Von Willebrand's disease (vWD) is a hereditary coagulation abnormality that arises from a qualitative or quantitative deficiency of von Willebrand factor (vWF), a substance that affects platelet adhesion. It is known to affect humans and, in veterinary medicine, dogs.
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 may occur.
When suspected, blood plasma of a patient needs to be investigated for vWF (termed "factor VIII-related antigen") and the ristocetin cofactor (RiCof). Normal levels do not exclude all forms of vWD: particularily type 2 may only be revealed by investigating platelet interaction with subendothelium under flow (PAF), a highly specialistic coagulation study not routinely performed in most medical laboratories.
Other tests performed in any patient with bleeding problems are a full blood count (especially platelet counts), APTT (activated partial thromboplastin time), prothrombin time and international normalized ratio (INR). Testing for Factor VIII and antibody inhibitor levels may also be performed if hemophilia is suspected.
Classification and types
There are three described types of vWD - type 1, type 2 and type 3. There are inherited and acquired forms of all types of vWD. Most cases are hereditary, but acquired forms of vWD have been described. A form of vWD (type 2A) 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.
Type 1 vWD patients (60-80% of all vWD cases) have clearly impaired clotting but usually end up leading a nearly normal life (trouble usually arises in the form of dental surgery or troublesome menorrhagia/periods). Decreased levels of vWF are detected (10-30% of normal, i.e. 10-30 IU).
Type 2 vWD patients (20-30%) the bleeding tendency is mild. There are normal levels of vWF, but the multimers are structurally deficient. Five subtypes exist: 2A (most common), 2B, 2C, 2M and 2N.
Type 3 is the most severe form of vWD and may have severe mucosal bleeding, no detectable vWF antigen, and/or may have sufficiently low factor VIII that they have occasional hemarthoses (joing bleeding) as in cases of mild hemophilia.
See also von Willebrand factor for the normal function of that coagulation factor
vWF is mainly active in conditions of high blood flow and shear stress. Deficiency of vWF therefore shows primarily in organs with extensive small vessels, such as the skin, the gastrointestinal tract and the uterus. In angiodysplasia, a form of teleangiectasia of the colon, shear stress is much higher than in average capillaries, and the risk of bleeding is increased concomitantly.
The vWF gene is located on the twelfth chromosome. Types 1 and 2 are inherited as autosomal dominant traits and type 3 is inherited as autosomal recessive. Occasionally type 2 also inherits recessively.
In humans, the incidence of vWD is roughly about 1 in 1000 individuals. Because most forms are rather mild, they are detected more often in women, whose bleeding tendency shows during menstruation. The actual clotting abnormality (which does not necessarily lead to disease) occurs in 0.9-3% of the population.
Patients with vWD normally require no regular treatment. However, 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 cryoprecipitate or with Factor VIII. Mild cases of vWD can be trialled on 1-desamino-8-D-arginine vasopressin (DDAVP, desmopressin), which works by raising the patient's own plasma levels of vWF.
vWD is named after Erik Adolf von Willebrand (http://www.whonamedit.com/doctor.cfm/2690.html), a Finnish pediatrician (1870-1949). He first described the disease in 1926.
Harrison's textbook of Internal Medicine, Chapter 177.
Sadler, J. E. "Biochemistry and Genetics of von Willebrand factor." Annu Rev Biochem 1998; 67:395-424. (fulltext (http://arjournals.annualreviews.org/doi/abs/10.1146%2Fannurev.biochem.67.1.395))
Mannucci PM. Treatment of von Willebrands disease. N Engl J Med 2004;351:683-94.