Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation.
AuthorsNi Ainle, Fionnuala
Preston, Roger J S
Jenkins, P Vincent
Nel, Hendrik J
Johnson, Jennifer A
Smith, Owen P
Fallon, Padraic G
O'Donnell, James S
AffiliationHaemostasis Research Group, St James's Hospital, Dublin, Republic of Ireland.
MetadataShow full item record
CitationProtamine sulfate down-regulates thrombin generation by inhibiting factor V activation. 2009, 114 (8):1658-65 Blood
AbstractProtamine sulfate is a positively charged polypeptide widely used to reverse heparin-induced 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 down-regulation of thrombin generation via a novel mechanism, specifically inhibition of factor V activation.
- Coagulation protein function VI: augmentation of anticoagulant function by acetaldehyde-treated heparin.
- Authors: Brecher AS, Hellman K, Basista MH
- Issue date: 1999 Jul
- Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study.
- Authors: Radulovic V, Laffin A, Hansson KM, Backlund E, Baghaei F, Jeppsson A
- Issue date: 2015
- Studies on the neutralizing effects of protamine on unfractionated and low molecular weight heparin (Fragmin) at the site of activation of the coagulation system in man.
- Authors: Wolzt M, Weltermann A, Nieszpaur-Los M, Schneider B, Fassolt A, Lechner K, Eichler HG, Kyrle PA
- Issue date: 1995 Mar
- Anticoagulant synergism of heparin and activated protein C in vitro. Role of a novel anticoagulant mechanism of heparin, enhancement of inactivation of factor V by activated protein C.
- Authors: Petäjä J, Fernández JA, Gruber A, Griffin JH
- Issue date: 1997 Jun 1
- The pharmacological profile of the low molecular weight heparin 21-23 in man: anticoagulant, lipolytic and protamine reversible effects.
- Authors: Harenberg J, Stehle G, Dempfle CE, von Hodenberg E, Heene DL
- Issue date: 1989