Population Prevalence and Incident HPA-1a Alloimmunisation in Pregnancy: A Prospective, Multi-Ethnic, Natural History Study.

OBJECTIVE: Foetal-neonatal alloimmune thrombocytopaenia (FNAIT) is a rare disease, most commonly caused by maternal alloantibodies to human platelet antigen (HPA)-1a that can result in severe bleeding. The present study was designed to determine the frequency of higher risk for HPA-1a alloimmunisation and development of FNAIT among a racially and ethnically diverse cohort of pregnant women. DESIGN: Longitudinal, prospective, non-interventional, natural history study. SETTING: Conducted across 28 sites in North America and Europe. POPULATION: Pregnant women (≥ 18 years) with no history of FNAIT. METHODS: Blood samples were collected at 10-14 weeks' gestation and a sequential screening algorithm applied: maternal HPA-1a/1b genotyping, human leukocyte antigen [HLA]-DRB3*01:01 allele status, anti-HPA-1a antibody status and foetal HPA-1 genotype. MAIN OUTCOME MEASURES: Number of women at higher risk for HPA-1a alloimmunisation (i.e., those who are HPA-1b/b, HLA-DRB3*01:01 positive, anti-HPA-1a antibody negative and carrying an HPA-1a-positive foetus) that alloimmunise. RESULTS: Of the 14 114 participants screened, 1.7% were HPA-1b/1b genotype, which varied according to race and geography. Of 24 women at higher risk for FNAIT, five were lost to follow-up with no post-partum test for alloimmunisation. At Week 10 post-partum, 2/19 higher risk participants (11%; 95% confidence interval [CI]: 1.3%, 33.1%) demonstrated anti-HPA-1a antibodies, while 17 remained negative. Pre-existing anti-HPA-1a antibodies were identified in 18 other HPA-1bb, DRB3*01:01 positive women at screening. CONCLUSIONS: This prospective study confirms the rarity of a population at higher risk for HPA-1a alloimmunisation and FNAIT, describes the risk among Black and Asian women, and establishes a rigorous methodology to assess for risk of HPA-1a immunisation.