The relationship between hirudin and activated clotting time: Implicationsfor patients with heparin-induced thrombocytopenia undergoing cardiac surgery

Anticoagulation with recombinant hirudin (r-hirudin) (Refludan (TM) has bee n suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified activated coagulation time (ACT) that would allow quantification of the le vels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB w ere enrolled in this IRE-approved study. R-hirudin was added to blood speci mens obtained before heparin administration (before CPB) and 30 min after h eparin neutralization with protamine (after CPB) to result in concentration s of 0,2, 4, 6, 7,or 8 mug/mL. Kaolin/ ACT and complete blood count measure ments were assayed in native specimens (first 10 patients, Phase I) or in s pecimens mixed with equal volumes of commercial normal plasma (second 11 pa tients, Phase II). In Phase I,good (P = 0.83) linear relationships between ACT values and r-hirudin concentrations (less than or equal to4 mug/mL) wer e observed in specimens obtained before CPB. However, ACT values were marke dly prolonged (P < 0.0001) by r-hirudin in specimens obtained after CPB, wi th ACT values generally exceeding the ACT's detection limit (> 999 s) at hi rudin concentrations >2 mug/mL. In patient specimens mixed with normal plas ma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values ob tained with hirudin concentration less than or equal to4 mug/mL) in the pos t-CPB period (0.022 +/- 0.004 mug mL(-1) s(-1)) were similar (P = 0.47) to those (0.019 +/- 0.004 mug.mL(-1).s(-1)) obtained in the pre-CPB period. Ac cordingly, a significant relationship between normal plasma-supplemented AC T values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period. Although our data demonst rate that the ACT test cannot be used to monitor hirudin during CPB, the ad dition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT valu es up to a predilution concentration of 8 mug/mL Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB.