Neonatal alloimmune thrombocytopenia is the platelet equivalent of hemolytic (Rh) disease of the newborn, developing as a result of maternal alloimmunization to fetal platelet antigens. It affects one in 1,000-2,000 live births and can be a serious and potentially life-threatening condition. Unlike Rh disease, neonatal alloimmune thrombocytopenia can occur during a first pregnancy. Almost half of the clinically evident cases of neonatal alloimmune thrombocytopenia are discovered in the first live-born infant.
In typical cases of unanticipated neonatal alloimmune thrombocytopenia, the mother is healthy and has a normal platelet count, and her pregnancy, labor, and delivery are indistinguishable from those of other low-risk obstetric patients. The neonates, however, are either born with evidence of profound thrombocytopenia or develop symptomatic thrombocytopenia within hours after birth. Affected infants often manifest generalized petechiae or ecchymoses over the presenting fetal part. Hemorrhage into viscera and bleeding following circumcision or venipuncture also may ensue. The most serious complication of neonatal alloimmune thrombocytopenia is intracranial hemorrhage, which occurs in 10-20% of infants. Fetal intracranial hemorrhage due to neonatal alloimmune thrombocytopenia can occur in utero, and 25-50% of fetal intracranial hemorrhage in untreated mothers may be detected by ultrasonography before the onset of labor. Ultrasonographic findings may include intracranial hemorrhage, porencephalic cysts, and obstructive hydrocephalus. These observations are in contrast to neonatal intracranial hemorrhage due to ITP, which is exceedingly rare and usually occurs during the neonatal period.
Several polymorphic, diallelic antigen systems residing on platelet membrane glycoproteins are responsible for neonatal alloimmune thrombocytopenia. Many of these antigen systems have several names because they were identified in different parts of the world concurrently. Recently, a uniform nomenclature has been adopted that describes these antigens as human platelet antigens (HPA-1 and HPA-2), with alleles designated as "a" or "b". Although there are at least 10 officially recognized platelet-specific antigens at this time, more than 50% of the reported cases in Caucasians and most of the severe cases have occurred as a result of sensitization against HPA-1a, also known as PlA1 and Zwa.
Fetal thrombocytopenia due to HPA-1a sensitization tends to be severe and can occur early in gestation. In a cohort study of 107 fetuses with neonatal alloimmune thrombocytopenia (97 with HPA-1a incompatibility) studied in utero before receiving any therapy, 50% had initial platelet counts of less than 20,000/mL. This percentage included 21 of 46 fetuses tested before 24 weeks of gestation. Furthermore, this series documented that the fetal platelet count decreases at a rate of more than 15,000/mL per week in the absence of therapy.The recurrence risk of neonatal alloimmune thrombocytopenia is extremely high and approaches 100% in cases involving HPA-1a if the subsequent sibling carries the pertinent antigen. Thus, the recurrence risk is related to the zygosity of the father. As with red cell alloimmunization, the disease tends to be equally severe or progressively worse in subsequent pregnancies.