Fetal/neonatal alloimmune thrombocytopenia: a systematic review of impact of HLA-DRB3*01:01 on fetal/neonatal outcome
Jens Kjeldsen‐Kragh, Dean Fergusson, Mette Kjær, Lani Lieberman, Andreas Greinacher, Michael Murphy, James B. Bussel, Tamam Bakchoul, Stacy Corke, Gérald Bertrand, Dick Oepkes, Jillian M. Baker, Heather Hume, Edwin Massey, Cécile Kaplan, Donald M. Arnold, Shoma Baidya, Greg Ryan, Helen Savoia, Denise Landry, Nadine Shehata
Abstract
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-.