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Semin Thromb Hemost 2004; 30(3): 369-377
DOI: 10.1055/s-2004-831050
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Recombinant Platelet Factor 4 for Heparin Neutralization

Timothy A. Mixon1 , Gregory J. Dehmer1 , 2
  • 1Department of Medicine (Division of Cardiology), Scott & White Memorial Hospital and Clinic, Temple, Texas; The Texas A&M University System Health Science Center College of Medicine, College Station, Texas
  • 2Professor of Medicine, Department of Medicine (Division of Cardiology), Scott & White Memorial Hospital and Clinic, Temple, Texas; The Texas A&M University System Health Science Center College of Medicine, College Station, Texas
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Publication History

Publication Date:
29 July 2004 (online)

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Protamine sulfate has been used for many years to reverse the effects of unfractionated heparin, but it can cause hemodynamic changes and other serious side effects. Platelet factor 4 (PF4) is a naturally occurring protein synthesized in megakaryocytes and eventually stored in the α granules of platelets for later release. Although the complete physiologic role of PF4 is unknown, it is highly effective for the neutralization of heparin anticoagulation. Several preliminary animal studies and trials using blood obtained from cardiopulmonary bypass circuits suggested recombinant PF4 (rPF4) would be an effective alternative to protamine. In the first open-label, phase 1 human study, patients received rPF4 in doses of 0.5, 1.0, 2.5, or 5.0 mg/kg over 3 minutes to reverse heparin anticoagulation after diagnostic cardiac catheterization. There were no important hemodynamic changes and the rPF4 was highly effective in neutralizing heparin. Serial measurements of rPF4 levels showed a monophasic elimination pattern with a serum half-life of 25.5 ± 13.5 minutes that was independent of dose administered. A randomized and blinded trial comparing rPF4 to protamine confirmed the safety and effectiveness of rPF4. Although rPF4 was initially being evaluated as a clinical alternative to protamine, it is not currently being developed for general clinical use.

KEYWORDS

Heparin - platelet factor 4 - protamine - anticoagulation

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Gregory J DehmerM.D. 

Texas A&M College of Medicine, Division of Cardiology, Scott & White Hospital

2401 South 31st Street, Temple, TX 76508

Email: gdehmer@swmail.sw.org

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