Heparin Neutralization by Recombinant Platelet Factor 4 and Protamine

Levy, Jerrold H.; Cormack, James G.; Morales, A.F.

doi:10.1097/00132586-199606000-00011

Cited by 9 publications

(11 citation statements)

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“…Extensive platelet activation occurs during CPB, and platelets undergo morphological changes to form aggregates. Heparin anticoagulation is also susceptible to neutralization by platelet factor 4, 25 which is released upon platelet activation. Addition of GPIIb=IIIa inhibitor to heparin has significantly improved the outcome of patients undergoing coronary interventions.…”

Section: Discussionmentioning

confidence: 99%

Effects of tirofiban on haemostatic activation in vitro

Tanaka

Katori

Szlam

et al. 2004

British Journal of Anaesthesia

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Section: Discussionmentioning

confidence: 99%

Effects of tirofiban on haemostatic activation in vitro

Tanaka

Katori

Szlam

et al. 2004

British Journal of Anaesthesia

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“…42 They proposed a 2:1 ratio on a milligram basis for the dose of rPF4 compared with that of protamine. Levy and associates, 43 using similar methods, reported a 3:1 ratio for the reversal of heparin by rPF4. In addition, viscoelastic analysis of the clotting process using a Thrombelastograph 1 (Haemoscope, Skokie, IL) showed no differences in the properties of the clot that formed after protamine or PF4.…”

Section: Use Of Rpf4 In Animal and Ex Vivo Human Studiesmentioning

confidence: 88%

Recombinant Platelet Factor 4 for Heparin Neutralization

Mixon¹,

Dehmer²

2004

Semin Thromb Hemost

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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 alpha 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.

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“…Platelet concentrates instead of protamine were used to neutralise polypeptide stored in platelets in humans that reverses heparin, it would also have the advantage of being less antigenic [1]. Platelets, however, are known to contain platelet factor 4, which has potent antiheparin activity and others investigated the use of platelet concentrates instead of protamine for reversing the systemic heparinisation during cardiopulmonary bypass in two patients with a history of serious anaphylactoid reactions to Protamine [2].…”

Section: Discussionmentioning

confidence: 99%

“…The administration of protamine sulfate is currently widely used method of reversing heparin anticoagulation after the cardiac surgery. Protamine, a basic polypeptide derived from salmon sperm, reverses heparin, an acidic glycosaminoglycan derived from bovine or porcine tissues by nonspecific acid-base interactions to form heparin-protamine complexes [1].…”

Section: Introductionmentioning

confidence: 99%