Cleaved antithrombin (ATc): a new marker for thrombin generation and activation of the coagulation system

A modified form of antithrombin (AT) cleaved at the active site by thrombin (ATc) has been shown to be generated in vivo, corresponding to 1-4% of the circulating AT. An enzyme immunoassay has been developed for measuring ATc following plasma treatment with ammonium sulphate and heat denaturation of native AT. ATc plasma levels were found to be significantly higher (P = 0.003) in patients developing venous thromboembolism when compared to patients without such events or healthy controls (age and sex matched). In addition, ATc levels correlated with thrombin generation markers: thrombin-AT complex (r2 = 0.66, P = 0.005) and prothrombin fragment 1 + 2 (r2 = 0.58, P = 0.018), but, in contrast to both these markers, elevated ATc levels were detected for at least 2 weeks after the thromboembolic event. In conclusion, ATc appears to be a new marker for thrombin generation and overall activation of the coagulation system, having the advantage of being detected in the circulation for a longer period than other thrombin generation markers.