INCREASED ACTIVATION OF THE COAGULATION AND FIBRINOLYTIC SYSTEMS LEADS TO HEMORRHAGIC COMPLICATIONS DURING LEFT-VENTRICULAR ASSIST IMPLANTATION

Background Left ventricular assist devices (LVADs) have provided a new therapeutic option for patients with end-stage heart failure. Despite advances in device design, there remains an apparent bleeding diathes is, which leads to increased transfusion requirements and reoperative rates. The purpose of our study was to examine the abnormalities that might contribute to these clinical sequelae. Methods and Results To se parate the effects of cardiopulmonary bypass (CPB), eight patients und ergoing coronary revascularization (CABG) were compared with seven LVA D (TCI HeartMate) recipients intraoperatively and 2 hours postoperativ ely. We evaluated several well-characterized indexes of platelet activ ation: platelet count, platelet factor 4 (PF4), beta-thromboglobulin ( beta-TG), and thromboxane B-2 (TXB(2)). We also measured activation of thrombin: thrombin-antithrombin III (TAT), prothrombin fragment 1+2 ( F1+2), and fibrinopeptide A (FPA) as well as markers of fibrinolysis: plasmin-alpha(2)-antiplasmin (PAP) and D-dimer. Patterns of intraopera tive platelet adhesion and activation were not statistically different in the CABG control and LVAD groups. In the immediate postoperative p eriod, however, there was significant release of PF4 and beta-TG and g eneration of TXB(2). Compared with the CABG controls (TAT, 26+/-8 mu g /L; F1+2, 4+/-1 nmol/L; mean+/-SEM), there was a significant increase in TAT (380+/-112 mu g/L) and F1+2 (23+/-4 nmol/L) in LVAD patients 2 hours after surgery. Furthermore, a sharp rise in FPA was noted 20 min utes after LVAD initiation (CABG, 8+/-4 ng/mL; LVAD, 235+/-63 ng/mL; P <.05). A concomitant increase in both PAP (CABG, 987+/-129 mu g/L; LVA D 3456+/-721 mu g/L; P<.05) and D-dimer (CABG, 1678+/-416 ng/mL; LVAD, 15 243+/-4682 ng/mL; P<.05) was observed. Conclusions The additive ef fects of CPB and LVAD lead to platelet activation as well as elevation of markers of in vivo thrombin generation, fibrinogen cleavage, and f ibrinolytic activity. The etiology of these findings may be secondary to the LVAD surface, flow characteristics, and/or operative procedure. Nevertheless, platelet alterations and exaggerated activation of the coagulation and fibrinolytic systems may contribute to the clinically observed hemostatic defect.