Pathogenesis of heparin-induced thrombocytopenia.

Journal Article (Review)

There are currently no effective substitutes for high intensity therapy with unfractionated heparin (UFH) for cardiovascular procedures based on its rapid onset of action, ease of monitoring and reversibility. The continued use of UFH in these and other settings requires vigilance for its most serious nonhemorrhagic complication, heparin induced thrombocytopenia (HIT). HIT is an immune prothrombotic disorder caused by antibodies that recognize complexes between platelet factor 4 (PF4) and polyanions such as heparin (H).The pathogenicity of anti-PF4/H antibodies is likely due to the formation of immune complexes that initiate intense procoagulant responses by vascular and hematopoietic cells that lead to the generation of platelet microparticles, monocyte and endothelial cell procoagulant activity, and neutrophil extracellular traps, among other outcomes. The development of anti-PF4/H antibodies after exposure to UFH greatly exceeds the incidence of clinical disease, but the biochemical features that distinguish pathogenic from nonpathogenic antibodies have not been identified. Diagnosis relies on pretest clinical probability, screening for anti-PF4/H antibodies and documentation of their platelet activating capacity. However, both clinical algorithms and test modalities have limited predictive values making diagnosis and management challenging. Given the unacceptable rates of recurrent thromboembolism and bleeding associated with current therapies, there is an unmet need for novel rational nonanticoagulant therapeutics based on the pathogenesis of HIT. We will review recent developments in our understanding of the pathogenesis of HIT and its implications for future approaches to diagnosis and management.

Full Text

Duke Authors

Cited Authors

  • Arepally, GM; Cines, DB

Published Date

  • November 2020

Published In

Volume / Issue

  • 225 /

Start / End Page

  • 131 - 140

PubMed ID

  • 32417430

Pubmed Central ID

  • 32417430

Electronic International Standard Serial Number (EISSN)

  • 1878-1810

Digital Object Identifier (DOI)

  • 10.1016/j.trsl.2020.04.014


  • eng

Conference Location

  • United States