Back to Search
Start Over
Pathogenesis of heparin-induced thrombocytopenia
- Source :
- Transl Res
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- 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 non-hemorrhagic 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 (NETs), 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 non-pathogenic 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 non-anticoagulant 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.
- Subjects :
- 0301 basic medicine
Article
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Immune system
Physiology (medical)
Heparin-induced thrombocytopenia
medicine
Humans
Platelet
biology
Heparin
business.industry
Biochemistry (medical)
Public Health, Environmental and Occupational Health
Anticoagulants
General Medicine
Neutrophil extracellular traps
medicine.disease
Thrombocytopenia
030104 developmental biology
030220 oncology & carcinogenesis
Immunology
biology.protein
Antibody
business
Platelet factor 4
medicine.drug
Subjects
Details
- ISSN :
- 19315244
- Volume :
- 225
- Database :
- OpenAIRE
- Journal :
- Translational Research
- Accession number :
- edsair.doi.dedup.....67391f6822d3c6b5d30a59ede048956e