PMID- 32417430
OWN - NLM
STAT- MEDLINE
DCOM- 20201014
LR  - 20240216
IS  - 1878-1810 (Electronic)
IS  - 1931-5244 (Print)
IS  - 1878-1810 (Linking)
VI  - 225
DP  - 2020 Nov
TI  - Pathogenesis of heparin-induced thrombocytopenia.
PG  - 131-140
LID - S1931-5244(20)30077-3 [pii]
LID - 10.1016/j.trsl.2020.04.014 [doi]
AB  - 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.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Arepally, Gowthami M
AU  - Arepally GM
AD  - Division of Hematology, Duke University Medical Center, Durham, North Carolina. 
      Electronic address: arepa001@mc.duke.edu.
FAU - Cines, Douglas B
AU  - Cines DB
AD  - Department of Pathology and Laboratory Medicine, Perelman-University of 
      Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
LA  - eng
GR  - R01 HL128895/HL/NHLBI NIH HHS/United States
GR  - R01 HL136512/HL/NHLBI NIH HHS/United States
GR  - R01 HL139448/HL/NHLBI NIH HHS/United States
GR  - R01 HL142122/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20200515
PL  - United States
TA  - Transl Res
JT  - Translational research : the journal of laboratory and clinical medicine
JID - 101280339
RN  - 0 (Anticoagulants)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anticoagulants/therapeutic use
MH  - Heparin/*adverse effects
MH  - Humans
MH  - Thrombocytopenia/chemically induced/drug therapy/*physiopathology
PMC - PMC7487042
MID - NIHMS1594308
COIS- Conflict of Interest GMA receives royalties from Biokit manufacturer of a HIT 
      diagnostic assay. GMA and DBC have pending intellectual property applications.
EDAT- 2020/05/18 06:00
MHDA- 2020/10/21 06:00
PMCR- 2021/11/01
CRDT- 2020/05/18 06:00
PHST- 2020/03/11 00:00 [received]
PHST- 2020/04/15 00:00 [revised]
PHST- 2020/04/21 00:00 [accepted]
PHST- 2020/05/18 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/05/18 06:00 [entrez]
PHST- 2021/11/01 00:00 [pmc-release]
AID - S1931-5244(20)30077-3 [pii]
AID - 10.1016/j.trsl.2020.04.014 [doi]
PST - ppublish
SO  - Transl Res. 2020 Nov;225:131-140. doi: 10.1016/j.trsl.2020.04.014. Epub 2020 May 
      15.