Pregnancy‐associated autoimmune neonatal thrombocytopenia: role of maternal HLA genotype

Abstract

Summary. In a prospective study between 1993 and 1998, data was collected from 46 pregnant women and subsequently from their babies. 25 pregnant women with active autoimmune thrombocytopenic purpura (AITP) or a history of AITP (group A) and 21 pregnant women with isolated thrombocytopenia and identification of specific platelet autoantibodies detected by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay (group B) were evaluated for platelet-associated immunoglobulin-G (PAIgG), MAIPA assay and HLA genotype. Neonatal platelet counts were performed at least three times in the first week. 11 neonates were thrombocytopenic (23·9%). No severe haemorrhage occurred. There were no significant differences regarding the values of PAIgG or positive MAIPA tests between mothers of thrombocytopenic or healthy newborns. A significant difference, however, regarding the HLA DRB3* allele was found, with a high incidence in the subgroup of mothers of healthy newborns (P ¼ 0·005). A similar trend was found among mothers with anti-GPIIbIIIa antibodies (P ¼ 0·06). In contrast, HLA DRB5* allele appeared to be present especially in mothers of thrombocytopenic newborns (not significant). Our data suggest that mothers with AITP who have the HLA DRB3* genotype are unlikely to give birth to a thrombocytopenic baby. This study provides a preliminary report on a noninvasive test to identify infants who are likely to be affected.

Reassessing the role of HLA‐DRB3 T‐cell responses: Evidence for significant expression and complementary antigen presentation

“…Based on these allele frequencies, it is expected that 2/3 of the caucasoid population has a DRB3 allele. Several diseases have been associated with DRB3 alleles, including neonatal alloimmune thrombocytopenia [30, 45] post-transfusion purpura [46] and inclusion body myositis [47]. In addition, the strong association between DRB3*0101 and DRB1*0301 (a member of the A1-B8-DR3 haplotype) could implicate this DRB3 allele in the presentation of peptides in certain DR3-linked autoimmune disorders.…”

Outcome and management in neonatal thrombocytopenia due to maternal idiopathic thrombocytopenic purpura

“…Most consistent are a previous sibling with thrombocytopenia and maternal splenectomy for therapy resistant ITP . Other factors such as maternal platelet counts (during pregnancy and delivery), presence of detectable antiplatelet antibodies in maternal serum and maternal treatment with corticosteroids and/or intravenous immunoglobulin (IVIG) do not correlate with neonatal platelet count at birth . A small randomized controlled trial comparing maternal betamethasone with placebo showed no difference in neonatal platelet count .…”

Guidelines on the treatment of primary immune thrombocytopenia in children and adolescents: Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Guidelines Project: Associação Médica Brasileira - 2012

“…Five newborns (10.8%) presented hemorrhage symptoms at birth: two (4.3%) had thrombocytopenia(53 x 10 9 /Land 50 x 10 9 /L) and hematuria (n = 1) or petechiae and cephalohematoma (n = 1); three (6.5%), despite normal platelet counts at birth, had petechiae and one also had cephalohematoma. Due the potential risk of bleeding, three patients with platelet counts≤ 30 x 10 9 /L received IVIg (1 g/kg/day) for two days, with adequate responses in eight, eight and 42 days after treatment (61) (C).…”