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The in vivo concentration of active thrombin and the second-order rate constant for the inhibition of thrombin by antithrombin (k(inh)) were estimated in patients undergoing cardiopulmonary bypass (CPB) based on measured levels of hemostatic markers in combination with a computer model of the patient's hemostatic and vascular systems. At baseline k(inh) = 0.6 +/- 0.1 microM(-1) s(-1) leaving 270 +/- 101 fM of active thrombin in the circulation. These factors were unchanged after sternotomy. Soon after heparin administration and the start of CPB, k(inh) increased 25-fold resulting in decreased active thrombin. After CPB and heparin neutralization, k(inh) decreased to 8-fold above baseline allowing active thrombin levels to rise. Both factors had returned to normal 2 h after surgery. We conclude that CPB with heparinization results in a rapid increase in thrombin inhibition leading to decreased active thrombin levels in vivo.

Effects of Surgical Trauma and Cardiopulmonary Bypass on Active Thrombin Concentrations and the Rate of Thrombin Inhibition in vivo