Thromboplastin calibration revisited to look for possible revision of the World Health Organization recommendations

Background: Thromboplastin calibration is essential to determine the international sensitivity index required to calculate the international normalized ratio (INR). The procedure for calibration recommended by the World Health Organization (WHO) calls for the selection of patients on stable anticoagulation in the range of 1.5 to 4.5 INR. These patients are difficult to be recruited as the conventional therapeutic interval for warfarin is 2.0 to 3.0. A possible solution could be including patients with less intense anticoagulation in the calibration. Objectives: We sought to investigate the impact of this amended procedure on the parameters of calibration. Methods: Eight data sets from previous calibrations of a rabbit thromboplastin that included patients on anticoagulation as required by WHO were used for this pilot study. Parameters of calibration as determined by the full data sets are identified as "full calibrations" and are considered reference. Each of the data sets were used to recalculate the calibration parameters after including patients with INRs of <4.0, <3.5, or <3.0, which were identified as "trimmed calibrations" and compared with those from the full calibrations. Results: There was marginal variation of the international sensitivity index, CV, and INR that can be hardly of practical significance. CV was the most affected parameter, which increased from the full to the trimmed <3.0 calibration, but never exceeded the 3% cutoff value recommended by WHO. Conclusions: Should the results of this pilot study be confirmed for the calibration of other thromboplastins, revision of the WHO recommendations to include patients with INR from 1.5 to 4.0 is warranted.