title: Two-chain factor VIIa generated in the pericardium during surgery with cardiopulmonary bypass : relationship to increased thrombin generation and heparin concentration.
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 microg/L, respectively; preoperative mean, 0.33, 32.3, and 1.90 microg/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 approximately 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.
authors.affiliation: Imperial College School of Medicine, Charing Cross Hospital, London, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Philippou
authors.forename: S J
authors.initials: SJ
authors.lastname: Davidson
authors.forename: M T
authors.initials: MT
authors.lastname: Mole
authors.forename: J R
authors.initials: JR
authors.lastname: Pepper
authors.forename: J F
authors.initials: JF
authors.lastname: Burman
authors.forename: D A
authors.initials: DA
authors.lastname: Lane
mesh_terms: D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D001026:Coronary Artery Bypass; D004797:Enzyme-Linked Immunosorbent Assay; D015942:Factor VIIa / Q000096:biosynthesis* / Q000737:chemistry; D005260:Female; D006493:Heparin / Q000097:blood; D006801:Humans; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010496:Pericardium / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis