CLEAVED ANTITHROMBIN (ATC) - A NEW MARKER FOR THROMBIN GENERATION ANDACTIVATION OF THE COAGULATION SYSTEM

A modified form of antithrombin (AT) cleaved at the active site by thr ombin (ATc) has been shown to be generated in vivo, corresponding to 1 -4% of the circulating AT. An enzyme immunoassay has been developed fo r measuring ATc following plasma treatment with ammonium I sulphate an d heat denaturation of native AT. ATc plasma levels were found to be s ignificantly higher (P = 0.003) in patients developing venous thromboe mbolism when com pared to patients without such events or healthy cont rols (age and sex matched), In addition, ATc levels correlated with th rombin generation markers: thrombin-AT complex (r(2) = 0.66, P = 0.005 ) acid prothrombin fragment 1 + 2 (r(2) = 0.58, P = 0.018), but, in co ntrast to both these markers, elevated ATc levels were detected for at least 2 weeks after the thromboembolic event. In conclusion, ATc appe ars to be a new marker for thrombin generation and overall activation of the coagulation system, having the advantage of being detected in t he circulation for a longer period than other thrombin generation mark ers.