Von Willebrand disease
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A teenage girl has heavy menstrual bleeding and easy bruising. She also has prolonged bleeding after dental extraction. Both PTT and bleeding time are mildly prolonged.
AD (types 1 and 2A/2B/2M) or AR (type 2N and type 3); VWF
Types:
- Type 1 (70-80%): Partial quantitative deficiency, mild
- Type 2: Qualitative defects. Subtypes 2A, 2B, and 2M are typically AD; 2N (Normandy) disrupts the VWF binding site for factor VIII and is AR, producing a hemophilia-A-like picture (low factor VIII with normal VWF antigen)
- Type 3: Severe quantitative deficiency, AR
- Most common inherited bleeding disorder
- Mucocutaneous bleeding (epistaxis, menorrhagia, GI)
- VWF carries factor VIII (low VWF → low VIII)
- Prolonged bleeding time, may have prolonged PTT
- Initial panel: VWF antigen (quantity), ristocetin cofactor activity (function), and factor VIII level
- VWF multimer analysis distinguishes subtypes (loss of high-molecular-weight multimers in types 2A and 2B)
- Ristocetin-induced platelet aggregation (RIPA): increased response at low ristocetin concentrations suggests type 2B
- Confirmatory VWF molecular testing helps subtype classification and family testing
- Desmopressin (DDAVP) for types 1 and some type 2, VWF concentrate
VWD is the only common AD bleeding disorder: Clotting/bleeding disorders that predispose to bleeding are mostly AR or XLR. VWD is the exception as the most common inherited bleeding disorder, with the major types (1, 2A, 2B, 2M) inherited AD. The recessive types are 2N and 3.
VWF stabilizes factor VIII: Low VWF leads to low factor VIII, which is why VWD can mimic hemophilia A on lab testing (prolonged PTT). VWF also mediates platelet adhesion via glycoprotein 1b.