Monocyte Tissue Factor Expression and Ongoing Complement Generation in Ventricular Assist Device Patients

Background. Ongoing complement activation in patients with a ventricular assist device may contribute to observed hemostatic abnormalities and cellular aggregation by mediating leukocyte and platelet activation, formation of leukocyte-platelet conjugates, and the tissue factor pathway of coagulation. Methods. Blood from 30 patients was collected before ventricular assist device implantation and during the implantation period. Plasma levels of thrombin–antithrombin III complexes, C3a, and SC5b-9 were measured by commercial enzyme-linked immunosorbent assay. Flow cytometry was used to measure circulating monocyte tissue factor expression and circulating monocyte–platelet and granulocyte–platelet conjugates. Results. Thrombin–antithrombin III complex level and monocyte tissue factor expression peaked in the early postoperative period, with maxima occurring on postoperative days 5 and 3, respectively. Levels of C3a and SC5b-9 remained dramatically elevated over normal values for the duration of the study (6 and 5 times upper normal, respectively). Levels of monocyte–platelet conjugates were normal before implantation, decreased during the first 4 postoperative days, and then increased and remained elevated. Levels of granulocyte–platelet conjugates were elevated over the normal range before implantation and remained elevated from postoperative days 3 to 21. A positive correlation was found between levels of SC5b-9 and granulocyte–platelet conjugates (Spearman R = 0.66; p < 0.001), and between levels of C3a and thrombin–antithrombin III complex (Spearman R = 0.13; p = 0.021). Conclusions. The data suggest a model in which complement mediates formation of leukocyte–platelet aggregates and may indirectly contribute to thrombin generation through monocyte tissue factor expression.