Antenatal Treatment of Neonatal Alloimmune Thrombocytopenia

Abstract

Neonatal alloimmune thrombocytopenia results from the formation of a maternal antibody to a paternal antigen on fetal platelets. Intracranial hemorrhage, which may be antenatal, occurs in approximately 15 to 20 percent of infants with this form of thrombocytopenia. In families with an affected infant, 75 percent of subsequent infants are affected. We report the results of antenatal treatment with intravenous gamma globulin, with or without dexamethasone, in seven pregnant women who had previously had infants who had severe alloimmune thrombocytopenia. The platelet count increased by a mean (+/- SD) of 72.5 +/- 62 x 10(9) per liter in the six fetuses in whom periumbilical blood sampling was performed. All seven treated fetuses had platelet counts above 30 x 10(9) at birth, and none had an intracranial hemorrhage, in contrast to all seven of their respective untreated siblings, who had lower platelet counts and three of whom had intracranial hemorrhages (antenatal in two infants). Mild intrauterine growth retardation was observed in one treated infant; all seven infants have developed normally in the two months to four years since birth. We conclude that intravenous gamma globulin, with or without dexamethasone, is effective in elevating the fetal platelet count in severe cases of neonatal alloimmune thrombocytopenia and in helping to avoid intracranial hemorrhage.

Antenatal treatment of fetal alloimmune thrombocytopenia: a current perspective

“…3 Administration of intravenous immunoglobulin (IVIG) to the mother, initially given in conjunction with dexamethasone, was first used to prevent recurrence of antenatal intracranial hemorrhage in 1988. 4 This approach of providing IVIG-based medical therapy administered to the mother to increase the fetal platelet count has since been extensively investigated in hundreds of maternal-fetal pairs. 5 The efficacy of IVIG-based therapy has been supported by numerous studies [6][7][8][9][10][11][12][13][14][15][16] (Table 1A) but not by others [17][18][19] (Table 1B).…”

“…3 In humans, at least some of these B cells produce known autoantibodies. 4 Our laboratory has previously shown that Y chromosome-encoded minor histocompatability antigens elicit specific antibody responses following sex-mismatched hematopoietic stem cell transplantation, and the presence of these allo-antibodies correlates with the development of chronic GVHD. 5,6 Patients with minor histocompatability antigen-specific antibodies have also been found to have alloreactive CD4 + T cells directed against different epitopes derived from the same protein 7 but the pathogenicity of these antibodies remains unproven.…”

Neonatal Immune Thrombocytopenia

“…In contrast, maternal alloantibodies developed against a fetal platelet alloantigen inherited from the father, induce a severe fetal TP but is associated with normal maternal platelet counts. TP in the thus affected fetus may occur as early as 18 th week of gestation and carries the risk of severe antenatal cerebral hemorrhage and/or porencephaly warranting specific antenatal management [10][11][12][13].…”

A case of thrombotic thrombocytopenic purpura and neonatal alloimmune thrombocytopenia in the same pregnancy

“…Often, the diagnosis cannot be made until after the first affected child, although sometimes pregnancies at risk are identified when female siblings of an affected mother are tested for platelet type. Once recognised, weekly administration of immune globulin intravenously beginning at 20 weeks of gestation has been shown to stabilise or increase the fetal platelet count and reduce the risk of bleeding in most affected fetuses 18,19 . The place of corticosteroids is unclear.…”