Background Alloimmune thrombocytopenia is a serious fetal disorder resulting from platelet-antigen incompatibility between the mother and fetus. The diagnosis is usually made after the discovery of unexpected ted neonatal thrombocytopenia. Approximately 10 to 20 percent of affected fetuses have intracranial hemorrhages, one quarter to one half of which occur in utero. We studied the correlates of thrombocytopenia in affected fetuses. Methods We studied 107 fetuses with alloimmune thrombocytopenia at a mean (+/-SD) gestational age of 25+/-4 weeks, before their entry into one of three treatment protocols. The fetuses were initially evaluated because an older sibling had been given this diagnosis at birth, We compared the initial platelet counts in utero in these 107 fetuses with the platelet count at birth and the history of intracranial hemorrhage in the affected sibling. Results The initial platelet count was less than or equal to 20,000 per cubic millimeter in 53 of the 107 fetuses (50 percent), including 21 of 46 fetuses (46 percent) studied before 24 weeks of gestation. The 97 fetuses with PIA1 incompatibility had more severe thrombocytopenia than the 10 fetuses with other antigen incompatibilities, Among seven fetuses with platelet counts of more than 80,000 per cubic millimeter that were not treated initially, the counts decreased by more than 10,000 per cubic millimeter per week. Although 41 fetuses had initial platelet counts that were lower than those measured at birth in an older affected sibling, only a history of antenatal intracranial hemorrhage in the sibling predicted greater severity of thrombocytopenia in the fetus. Only one treated fetus had an intracranial hemorrhage, and the thrombocytopenia resolved after birth in all cases. Conclusions Fetal alloimmune thrombocytopenia occurs early in gestation, is severe, and is more severe in fetuses with an older affected sibling who had an antenatal intracranial hemorrhage. (C) 1997, Massachusetts Medical Society.