Identification and follow-up of pregnant women with platelet-type human platelet antigen (HPA)-1bb alloimmunized with fetal HPA-1a

Abstract

IntroductionPregnant women negative for human platelet antigen 1a (HPA-1a) are at risk of alloimmunization with fetal HPA-1a antigen inherited from the father, and their offspring may develop fetal and neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to analyze the frequency of HPA-1a alloimmunization in pregnant Polish women, the feasibility of using maternal platelets for intrauterine transfusions in women subjected to diagnostic fetal blood sampling (FBS) and to discuss potential consequences of alloimmunization.Material and methodsFifteen thousand two hundred and four pregnant women were typed for HPA-1a; HPA-1a negative were screened for anti-HPA-1a. Alloimmunized women received specialist perinatology care; some of them were subjected to FBS, followed by transfusion of HPA-1a negative platelet concentrates (PC) prepared from maternal blood.ResultsThree hundred seventy-three (2.5%) women were HPA-1a negative, and 32 (8.6%) tested positively for anti-HPA-1a. Antibodies were detected in 22 women during pregnancy. Diagnostic FBS followed by PC transfusion was performed in 14 woman, who were platelet donors for their 16 unborn babies. Blood donations were tolerated well by the patients, and also intrauterine platelet transfusions were uneventful. Pharmacotherapy with intravenous immunoglobulins was implemented in 11/22 patients.ConclusionsHPA-1a negative women (ca. 2.5% of all pregnant patients) are at risk of alloimmunization with HPA-1a antigen and developing FNAIT. Alloimmunized women can be donors of platelets for their offspring providing removal of antibodies from PC. Owing to potential complications, special care should be taken if an alloimmunized woman was qualified as a blood or stem cell recipient.

Prediction of fetal blood group and platelet antigens from maternal plasma using next‐generation sequencing

“…Currently, Doppler ultrasound performed by highly experienced staff is used to make the decision on early clinical intervention if anti‐RBC antigen antibodies are detected during pregnancy . In the case of platelet antigen incompatibility it is not possible to use ultrasound to indicate when or whether or not to start expensive weekly administration of intravenous immunoglobulins (sometimes combined with steroids) . In both cases, therefore, it is very important to predict the fetal antigen genotype in order to monitor and treat only women whose fetuses are at real risk of disease.…”

“…The number of pregnant women with antibodies against different antigens varies in Poland . Despite obligatory postnatal anti‐D immunoprophylaxis, anti‐D antibodies are detected in about 1/500 pregnancies per year; the same frequency applies to anti‐HPA‐1a.…”

Noninvasive prenatal HPA‐1 typing in HPA‐1a negative pregnancies selected in the Polish PREVFNAIT screening program

“…The next aspect we investigated was the impact of gestational time on HPA‐1a fetal genotype determination. From the clinical point of view, the decision on the antenatal treatment is made as early as the 12th gw in high‐risk cases and approximately 20 gw in standard‐risk pregnancies, and in both cases the NIPT result in week 28 may therefore be too late . Thus we tested plasma collected from women carrying an HPA‐1a positive fetus at 16 to 20 gw, but the results were not accurate enough to predict the fetal HPA‐1a status.…”

“…In our PREVFNAIT study cohort, the fetal and maternal HPA‐1a genotypes were compatible in 18% of pregnancies. In 2 of 21 tested mothers who had anti‐HPA‐1a antibodies detected, the test predicted fetal genotype as HPA‐1a negative (10%) …”

“…From the clinical point of view, the decision on the antenatal treatment is made as early as the 12th gw in high-risk cases and approximately 20 gw in standard-risk pregnancies, and in both cases the NIPT result in week 28 may therefore be too late. 18,19 Thus we tested plasma collected from women carrying an HPA-1a positive fetus at 16 to 20 gw, but the results were not accurate enough to predict the fetal HPA-1a status. Scheffer and colleagues also suggested the test be performed later in pregnancy to avoid the potential risk of false-negative results caused by the low amount of fetal fraction.…”