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Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin.

Publication ,  Journal Article
Blank, M; Cines, DB; Arepally, G; Eldor, A; Afek, A; Shoenfeld, Y
Published in: Clin Exp Immunol
May 1997

Heparin-induced thrombocytopenia/thrombosis (HIT) is a severe thrombotic disorder that occurs in approximately 1% of patients treated with heparin. Affected patients commonly develop antibodies that recognize PF4/heparin complexes that may form on the surface of activated platelets and on the endothelium. However, it has not been established that anti-PF4/heparin antibodies are responsible for the clinical manifestations of HIT. To address this issue, we employed a recently developed model of active immunity to study the effect of IgG anti-PF4/heparin antibody in vivo. In previous studies we have shown that it is possible to induce autoimmune diseases such as systemic lupus erythematosus (SLE), anti-phospholipid syndrome (APS) or vasculitis in naive mice by active immunization with anti-DNA, anti-cardiolipin and anti-neutrophil cytoplasmic antibodies, respectively. Immunized animals develop anti-idiotypic antibodies (Ab2) and, after 2-4 months, anti-anti-idiotypic antibodies (Ab3). Ab3s generated in this manner often simulate the binding activity of Ab1 and their expression correlates with the development of specific clinical manifestations typical of the respective human disease. Based on this experience, naive BALB/c mice were immunized with IgG anti-PF4/heparin antibodies isolated from two patients with HIT. The actively immunized mice developed mouse anti-PF4/heparin antibody (Ab3). Administration of unfractionated heparin, but not low molecular weight heparin (LMWH), to the actively immunized animals induced thrombocytopenia by day 4 of drug exposure. There was no evidence of thrombosis. The results of this study support the importance of anti-PF4/heparin antibodies in the pathogenesis of HIT. Further, this model may help to elucidate the factors responsible for thrombosis as well as providing means to assess new treatment options for patients with this disorder.

Duke Scholars

Published In

Clin Exp Immunol

DOI

ISSN

0009-9104

Publication Date

May 1997

Volume

108

Issue

2

Start / End Page

333 / 339

Location

England

Related Subject Headings

  • Thrombocytopenia
  • Platelet Factor 4
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • Immunization, Secondary
  • Humans
  • Heparin, Low-Molecular-Weight
  • Heparin
  • Autoantibodies
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Blank, M., Cines, D. B., Arepally, G., Eldor, A., Afek, A., & Shoenfeld, Y. (1997). Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin. Clin Exp Immunol, 108(2), 333–339. https://doi.org/10.1046/j.1365-2249.1997.d01-1008.x
Blank, M., D. B. Cines, G. Arepally, A. Eldor, A. Afek, and Y. Shoenfeld. “Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin.Clin Exp Immunol 108, no. 2 (May 1997): 333–39. https://doi.org/10.1046/j.1365-2249.1997.d01-1008.x.
Blank M, Cines DB, Arepally G, Eldor A, Afek A, Shoenfeld Y. Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin. Clin Exp Immunol. 1997 May;108(2):333–9.
Blank, M., et al. “Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin.Clin Exp Immunol, vol. 108, no. 2, May 1997, pp. 333–39. Pubmed, doi:10.1046/j.1365-2249.1997.d01-1008.x.
Blank M, Cines DB, Arepally G, Eldor A, Afek A, Shoenfeld Y. Pathogenicity of human anti-platelet factor 4 (PF4)/heparin in vivo: generation of mouse anti-PF4/heparin and induction of thrombocytopenia by heparin. Clin Exp Immunol. 1997 May;108(2):333–339.
Journal cover image

Published In

Clin Exp Immunol

DOI

ISSN

0009-9104

Publication Date

May 1997

Volume

108

Issue

2

Start / End Page

333 / 339

Location

England

Related Subject Headings

  • Thrombocytopenia
  • Platelet Factor 4
  • Mice, Inbred BALB C
  • Mice
  • Immunology
  • Immunization, Secondary
  • Humans
  • Heparin, Low-Molecular-Weight
  • Heparin
  • Autoantibodies