Prenatal Exclusion Of Haemophilia B By Assay Of Fetal Factor IXC and IXAg

Recognition of haemophilia B in utero has lagged behind that of classical haemophilia because of lower prevalence and wide emphasis on technical constraints. Pure fetal blood has been obtained at 18-20 weeks by fetoscopy (C.H.R) from 49 of 50 consecutive male fetuses at risk of haemophilia; 4 were pregnancies in obligate or strongly putative carriers of severe haemophilia B.

Current immunoradiometric assays for VIII:CAg depend on both the availability of high titre human antibodies directed against VIII:C and the possibility of preparing highly specific ¹²⁵I-IgG from human antiserum

Plasma factor IXC in 40 control fetuses was 5.9-12.8 (mean 8.4) U/dl. A sensitive immunoradiometric assay (IRMA) for factor IXAg in 20 of these fetal plasmas gave values of 2.9-7.8 (mean 4.1) U/dl, and 1.8-10.0 U/dl in 9 other control fetuses.

The 4 fetuses at risk of haemophilia B had plasma IXC levels of 7.9, 12.3, 9.4 ö 6.6 U/dl; they were regarded as unaffected, and the parents were counselled accordingly. To date, 3 of the 4 have been born and their clinical and laboratory normality confirmed. The corresponding IXAg levels (Malmö) were also normal — 3.6, 5.4, 4.8 ö 2.0 U/dl; but, despite absence of extraneous IXAg in these samples, exclusion of haemophilia B was not feasible in 2 of the 4 whose affected relatives were found to be CRM

Using pure cord blood obtained at fetoscopy, prenatal diagnosis by coagulant bioassay promises to be definitive and is not limited to CRM fetuses. The IRMA is valuable for diagnosis or confirmation in CRM cases, and in the rare instance (2%) of dilution by amniotic fluid.