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.
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