
• bleeding into joints
• Tendency to develop large hematomas

A reliable diagnosis of Willebrand-Jürgens syndrome can only be made using laboratory tests. Since the standard tests for blood coagulation disorders, such as the quick value (INR) or the blood count, are normal in almost all cases, the activity of the blood coagulation factor VIII and the Von Willebrand factor antigen, among other things, must be determined with the aid of special examination procedures.

In order to distinguish between the different types of Willebrand-Jürgens syndrome, both qualitative and quantitative tests of the Von Willebrand factor must be carried out. Certain methods such as ELISA, multimer analysis or electrophoresis are used.

These tests can also be used to differentiate the disease from other blood coagulation disorders such as haemophilia A.

Since Willebrand-Jürgens syndrome often causes only mild symptoms, long-term therapy is usually not necessary. However, medications containing acetylsalicylic acid (such as aspirin) should be avoided, as they inhibit platelet function, which temporarily increases the tendency to bleed.

Excessive menstrual bleeding can be controlled by using hormonal contraceptives with a high progestogen content.

The prophylactic administration of desmopressin is recommended before surgery. Desmopressin causes an increase in the concentration of Von Willebrand factor in the blood by up to five times its original value, which can reduce the risk of bleeding.

However, desmopressin has no effect on type 2B Willebrand-Jürgens syndrome - factor concentrates are used in these cases.

Since Willebrand-Jürgens syndrome is quite mild in most cases, most of those affected live without any significant health restrictions and without knowing about their disease. In severe forms of the disease, however, sufferers must refrain from extreme physical exertion and from sports such as boxing, winter sports or athletics.

Before operations, excessive postoperative bleeding can be prevented by administering the active substance desmopressin.

Since Willebrand-Jürgens syndrome is a genetically inherited blood clotting disorder, the disease cannot be prevented.