Abstract
We investigated the anticoagulant effects of recombinant human activated protein C (rhAPC), unfractionated heparin (UH) and melagatran (a new direct thrombin inhibitor [DTI]), when administered individually and in combinations of rhAPC with either UH or melagatran, in umbilical cord and adult plasma. rhAPC is a promising candidate treatment to improve the outcome of severe sepsis in neonates and adults; the DTI melagatran represents a potential advance in antithrombotic therapy. The anticoagulant efficacy of these drugs was measured using the standard coagulation assays activated partial thromboplastin time (aPTT) and prothrombin time (PT). Administered individually, rhAPC, UH and melagatran dose-dependently prolonged aPTT to a significantly greater extent in umbilical cord than in adult plasma. Melagatran alone, but not rhAPC or UH alone, dose-dependently prolonged the PT in both umbilical cord and adult plasma. Combining rhAPC with either UH or melagatran significantly augmented aPTT prolongation in both umbilical cord and adult plasma. Our results, which facilitate estimation of rhAPC and melagatran dose requirements in umbilical cord plasma, may be of benefit in critically sick newborns with severe sepsis.
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