Use of a simple visual assay of Willebrand factor for diagnosis and carrier identification.
A visual assay of factor VIII-related Willebrand factor (VIIIR:WF) is described which utilizes formaldehyde-fixed platelets, end points being read in microflocculation tiles. Four dilutions of a sample can be assessed simultaneously, and the correlation with aggregometric assays is high (r = 0.91). Measurement error is 8.0% for a single assay in triplicate and less than 5% if an assay is repeated three times. The method has been used for 2 years by the coagulation genetics group at Chapel Hill for diagnosing subjects with von Willebrand's disease and assigning genotypes to members of families transmitting this disorder. Its utility in classifying known carriers of haemophilia A has also been examined, both in conjunction with assays of VIII:C and in a three-way test with assays of VIII:C and VIIIR:Ag. As predicted by the Lyon hypothesis, the rate of false negative diagnosis was higher than false positive diagnosis, but the overall rate of misclassification on single plasma samples was 7/51 = 13.7%. The error rate was the same whether discrimination was based upon assays of VIII:C vs. VIIIR:Ag, VIII:C vs. VIIIR:WF, or VIII:C vs. VIIIR:Ag vs VIIIR:WF, the same individuals being misclassified by each method. The observed rate of misclassification was well within the rates reported by others and very similar to our previous experience. We have concluded that this method of assaying VIIIR:WF is highly useful for diagnosing vWd, detecting inhibitors to VIIIR:WF, and examining large numbers of column fractions. It is a useful supplement, although it cannot yet substitute for, assays of VIIIR:Ag in detecting carriers of haemophilia A.
D000941:Antigens / Q000032:analysis; D001779:Blood Coagulation Factors / Q000032:analysis*; D001792:Blood Platelets; D005169:Factor VIII / Q000032:analysis; D006580:Genetic Carrier Screening / Q000379:methods; D005838:Genotype; D006801:Humans; D008722:Methods; D014842:von Willebrand Diseases / Q000175:diagnosis / Q000235:genetics; D014841:von Willebrand Factor / Q000032:analysis*
D000941:Antigens; D001779:Blood Coagulation Factors; D014841:von Willebrand Factor; D005169:Factor VIII