hematology and oncology
Von Willebrand Disease
Diagnosis of Von Willebrand Disease
Total plasmavon Willebrand factor(VWF) antigen concentration VWF function testing Plasma factor VIII level Partial thromboplastin time (PTT) Von Willebrand disease is suspected in patients with unexplained bleeding, particularly those with a family history of a similar bleeding diathesis. Screening coagulation tests reveal a normal platelet count, normal international normalized ratio (INR), and sometimes a slightly prolonged PTT. Bleeding time testing is unreliable and no longer done. Diagnosis requires measuring total plasma VWF antigen, VWF function as determined by the ability of plasma to support agglutination of normal platelets by ristocetin (ristocetin cofactor activity), and plasma factor VIII level. Stimuli (such as pregnancy and inflammation) that temporarily increase VWF levels can cause false-negative results in type I VWD; tests may need to be repeated after the resolution of such stimuli. In the type 1 form of VWD, results are concordant; ie, VWF antigen, VWF function, and plasma factor VIII level are equally depressed. The degree of depression varies from about 15 to 60% of normal and determines the severity of a patient’s abnormal bleeding. Levels of VWF antigen can also be as low as 40% of normal in healthy people with type O blood. Type 2 subtypes are suspected if test results are discordant, ie, VWF antigen is higher than expected for the degree of abnormality in ristocetin cofactor activity. VWF antigen is higher than expected because the VWF defect in type 2 is qualitative (loss of high molecular weight VWF multimers) not quantitative. Diagnosis is confirmed by demonstrating a reduced concentration of large VWF multimers on agarose gel electrophoresis. Further specialized functional studies of high molecular VWF binding allow identification of the four specific type 2 subtypes. Patients with type 3 VWD have no detectable VWF and a marked deficiency of factor VIII. In most women with type 1 VWD, VWF levels commonly return to normal during pregnancy. 