Robustness of factor assays following cordocentesis in the prenatal diagnosis of haemophilia and other bleeding disorders

Abstract

Prenatal diagnosis is the generally accepted option for genetic disorders including haemophilias and other bleeding disorders. Cord blood analysis between 17.4 and 20.6 weeks of gestation was performed in 172 confirmed carriers belonging to families of haemophilia A, haemophilia B, von Willebrand disease (VWD), factor VII and X deficiency; 133 were carriers for haemophilia A, 30 for haemophilia B, six for type 3 VWD, two for FX deficiency and one for FVII deficiency. The approach to the cord was either transabdominal or transamniotic. The volume of blood collected varied between 1 and 2 mL. In case of haemophilias, the diagnosis was offered by factor VIII/IX:C activity and antigen assays wherever required. In case of VWD, the diagnosis was based on von Willebrand factor antigen assays as detected by ELISA along with FVIII:C assay while in cases of FVII and FX deficiency, the diagnosis was based on FVII:C and FX:C respectively. The factor levels were compared with the normal range established in the laboratory for different coagulation factors between 18 and 21 weeks of gestation in women tested for other haematological disorders. Only in two cases, the procedure had to be repeated for reasons of extensive maternal contamination. All the deliveries have been followed up and the diagnoses reconfirmed by repeat clotting factor assays and DNA analysis whenever informative. Simple precautions like collection of fetal blood samples in smaller volumes in separate tubes, assaying multiple coagulation factors in the fetal blood samples helped us to offer diagnoses in all the women analysed. No fetal death or abortion was reported following the procedure. We suggest that accurate fetal blood sampling is a safe technique for the diagnosis of many of the bleeding disorders in places where genetic diagnostic services are not available.