Pathophysiology
About 80% of cases of NAIT are caused by antibodies against platelet antigen HPA-1a, 15% by anti-HPA-5b, and 5% by other antibodies. 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 FNAIT during pregnancy ., Of course, the antigen expression of the father must also be taken into account. Some studies have also 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 (HDFN), NAIT occurs during the first pregnancy in up to 50% of cases, and the affected fetuses may develop severe thrombocytopenia (<50,000 /μL) very early during pregnancy (as early as 20 weeks gestation, consistent with the development of platelet antigens ). 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 thrommbocytopenia- greater than all other etiologies of thrombocytopenia combined) Approximately half of cases of intracranial hemorrhage occur in utero. The risk of hemorrhage is inversely related to the platelet count with the greatest risk when the platelet count is below 100,000/uL
The recurrence of NAIT has been estimated to be more than 80% in subsequent pregnancies with incompatible fetuses (ie subsequent pregnancies which also carry the target platelet antigen). Subsequent cases of NAIT may be equivalent or more severe.
The fetal response to FNAIT is variable and may include compensatory extramedullary hematopoiesis. Rarely, fetal hydrops may develop. Fetal anemia (in absence of red cell incompatibility) may also occur.
Read more about this topic: Neonatal Alloimmune Thrombocytopenia