Immunological Diagnosis Of Von Willebrand’S Disease (vWD) And Haemophilia A (HAEM A)

Most immunological tests for vWd are based on xenogeneic antisera to factor VIII related antigen (VIIIRAg/WF). Immunoprecipitin methods quantitate the antigen and may indicate abnormal electrophoretic mobility. Several groups have demonstrated polymeric variation of VIIIRAg using radioimmunoprecipitation, large-pore electrophoresis and autoradiography. An immunoradiomeh ic assay (IRMA) correlated with ristocetin cofactor activity in vWd or showed non-parallel dose response curves suggesting abnormal antigen- antibody binding. The IRMA may preferentially quantitate higher oligomers of VIIIRAg/WF. Based on these studies a simplified classification of vWd is suggested. Immunological tests for Haem A originally demonstrated cross-reacting material (CRM) in 10% of patients or in greater number when tested by inhibitor neutralisation (IN) in antibody excess. Several IRMA’s for VIII coagulant antigen (VIIICAg) have been developed. Utilising alloantibodies in a two- site method VIIICAg was quantitated in normal plasma and serum and was reduced in most haemophilic kindreds (CRM- or CRM^R). IRMA’s using three different inhibitor igG’s showed slightly different patterns of results suggesting that the antibodies react with different but related epitopes. Only one CRM+ kindred has been detected in over forty tested. The IRMA for VIIICAg has improved discrimination of tests for carriers of Haem A in non-pregnant women and has complemented the VIIIC assay for prenatal diagnosis; results in 48 pregnancies (Feb. 1981) have confirmed the predictive value. Levels of VIIIRAg were normal in 28 patients with combined VC and VIIIC deficiency. Levels of VIIICAg and VCAg (IN) were reduced in many but not all patients. Correlation was noted in (IN) assays using one combination of antibodies suggesting a bio-relationship between the proteins. The results emphasise the role of immunoassays in assessing Vlll-deficiency states.