Characterization of prothrombin activation during cardiac surgery by hemostatic molecular markers.
BACKGROUND
Prothrombin activation represents the key regulatory step in the hemostatic process. Once formed, thrombin contributes to the generation of fibrin as well as the activation of platelets and fibrinolysis. Failure to suppress thrombin formation during cardiac surgery could result in disorders of hemostasis and thrombosis in the perioperative period. The aim of this study was to determine the time course for prothrombin activation during the perioperative period associated with cardiac surgery.


METHODS
We measured prothrombin activation during the perioperative period in 19 adult patients undergoing primary cardiac surgery using enzyme-linked immunosorbent assays for the detection of thrombin formation (prothrombin fragment 1.2 and thrombin-antithrombin III complex) and thrombin activity (fibrinopeptide A and fibrin monomer). Blood samples were obtained preoperatively; at 30-min intervals during cardiopulmonary bypass (CPB); and 1, 3, and 20 h after completion of CPB.


RESULTS
Despite anticoagulation with heparin, plasma concentrations of prothrombin fragment 1.2, thrombin-antithrombin III complex, and fibrin monomer increased throughout CPB. Peak concentrations for all hemostatic markers occurred in the samples obtained 3 h after completion of CPB. By the morning after surgery, plasma prothrombin fragment 1.2 returned to preoperative concentrations; however, fibrinopeptide A and fibrin monomer concentrations remained significantly increased (P < 0.05) compared to preoperative values.


CONCLUSIONS
These data clearly demonstrate the occurrence of prothrombin activation and thrombin activity during CPB despite heparin concentrations adequate to maintain the activated clotting time greater than 400 s. Hemostatic markers for the activation of prothrombin demonstrated peak concentrations 3 h after completion of CPB with a return to baseline concentrations by the morning after surgery. Markers for thrombin activity, however, suggest the presence of active thrombin through the morning after surgery. Further investigations will be necessary to determine the role of hemostatic activation in thrombotic complications after cardiac surgery.
Slaughter
T F
TF
Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710.
LeBleu
T H
TH
Douglas
J M
JM
Leslie
J B
JB
Parker
J K
JK
Greenberg
C S
CS
D000368:Aged; D000990:Antithrombin III / Q000032:analysis / Q000502:physiology; D015415:Biomarkers; D006348:Cardiac Surgical Procedures; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis / Q000502:physiology; D005344:Fibrinopeptide A / Q000032:analysis / Q000502:physiology; D006487:Hemostasis / Q000502:physiology*; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis / Q000502:physiology; D010447:Peptide Hydrolases / Q000032:analysis / Q000502:physiology; D011516:Prothrombin / Q000032:analysis / Q000502:physiology*; D011517:Prothrombin Time; D013917:Thrombin / Q000096:biosynthesis / Q000502:physiology
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C011468:fibrinmonomer; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D013917:Thrombin