Decreased concentration of antithrombin after preoperative therapeutic heparin does not cause heparin resistance in cardiopulmonary bypass

Objective: To determine if preoperative heparin therapy causes an increase in the incidence of intraoperative heparin resistance by reducing the concentration of antithrombin in plasma. Design: Prospective laboratory investigation of clinical samples. Setting: Public tertiary care hospital and public pathology service. Participants: Forty-six patients undergoing cardiac surgery involving cardiopulmonary bypass. Interventions: Fourteen patients received preoperative heparin therapy (POHI group) and 32 patients were controls (CONT group). Measurements and Main Results: The concentration of antithrombin, activated coagulation time (ACT), and clinical parameters were measured at intervals. More POHI patients had on-bypass heparin resistance than CONT (43% and 3%, respectively, p < 0.01). The POHI group had a lower concentration of antithrombin than the CONT group before (80.9% and 92.6%, respectively, p < 0.01) and while on cardiopulmonary bypass (51.6% and 57.5%, respectively, p = 0.04). Comparison of heparin-resistant and heparin-responsive POHI patients showed that the concentration of antithrombin did not differ before bypass (82.4% and 79.8%, respectively, p = 0.53) or during bypass (51.8% and 51.4%, respectively, p = 0.91). In fact, antithrombin concentrations were slightly higher in the heparin-resistant POHI patients (not significant). POHI patients received more heparin than CONT patients (medians 787 U/kg and 600 U/kg, respectively, p = 0.01) and were transfused with more fresh frozen plasma on bypass (p = 0.03). Conclusions: Preoperative heparin causes an increased incidence of heparin resistance and reduced antithrombin concentrations. However, heparin resistance was not causally related to reduced antithrombin because antithrombin concentrations were not different between heparin-resistant and heparin-responsive patients in the POHI group.