.Snapshot A 30-year-old woman presents with a recurrent history of nosebleeds and heavy menses. She recently read that taking a baby aspirin was good for the heart. However, ever since she started taking aspirin, she has been experiencing more and more nosebleeds. Her father and paternal uncle similarly have histories of prolonged nosebleeds. Labs show increased PTT, normal PT, and increased bleeding time. Introduction Inherited mixed platelet and coagulation disorder from deficiency in von Willebrand factor (vWF) Epidemiology Most common inherited bleeding disorder Female to male ratio 2:1 likely due to more women being diagnosed due to menorrhagia More likely in Caucasians Genetics autosomal dominant ETIOLOGY Pathogenesis affects coagulation - vWF carries and protects factor VIII produced by endothelial cells and megakaryocytes intrinsic pathway coagulation defect affects platelets – vWF is important in platelet adherence to endothelial lining platelet aggregation is normal (mediated by fibrinogen) Presentation Symptoms mucocutaneous bleeding epistaxis gingival bleeding petechiae easy bruising menorrhagia can be asymptomatic increased bleeding after aspirin use STUDIES Normal or ↑ PTT (like hemophilia) Normal PT ↑ bleeding time (unlike hemophilia) CBC normal platelet count and appearance may have anemia ↓ von Willebrand factor antigen Differential Diagnosis Bernard-Soulier syndrome Glanzmann thrombasthenia Hemophilia DIAGNOSIS Diagnosis by ristocetin cofactor assay tests ability of platelets to bind to ristocetin (artificial endothelial surface) ↓ platelet agglutination Repeat testing may be required as vWF is an acute phase reactant stress, surgery, pregnancy and oral contraceptives may increase vWF levels Treatment Prevention avoid aspirin DDAVP (desmopressin acetate) releases vWF stored in endothelial cells Factor VIII replacement if refractory to DDAVP contains vWF Cryoprecipitate no longer used Complications Excessive bleeding, especially during childbirth Prognosis Most are mild or moderate in severity Variable prognosis