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Koestenberger, M; Cvirn, G; Gallistl, S; Muntean, W.
Drotrecogin alfa activated (recombinant human activated protein C) in combination with heparin or melagatran: effects on prothrombin time and activated partial thromboplastin time.
BLOOD COAGULAT FIBRINOL. 2004; 15(8): 693-697.
Doi: 10.1097/00001721-200412000-00010
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
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Koestenberger Martin
- Co-authors Med Uni Graz
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Cvirn Gerhard
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Gallistl Siegfried
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Muntean Eugen
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- Abstract:
- Recombinant human activated protein C (rhAPC) has recently been demonstrated to be a promising candidate to improve the outcome for patients with severe sepsis. Plasma-derived activated protein C and unfractionated heparin (UH) exert anticoagulant synergy due to mechanisms that simultaneously decrease thrombin generation. Melagatran, a new direct thrombin inhibitor, does not bind to plasma proteins or requires antithrombin as a cofactor. The latter is often consumed in patients with severe sepsis. We investigated the anticoagulant efficiency in combined administration of rhAPC and UH or melagatran in terms of prolongation of the standard clotting assays activated partial thromboplastin time (aPTT) and prothrombin time (PT) in pooled plasma samples in vitro. RhAPC dose-dependently prolonged the aPTT but not the PT. The ability of UH and melagatran to prolong the aPTT was significantly enhanced in combination with rhAPC. The combined administration of rhAPC and melagatran, but not UH, resulted in additive prolongation of the PT. In control measurements the capability of rhAPC to suppress prothrombin fragment 1.2 generation dose-dependently increased in combination with heparin and melagatran. Our study demonstrates the respective effects of rhAPC, UH, melagatran and further different additive effects in combined administration of rhAPC and UH or melagatran on the prolongation of the aPTT and PT clotting assays usually used to monitor anticoagulant treatment.
- Find related publications in this database (using NLM MeSH Indexing)
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Azetidines -
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Benzylamines -
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Blood Coagulation - drug effects
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Dose-Response Relationship, Drug - drug effects
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Drug Evaluation - drug effects
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Drug Therapy, Combination - drug effects
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Fibrinolytic Agents - pharmacology
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Glycine - analogs and derivatives
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Heparin - pharmacology
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Humans - pharmacology
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Partial Thromboplastin Time - pharmacology
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Peptide Fragments - biosynthesis
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Protein C - pharmacology
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Prothrombin - biosynthesis
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Prothrombin Time - biosynthesis
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Recombinant Proteins - pharmacology
- Find related publications in this database (Keywords)
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melagatran
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recombinant human activated protein C
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unfractionated heparin
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activated partial thromboplastin time
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prothrombin time