Estimation of the Risk of HPA-1a-Immunization in HPA-1a Negative Women after Giving Birth to an HPA-1a Positive Child

BACKGROUNDFetal/neonatal alloimmune thrombocytopenia (FNAIT) is the platelet counterpart of hemolytic disease of the newborn. Most severe cases of FNAIT are caused by antibodies against human platelet antigen-1a (HPA-1a). HPA-1a-negative women giving birth to an HPA-1a-positive child are at risk of becoming HPA-1a-immunized, particularly women who are HLA-DRB3*01:01-positive. The aim of the study was to estimate the risk of HPA-1a-immunization in both HPA-1a-negative/HLA-DRB3*01:01-positive and HPA-1a-negative/HLA-DRB3*01:01-negative women after delivery of an HPA-1a-positive child. STUDY DESIGN AND METHODSA literature search was conducted, which identified 10 prospective FNAIT studies. The risk of becoming HPA-1a-immunized postpartum was calculated by Bayes' theorem. The results of HLA-DRB3/4/5 typing of 212,472 European Caucasians from the National Marrow Donor Program were used as estimate of the frequency of the HLA-DRB3*01:01 allele. RESULTSIn HPA-1a-negative/HLA-DRB3*01:01-positive women, the risk of HPA-1a-immunization after delivery of an HPA-1a-positive child was estimated to 12.7% (95% confidence interval, 8.6%-16.8%) as compared to 0.5% (95% confidence interval, 0.1%-0.9%) in women who were HPA-1a-negative/HLA-DRB3*01:01-negative. Potential differences between nulliparous and multiparous and the role of one versus two doses of HLA-DRB3*01:01 could not be determined. CONCLUSIONIn HPA-1a-negative/HLA-DRB3*01:01-positive women, the risk of HPA-1a-immunization is 12.7% after delivery of an HPA-1a-positive child, which is 25 times higher than in HPA-1a-negative/HLA-DRB3*01:01-negative women. Thus, the risk of HPA-1a-immunization in high-risk pregnancies is in the same range as the risk of RhD immunization in RhD-negative women after delivery of a RhD-positive child without RhD prophylaxis.