Modified plasma-based ecarin clotting time assay for monitoring of recombinant hirudin during cardiac surgery.
Recombinant hirudin (r-hirudin) is being used increasingly for therapeutic anticoagulation in patients with heparin-induced thrombocytopenia undergoing cardiovascular surgery. Although multiple laboratory methods are available for measuring r-hirudin, the ecarin clotting time (ECT) is the most commonly used for this purpose. Ecarin (extracted from snake venom) converts prothrombin to meizothrombin, which promotes clot formation. Direct thrombin inhibitors, like r-hirudin, bind meizothrombin and yield a linear, dose-dependent prolongation of ECT. Low levels of prothrombin and fibrinogen in plasma samples can lead to higher ECT; suggesting falsely elevated r-hirudin levels. A modified ECT assay with prothrombin and fibrinogen in excess was optimized using an orthogonal array method to eliminate the variations in patients' plasma prothrombin and/or fibrinogen levels for accurate determinations of plasma r-hirudin levels. By using the modified ECT assay, falsely elevated r-hirudin levels can be avoided in patients undergoing cardiopulmonary bypass, thus providing reliable and accurate r-hirudin monitoring in this clinical setting.
Choi
Tak-Shun
TS
Department of Pathology, University of Texas Southwestern Medical Center, USA.
Khan
Adil I
AI
Greilich
Philip E
PE
Kroll
Martin H
MH
D001780:Blood Coagulation Tests / Q000379:methods*; D002315:Cardiopulmonary Bypass; D016903:Drug Monitoring / Q000379:methods*; D010450:Endopeptidases; D005340:Fibrinogen / Q000032:analysis; D006493:Heparin / Q000009:adverse effects; D024764:Hirudin Therapy; D006629:Hirudins / Q000097:blood*; D006801:Humans; D011516:Prothrombin / Q000032:analysis; D011994:Recombinant Proteins / Q000097:blood; D015203:Reproducibility of Results
D006629:Hirudins; D011994:Recombinant Proteins; D011516:Prothrombin; D005340:Fibrinogen; D006493:Heparin; D010450:Endopeptidases; C020097:ecarin