Prenatal Diagnosis of Haemophilia by Assay of Fetal Factors VIIIC and IX and Immunoradiometric Assay of Factor VIII Clotting Antigen (VIIICAg)

Initial studies in adults measured foetor VIII clotting antigen (VIIICAg) in normal serum or plasma by on immunaradiometric assay (IRMA) and showed it grossly reduced or absent in 29 of 30 haemophilic kindreds. Pure fetal blood has been obtained (C.H.R.) at 15-22 weeks by direct fetoscopy with realtime ultra-sound in 64 (86%) of 74 patients studied diagnostically or pre-abortion. At 18-22 weeks 48 of 51 fetoscopies (94%) yielded pure fetal blood. In 22 consecutive somples of fetal citrate-plasma VIIIC was 32-79 ( 50) u/ dl, and FIX 8-18 ( 12) u/dl. VIIICAg in 9 fetoscopic plasmas ranged from 11-29 ( 20) u/ dl, and in 8 su ch sera VIIICAg was 4-14 ( 9) u/dl. VIIICAg levels in amniotic fluid were < 0.1 u/dl. Blood was obtained from 6 mole fetuses of obligate hoemophilia A carriers: In 3 only post-termination serum was available, and in one of these VIIICAg of <0.1 u/dl was found. In another both fetoscopic plasma and abortus serum hod < 0.1 u/dl VIIICAg. In the other 2, fetal blood-sampling gave plasma VIIIC levels of 49 and 63 u/dl, and VIIICAg of 13 and 16 u/dl; since these values were within their normal ranges, the pregnancies continued and their neonatal status is still awaited (Feb .79). The results suggest that prenatal diagnosis of haemophilia is possible by combining modified coagulant assays or IRMA with meticulous fetal blood sampling. Further definition of their normal ranges, relative predictive value and added value of VIIIRAg assay is needed.