The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers – two independent studies

Abstract

Summary. Background: The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP). Methods: The value of a new simpler procedure to derive international normalized ratio (INR), the PT/INR Line, based on only five European Concerted Action on Anticoagulation (ECAA) calibrant plasmas certified by experienced centres has been assessed in two independent exercises using a range of commercial thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations. Results: In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human reagents, and from 7.0% to 2.6% with rabbit reagents. In the second study, deviation was reduced from 11.2% to 0.4% with human reagents by both local ISI calibration and the PT/INR Line. With rabbit reagents, 10.4% deviation was reduced to 1.1% with both procedures; 4.9% deviation was reduced to 0.5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line. Conclusions: The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI calibration across the range of locally used commercial thromboplastins and automated PT systems included in two independent international studies.

Evaluation of European Concerted Action on Anticoagulation Lyophilized Plasmas for INR Derivation Using the PT/INR Line

“…1,2 There is no need for local manual PT testing using the World Health Organization (WHO) thromboplastin international reference preparations (IRPs) required in the conventional WHO method for international sensitivity index (ISI) calibration to obtain INRs. 3 The PT/ INR Line is a development of the "direct INR" method of Houbouyan and Goguel, 4 later modified in the Scientific and Standardization Committee Guidelines and in the Clinical and Laboratory Standards Institute document, 5,6 that gave discouraging results in a previous European Concerted Action on Anticoagulation (ECAA) study.…”

Policies and practices in haemostasis testing among laboratories in Croatia: a survey on behalf of a Working Group for Laboratory Coagulation of the Croatian Society of Medical Biochemistry and Laboratory Medicine

“…As variable INR values in the same plasma sample could be obtained on different coagulometers, ISI calibration of all routinely used reagents is very important ( 9 ). This survey showed that most respondents use PT reagents derived from human placenta and rabbit brain although recombinant tissue factor reagents have better sensitivity to factor deficiencies and plasma samples from patients treated with OAT ( 10 ).…”

Interpretation of coagulation test results under direct oral anticoagulants

“…The INR is based on ISI values derived from plasma of patients on stable warfarin doses for more than 6 weeks. The INR values determined with warfarintreated patients are transferred for patients treated with other coumarin derivatives [1][2][3]. Rivaroxaban binds competitively and reversibly to free factor Xa and to factor Xa bound in the prothrombinase complex.…”