TISSUE FACTOR IS EXPRESSED ON MONOCYTES DURING SIMULATED EXTRACORPOREAL-CIRCULATION

Certain forms of extracorporeal circulation exemplified by cardiopulmonary bypass require continuous high-dose anticoagulation to prevent thromboembolic complications. We hypothesized that monocytes may be stimulated to express tissue factor (TF) during prolonged simulated extracorporeal circulation. TF was identified both by flow cytometry by using three TF-specific monoclonal antibodies and functional assay of procoagulant activity (PCA). TF significantly increased between 2 and 6 hours of simulated extracorporeal circulation by both analyses. Relative fluorescence on monocytes increased from a control value of 100 to 313+/-79 on cells from the simulated extracorporeal circuit (p<0.05). PCA increased from 21+/-8 to 775+/-326 pg TF/10(6) monocytes (p<0.05) and was blocked 99.6% by preincubation of cells with a mixture of monoclonal antibodies to TF. By 6 hours, the number of leukocytes in the circuit was decreased by 43%. The cells were recovered from the oxygenator membrane by washing with EDTA. Compared with initial values, by 6 hours, both TF antigen at 378+/-90 (p<0.05) and PCA at 1,357+/-280 pg TF/10(6) monocytes (p<0.01) were highest in the recovered cells. Cells incubated for 6 hours and not subjected to simulated extracorporeal circulation did not increase TF. Examination of monocytes for the adhesive receptor CD11b/18 (Mac-1) paralleled TF expression, providing an additional putative receptor for the coagulant proteins, factor X and fibrinogen or fibrin. Our data support the hypothesis that TF expression by monocytes is induced during prolonged simulated extracorporeal circulation and lead to the suggestion that this may significantly contribute to the increased risk of thrombotic events during prolonged extracorporeal circulation.