The Anticoagulant Effect of Protamine Sulfate Is Attenuated in the Presence of Platelets or Elevated Factor VIII Concentrations.
Summary of "The Anticoagulant Effect of Protamine Sulfate Is Attenuated in the Presence of Platelets or Elevated Factor VIII Concentrations."
Background: Protamine sulfate is the antidote for heparin, but in excess it exerts weak anticoagulation. Methods: We evaluated the effects of increasing protamine concentrations (0 to 24 mug/mL) on prothrombin time and diluted Russell's viper venom time measurements on thrombin generation in platelet-poor and platelet-rich plasma after activation by tissue factor or actin, and on thromboelastometry in platelet-poor plasma and whole blood from 6 healthy volunteers. The reversibility of excess protamine (24 mug/mL) by recombinant factor VIIa or factor VIII/von Willebrand factor concentrate was also tested. Results: Protamine prolonged prothrombin time and Russell's viper venom time, concentration dependently. Protamine also increased lag time and decreased peak of thrombin generation in platelet-poor plasma after tissue factor and actin activation. In platelet-rich plasma with platelets at 50 to 200 x 10(3)/muL, protamine (24 mug/mL) prolonged the lag time, but had no effect on peak thrombin generation. The addition of factor VIII/von Willebrand factor (1.5-3.0 U/mL) to platelet-poor plasma with protamine (24 mug/mL) decreased lag time and increased peak thrombin generation with actin activation. A therapeutic concentration of recombinant factor VIIa (60 nM) only affected the lag time of thrombin generation triggered with actin. In agreement, protamine increased coagulation time evaluated by thromboelastometry significantly more in platelet-poor plasma than in whole blood. Conclusions: We demonstrated that protamine affects the propagation of thrombin generation, which is partially reversed by platelets or increased factor VIII/von Willebrand factor concentrations. The present data suggest that excess protamine might potentially increase bleeding in the case of severe thrombocytopenia or low factor VIII.
Affiliation
From the *Department of Anesthesiology and.
Journal Details
This article was published in the following journal.
Name: Anesthesia and analgesia
ISSN: 1526-7598
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20686004
- DOI: http://dx.doi.org/10.1213/ANE.0b013e3181e9ed15
Medical and Biotech [MESH] Definitions
Protamines
A group of simple proteins that yield basic amino acids on hydrolysis and that occur combined with nucleic acid in the sperm of fish. Protamines contain very few kinds of amino acids. Protamine sulfate combines with heparin to form a stable inactive complex; it is used to neutralize the anticoagulant action of heparin in the treatment of heparin overdose. (From Merck Index, 11th ed; Martindale, The Extra Pharmacopoeia, 30th ed, p692)
Arylsulfotransferase
A sulfotransferase that catalyzes the sulfation of a phenol in the presence of 3'-phosphoadenylylsulfate as sulfate donor to yield an aryl sulfate and adenosine 3',5'-bisphosphate. A number of aromatic compounds can act as acceptors; however, organic hydroxylamines are not substrates. Sulfate conjugation by this enzyme is a major pathway for the biotransformation of phenolic and catechol drugs as well as neurotransmitters. EC 2.8.2.1.
Chondroitin Sulfates
Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.
Protamine Kinase
An aspect of protein kinase (EC 2.7.1.37) in which serine residues in protamines and histones are phosphorylated in the presence of ATP. EC 2.7.1.70.
Sulfate Adenylyltransferase
An enzyme that catalyzes the activation of sulfate ions by ATP to form adenosine-5'-phosphosulfate and pyrophosphate. This reaction constitutes the first enzymatic step in sulfate utilization following the uptake of sulfate. EC 2.7.7.4.
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