Dynamic intercellular redistribution of HIT antigen modulates heparin-induced thrombocytopenia.

Published

Journal Article

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies to platelet factor 4 (PF4)/heparin complexes. PF4 released from platelets binds to surface glycosaminoglycans on hematopoietic and vascular cells that are heterogenous in composition and differ in affinity for PF4. PF4 binds to monocytes with higher affinity than to platelets, and depletion of monocytes exacerbates thrombocytopenia in a murine HIT model. Here we show that the expression of PF4 on platelets and development of thrombocytopenia are modulated by the (re)distribution of PF4 among hematopoietic and endothelial cell surfaces. Binding of PF4 to platelets in whole blood in vitro varies inversely with the white cell count, likely because of the greater affinity of monocytes for PF4. In mice, monocyte depletion increased binding of PF4 to platelets by two- to three-fold. Induction of HIT in mice caused a transient >80-fold increase in binding of HIT antibody to monocytes vs 3.5-fold increase to platelets and rapid transient monocytopenia. Normalization of monocyte counts preceded the return in platelet counts. Exposure of blood to endothelial cells also depletes PF4 from platelet surfaces. These studies demonstrate a dynamic interchange of surface-bound PF4 among hematopoetic and vascular cells that may limit thrombocytopenia at the expense of promoting prothrombotic processes in HIT.

Full Text

Duke Authors

Cited Authors

  • Dai, J; Madeeva, D; Hayes, V; Ahn, HS; Tutwiler, V; Arepally, GM; Cines, DB; Poncz, M; Rauova, L

Published Date

  • August 16, 2018

Published In

Volume / Issue

  • 132 / 7

Start / End Page

  • 727 - 734

PubMed ID

  • 29914979

Pubmed Central ID

  • 29914979

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2018-02-830737

Language

  • eng

Conference Location

  • United States