Von Willebrand Disease Essay

Von Willebrand disease (VWD) is a genetic disorder caused by a missing or defective clotting protein in the blood called von Willebrand factor. VWD causes prolonged or excessive bleeding. As the most common inherited bleeding disorder, it affects approximately 1% of the population. VWD occurs equally in men and women.

Von Willebrand disease is due to an abnormality, either quantitative or qualitative, of the von Willebrand factor, which is a large multimeric glycoprotein that functions as the carrier protein for factor VIII (FVIII) (1). Von Willebrand factor is also required for normal platelet adhesion. As such, von Willebrand factor functions in both primary (involving platelet adhesion) and secondary (involving FVIII) hemostasis. In primary hemostasis, von Willebrand factor attaches to platelets by its specific receptor to glycoprotein 1b on the platelet surface and acts as an adhesive bridge between the platelets and damaged sub-endothelium at the site of vascular injury. In secondary hemostasis, von Willebrand factor protects FVIII from degradation and delivers it to the site of injury.

The laboratory evaluation of a patient with a bleeding disorder will be guided by the clinical and family history.

Medications and other conditions, such as uremia, should be considered before embarking on an extensive workup. The starting point of the laboratory evaluation is a basic coagulation panel including a platelet count, PT and PTT. The peripheral blood smear should be reviewed for the presence of schistocytes, as seen in DIC and other micro -angiopathic hemolytic anemia’s. If the history suggests a qualitative platelet type bleeding disorder, platelet aggregation studies can be performed. In the case of vWD, the platelet aggregation studies will likely show decreased aggregation with Ristocetin. VWD can be confirmed by evaluation of vWF multimers; this can also assist in subclassifying the type of

vWD.
If the PT or PTT is prolonged, a mixing study should be performed to distinguish between a factor deficiency or an inhibitor as the cause of the prolongation. Upon mixing the patient’s plasma with normal plasma, a factor deficiency will be corrected and the PT or PTT will correct to the normal range. If a factor deficiency is suspected, individual factor assays can be per- formed. Knowledge of the coagulation cascade can assist in predicting which factor is most likely deficient. For example, if the PT is prolonged, but the PTT is normal, then a factor VII deficiency can be confirmed by specific assay. If the PTT is prolonged, but the PT is normal, a factor VIII or IX or vWF deficiency may be present.
Treatment for VWD depends on the
type and severity. The most common treatment, DDAVP, boosts factor levels in the blood. It can be taken by injection or nasal spray. Other treatments may include injections to replace missing factor proteins; agents to help prevent the breakdown of blood clots; and, for women, hormone therapy, such as birth control pills.