THE PRENATAL IDENTIFICATION OF FETAL COMPATIBILITY IN NEONATAL ALLOIMMUNE THROMBOCYTOPENIA USING AMNIOTIC-FLUID AND VARIABLE NUMBER OF TANDEM REPEAT (VNTR) ANALYSIS

Most severe episodes of neonatal alloimmune thrombocytopenic purpura ( NATP) are caused by antiplatelet alloantibodies against the HPA-1a (PI A1) antigen. However, half of subsequent fetuses produced from a HPA-1 a/b father (genotypic frequency 28%) will result in a child who is not affected. Some investigators manage NATP by confirming the fetal plat elet phenotype using percutaneous umbilical cord sampling, a procedure that carries a low but real risk of fetal morbidity and mortality. Mo re recently, physicians determine the fetal platelet antigen genotype using DNA derived from amniotic fluid or chorionic villus samples. All therapy is withdrawn for a fetus who genotypes as HPA-1b/b. However, since the fetus is the same genotype as the mother, there can be uncer tainty about the origin of the genetic material and thus the validity of the fetal genotype, The inappropriate withdrawal of therapy for a e rroneously genotyped fetus could be fatal, and consequently many physi cians advocate fetal HPA-1 phenotyping with confirmation using percuta neous umbilical blood sampling. In this report we describe the managem ent of two pregnancies with previously affected infants due to anti-HP A-1a alloantibodies. Both husbands were HPA-1a/b. For the current preg nancies, amniotic fluid was collected at 20 or 29 weeks of gestation, and the platelet genotype indicated that the fetuses were HPA-1b/b. Th e fetal origin of the amniotic fluid derived DNA was confirmed by the forensic technique of DNA profiling using variable number of tandem re peat (VNTR) analysis. AU therapy was withdrawn, percutaneous umbilical blood sampling was not: performed, and both women vaginally delivered healthy non-thrombocytopenic infants. The application of platelet all oantigen genotyping using DNA from amniotic fluid cells identified the HPA-1b/b fetus, and VNTR analysis confirmed that the tissue was fetal derived, thus avoiding the necessity for percutaneous umbilical blood sampling. The use of this approach in patients at risk will avoid add itional investigation and treatment in approximately one-seventh of al l NATP pregnancies involving the HPA-1a antigen.