Syndrome of the week

Von Willebrand disease (vWD) is the most common hereditary coagulation abnormality described in humans, although it can also be acquired as a result of other medical conditions. It arises from a qualitative or quantitative deficiency of von Willebrand factor (vWF), a multimeric protein that is required for platelet adhesion. It is known to affect humans and in veterinary medicine, dogs. There are four types of hereditary vWD. Other factors including ABO blood groups may also play a part in the severity of the condition.

The various types of vWD present with varying degrees of bleeding tendency. Severe internal or joint bleeding is rare (only in type 3 vWD); bruising, nosebleeds, heavy menstrual periods (in women) and blood loss during childbirth (rare) may occur. Death may occur.

When suspected, blood plasma of a patient needs to be investigated for quantitative and qualitative deficiencies of vWF. This is achieved by measuring the amount of vWF in a vWF antigen assay and the functionallity of vWF with a glycoprotein (GP)Ib binding assay, a collagen binding assay or, a ristocetin cofactor activity (RiCof) or ristocetin induced platelet agglutination (RIPA) assays. Factor VIII levels are also performed as factor VIII is bound to vWF which protects the factor VIII from rapid breakdown within the blood. Deficiency of vWF can therefore lead to a reduction in factor VIII levels. Normal levels do not exclude all forms of vWD: particularly type 2 which may only be revealed by investigating platelet interaction with subendothelium under flow (PAF), a highly specialized coagulation study not routinely performed in most medical laboratories.

Acquired vWD can occur in patients with autoantibodies. In this case the function of vWF is not inhibited but the vWF-antibody complex is rapidly cleared from the circulation.
A form of vWD occurs in patients with aortic valve stenosis, leading to gastrointestinal bleeding (Heyde's syndrome). This form of acquired vWD may be more prevalent than is presently thought.
Acquired vWF has also been described in the following disorders: Wilms' tumour, hypothyroidism and mesenchymal dysplasias.

Patients with vWD normally require no regular treatment, although they are always at increased risk for bleeding. Prophylactic treatment is sometimes given for patients with vWD who are scheduled for surgery. They can be treated with human derived medium purity factor VIII concentrates complexed to vWF(antihemophilic factor, more commonly known as Humate-P®) Mild cases of vWD can be trialled on desmopressin (1-desamino-8-D-arginine vasopressin, DDAVP) (desmopressin acetate, Stimate®), which works by raising the patient's own plasma levels of vWF by inducing release of vWF stored in the Weibel-Palade bodies in the endothelial cells.

vWD is named after Erik Adolf von Willebrand, a Finnish paediatrician (1870–1949). He first described the disease in 1926.