Thromb Haemostasis
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Randomized Controlled Trial Multicenter Study
Benefit/risk profile of high-dose antithrombin in patients with severe sepsis treated with and without concomitant heparin.
A randomised, prospective, placebo-controlled phase III multicentre clinical trial (KyberSept) has been performed to test the efficacy of high-dose antithrombin therapy in patients with severe sepsis. Concomitant low-dose heparin has been routinely given in two thirds of patients for deep vein thrombosis prophylaxis. This study analyses heparin - antithrombin interactions in terms of long-term mortality, adverse events, and thromboembolic events. ⋯ Rates of thromboembolic events were similar when antithrombin was given with or without concomitant heparin. In the treatment of severe sepsis, high-dose antithrombin may sufficiently protect against development of venous thromboembolism when no concomitant heparin is given. Combined administration of the two increases bleeding risk and probably abolishes efficacy of antithrombin.
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Thromboelastography analysis providing a global assessment of coagulation is gaining new interest in clinical practice. MinimalTF triggered whole blood thromboelastography provides a valuable tool for studying the kinetics of clot formation (expressed by the parameters R, K and alpha-angle) and the physical characteristics of the clot, such as its firmness and the elastic modulus shear (expressed by the parameters maximal amplitude MA and G). We studied the influence of fibrin polymerization and platelet functional status on each parameter of thromboelastographic trace obtained by minimalTF activation inWB by employing increasing concentrations of a fibrin polymerization inhibitors (the tetrapeptide Gly-Pro-Arg-Pro-OH. ⋯ However, G value was dramatically reduced in the presence of cytochalasin D exposure, without any additional effect when both inhibitors were combined. This study confirms the importance of fibrin polymerisation on the kinetics of thrombus formation and demonstrates the close association between the quality of the thrombus and the functional status of platelets. Normal platelet contractile forces are of major importance for the maximum amplitude of TEG which is related to the strength and elastic modulus of the thrombus.