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Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications.

Publication ,  Journal Article
Rauova, L; Zhai, L; Kowalska, MA; Arepally, GM; Cines, DB; Poncz, M
Published in: Blood
March 15, 2006

Heparin-induced thrombocytopenia (HIT) antibodies recognize complexes between heparin and platelet factor 4 (PF4). Heparin and PF4 bind HIT antibodies only over a narrow molar ratio. We explored the involvement of platelet surface-bound PF4 as an antigen in the pathogenesis of experimental HIT. We show that cell-surface PF4 complexes are also antigenic only over a restricted concentration range of PF4. Heparin is not required for HIT antibody binding but shifts the concentration of PF4 needed for optimal surface antigenicity to higher levels. These data are supported by in vitro studies involving both human and murine platelets with exogenous recombinant human (h) PF4 and either an anti-PF4-heparin monoclonal antibody (KKO) or HIT immunoglobulin. Injection of KKO into transgenic mice expressing different levels of hPF4 demonstrates a correlation between the severity of the thrombocytopenia and platelet hPF4 expression. Therapeutic interventions in this model using high-dose heparin or protamine sulfate support the pathogenic role of surface PF4 antigenic complexes in the etiology of HIT. We believe that this focus on surface PF4 advances our understanding of the pathogenesis of HIT, suggests ways to identify patients at high risk to develop HIT upon heparin exposure, and offers new therapeutic strategies.

Duke Scholars

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Published In

Blood

DOI

ISSN

0006-4971

Publication Date

March 15, 2006

Volume

107

Issue

6

Start / End Page

2346 / 2353

Location

United States

Related Subject Headings

  • Thrombocytopenia
  • Protamines
  • Platelet Factor 4
  • Phenotype
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • Heparin
  • Blood Platelets
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rauova, L., Zhai, L., Kowalska, M. A., Arepally, G. M., Cines, D. B., & Poncz, M. (2006). Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood, 107(6), 2346–2353. https://doi.org/10.1182/blood-2005-08-3122
Rauova, Lubica, Li Zhai, M Anna Kowalska, Gowthami M. Arepally, Douglas B. Cines, and Mortimer Poncz. “Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications.Blood 107, no. 6 (March 15, 2006): 2346–53. https://doi.org/10.1182/blood-2005-08-3122.
Rauova L, Zhai L, Kowalska MA, Arepally GM, Cines DB, Poncz M. Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood. 2006 Mar 15;107(6):2346–53.
Rauova, Lubica, et al. “Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications.Blood, vol. 107, no. 6, Mar. 2006, pp. 2346–53. Pubmed, doi:10.1182/blood-2005-08-3122.
Rauova L, Zhai L, Kowalska MA, Arepally GM, Cines DB, Poncz M. Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood. 2006 Mar 15;107(6):2346–2353.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

March 15, 2006

Volume

107

Issue

6

Start / End Page

2346 / 2353

Location

United States

Related Subject Headings

  • Thrombocytopenia
  • Protamines
  • Platelet Factor 4
  • Phenotype
  • Mice, Transgenic
  • Mice
  • Immunology
  • Humans
  • Heparin
  • Blood Platelets