Another point of view on the mechanism of thrombin generation during cardiopulmonary bypass: role of tissue factor pathway inhibitor.
OBJECTIVE
To determine the role of tissue factor and tissue factor pathway inhibitor (TFPI) in coagulation activation during cardiopulmonary bypass (CPB).


METHODS
Prospective, observational study.


METHODS
Operating room in a city hospital.


METHODS
Thirty-one patients undergoing cardiac surgery.


RESULTS
The plasma levels of tissue factor antigen (tissue factor), total and free TFPI, several markers of thrombin generation (prothrombin fragment F1+2, thrombin antithrombin complex, and fibrinopeptide A), and heparin concentration were measured. Blood samples were obtained after induction of anesthesia (baseline level), before and after CPB, and at the end of the surgery. Despite an average heparin concentration of 2.9 +/- 0.2 IU/ mL, markers of thrombin generation, fibrin formation and its degradation (D-dimer) were observed during CPB. Significant increases of total and free TFPI levels (p < 0.0001) were found during CPB associated with lower tissue factor concentration (p < 0.0001) compared with the baseline values. Heparin concentration correlated with levels of total TFPI (r2 = 0.613, p < 0.0001) and free TFPI (r2 = 0.689, p < 0.0001). Tissue factor concentration showed significant negative correlations with levels of total TFPI (r2 = 0.128, p = 0.0003) and free TFPI (r2 = 0.070, p = 0.0078).


CONCLUSIONS
These data indicate that TFPI release by heparin probably has an important role in the suppression of the tissue factor-dependent coagulation pathway during CPB. These changes occur along with ongoing thrombin generation and its activation. Either insufficient prevention of thrombin generation by TFPI or indirect activation of the intrinsic coagulation pathway occurs during CPB.
Department of Anesthesiology and Critical Care Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
T
T
Kojima
S
S
Gando
O
O
Kemmotsu
H
H
Mashio
Y
Y
Goda
H
H
Kawahigashi
N
N
Watanabe
D000368:Aged; D000758:Anesthesia; D000925:Anticoagulants / Q000097:blood / Q000627:therapeutic use; D000991:Antithrombins / Q000378:metabolism; D001777:Blood Coagulation / Q000502:physiology; D002315:Cardiopulmonary Bypass; D005260:Female; D005344:Fibrinopeptide A / Q000378:metabolism; D006493:Heparin / Q000097:blood / Q000627:therapeutic use; D006801:Humans; D008074:Lipoproteins / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000378:metabolism
D000925:Anticoagulants; D000991:Antithrombins; D008074:Lipoproteins; C051928:lipoprotein-associated coagulation inhibitor; D005344:Fibrinopeptide A; D011516:Prothrombin; D006493:Heparin; D013925:Thromboplastin; D013917:Thrombin