Measurement of Bivalirudin Thrombin Inhibition Activity in Plasma with Clotting or Chromogenic Assays and Dedicated Calibrators and Controls

Abstract

Bivalirudin is a parenteral direct thrombin inhibitor anticoagulant and does not induce any impairment of the Protein C pathway, which function remains preserved. This drug meets increasing applications for cardiac surgery and heart diseases, especially when heparin is contra-indicated in presence of heparin-induced thrombocytopenia. Major indications concern Extra Corporeal Circulation, PCI/PTCA, and myocardial infarction. Drug clearance occurs partly through kidney. Patients with moderate or severe renal dysfunctions are exposed to drug accumulation and subsequent bleeding, the major adverse effect reported. This study presents 2 automated assays, a clotting method, and a kinetics chromogenic technique, proposed for the quantitative measurement of bivalirudin in citrated plasma. Both assays need a specific bivalirudin calibration, are fully automatable on coagulation instruments, and can be available at any time in specialized clinical laboratories for an on time monitoring of treated patients. Assay ranges are from 0.3 to 5.0 μg/ml (clotting assay) or to 6.0μg/ml (chromogenic assay), and up to 20.0μg/ml with an additional automatic plasma dilution. These methods offer excellent performances, with good reproducibility and repeatability. This study reports the results obtained with both assays on bivalirudin measurements in 26 treated patients collected at 4 timings. Both methods are fully consistent and contribute to facilitate and secure the use of this anticoagulant when it is indicated.