Von Willebrand disease (vWD) is caused by genetic mutations that lead to decreased quantity or impaired function of von Willebrand factor (vWF), a multimeric glycoprotein produced by platelets and endothelial cells.  VWF has 2 important hemostatic functions:

1. It binds platelets to vascular subendothelial components at sites of injury (and platelets to each other), which results in the formation of hemostatic platelet plugs.  Therefore, patients with VWD have impaired platelet aggregation but normal platelet count (as platelet consumption/production is unaffected).

2. VWF acts as a carrier protein for factor VIII and protects it from degradation.  Because factor VIII is part of the intrinsic (contact activation) coagulation pathway, patients with VWD sometimes have prolonged PTT (due to increased destruction of factor VIII), but PT will be normal.

VWD is typically transmitted in an autosomal dominant fashion so a family history of bleeding is often an important diagnostic clue.  Most cases are asymptomatic, but a minority (~1%) have easy bruising, skin bleeding, and bleeding from mucous membranes (eg, oropharyngeal, gastrointestinal, uterine).  Testing for vWF level and activity (eg, ristocetin cofactor assay) can help confirm the diagnosis.

(Choice A)  Primary immune thrombocytopenia (ITP) is an autoimmune disease associated with immune-mediated platelet destruction.  Although patients with ITP often have easy bleeding, VWF levels and activity are normal, and a family history of bleeding is uncommon (as ITP is an acquired disorder).  ITP is marked by thrombocytopenia and normal PT/PTT.

(Choice B)  Disseminated intravascular coagulation is caused by widespread activation of coagulation and fibrinolysis due to sepsis, malignancy, trauma, or obstetric complication.  It is an acquired disorder, so a family history of bleeding is uncommon.  Disseminated intravascular coagulation is associated with low platelets and elevated PT and PTT.

(Choice D)  Vitamin K deficiency and warfarin use impair synthesis of vitamin K–dependent clotting factors (II, VII, IX, and X), which leads to prolonged PT and normal platelet count and PTT (PTT can sometimes be mildly elevated).  Although vitamin K deficiency is common in newborns, it is very uncommon in otherwise healthy children and adults.  In addition, the family history of bleeding disorder makes this much less likely than vWD.

(Choice E)  Patients with severe liver disease often have impaired hepatic synthetic function and are unable to generate sufficient quantities of clotting factors.  Therefore, they often have elevated PT and PTT (with normal or low platelets).  This otherwise healthy boy is unlikely to have significant liver disease.

Educational objective:
Von Willebrand disease is the most common inherited bleeding disorder and is usually transmitted in an autosomal dominant fashion.  Symptomatic patients typically present with easy bruising and mucosal bleeding.  Laboratory evaluation will show normal platelets, normal PT, and either normal or prolonged PTT due to low levels of factor VIII.