What is von Willebrand disease?

Causes and Symptoms

Von Willebrand disease (vWD) is a genetic disorder affecting the normal clotting
function of platelets in the blood. There are three types of vWD that run in families, all due to inheriting a gene mutation. The pattern of inheritance may be autosomal dominant or autosomal recessive, although with either, both males and females are affected equally; some persons could be carriers of the defective gene without exhibiting any symptoms. There is another form of vWD called acquired von Willebrand syndrome. This disease is not caused by inheriting a gene mutation, and thus does not run in families. This disease is characterized by the qualitative or quantitative deficiency of von Willebrand factor
(vWF). This glycoprotein, present in platelets and the endothelium of blood vessels, facilitates the adhesion of platelets to one another to form a stable clot when there has been injury to a blood vessel. Therefore, patients with vWD exhibit the signs and symptoms of blood clotting abnormality.

Three types of vWD are recognized: type I vWD, with decreased levels of the protein vWF; type II vWD, with normal levels but decreased activity of vWF; and type III vWD, the most severe form of the disease, with a nearly complete deficiency of vWF.

Patients with mild or moderate vWD (type I or type II) can become symptomatic at any age and usually exhibit one or more of the following symptoms: easy bruisability, bleeding gums, frequent nosebleeds, bleeding points under the skin (subcutaneous hemorrhages), prolonged bleeding after injury or surgery of any kind, and, in women, menorrhagia, or excessive bleeding during menstrual periods. Patients with severe type III vWD become symptomatic at an early age and exhibit symptoms similar to hemophilia, with bleeding into and pain in the joints (hemathrosis), spontaneous bleeding into the gastrointestinal tract and from the mucous membranes that is potentially life-threatening, and painful bleeding into the muscles (hematomas). Some patients with type III disease also have multiple episodes of acute gastrointestinal bleeding and are often misdiagnosed. Some patients also have decreased factor VIII, which is deficient in hemophilia. The symptoms of vWD appear to decrease with advancing age, and they are milder in pregnancy, when factor VIII levels
are high. Typically, bleeding time is prolonged in all patients with vWD.

The disease is diagnosed in the laboratory using specialized blood tests, such as the von Willebrand factor antigen (which measures the amount of vWF in blood), Ristocetin cofactor (which measures the function of vWF in blood), vWF multimers, and factor VIII levels. A careful family history of the disease should help distinguish it from the rarer hemophilia. A correlation of family history, laboratory findings, and clinical findings may be needed in order to diagnose the condition in mild cases of vWD, in which diagnosis is difficult.

A few cases of acquired vWD have been identified, with antibodies against vWF being present. Such persons may be otherwise healthy or may also exhibit other immune-mediated diseases.

Treatment and Therapy

The aim of therapy for vWD is to stop the bleeding and to prevent further episodes. Both goals can be met by increasing vWF and/or factor VIII levels in the blood. This result can be achieved by many methods, the most common being the administration of the drug DDAVP (desmopressin acetate) by a nasal or intravenous route. This drug does not seem to have a beneficial effect in type III disease, and these patients may need intravenous infusions of concentrates of factor VIII and vWF. For women with heavy menstrual bleeding, estrogen therapy in the form of oral contraceptive (birth control) pills is a good alternative, as it has been observed that estrogen increases the levels of vWF in the blood. Local antifibrinolytic drugs, which delay the dissolution of the clot, are useful in milder presentations of the disease (such as nosebleeds) or following dental procedures.

Preventive care should be taken by all persons suspected of having vWD. Adequate care and treatment taken prior to any dental procedure or surgical intervention should prevent the excessive loss of blood. Children with the disease are advised against engaging in rough and vigorous sports activities with a high potential for injury. Patients should also be cautioned against the excessive intake of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), as they worsen the symptoms of vWD.

Perspective and Prospects

In 1925, Finnish physician Erik von Willebrand identified a bleeding disorder in the natives of the Aland Islands and named it after himself. Later, it was found that the disease was caused by a defect in one of the clotting factors, and the factor was also named after the brilliant physician. Today, vWD is recognized as the most common inherited bleeding disorder; it is thought to affect 1 to 3 percent of the population, with an equal distribution between the two sexes. It is important to distinguish this condition from the better-known hemophilia. The diagnosis of vWD in women is significant, as it is a popular misconception that bleeding disorders occur only in men.

The present drug therapy available to combat the disease is quite effective in reducing the bleeding that occurs. Modern-day medicine has reduced the problems of blood infections associated with the administration of cryoprecipitates. Further research is being conducted to develop an effective recombinant vWF.

Bibliography

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