HPA-1a is present in 98% of the population of the United States, suggesting that approximately 2% of women who are HPA-1a negative may be at risk for NAIT during pregnancy. Of course, the antigen expression of the father must also be taken into account - in most cases the father is HPA-1a/1a or 1a/1b and the mother is HPA-1b/1b with anti-HPA-1a antibodies. In women of Asian descent, HPA-4 antigens are the most frequently implicated.Studies have shown a relationship between maternal HLA type DRw52a (DRB3* 0101) and the development of anti-HPA-1a.The offending antibodies are IgG subtype and therefore capable of crossing the placenta and entering the fetal circulation.Unlike hemolytic disease of the fetus and newborn, NAIT occurs during the first pregnancy in up to 50% of cases, and the affected fetuses may develop severe thrombocytopenia (<50,000 μL−1) very early during pregnancy (as early as 20 weeks gestation, consistent with the development of platelet antigens, and the majority of the time in utero). Usually, the thrombocytopenia increases as gestation progresses. During the first pregnancy, NAIT is often not detected until birth when the newborn presents with classic symptoms of thrombocytopenia including petechiae, bruising or intracranial hemorrhage. In utero intracranial hemorrhage occurs in about 10% to 30% of affected cases (and NAIT is thought to be the underlying cause in the majority of cases of intracranial hemorrhage due to thrombocytopenia- greater than all other causes of thrombocytopenia combined).
Other conditions causing a low platelet count
Other conditions that can cause a low platelet count in the neonate include bacterial and viral infection, disseminated intravascular coagulation and other rare congenital conditions associated with a low platelet count. Pathophysiology
Platelets have many proteins on their surface. Each person has a different set of proteins, which are inherited from their parents. These different platelet proteins make different platelet groups, just like different proteins on red blood cells make different blood groups. These differences do not affect how the platelets work. However, if a baby inherits a protein that is found on the fathers platelets but is absent from the mothers platelets, the mother may respond to this foreign protein by developing an antibody that fights against it.This antibody may pass from the mothers blood into the babys blood and attach to the babys platelets. This antibody destroys the babys platelets and suppresses production of fetal platelets, they are also thought to weaken the blood vessel walls (vascular integrity) and affect production of new blood vessels (angiogenesis). This results in an increased risk of bleeding for the baby, and this can lead to the babys death. The mothers antibodies can remain in the babys bloodstream for weeks, and bleeding can occur in the baby before birth (fetal), during birth or after birth (neonatal).A number of different proteins can cause NAIT, about 80% of cases are caused by antibodies against platelet antigen HPA-1a, 15% by anti-HPA-5b, and 5% by other antibodies (e.g. HPA-1b, HPA-15, HPA-3 and HPA-9b).