Heparin Resistance and Increased Platelet Activation in Coronary Surgery Patients Treated With Enoxaparin Preoperatively

Objective: Patients with unstable coronary disease have changes in the hemostatic system. These patients are often treated with low molecular weight heparin. In patients who are accepted for coronary artery bypass grafting, treatment with low molecular weight heparin is frequently continued until surgery. We hypothesized that in coronary artery bypass grafting, the hypercoagulable state seen in unstable patients persists into the intra- and postoperative phase despite preoperative treatment with low molecular weight heparin. The aim of this study was to explore and describe the perioperative hemostatic process in patients with unstable coronary artery disease undergoing coronary artery bypass grafting.

Methods: Thirty-two patients with unstable coronary disease treated preoperatively with enoxaparin, and 32 stable control patients not treated with enoxaparin, were included. All patients were taking low dose aspirin until the day before surgery. Before cardiopulmonary bypass, all patients were given tranexamic acid as a bolus injection. Blood samples for analysis of platelet counts, international normalized ratio, activated partial thromboplastin time, fibrinogen, protein S, protein C, prothrombin fragment 1+2, thrombin-antithrombin complex, antithrombin, plasmin-antiplasmin complex, D-dimer, neutrophil-activating peptide 2, platelet-monocyte complexes, and heparin concentrations were drawn preoperatively, after 30min on cardiopulmonary bypass, and 30min, 3h, and 20h postoperatively. Heparin was given during cardiopulmonary bypass to maintain an activated clotting time above 480s.

Results: Patients in the enoxaparin group needed more heparin to maintain an activated clotting time above 480s, and had higher heparin concentrations and lower antithrombin values compared with control patients. Neutrophil-activating peptide 2 concentrations were higher in the enoxaparin group.

Conclusions: Patients treated with enoxaparin before coronary artery bypass grafting showed signs of heparin resistance intraoperatively. Enoxaparin-treated patients also had increased perioperative platelet activation. Reasons for the observed difference in platelet activation remain unclear.