Pathophysiology
1) type of bleeding disorder (can be inherited or acquired) due to a defect in, or reduction of, von Willebrand factor 2) four inherited forms exist – type I, type IIb, type IIN, and type III 3) type I – most common with mild to moderate symptoms; vWF is 50% decreased 4) types IIb and IIN – amount of vWF is near normal but activity is decreased 5) type III – defect in both amount and activity of vWF; a rare and severely hemorrhagic condition
Signs and Symptoms
1) severity of symptoms is highly variable -from bleeding only after surgery or trauma to spontaneous 2) epistaxis 3) gastrointestinal bleeding 4) genitourinary tract bleeding 5) petechiae 6) ecchymosis 7) hemarthrosis
Characteristic Test Findings
Laboratory – 1) prolonged bleeding time 2) decreased amount of plasma vWF 3) decreased biologic activity of vWF as measured by ristocetin cofactor assay 4) decreased factor 8 5) thrombocytopenia
Histology/Gross Pathology
vWF is a multivalent protein that can bind two or more platelets
Associated Conditions
acquired von Willebrand’s disease occurs in multiple transfusions, autoimmune disorders (e.g., Waldenstrom’s macroglobulinemia), lymphoproliferative disorders (e.g., lymphoma), and Wilms’ tumor
Biochemistry
1) inherited form – see “Pathology” above 2) acquired form – occurs when antibodies develop that absorb or inhibit vWF
Inheritance/Epidemiology
1) most common type of inherited bleeding disorder 2) types I, IIb, and IIN – autosomal dominant 3) type III – autosomal recessive
Treatment
Inherited type I – 1) factor 8 concentrate (contains vWF) every 12 h for 2-3 days before and after surgical procedure 2) DDAVP (raises amount of vWF) can be given for maximum of 48 h and requires pretesting to ensure efficacy 3) if menorrhagia occurs, use oral contraceptives to stop menses Acquired disease – 4) requires adequate treatment of underlying causes 5) factor 8 concentrate and DDAVP don’t work
Tips for USMLE
1) main functions of vWF are to facilitate platelet adhesion and to carry the anti-hemophilic factor 8 intravascularly 2) four most consistent lab findings – prolonged bleeding time, decreased amount and activity of vWF, and decreased amount of factor 8 3) other lab findings (and to some degree the four listed above) can vary over time and are occasionally even normal 4) factor 8 concentrate and DDAVP are both effective treatments; DDAVP is preferred by some patients to avoid risks associated with transfusion of blood factors 5) factor 8 works in types I, IIb, and III 6) DDAVP works in only some cases of type I 7) if ristocetin cofactor assay is mentioned, think vWD
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