Maternal platelet alloimmunization is most often against human platelet antigen-1a (HPA-1a). It accounts for 80 to 90 percent of cases and is associated with the greatest severity (Bussel, 1997; Knight, 2011; Tiller, 2013). his is followed in order of frequency by HPA-5b, HPA-1b, and HPA-3a. Alloimmunization to other antigens accounts for only 1 percent of reported cases.
Approximately 85 percent of non-Hispanic white individuals are HPA-1a positive. Two percent are homozygous for HPA-1b and thus at risk for alloimmunization. Importantly, however, only 10 percent of homozygous HPA-1 b mothers who carry an HPA-1a fetus will produce anti-platelet antibodies. Approximately a third of afected fetuses or neonates will develop severe thrombocytopenia, and 10 to 20 percent of those with severe thrombocytopenia sustain an intracranial hemorrhage (ICH) (Kamphuis, 2010). As a result, population-based screening studies have identified FNAIT-associated ICH in 1 per 25,000 to 60,000 pregnancies (Kamphuis, 2010; Knight, 2011).
FNAIT may present in various ways. In some cases, neonatal thrombocytopenia may be an incidental finding or the newborn may manifest petechiae. In the other extreme, a fetus or neonate may develop devastating ICH-often before birth. Of 600 pregnancies with FNAIT identified through a large international registry, fetal or neonatal ICH complicated 7 percent of cases (Tiller, 2013). Hemorrhage afected the irst-born child in 60 percent and occurred before 28 weeks' gestation in half. A third of afected children died soon after birth, and 50 percent of survivors had severe neurological disabilities. Bussel and coworkers (1997) evaluated fetal platelet counts before therapy in 107 fetuses with FNAIT. Thrombocytopenia severity was predicted by a prior sibling with perinatal ICH, and 98 percent of cases were identiied this way. he initial platelet count was <20,000/�L in 50 percent. In cases in which the platelet count was initially >80,000/�L, they noted that it dropped by more than 1 O,OOO/�L each week in the absence of therapy.
Alloimmune thrombocytopenia is typically diagnosed following delivery of a neonate with severe and unexplained thrombocytopenia to a woman whose platelet count is normal. Rarely, the diagnosis is ascertained after identiYing fetal ICH. he condition recurs in 70 to 90 percent of subsequent pregnancies, is often severe, and usually develops earlier with each successive pregnancy. Traditionally, fetal blood sampling was performed to detect fetal thrombocytopenia and to tailor therapy, with transfusion of platelets if the fetal platelet count was < 50,000/�L. Because of procedure-related complications, however, experts recommend abandoning routine fetal platelet sampling in favor of empirical treatment with intravenous immune globulin (IVIG) and prednisone (Berkowitz, 2006; Pacheco, 2011).