Fetal/neonatal alloimmune thrombocytopenia: a systematic review of impact of HLA-DRB3*01:01 on fetal/neonatal outcome

The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3*01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count <50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3*01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3*01:01+ women. For HLA-DRB3*01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3*01:01-.