The in vitro effects of antithrombin III on the activated coagulation time in patients on heparin therapy

Heparin requires antithrombin III (AT) to achieve anticoagulation, and patients on continuous small-dose heparin preoperatively experience decreased levels of AT-causing heparin resistance. When this occurs, 2-4 units of fresh frozen plasma ( approximately 1000 units of AT) are often administered to increase AT levels and restore heparin responsiveness. We evaluated purified human AT concentrate (Thrombate III; Bayer, Inc., Elkhart, IN) to restore in vitro anticoagulation responses in patients receiving heparin. Blood samples were obtained from cardiac surgery patients including 22 patients receiving heparin and 21 patients not receiving heparin preoperatively. Heparin was added to blood in final concentrations of 4.1, 5.4, and 6.8 U/mL (equivalent to 300, 400, and 500 U/kg), and kaolin-activated clotting times (ACTs) were determined with and without AT at a final concentration of 0.2 units/mL to mimic fresh frozen plasma administration. The mean duration of preoperative heparin therapy was 4.0 days (range 2-10 days). AT activity was 69% +/- 9% in patients receiving heparin and 92% +/- 8% in patients not receiving heparin (P < 0.01). Heparin >4.1 U/mL failed to further increase ACT values in all patients. Attempts to increase ACT in patients receiving heparin may require supplemental AT administration. Purified AT even in small doses significantly prolongs the ACT response to heparin. Implications: In vitro addition of antithrombin III (0.2 U/mL) to heparinized blood samples (4.1-6.8 units of heparin/mL) from patients on previous heparin therapy increases sensitivity to supplemental heparin as reflected by significantly prolonged activated clotting time.