THROMBIN GENERATION TEST IN THE MONITORING OF PROTHROMBIN COMPLEX CONCENTRATES
Abstract number: P-S-046
Dargaud1 Y., Marin1 S., Bordet1 J., Poplavsky2 J., Negrier1 C.
11Haematology, Hopital Edouard Herriot, Lyon, France 22Haematology, EDDC, Amay, Belgium
How-to-cite Dargaud Y, Marin S, Bordet J, Poplavsky J, Negrier C. THROMBIN GENERATION TEST IN THE MONITORING OF PROTHROMBIN COMPLEX CONCENTRATES. J Thromb Haemost 2007; 5 Supplement 2: P-S-046
Introduction: Human prothrombin complex concentrates (PCCs) are used for prevention and treatment of bleeding episodes in patients under warfarin therapy. PCCs contain human FII, FVII, FIX, FX, protein C (PC) and protein S (PS). The concentrations of the coagulation factors contained in PCCs are variable and do not reflect entirely the capacity of these drugs to correct haemostasis. Furthermore, commercially available PCCs do not have exactly the same composition, though they are all labelled and prescribed in units per kg of FIX (10 to 40 IU of FIX/kg). As the final product generated by PCCs is thrombin, thrombin generation (TG) test could theoretically be used for monitoring the haemostatic correction.
Methods: TG was measured in platelet free plasma in the presence of tissue factor 5pM and phospholipids 4mM with a final concentration of PCC of 0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.75 -1 IU/ml. The activity of vitamin K-dependent coagulation factors, i.e. FII, FVII, FIX, FX, PC and PS were determined with each concentration of PCC.
Results: Our results showed that the addition of 2 different PCCs dose-dependently increased the TG capacity in patients with INR of 22.534 and >7 (n=12 subjects) and reached the normal values determined in 100 healthy subjects. We also found a significant correlation between endogenous thrombin potential (ETP) and INR (Pearson test, p<0.0001). The two PCCs improved the TG parameters differently at increasing concentrations. The difference in the correction of TG capacity observed between the 2 drugs could be explained by a variable increase in FX, FVII and PC with similar doses.
Conclusions: These results strongly suggest that TG assay could be used for monitoring the clinical efficacy of PCC and for optimizing the therapeutic regimen.
To cite this abstract use the following format:
Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number
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