A Multi-Centre Study to Evaluate Method Dependency of the International Sensitivity Index of Bovine Thromboplastin

Summary

In The Netherlands, a particular coagulometer method for prothrombin time (PT) determination with reduced sample and reagent volumes is used by 62% of the laboratories controlling oral anticoagulant therapy. This “micro-method” has been calibrated against the manual tilt-tube technique for PT determination by six Dutch laboratories. Each laboratory tested 20 fresh normal blood samples and 60 fresh patient blood samples using both methods with the same batch of bovine thromboplastin reagent, according to a detailed protocol. Both methods were comparable as to their precision, but PTs measured by the micromethod were significantly prolonged (p <0.001, Student’s t-test) as compared to the manual method. This effect is stronger for samples of normal subjects than for patients’ samples. It was assumed that the International Sensitivity Index (ISI) of the bovine thromboplastin for the manual method was 1.00 in each laboratory. The ISI-values of the bovine thromboplastin for the micro-method determined by the six laboratories ranged from 1.00 to 1.07 (mean 1.03, SD 0.03). Our results indicate that any other laboratory, using this thromboplastin and the micromethod, should obtain accurate assessment of the International Normalized Ratio from their own mean normal PT and an ISI which is 3% higher than the ISI supplied by the thromboplastin manufacturer for the manual tilt-tube method.

Keywords

International Sensitivity Index - International Normalized Ratio - Oral anticoagulant control - Prothrombin time

• References

• 1 Loeliger EA. International Committee for Standardization in Haematology and International Committee on Thrombosis and Haemostasis. ICSH/ICTH recommendations for reporting prothrombin time in oral anticoagulant control Thromb Haemostas 1985; 53: 155-156
• 2 WHO Expert Committee on Biological Standardization. 33rd Report. WHO Tech Rep Ser. 1983; 687: 81-105
• 3 Loeliger EA, van den Besselaar AM H P, Lewis SM. Reliability and Clinical Impact of the Normalization of the Prothrombin Times in Oral Anticoagulant Control. Thromb Haemostas 1985; 53: 148-154
• 4 Hermans J, van den Besselaar AM H P, Loeliger EA, van der Velde EA. A Collaborative Calibration Study of Reference Materials for Thromboplastins. Thromb Haemostas 1983; 50: 712-717
• 5 Van den Besselaar AM H P. Standardization of the Prothrombin Time in Oral Anticoagulant Control. Haemostasis 1985; 15: 271-277
• 6 Van der Velde EA. Orthogonal Regression equation. In: Thromboplastin Calibration and Oral Anticoagulant Control. Van den Besselaar AM H P. et al. (eds) Martinus Nijhoff; The Hague: 1984
• 7 Kirkwood TB L. Calibration of Reference Thromboplastins and Standardisation of the Prothrombin Time Ratio. Thromb Haemostas 1983; 49: 238-244
• 8 Loeliger EA, van den Besselaar AM H P, Bertina RM. Critical appraisal, clinical usefulness, and implementation of the thromboplastin concept of prothrombin-time standardization. Scand J Haematol 1980; (Suppl. 25) suppl 37: 34-48