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

Br J Haematol. 2021 Nov;195(4):595-603. doi: 10.1111/bjh.17731. Epub 2021 Aug 16.

Abstract

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.

Keywords: alloimmune thrombocytopenia; alloimmunisation during pregnancy; human platelet antigen; neonatology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Human Platelet / immunology*
  • Female
  • Hemorrhage / etiology*
  • Histocompatibility, Maternal-Fetal*
  • Humans
  • Immunity, Maternally-Acquired
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Integrin beta3 / immunology*
  • Intracranial Hemorrhages / etiology
  • Isoantibodies / immunology*
  • Maternal-Fetal Exchange
  • Parity
  • Platelet Count
  • Pregnancy
  • Retrospective Studies
  • Surveys and Questionnaires
  • Thrombocytopenia, Neonatal Alloimmune / immunology*

Substances

  • 5b alloantigen, human
  • Antigens, Human Platelet
  • ITGB3 protein, human
  • Integrin beta3
  • Isoantibodies