© 1999 American Heart Association, Inc.
Original Contributions |
Two-Chain Factor VIIa Generated in the Pericardium During Surgery With Cardiopulmonary Bypass
Relationship to Increased Thrombin Generation and Heparin Concentration
From the Imperial College School of Medicine, Charing Cross Hospital (H.P., D.A.L.), and the Royal Brompton Hospital (S.J.D., M.T.M., J.R.P., J.F.B.), London, United Kingdom.
Correspondence to David A. Lane, PhD, Department of Haematology, Charing Cross Hospital, Imperial College School of Medicine, Hammersmith, London W6 8RP, United Kingdom. E-mail d.lane{at}ic.ac.uk
Abstract—Several recent studies
have proposed that coagulation is triggered during
cardiopulmonary bypass surgery by extrinsic pathway activation
involving factor VIIa generation, but the methodology was indirect.
Therefore, 12 patients were studied during routine cardiac and
cardiopulmonary bypass surgery. Samples were taken before,
during, and after bypass from the perfusate, from the aorta (retrograde
cardiac drainage), pericardium, and collected suction fluid originating
from the whole operative field. These samples were analyzed by
enzyme-linked immunosorbent assay for 2-chain factor VIIa, by
prothrombin F1+2 assay, by thrombin-antithrombin (TAT)
assay, and for heparin concentration. Factor VIIa, F1+2,
and TAT levels in samples from the pericardium were greatly elevated
(mean, 0.92 to 1.01, 227 to 334, and 399 to 526 µg/L, respectively;
preoperative mean, 0.33, 32.3, and 1.90 µg/L, respectively;
P<0.05 for all), whereas levels in suction fluid were
less consistently high. Factor VIIa and both F1+2
and thrombin-antithrombin levels in samples from the aorta,
pericardium, and suction fluid were significantly correlated
(r=0.57, P<0.001, n=111; and
r=0.51, P<0.001, n=105, respectively),
and all were inversely correlated with heparin levels
(r>-0.35, P<0.001, n>92). There was
no evidence of factor VIIa generation in the circuit during bypass
surgery, and both F1+2 and thrombin-antithrombin levels
rose only 
2-fold, probably because heparin levels were higher than
they were in the pericardium (P<0.05). We concluded
that appreciable activation of factor VII occurs on the pericardium and
that this is associated with increased thrombin generation. Ineffective
local heparinization may be partly responsible. These results suggest
that pericardium-induced activation of factor VII should be the target
of anticoagulant strategies during cardiopulmonary bypass
surgery.
Key Words: cardiopulmonary bypass • coagulation • heparin • pericardium
This article has been cited by other articles:
 |
|
 |
|
  O. Fabre, A. Vincentelli, D. Corseaux, F. Juthier, S. Susen, A. Bauters, E. Van Belle, F. Mouquet, T. Le Tourneau, C. Decoene, et al. Comparison of Blood Activation in the Wound, Active Vent, and Cardiopulmonary Bypass Circuit Ann. Thorac. Surg., August 1, 2008; 86(2): 537 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. D Raymond, M. Radel, M. J Ray, A. D Hinton-Bayre, and N. A Marsh Investigation of factors relating to neuropsychological change following cardiac surgery Perfusion, January 1, 2007; 22(1): 27 - 33. [Abstract] [PDF]
|
|
|
|
 |
|
 T. Hattori, M. M.H. Khan, R. W. Colman, and L. H. Edmunds Jr Plasma Tissue Factor Plus Activated Peripheral Mononuclear Cells Activate Factors VII and X in Cardiac Surgical Wounds J. Am. Coll. Cardiol., August 16, 2005; 46(4): 707 - 713. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Johnell, G. Elgue, R. Larsson, A. Larsson, S. Thelin, and A. Siegbahn Coagulation, fibrinolysis, and cell activation in patients and shed mediastinal blood during coronary artery bypass grafting with a new heparin-coated surface J. Thorac. Cardiovasc. Surg., August 1, 2002; 124(2): 321 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Al-Obaidi, H. Philippou, P. J. Stubbs, A. Adami, R. Amersey, M. M. Noble, and D. A. Lane Relationships Between Homocysteine, Factor VIIa, and Thrombin Generation in Acute Coronary Syndromes Circulation, February 1, 2000; 101(4): 372 - 377. [Abstract] [Full Text] [PDF]
|
|