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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3173-3180. Prepublished online as a Blood First Edition Paper on February 5, 2004; DOI 10.1182/blood-2003-11-3994. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3994v1 104/10/3173    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 Eslin, D. E. Articles by Kowalska, M. A. Search for Related Content PubMed PubMed Citation Articles by Eslin, D. E. Articles by Kowalska, M. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Transgenic mice studies demonstrate a role for platelet factor 4 in thrombosis: dissociation between anticoagulant and antithrombotic effect of heparin Don E. Eslin, Chunyan Zhang, Kathleen J. Samuels, Lubica Rauova, Li Zhai, Stefan Niewiarowski, Douglas B. Cines, Mortimer Poncz, and M. Anna Kowalska From the Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, PA; the University of Pennsylvania School of Medicine, Philadelphia; and the Temple University School of Medicine, Philadelphia, PA. The platelet-specific chemokine platelet factor 4 (PF4) is released in large amounts at sites of vascular injury. PF4 binds to heparin with high affinity, but its in vivo biologic role has not been defined. We studied the role of PF4 in thrombosis using heterozygote and homozygote PF4 knock-out mice (mPF4+/– and mPF4–/–, respectively) and transgenic mice overexpressing human PF4 (hPF4+). None of these lines had an overt bleeding diathesis, but in a FeCl3 carotid artery thrombosis model, all showed impaired thrombus formation. This defect in thrombus formation in the mPF4–/– animals was corrected by infusing hPF4 over a narrow concentration range. The thrombotic defect in the mPF4+/– and mPF4–/– animals was particularly sensitive to infusions of the negatively charged anticoagulant heparin. However, the same amount of heparin paradoxically normalized thrombus formation in the hPF4+ animals, although these animals were anticoagulated systemically. Upon infusion of the positively charged protein, protamine sulfate, the reverse was observed with mPF4+/– and mPF4–/– animals having improved thrombosis, with the hPF4+ animals having worsened thrombus formation. These studies support an important role for PF4 in thrombosis, and show that neutralization of PF4 is an important component of heparin's anticoagulant effect. The mechanisms underlying these observations of PF4 biology and their clinical implications remain to be determined. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Flaumenhaft Platelet proteoglycans packing it in Blood, April 1, 2008; 111(7): 3308 - 3309. [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. 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