Mathematical derivative applied to international normalised ratio and analytical variations in oral anticoagulant therapy control

G. Introcaso, A. Cuboni, A. Ratto, F. Foieni

Research output: Contribution to journalArticle


A reliable prothrombin time (PT) testing and a careful drug dosage can prevent thrombotic or bleeding complications of the oral anticoagulant therapy. The international normalised ratio (INR) as PT standardisation introduced an analytical variation that increases with higher PT measures and higher international sensitivity index (ISI) values. Our study was conducted to investigate the INR accuracy through the mathematical derivative application to reduce the analytical component of the INR uncertainty. The evaluation of accuracy among four different systems (prothrombin activity percent, PT seconds, PT ratio and INR) was determined by the simulation of a systematic error. Plasma samples were diluted 1:2; then they were compared observed with the expected values. We analysed the calculation system of the INR through the mathematical derivative in 87 PT ratio measurements. The analytical incidence of thromboplastin ISI was performed through an elaboration of INR mathematical derivative considering 10 different ISI values ranging from 1.1 to 2. The data expressed as PT ratios revealed a lower systematic error propagation suggesting that a linear system is more accurate. According to the calculation formula of INR, analytical variability increases with the PT measurements, then with the intensity of anticoagulation. Mathematical derivative suggests that the INR uncertainty due to the ISI can be reduced using a thromboplastin reagent with a low ISI or with ISI close to 1.

Original languageEnglish
Pages (from-to)281-289
Number of pages9
Issue number6
Publication statusPublished - Nov 2000



  • Anticoagulant therapy, oral
  • International normalised ratio
  • Mathematical derivative
  • Variability, analytical

ASJC Scopus subject areas

  • Hematology

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