BACKGROUND:The need to perform local International Sensitivity Index (ISI) calibrations and in particular the requirement for a manual method for prothrombin time (PT) determination, have proved to be obstacles to application of the WHO scheme for PT standardization.

Our results suggest that arachidonic acid-induced aggregation in whole blood may be a better predictor of platelet-related coagulopathy and platelet transfusion than the assessment of aspirin intake by patient self-reporting.

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.

The prothrombin time/international normalized ratio (PT/INR) Line method based on 5 certified European Concerted Action on Anticoagulation (ECAA) plasmas provides reliable local INR values without conventional World Health Organization international sensitivity index calibrations. The present study investigated the use of different numbers and types of ECAA calibrant plasmas to derive accurate PT/INR Lines and reliable INR values. The numbers ranged from 3 to 10 plasmas in a set with normal or abnormal samples. Sets were selected, and sampling was repeated 1,000 times for each center to derive PT/INR Lines. The lines were selected randomly or from clusters. The INR values of 5 independent "validation" plasmas were compared before and after correction. In 56 calibrations, 5 ECAA plasmas gave better results than did fewer plasmas. Plasmas with wide-ranging INR values gave better results than randomly selected sets, and including a normal plasma was not essential. The INR deviations of validation plasmas from certified values were reduced with sets of human, bovine/combined, and rabbit reagents. Deviations of more than 10% from certified INR values were significantly reduced (P < .001).

Summary.  Background: It is no longer feasible to check local International Normalized Ratios (INR) by the World Health Organization International Sensitivity Index (ISI) calibrations because the necessary manual prothrombin time technique required has generally been discarded. Objectives: An international collaborative study at 77 centers has compared local INR correction using the two alternative methods recommended in the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis guidelines: local ISI calibration and ‘Direct INR’. Methods: Success of INR correction by local ISI calibration and with Direct INR was assessed with a set of 27 certified lyophilized plasmas (20 from patients on warfarin and seven from normals). Results: At 49 centers using human thromboplastins, 3.0% initial average local INR deviation from certified INR was reduced by local ISI calibration to 0.7%, and at 25 centers using rabbit reagents, from 15.9% to 7.5%. With a minority of commercial thromboplastins, mainly ‘combined’ rabbit reagents, INR correction was not achieved by local ISI calibration. However, when rabbit combined reagents were excluded the overall mean INR deviation after correction was reduced further to 3.9%. In contrast, with Direct INR, mean deviation using human thromboplastins increased from 3.0% to 6.6%, but there was some reduction with rabbit reagents from 15.9% to 10% (12.3% with combined reagents excluded). Conclusions: Local ISI calibration gave INR correction for the majority of PT systems but failed at the small number using combined rabbit reagents suggesting a need for a combined reference thromboplastin. Direct INR correction was disappointing but better than local ISI calibration with combined rabbit reagents. Interlaboratory variability was improved by both procedures with human reagents only.