Two-chain factor VIIa generated in the pericardium during surgery with cardiopulmonary bypass - Relationship to increased thrombin generation and heparin concentration

Several recent studies have proposed that coagulation is triggered during c ardiopulmonary bypass surgery by extrinsic pathway activation involving fac tor VIIa generation, but the methodology was indirect, Therefore, 12 patien ts were studied during routine cardiac and cardiopulmonary bypass surgery. Samples were taken before, during, and after bypass from the perfusate, fro m the aorta (retrograde cardiac drainage), pericardium, and collected sucti on fluid originating from the whole operative field. These samples were ana lyzed by enzyme-linked immunosorbent assay for 2-chain factor VIIa, by prot hrombin F1+2 assay, by thrombin-antithrombin (TAT) assay, and for heparin c oncentration. Factor VIIa, F1+2, and TAT levels in samples from the pericar dium were greatly elevated (mean, 0.92 to 1.01, 227 to 334, and 399 to 526 mu g/L, respectively; preoperative mean, 0.33, 32.3, and 1.90 mu g/L, respe ctively; P<0.05 for all), whereas levels in suction fluid were less consist ently high. Factor VIIa and both F1+2 and thrombin-antithrombin levels in s amples from the aorta, pericardium, and suction fluid were significantly co rrelated (r = 0.57, P<0.001, n=111; and r = 0.51, P<0.001, n = 105, respect ively), 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 approximate to 2-fold, probably because heparin levels were higher th an they were in the pericardium (P<0.05). We concluded that appreciable act ivation of factor VII occurs on the pericardium and that this is associated with increased thrombin generation. Ineffective local heparinization may b e partly responsible. These results suggest that pericardium-induced activa tion of factor VII should be the target of anticoagulant strategies during cardiopulmonary bypass surgery.