2. Academic Validation
  3. Fetal and neonatal alloimmune thrombocytopenia: Current pathophysiological insights and perspectives for future diagnostics and treatment

Fetal and neonatal alloimmune thrombocytopenia: Current pathophysiological insights and perspectives for future diagnostics and treatment

  • Blood Rev. 2023 May:59:101038. doi: 10.1016/j.blre.2022.101038.
Wendy Stam 1,  Gabriela Elis Wachholz 2,  Jose Maria de Pereda 3,  Rick Kapur 4,  Ellen van der Schoot 5,  Coert Margadant 6
Affiliations

Affiliations

  • 1 Institute of Biology, Leiden University, Leiden, the Netherlands; Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. Electronic address: [email protected].
  • 2 Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. Electronic address: [email protected].
  • 3 Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC), Universidad de Salamanca, 37007 Salamanca, Spain. Electronic address: [email protected].
  • 4 Sanquin Research, Department of Experimental Immunohematology, Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: [email protected].
  • 5 Sanquin Research, Department of Experimental Immunohematology, Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: [email protected].
  • 6 Institute of Biology, Leiden University, Leiden, the Netherlands; Cancer Center Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. Electronic address: [email protected].
PMID: 36581513 DOI: 10.1016/j.blre.2022.101038
Abstract

FNAIT is a pregnancy-associated condition caused by maternal alloantibodies against paternally-inherited platelet antigens, most frequently HPA-1a on Integrin β3. The clinical effects range from no symptoms to fatal intracranial hemorrhage, but underlying pathophysiological determinants are poorly understood. Accumulating evidence suggests that differential antibody-Fc-glycosylation, activation of complement/effector cells, and Integrin function-blocking effects contribute to clinical outcome. Furthermore, some antibodies preferentially bind platelet Integrin αIIbβ3, but Others bind αvβ3 on endothelial cells and trophoblasts. Defects in endothelial cells and angiogenesis may therefore contribute to severe anti-HPA-1a associated FNAIT. Moreover, anti-HPA-1a antibodies may cause placental damage, leading to intrauterine growth restriction. We discuss current insights into diversity and actions of HPA-1a antibodies, gathered from clinical studies, in vitro studies, and mouse models. Assessment of all factors determining severity and progression of anti-HPA-1a-associated FNAIT may importantly improve risk stratification and potentially reveal novel treatment strategies, both for FNAIT and Other immunohematological disorders.

Keywords

Alloimmune response; Angiogenesis; Development; HPA-1a; Hemorrhage; Human platelet antigen incompatibility; Immunohematology; Integrin; Pregnancy; Thrombocytopenia.

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