A Comparison of the Quantitative Action of Protamine and Heparin on Blood Coagulation: Significance in Clinical and Laboratory Usage

Perkash, A

doi:10.1093/ajcp/73.5.676

Cited by 26 publications

(17 citation statements)

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“…Interestingly, APTT had a modest association, though not statistically significant, with the amount of protamine administered to patients. Excess protamine can prolong APTT, [48][49][50] hence, we speculate that elevated APTT in our patients may have been related, at least in part, to an excessive protamine dose in an attempt to reverse heparin. Further work is needed to clarify the effect of protamine on APTT in the cardiac surgery setting.…”

Section: Discussionmentioning

confidence: 76%

Un temps de céphaline activée élevé n’est pas associé à un rebond d’héparine après une chirurgie cardiaque

Taneja

Marwaha

Sinha

et al. 2009

Can J Anesth/J Can Anesth

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Section: Discussionmentioning

confidence: 76%

Un temps de céphaline activée élevé n’est pas associé à un rebond d’héparine après une chirurgie cardiaque

Taneja

Marwaha

Sinha

et al. 2009

Can J Anesth/J Can Anesth

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“…Previous studies in which incremental concentrations of protamine (50-300 g/mL) were added to heparinized patient samples ex vivo demonstrated that heparin anticoagulation was maximally reversed at a protamine to heparin ratio of 1.3:1. 8,14 However, addition of higher protamine: heparin ratios (ie, excess free protamine) resulted in significant prolongation of the activated clotting time (ACT) through an unidentified mechanism. 8 Similarly, ex vivo addition of protamine to normal pooled plasma markedly attenuated tissue factor (TF)-initiated thromboelastography.…”

Section: Introductionmentioning

confidence: 99%

Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation

Áinle¹,

Preston²,

Jenkins³

et al. 2009

Blood

114

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Protamine sulfate is a positively charged polypeptide widely used to reverse heparininduced anticoagulation. Paradoxically, prospective randomized trials have shown that protamine administration for heparin neutralization is associated with increased bleeding, particularly after cardiothoracic surgery with cardiopulmonary bypass. The molecular mechanism(s) through which protamine mediates this anticoagulant effect has not been defined. In vivo administration of pharmacologic doses of protamine to BALB/c mice significantly reduced plasma thrombin generation and prolonged tail-bleeding time (from 120 to 199 seconds). Similarly, in pooled normal human plasma, protamine caused significant dose-dependent prolongations of both prothrombin time and activated partial thromboplastin time. Protamine also markedly attenuated tissue factor-initiated thrombin generation in human plasma, causing a significant decrease in endogenous thrombin potential (41% ؎ 7%). As expected, low-dose protamine effectively reversed the anticoagulant activity of unfractionated heparin in plasma. However, elevated protamine concentrations were associated with progressive dose-dependent reduction in thrombin generation. To assess the mechanism by which protamine mediates down-regulation of thrombin generation, the effect of protamine on factor V activation was assessed. Protamine was found to significantly reduce the rate of factor V activation by both thrombin and factor Xa. Protamine mediates its anticoagulant activity in plasma by downregulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation. (Blood. 2009;114: 1658-1665) IntroductionProtamine sulfate is a 5-kDa cationic polypeptide derived from salmon sperm that can bind negatively charged unfractionated heparin (UFH). 1 Although the mechanisms of the molecular interaction between protamine and heparin are not well defined, this binding serves to neutralize the antithrombin-mediated anticoagulant properties of heparin. Moreover, the resultant protamineheparin complex is rapidly cleared by the reticuloendothelial system. 2 Consequently, for more than 30 years, protamine has been widely used to reverse the anticoagulant effects of UFH. Protamine is considered the treatment of choice for patients who develop significant bleeding complications while on UFH. 3,4 Furthermore, protamine is routinely administered postoperatively to reverse the high concentrations of UFH required for patients undergoing cardiac surgery and cardiopulmonary bypass (CPB). 5 As a result, estimates suggest that more than 2 million heparinized patients are managed with protamine each year. 2 Clinical use of protamine is, however, associated with several important adverse side effects, including potentially life-threatening systemic arterial hypotension and pulmonary artery hypertension. 1 Paradoxically, in vitro studies have also suggested that protamine may possess intrinsic anticoagulant properties. [6][7][8] Administration of excess protamine in the neutralization of UFH has b...

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“…There is some disagreement over proper protamine dosing for heparin neutralization [12,14,17,18]. However, it appears that effective protamine dosing for heparin neutralization is about 1 mg/100U of unfractionated H, but should not be lower [17].…”

Section: Isrn Cell Biologymentioning

confidence: 99%

“…Yet, PS overdose has a number of side effects including hypotension and platelet dysfunction [19]. Further, PS has been demonstrated to prolong clotting time [12,20,21].…”

Section: Isrn Cell Biologymentioning

confidence: 99%

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The Modification of Xa-ATIII-Heparin Dynamics by Protamine Sulfate

Coggin

Brecher

2012

ISRN Cell Biology

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Heparin promotes the formation of 1∘FXaα-ATIII and FXaβ-ATIII complexes from the free enzymes and antithrombin III. It further stimulates the transformations of the 1∘complexes into the corresponding 3∘complexes. Additionally, it stimulates the degradation of the 1∘FXaα-ATIII and FXaβ-ATIII complexes into free FXaα, FXaβand ATIIIM. Protamine sulfate (PS) stimulates the transformation of FXaαinto FXaβand hence to FXaγ. It also stimulates the transformation of the 1∘-, 2∘-, and 3∘- FXα-ATIII complexes into their correspondingβ-complexes. It further promotes the degradation of the 1∘FXaα- and FXaβ-ATIII complexes into their corresponding 3∘- FXaα- and FXaβ-ATIII complexes, with the concommittant release of FXaγ. The addition of PS to FXa/ATIII/H mixtures results in a reduction in free FXa, ATIII, and 1∘Xa-ATIII complex formation, together with the concommittant increase in 3∘-FXa- ATIII complex formation and release of FXaγ. The likeliest explanation of these results resides in the removal of the effective free heparin as a consequence of the generation of a stable heparin/PS salt upon the addition of the PS to the FXa/ATIII/H mixtures, thereby effectively lowering clotting times.

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A Comparison of the Quantitative Action of Protamine and Heparin on Blood Coagulation: Significance in Clinical and Laboratory Usage

Cited by 26 publications

References 0 publications

Un temps de céphaline activée élevé n’est pas associé à un rebond d’héparine après une chirurgie cardiaque

Un temps de céphaline activée élevé n’est pas associé à un rebond d’héparine après une chirurgie cardiaque

Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation

The Modification of Xa-ATIII-Heparin Dynamics by Protamine Sulfate

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