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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-08-2400.
Submitted August 8, 2002
Accepted November 17, 2002
Estimating the rate of thrombin and fibrin generation in vivo during cardiopulmonary bypass
Wayne L Chandler* and Tomas Velan
Laboratory Medicine, University of Washington, Seattle, WA, USA
* Corresponding author; email: wlc{at}u.washington.edu.
Our objective was to estimate the in vivo rates of thrombin and fibrin generation to better understand how coagulation is regulated. Nine males undergoing cardiopulmonary bypass (CPB) were studied. The rates of thrombin, total fibrin and soluble fibrin generation in vivo were based on measured levels of prothrombin activation peptide F1.2, thrombin-antithrombin complex, fibrinopeptide A and soluble fibrin combined with a computer model of the patient's vascular system that accounted for marker clearance, hemodilution, blood loss and transfusion. Prior to surgery, the average thrombin generation rate was 0.24±0.11 picomoles/sec. Each thrombin molecule in turn generated about 100 fibrin molecules of which 1% was soluble fibrin. The thrombin generation rate did not change after sternotomy or administration of heparin, then rapidly increased 20-fold to 5.60±6.65 pmol/s after 5 minutes of CPB (p = 0.00005). Early in CPB each new thrombin generated only 4 fibrin molecules of which 35% were soluble fibrin. The thrombin generation rate was 2.14±1.88 pmol/s during the remainder of CPB, increasing again to 5.47±4.08 pmol/s after reperfusion of the ischemic heart (p = 0.00008). After heparin neutralization with protamine, thrombin generation remained high (5.34±4.01 pmol/s, p = 0.0002) and total fibrin generation increased, but soluble fibrin generation decreased. By two hours after surgery thrombin and fibrin generation rates were returning to baseline levels. We conclude that cardiopulmonary bypass and reperfusion of the ischemic heart results in bursts of non-hemostatic thrombin generation and dysregulated fibrin formation, not just a steady increase in thrombin generation as suggested by previous studies.
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