Significance of local international sensitivity index systems for monitoring warfarin and liver function.

OBJECTIVES: Use of a local calibrator has been recommended for standardization of the international normalized ratio (INR) and international sensitivity index (ISI). We investigated the performance of two commercial local calibrators for warfarin monitoring and determined the significance of liver-specific INR. METHODS: ISI values were determined using the World Health Organization (WHO) method and two commercial local calibrators. Liver-specific ISI was determined using plasma samples from patients with liver cirrhosis and normal controls. RESULTS: In warfarin monitoring, the two local ISIs determined by the two local calibrators showed better consistency than uncorrected ISI, although they were inferior to the ISIs calibrated using the WHO method. Alternative calibration using calibration plasma from patients with liver cirrhosis instead of warfarinized plasma reduced the INR variability. CONCLUSIONS: Local ISI determined by a commercial local calibrator improved INR standardization among thromboplastins. The alternative ISI calibration using liver-specific calibration plasma is expected to reduce INR variability for the evaluation of liver function.

Coagulation proteins influencing global coagulation assays in cirrhosis: hypercoagulability in cirrhosis assessed by thrombomodulin-induced thrombin generation assay.

BACKGROUND: Liver disease is accompanied by profound hemostatic disturbances. We investigated the influences of pro- and anticoagulation factors on global coagulation tests including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA) in cirrhosis. We also investigated whether cirrhotic patients exhibit hypo- or hypercoagulability using the TGA. METHODS: The TGA was performed on a calibrated automated thrombogram, given lag time, endogenous thrombin potential (ETP), and peak thrombin in 156 cirrhotic patients and 73 controls. RESULTS: PT was determined according to the factor (F) II, FV, FVII, FIX, and protein C levels. We observed that aPTT was dependent on FII, FIX, and FX levels. The ETP was dependent on FII, antithrombin, and protein C with 5 pM tissue factor (TF) stimulation, and FIX and protein C at 1 pM TF. The ETP ratio with 1 pM TF increased significantly in cirrhosis, indicating hypercoagulability, whereas that with 5 pM TF did not increase in cirrhosis. CONCLUSION: PT and the TGA are sensitive to protein C levels. Even with prolonged PT, the TGA can detect hypercoagulability in cirrhosis. Further studies should evaluate global coagulation status in cirrhosis patients using the newly devised TGA system.