A mouse model for heparin-induced thrombocytopenia.

Published

Journal Article

Heparin-induced thrombocytopenia (HIT) occurs in 1% to 3% of patients receiving heparin and results from the development of antibodies that recognize heparin-platelet factor 4 (H-PF4) complexes that form on the surface of activated platelets and on the vascular endothelium. With the aim of studying the pathogenic importance of these anti-H-PF4 antibodies in vivo, we attempted to create an animal model of HIT. Such a model was produced by immunization of naive mice with affinity-purified IgG anti-H-PF4 antibodies from two patients with HIT. The immunized mice developed specific antibodies (anti-idiotypic) against the human anti-H-PF4 antibodies and 2 months later, anti-anti-idiotypic antibodies appeared, which functionally resembled the human HIT antibody. Indeed, when the animals bearing anti-anti-idiotypic antibodies were injected with heparin for 4 days, a significant decrease in their platelet counts was observed; however, heparin treatment was not associated with thrombosis in any of the immunized mice. Similar to the observation in HIT patients, injections of equivalent doses of low-molecular-weight (LMW) heparin to the immunized animals did not induce thrombocytopenia. The results of this study support the importance of anti-H-PF4 antibodies in the pathogenesis of HIT. The mouse HIT model may provide a convenient system for studies on the immunoregulation of anti-H-PF4 expression and for evaluation of potential therapeutic modalities.

Full Text

Duke Authors

Cited Authors

  • Blank, M; Eldor, A; Tavor, S; Ziporen, L; Cines, DB; Arepally, G; Afek, A; Shoenfeld, Y

Published Date

  • January 1999

Published In

Volume / Issue

  • 36 / 1 Suppl 1

Start / End Page

  • 12 - 16

PubMed ID

  • 9930558

Pubmed Central ID

  • 9930558

Electronic International Standard Serial Number (EISSN)

  • 1532-8686

International Standard Serial Number (ISSN)

  • 0037-1963

Language

  • eng