Carrier Detection In Haemophilia A By Measurement Of Factor VIII Clotting Antigen (VIIICAg) And Factor VIII Related Antigen (VIIIRAg
In order to assess the value of measurement of VIIICAg in the detection of carriers of haemophilia A, plasma samples were obtained on three separate occasions from each of 23 obligate carriers of mild and severe haemophilia, and 26 normal females. At each visit each sample was divided into three and each aliquot was then assayed for VIIICAg (immunoradiometric assay), clotting factor VIII (VIIIC) (two stage assay) and VIIIRAg (Laurell immu noelectrophoresis). After calculating median values at each visit, and for the three visits, a comparison of the ratios VIIIC/VIIIRAg and VIIICAg/VIIIRAg was made. Likelihood ratios (of being a carrier) were calculated using an unequal variance predictive method for both ratios. These showed that laboratory data calculated on the median of the three-visit medians had greater discriminatory power than a single-visit median value. Using the median of three visits both VII IC/VIIIRAg and VIIICAg/VIIIRAg gave the same proportional misclassification of carriers as normals (4 of 23- 17%). However the ratios VII ICAg/VIIIRAg were more discriminatory due to the greater reproducibility between visits of VIIICAg results than those of VIIIC. There was no statistically significait difference between VII ICAg/VIIIRAg (or VII IC/VIIIRAg) ratios obtained from carriers of mild or severe haemophilia. The ratio VII ICAg/VIIIRAg was therefore shown to be the method of choice for carrier detection except theoretically in the rare CRM+ families.