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 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.
Velan
Tomas
T
Department of Laboratory Medicine, University of Washington, Seattle, Wash. 98195-7110, USA.
Chandler
Wayne L
WL
D000368:Aged; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D006487:Hemostasis; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D008962:Models, Theoretical; D013917:Thrombin / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000097:blood*
D015415:Biomarkers; D006493:Heparin; D013917:Thrombin