Von Willebrand disease

The von Willebrand syndrome (often also called von Willebrand syndrome VWD ), after the Finnish physician Erik Adolf von Willebrand ( 1870-1949 ) and the German physician Rudolf Jürgens ( 1898-1961 ), ( syn. Angiohämophilie, of - Willebrand syndrome, von Willebrand 's disease) is the most common congenital disease with increased bleeding. This is a group of bleeding diathesis, whose common feature is a quantitative or qualitative deviation of the von Willebrand factor, which plays an important role in blood clotting. Many sufferers live without the knowledge of the disease and without significant adverse health effects.

Epidemiology

The von Willebrand Jürgens syndrome is the most common inherited bleeding disorder. The prevalence is estimated at 800/100.000 people and only 12.5 / 100,000 people have significant symptoms. A heavy of von Willebrand syndrome is very rare, affecting <0.3 / 100,000 people. Acquired forms are described, but very rare. The mode of inheritance is autosomal dominant in general, the more severe forms and some subtypes but are inherited in an autosomal recessive manner. Men and women are equally affected.

Etiology

It is a group of bleeding diathesis, which have in common is an inherited quantitative or qualitative defect of von Willebrand factor. By this, inter alia, platelet aggregation defect, and the cross-linking is affected and / or VIII (see Haemostasis ) inhibited only (depending on the severity of the disease ) the reduction of the coagulation factor is insufficient. The latter is explainable because of the Von Willebrand factor as a support and at the same time protecting protein for factor VIII in plasma acts. Its deficiency results in a quantitative reduction in the factor VIII as well as in a reduction of Factor VIII half-life of normal at 12-15 for 2.5 hours. Both points lead to a hemophilia A similar symptoms.

Rare acquired forms occur mostly as an accompanying disease in heart valve defects (especially in the aortic stenosis), in the context of some autoimmune diseases ( such as in Henoch-Schönlein purpura ), in diseases of the lymphatic system (for example, malignant lymphoma ), as a side effect of treatment with valproate and other things.

Classification

The VWD is one principle among the diseases of the plasmatic coagulation system, however it affects the cellular cascade and also in clinical appearance is more like a hybrid between plasmatic and corpuscular coagulopathy.

The von Willebrand Jürgens syndrome occurs in three forms.

Type 1

In type 1 von Willebrand - Jürgens syndrome there is a quantitative deficiency of von Willebrand factor. 60-80 % of cases are of the type 1 Clinically, however, most patients show mild symptoms. A nearly normal life is possible. Abnormalities caused by the inclination of the person concerned to prolonged bleeding and rebleeding after surgery, the training of large area hematoma and heaped menorrhagia in female victims.

Type 1 is an autosomal dominant, the penetrance is variable.

Type 2

Type 2 of the Von Willebrand syndrome is an autosomal dominant and is noted in about 15% of those affected. A characteristic feature is the presence of qualitative defects of von Willebrand factor. There are distinguished the subtypes 2A, 2B, 2M and 2N. Type 2A is among the most frequently encountered.

Type 3

The clinically most difficult runs, but also rarest form of von Willebrand 's disease is type 3 Sufferers have homozygous or compound heterozygous mutations of the VWF gene. This results in a total absence or strong reduction (<5 %) of the VWF. The type 3 is autosomal recessive.

Clinic

The clinical presentation is not uniform. A suspicion should arise in the following symptoms:

• Increased bleeding tendency
• Severe recurrent epistaxis ( nosebleeds )
• Tendency to form large-scale hematoma
• Long and extensive bleeding even after minor surgical procedures (eg, tooth extraction)
• Menorrhagia
• Joint bleeds ( hemarthrosis )

Diagnostics

The advanced diagnostics laboratory medical conduct. Standard tests of blood clotting as the blood count and prothrombin time (INR) are almost always normal. The PTT may be in some cases ( almost always in type 3, often for serious forms of type 1 ) changed. A determination of activity of individual coagulation factors, in particular the factor VIII, von Willebrand factor antigen and its activity ( ristocetin cofactor ) should be performed. Also the bleeding time is to be determined, but in many cases (especially in type 1 ) normal.

Characteristic findings are here:

• Prolongation of the activated thrombin time ( aPTT, while type 3)
• Normal coagulation factor VIII - value (factor VIIIc ) in type 1
• Decreased clotting factor VIII - value (factor VIIIc ) in type 3 and 2N
• Prolonged bleeding time in type 2 and 3, often normal in type 1
• Factor VIII - associated antigen ( = von Willebrand factor): reduced
• VWF activity: reduced

In order to distinguish the different types and subtypes that have both quantitative and qualitative studies of the von Willebrand factor ( such as ELISA and electrophoresis, the so-called multimer ) take place.

Differential diagnoses include other haemorrhagic conditions ruled out.

Therapy

Long-term therapy is usually not necessary. Should be avoided acetylsalicylic acid medications ( such as aspirin) because they inhibit platelet function in addition. In nosebleed vasoactive nasal sprays ( eg drug desmopressin ) can be given. Excessive menstrual bleeding can be controlled with hormonal contraceptive with a higher progestin content.

Before surgery, the administration of desmopressin is recommended. After a short desmopressin infusion, the concentration of von Willebrand factor increases by up to five times.

In type 2 B desmopressin does not work. In these and other cases with missing effect the substitution of the Von Willebrand factor and comes in acute cases, administration of activated factor VII or factor VIII in question.

In type 3, a von-Willebrand-Faktor/Blutgerinnungsfaktor VIII preparation is administered in most cases in trauma. Or will it be substituted prophylactically at regular intervals ( 2-5 days ).