Full Length Article| Volume 224, P32-37, April 2023

Estimating the measurement uncertainties of the international sensitivity index of 12 thromboplastins through Monte Carlo simulation

Published:February 13, 2023DOI:


      • Measurement uncertainty (MU) estimation has become an important process in clinical laboratories.
      • Complex mathematical calculations made it difficult to estimate the MU of international sensitivity index (ISI).
      • Monte Carlo simulation (MCS) is one of the alternatives for evaluating the MU.
      • We demonstrated that MCS is adequate to estimate the MU of ISI.



      Measurement uncertainty (MU) estimation has become an important process in clinical laboratories; however, calculating the MUs of the international sensitivity index (ISI) of thromboplastins is difficult because of the complex mathematical calculations required in calibration. Therefore, this study quantifies the MUs of ISIs through the Monte Carlo simulation (MCS), which involves random sampling of numerical values to solve a complex mathematical calculation.


      Eighty blood plasmas and commercially available certified plasmas (ISI Calibrate) were used to assign the ISIs of each thromboplastin. Prothrombin times were measured using reference thromboplastin and 12 commercially available thromboplastins (Coagpia PT-N, PT Rec, ReadiPlasTin, RecombiPlasTin 2G, PT-Fibrinogen, PT-Fibrinogen HS PLUS, Prothrombin Time Assay, Thromboplastin D, Thromborel S, STA-Neoplastine CI Plus, STA-Neoplastine R 15, and STA-NeoPTimal) with two automated coagulation instruments: ACL TOP 750 CTS (ACL TOP; Instrumentation Laboratory, Bedford, MA, USA) and STA Compact (Diagnostica Stago, Asnières-sur-Seine, France). Then, the MUs of each ISI were simulated through MCS.


      The MUs of ISIs ranged from 9.7 % to 12.1 % and 11.6 % to 12.0 % when blood plasma and ISI Calibrate were used, respectively. For some thromboplastins, the ISI claimed by manufacturers significantly differed from the estimated results.


      MCS is adequate to estimate the MUs of ISI. These results would be clinically useful for estimating the MUs of the international normalized ratio in clinical laboratories. However, the claimed ISI significantly differed from the estimated ISI of some thromboplastins. Therefore, manufacturers should provide more accurate information about the ISI value of thromboplastins.


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