SEARCH:   Advanced

Blood, 15 March 2006, Vol. 107, No. 6, pp. 2346-2353. Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-08-3122. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3122v1 107/6/2346    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rauova, L. Articles by Poncz, M. Search for Related Content PubMed PubMed Citation Articles by Rauova, L. Articles by Poncz, M. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications Lubica Rauova, Li Zhai, M. Anna Kowalska, Gowthami M. Arepally, Douglas B. Cines, and Mortimer Poncz From the Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; National Institute for Rheumatic Diseases, Piestany, Slovakia; Division of Hematology, Duke University Medical Center, Durham, NC; and Departments of Pathology and Laboratory Medicine and Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HIT without (more) heparin Theodore E. Warkentin Blood 2006 107: 2214-2215. [Full Text] [PDF] This article has been cited by other articles: S. Kapa and Q. Qian 84-Year-Old Woman With Hemodialysis-Associated Shortness of Breath Mayo Clin. Proc., February 1, 2009; 84(2): 187 - 190. [Full Text] [PDF] J. G. Kelton and T. E. Warkentin Heparin-induced thrombocytopenia: a historical perspective Blood, October 1, 2008; 112(7): 2607 - 2616. [Full Text] [PDF] Z. Xiao, G. P. Visentin, K. M. Dayananda, and S. Neelamegham Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion Blood, August 15, 2008; 112(4): 1091 - 1100. [Abstract] [Full Text] [PDF] M. P. Mullen, D. L. Wessel, K. C. Thomas, K. Gauvreau, E. J. Neufeld, F. X. McGowan Jr, and J. A. DiNardo The Incidence and Implications of Anti-Heparin-Platelet Factor 4 Antibody Formation in a Pediatric Cardiac Surgical Population Anesth. Analg., August 1, 2008; 107(2): 371 - 378. [Abstract] [Full Text] [PDF] D. S. Woulfe, J. K. Lilliendahl, S. August, L. Rauova, M. A. Kowalska, M. Abrink, G. Pejler, J. G. White, and B. P. Schick Serglycin proteoglycan deletion induces defects in platelet aggregation and thrombus formation in mice Blood, April 1, 2008; 111(7): 3458 - 3467. [Abstract] [Full Text] [PDF] S. Suvarna, B. Espinasse, R. Qi, R. Lubica, M. Poncz, D. B. Cines, M. R. Wiesner, and G. M. Arepally Determinants of PF4/heparin immunogenicity Blood, December 15, 2007; 110(13): 4253 - 4260. [Abstract] [Full Text] [PDF] T. E. Warkentin and A. Greinacher So, Does Low-Molecular-Weight Heparin Cause Less Heparin-Induced Thrombocytopenia Than Unfractionated Heparin or Not? Chest, October 1, 2007; 132(4): 1108 - 1110. [Full Text] [PDF] T. E. Warkentin, B. T. Maurer, R. H. Aster, J. Soffer, J. Patel, and R. Saltzman Heparin-Induced Thrombocytopenia Associated with Fondaparinux N. Engl. J. Med., June 21, 2007; 356(25): 2653 - 2655. [Full Text] [PDF] T. E. Warkentin and M. A. Crowther When is HIT Really HIT? Ann. Thorac. Surg., January 1, 2007; 83(1): 21 - 23. [Full Text] [PDF] T. E. Warkentin, J.-A. I. Sheppard, C. S. Sigouin, T. Kohlmann, P. Eichler, and A. Greinacher Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia Blood, November 1, 2006; 108(9): 2937 - 2941. [Abstract] [Full Text] [PDF] A. Greinacher, M. Gopinadhan, J.-U. Gunther, M. A. Omer-Adam, U. Strobel, T. E. Warkentin, G. Papastavrou, W. Weitschies, and C. A. Helm Close Approximation of Two Platelet Factor 4 Tetramers by Charge Neutralization Forms the Antigens Recognized by HIT Antibodies Arterioscler Thromb Vasc Biol, October 1, 2006; 26(10): 2386 - 2393. [Abstract] [Full Text] [PDF] T. E. Warkentin Think of HIT Hematology, January 1, 2006; 2006(1): 408 - 414. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020