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A mouse model for heparin-induced thrombocytopenia.

Publication ,  Journal Article
Blank, M; Eldor, A; Tavor, S; Ziporen, L; Cines, DB; Arepally, G; Afek, A; Shoenfeld, Y
Published in: Semin Hematol
January 1999

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.

Duke Scholars

Published In

Semin Hematol

ISSN

0037-1963

Publication Date

January 1999

Volume

36

Issue

1 Suppl 1

Start / End Page

12 / 16

Location

United States

Related Subject Headings

  • Thrombocytopenia
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans
  • Heparin
  • Disease Models, Animal
  • Animals
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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MLA
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Blank, M., Eldor, A., Tavor, S., Ziporen, L., Cines, D. B., Arepally, G., … Shoenfeld, Y. (1999). A mouse model for heparin-induced thrombocytopenia. Semin Hematol, 36(1 Suppl 1), 12–16.
Blank, M., A. Eldor, S. Tavor, L. Ziporen, D. B. Cines, G. Arepally, A. Afek, and Y. Shoenfeld. “A mouse model for heparin-induced thrombocytopenia.Semin Hematol 36, no. 1 Suppl 1 (January 1999): 12–16.
Blank M, Eldor A, Tavor S, Ziporen L, Cines DB, Arepally G, et al. A mouse model for heparin-induced thrombocytopenia. Semin Hematol. 1999 Jan;36(1 Suppl 1):12–6.
Blank, M., et al. “A mouse model for heparin-induced thrombocytopenia.Semin Hematol, vol. 36, no. 1 Suppl 1, Jan. 1999, pp. 12–16.
Blank M, Eldor A, Tavor S, Ziporen L, Cines DB, Arepally G, Afek A, Shoenfeld Y. A mouse model for heparin-induced thrombocytopenia. Semin Hematol. 1999 Jan;36(1 Suppl 1):12–16.
Journal cover image

Published In

Semin Hematol

ISSN

0037-1963

Publication Date

January 1999

Volume

36

Issue

1 Suppl 1

Start / End Page

12 / 16

Location

United States

Related Subject Headings

  • Thrombocytopenia
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Humans
  • Heparin
  • Disease Models, Animal
  • Animals
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology