A mouse model for heparin-induced thrombocytopenia

M. Blank, A. Eldor*, S. Tavor, L. Ziporen, D. B. Cines, G. Arepally, A. Afek, Y. Shoenfeld

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)12-16
Number of pages5
JournalSeminars in Hematology
Volume36
Issue numberSUPPL. 1
StatePublished - 1999
Externally publishedYes

Funding

FundersFunder number
National Heart, Lung, and Blood InstituteR01HL049517

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