Effects of surgical trauma and cardiopulmonary bypass on active thrombin concentrations and the rate of thrombin inhibition in vivo

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 μM^-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.