Antenatal screening for human platelet antigen-1a: results of a prospective study at a large maternity hospital in Ireland

Abstract

Objective Fetomaternal mismatch for human platelet antigen (HPA)-1a accounts for approximately 85% of cases of neonatal alloimmune thrombocytopenia. The purpose of the study was to determine the prevalence of the HPA-1a negative platelet phenotype in a cohort of pregnant women in Ireland, the rate of alloimmunisation to HPA-1a in HPA-1 mismatched pregnancies and the associated incidence of neonatal alloimmune thrombocytopenia. Design A prospective case -control study.Setting The antenatal clinics of a large maternity teaching hospital.Population or sample Pregnant women, regardless of parity, presenting at the antenatal clinics.Methods An enzyme-linked immunosorbent assay (ELISA) designed for simultaneous HPA-1a typing and antibody detection was used. Further analysis for HPA-1a alloantibodies was performed using commercial ELISA's (GTI PakPlus and Pak1) and the monoclonal antibody immobilisation of platelet antigens assay. Confirmation of serological typing was by the polymerase chain reaction technique using sequence-specific primers (PCR-SSP). Main outcome measures The presence of the HPA-1a negative phenotype and its association with the development of maternal anti-HPA-1a and infant thrombocytopenia. Results Eighty-four of 4090 consecutive women enrolled in the study tested positive for HPA-1a in the screening ELISA. Confirmatory genotyping was performed on 67 women (representing 80% of the cohort), and 54 women (representing 3272 non-selected pregnancies), were homozygous for the HPA-1b allele (1.7%). Three of 34 (9%) women who delivered HPA-1a positive babies had detectable anti-HPA-1a and all three babies had neonatal alloimmune thrombocytopenia, for an overall incidence of 1:1100 non-selected pregnancies. Conclusions The observed prevalence of 1.7% for the HPA-1a negative platelet phenotype is as expected from studies in other countries. While we have demonstrated the practicability of antenatal HPA-1a screening, further research is warranted to investigate maternal parameters predictive of severe fetal thrombocytopenia in HPA-1a alloimmunised pregnancies.

A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia

“…Although a multivariate analysis could have adjusted the risk assessment for potential confounders, such analysis was not carried out for the following reasons: first, the main result of the present study was based on small numbers (ie, neonates with severe NAIT); and second, because necessary information about confounders was not uniformly reported in the previously published studies. 7,8,[21][22][23][24][25][26][27][28][29][30][31]33,34 Differences in diagnostic procedures between the present study and the other prospective studies could potentially have biased our results. The 2 most important diagnostic procedures were counting of platelets and ultrasonographic examination of the newborn's brain.…”

“…The 6 prospective studies 24,25,28,29,31,32 in which platelet counts were obtained from the neonates immediately after delivery may reflect the natural history of NAIT better than the other prospective studies 7,8,[21][22][23]26,27,33,34 in which pregnant women were HPA 1a typed, because different interventions were employed in many of the latter studies. A comparison with the first group may therefore be more relevant in order to examine whether implementation of our screening and intervention program reduces the number of serious complications to severe NAIT.…”

Intravenous Immunoglobulins without Initial and Follow-Up Cordocentesis in Alloimmune Fetal and Neonatal Thrombocytopenia at High Risk for Intracranial Hemorrhage

“…In Caucasians, the immunodominant antigen is the human platelet antigen (HPA) 1a, responsible for approximately 85% of FNAIT cases [1,2] . Two percent of pregnant Caucasian women are HPA-1a negative [3][4][5][6] . Severe thrombocytopenia is estimated to occur in 6-12% of the HPA-1a-negative mothers with antibodies [4,7,8] .…”

Fast and low‐cost direct ELISA for high‐throughput serological HPA‐1a typing

“…A couple of prospective HPA‐1a screening studies that use an ELISA for HPA‐1a typing have been performed thus far . However, this study is the first to describe extensive validation with samples solely from pregnant women, to report in detail on (low) costs and to use moderate quality material, making it highly applicable for potential screening settings.…”