PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI.

Published

Journal Article

Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex. Despite a decrease in the platelet count, the most feared complication of HIT is thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and release of TF-positive microparticles in peripheral blood mononuclear cells and monocytes. To model these effects ex vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found that the HIT Ab complex induced TF expression in monocytes and the release of TF-positive microparticles. Further, we found that induction of TF is mediated via engagement of the FcγRI receptor and activation of the MEK1-ERK1/2 signaling pathway. Our data suggest that monocyte TF may contribute to the development of thrombosis in patients with HIT.

Full Text

Duke Authors

Cited Authors

  • Kasthuri, RS; Glover, SL; Jonas, W; McEachron, T; Pawlinski, R; Arepally, GM; Key, NS; Mackman, N

Published Date

  • May 31, 2012

Published In

Volume / Issue

  • 119 / 22

Start / End Page

  • 5285 - 5293

PubMed ID

  • 22394597

Pubmed Central ID

  • 22394597

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2011-06-359430

Language

  • eng

Conference Location

  • United States