Aim: 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.
Methods: The anticoagulant efficacy of these drugs was measured using the standard coagulation assays activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Results: 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.
Conclusion: 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.