Clinical characteristics of human platelet antigen (HPA)‐1a and HPA‐5b alloimmunised pregnancies and the association between platelet HPA‐5b antibodies and symptomatic fetal neonatal alloimmune thrombocytopenia

Abstract

Summary Fetal neonatal alloimmune thrombocytopenia (FNAIT) is caused by maternal alloantibodies directed against the human platelet antigens (mostly HPA‐1a or HPA‐5b) of the (unborn) child and can lead to severe bleeding. Anti‐HPA‐1a‐mediated FNAIT shows a severe clinical outcome more often than anti‐HPA‐5b‐mediated FNAIT. Given the relatively high prevalence of anti‐HPA‐5b in pregnant women, the detection of anti‐HPA‐5b in FNAIT‐suspected cases may in some cases be an incidental finding. Therefore we investigated the frequency of anti‐HPA‐5b‐associated severe bleeding in FNAIT. We performed a retrospective nationwide cohort study in cases with clinical suspicion of FNAIT. HPA antibody screening was performed using monoclonal antibody‐specific immobilisation of platelet antigens. Parents and neonates were typed for the cognate antigen. Clinical data were collected by a structured questionnaire. In 1 864 suspected FNAIT cases, 161 cases (8·6%) had anti‐HPA‐1a and 60 (3·2%) had anti‐HPA‐5b. The proportion of cases with severe bleeding did not differ between the cases with anti‐HPA‐1a (14/129; 11%) and anti‐HPA‐5b (4/40; 10%). In multigravida pregnant women with a FNAIT‐suspected child, 100% (81/81) of anti‐HPA‐1a cases and 79% (38/48) of anti‐HPA‐5b cases were HPA‐incompatible, whereas 86% and 52% respectively were expected, based on the HPA allele distribution. We conclude that anti‐HPA‐5b can be associated with severe neonatal bleeding symptoms. A prospective study is needed for true assessment of the natural history of anti‐HPA‐5b mediated FNAIT.

Anti‐human platelet antigen‐5b antibodies and fetal and neonatal alloimmune thrombocytopenia; incidental association or cause and effect?

“…To prove or reject this hypothesis, a large prospective screening study that focuses on the natural course of anti-HPA-5b-associated pregnancies is needed. 33 Severe bleeding complications (e.g. ICH) in rare cases could be the result of coincidence or may be caused by other anti-HPA-5b-associated mechanisms not related to thrombocytopenia.…”

“…No difference was found in the neonatal platelet counts between controls and cases with maternal anti-HPA-5b antibodies (median 81.00; 95% CI 52.00-122.00; ns, not significant, Mann-Whitney test, twotailed). CI, confidence interval; FNAIT, fetal and neonatal alloimmune thrombocytopenia; HPA, human platelet antigen tested due to intra-uterine fetal demise 33 -Thijs de Vos, personal communication). These findings are contrary to the neonatal platelet counts observed in anti-HPA-1a-associated ICH cases that were almost always <30 × 10 9 /l.…”

New Horizons in Fetal and Neonatal Alloimmune Thrombocytopenia

“…A retrospective study of 1,864 cases suspected for FNAIT has investigated the frequency of severe bleeding associated with anti-HPA-5b antibodies and found the proportion of bleeding amounting to 10%, which does not significantly differ from that caused by anti-HPA-1a (11%). 53 Of note, in that study, a relatively high proportion of women in the anti HPA-5b FNAIT group had other risk factors for thrombocytopenia. Additionally, in some HPA-5b cases complicated with bleeding, low platelet counts have not been documented, suggesting another cause for the bleeding symptoms.…”

Preliminary mechanism in fetal alloimmune thrombocytopenia associated with anti‐HPA 15b antibodies

“…Anti-HPA antibodies are well known for their association to fetal and neonatal alloimmune thrombocytopenia. 3,4 CD109 is a glycosylphosphatidylinositol (GPI)anchored protein with an apparent molecular weight of 170 kDa. In addition to being found on platelets, CD109 was also found on the surface of endothelial cells, circulating endothelial cells (CECs), activated T-cells, CD34 + hematopoietic stem/progenitor cells, and several tumor endothelial cell lines.…”