THREE DIFFERENT PATTERNS OF CALIBRATED AUTOMATED THROMBOGRAM OBTAINED WITH HIRUDIN, MELAGATRAN, DABIGATRAN, ARGATROBAN, FONDAPARINUX AND DANAPAROD
Abstract number: P-W-644
Samama1 M.M., Le Flem2 L., Guinet3 C., Depasse2 F.
11Haematology, Hotel Dieu University Hospital, Paris 22Haematology, Laboratory LCL, Ivry sur Seine 33Haematology, Laboratory LCL, Ivry, France
How-to-cite Samama MM, Le Flem L, Guinet C, Depasse F. THREE DIFFERENT PATTERNS OF CALIBRATED AUTOMATED THROMBOGRAM OBTAINED WITH HIRUDIN, MELAGATRAN, DABIGATRAN, ARGATROBAN, FONDAPARINUX AND DANAPAROÏD. J Thromb Haemost 2007; 5 Supplement 2: P-W-644
Introduction: Thrombin generation test (TGT) allowing to obtain calibrated automated thrombograms (CAT) could be useful for the evaluation of the anticoagulant activity of antithrombotic drugs, the investigation of their mechanism of action and the characteristics of the TGT at therapeutic concentrations.
Methods: Pools of normal human plasma were spiked with increasing concentrations of the six drugs and TGT was determined. Lag time (LT), time to peak (TTP), the endogenous thrombin potential (ETP) and the mean velocity rate of thrombin generation were measured.
Results: The mechanism of action on TGT was heterogeneous. At therapeutic concentrations, Hirudin delays dramatically TG without affecting significantly its velocity and the amount of thrombin formed (first pattern of CAT).
Argatroban, Melagatran and Dabigatran induce a far less marked LT and TTP prolongation than Hirudin, but they reduce the mean velocity of the reaction and the amount of active thrombin formed. Melagatran and Dabigatran were found more active than Argatroban, but the patterns of the CAT were similar (second pattern of CAT).
Danaparoïd exerts a minimal effect on LT and TTP wich is associated with a very significant influence on mean velocity rate, peak and ETP. Fondaparinux exerts a greater activity than Danaparoïd on the LT, but the patterns of the CAT are similar (third pattern of CAT).
Conclusions: Antithrombotic activity is associated with different alterations of TGT and 3 different patterns of CAT are described. The results could help to determine blood concentrations required for an effective anticoagulation or reciprocally the alterations of the thrombogram which are observed at therapeutic concentrations.