Carrier Detection Of Haemophilia A In Pregnancy By Measurement Of Factor VIIIc/Rag And VIIICAg/RAg Ratios

The 1977 WHO Memorandum on carrier detection highlighted the need to test the methods in pregnancy, when plasma modalities of facor VIII are augmented. At KCH blood was taken into citrate from 21 pregnant obligate carriers of severe haemophilia A and 28 pregnant women from unaffected families, matched for age and period of gestation. The women, who were basal after a night’s rest, were tested prior to prenatal diagnosis of haemophilia or other conditions, or to undergoing termination of pregnancy for unrelated causes. One-stage factor VIIIC assays were done immediately; VIIIRAg (Laurell) after -40°C storage within 6 days; and VIIICAg immunoradiometrically in Cardiff on the remainder after varying intervals. Careful standardization was ensured between both laboratories. At 17-22 weeks, VIIIRAg was elevated both in pregnant controls & carriers]; VIIIC & VIIICAg levels were also raised, though less, in the controls (values in units/dl) In pregnant carriers, VIIIC & VIIICAg are both lower than VIIIRAg (p<0.001). Likelihood ratios of carrier probability were plotted by the unequal variances predictive method: VIIIC/RAg discriminated much better between carriers & controls than VIIICAg/RAg, due to the wider spread of VIIICAg in each group, and unlike the findings in a related study of non-pregnant haemophilia A carriers.