Discrepant sensitivity of thromboplastin reagents to clotting factor levels explored by the prothrombin time in patients on stable oral anticoagulant treatment: Impact on the international normalized ratio system

Sophie Testa, Giampietro Morstabilini, Annalisa Fattorini, Laura Galli, Nadia Denti, Armando D'Angelo

Research output: Contribution to journalArticle

Abstract

Background and Objectives. We tested the principle of local International Normalized Ratio (INR) calibration using INR calibrator plasmas (PT Calibration Plasma Kit, Behring), two thomboplastin reagents (Neoplastin plus, rabbit brain, Stago, and Recombiplastin, recombinant human tissue factor, Ortho Diagnostics) and the same coagulometer (STA, Stago) on 92 patients on stable oral anticoagulant treatment. Design and Methods. A four-point calibration was obtained with each reagent by linear regression (sec/INR) on a log-log scale (r ≥ 0.999). The bias between the two reagents (Recombiplastin - Neoplastin Plus) was reduced from 31.7% to 17.5% and 7.5% (p=0.001) when results were expressed, respectively, as PT ratio (using the mean normal prothrombin time as denominator term), INR (using instrument-specific ISI supplied by the manufacturers) and calibrated INR, but there was a consistently significant regression of the differences over the average values even after log transformation (r ≥ 0.586). The bias between the reagents was reduced to 1% (p=ns) when assuming Recombiplastin as the reference thromboplastin and applying Tomenson's correction, but limits of agreements were as large as ± 20%. Factor VII, X, V and II activity was measured with the two thromboplastin reagents in all plasma samples using immunodepleted plasmas (Stago). Results. Statistically significant biases were observed for all clotting factors with the two reagents (Recombiplastin - Neoplastin Plus) and ranged from 3.5 % Fill to -37.2% (FVII). In addition, for FVII and FV there was a significant regression of the difference over the average value (after log-transformation, r ≥ 0.282). The patients were divided into 3 groups according to their degree of anticoagulation (INR 3.5). Factor levels differed significantly with the two reagents throughout the 3 groups of patients. In addition, the relative distributions of the 3 vitamin K-dependent factors also differed in the 3 groups with the two thromboplastin reagents. Interpretation and Conclusions. The discrepant sensitivity to factor VII X and V levels of the two thromboplastin reagents explored in this study prevents INR calibration with commercially available calibrator plasmas and is responsible for a significant variability in INR values even under optimal conditions of INR calibration.

Original languageEnglish
Pages (from-to)1265-1273
Number of pages9
JournalHaematologica
Volume87
Issue number12
Publication statusPublished - Dec 1 2002

Keywords

  • Factor V
  • INR
  • INR calibrator plasma
  • Oral anticoagulation
  • Prothrombin time
  • Vitamin K dependent clotting factors

ASJC Scopus subject areas

  • Hematology

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