Effects of Reagent and Instrument on Prothrombin Times, Activated Partial Thromboplastin Times and Patient/Control Ratios

Summary

Activated partial thromboplastin times accumulated from two proficiency testing surveys were analyzed to determine simultaneously the effects of the method and reagent used. Prothrombin time results were reevaluated concomitantly for comparison.

A robust two-way analysis of variance was applied to determine the effect of method and reagent on APTT results. The effect of the reagent and method on the ratio of abnormal to normal plasma clotting times was determined. We found a substantial difference in ratios for the PT using different reagents on the same instrument. There was an even larger effect of reagents on APTT ratios.

Our finding of substantial reagent effects for the PT and APTT clearly support the need for standardization. We found standardization to be feasible only for the PT, and only if applied in a form consistent with the inherent error structure of the data. For the APTT the present methodology and plasma samples did not achieve consistent standardization.

Keywords

Prothrombin time - Activated partial thromboplastin time - Proficiency testing - Statistic, robust estimation - Analysis of variance

• References

• 1 Loeliger EA. The optimal therapeutic range in oral anticoagulation. History and proposal Thromb Haemostas 1979; 42: 1141-1152
• 2 Leck I, Gowland E, Poller L. The variability of measurements of the prothrombin time ratio in the national quality control trials: a follow-up study. Br J Haematol 1974; 28: 601-612
• 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 Poller L. Standardization of the APTT test current status. Scand J Haematol (suppl) 1980; 37: 49-63
• 5 Stevenson KJ, Easton AC, Curry A, Thomson JM, Poller L. The reliability of activated partial thromboplastin time methods and the relationship to lipid composition and ultrastructure. Thromb Haemostas 1986; 55: 250-258
• 6 Bjornsson DT, Nash VP. Variability in heparin sensitivity of APTT reagents. Am J Clin Pathol 1986; 86: 199-204
• 7 Kendall M, Stuart A. The Advanced Theory of Statistics. MacMillan Co; New York: 1976. 3 30
• 8 Han Y, Lawson WB, Dodds WJ, Lawrence CE. Prothrombin time proficiency testing: a robust grading method. Thromb Haemostas 1985; 54: 704-708
• 9 Paulson AS, Delehanty TA. Sensitive analysis in experimental design. In: Computer Science and Statistics: Proceedings of the 14th Symposium on the Interface. Heiner KW, Sacher RS, Wilkinson JW. (eds.) Springer-Verlag; New York: 1982: 51-57
• 10 Anderson TW, Darling DA. A test of goodness of fit. J Am Statist Assoc 1954; 49: 765-769
• 11 Levene H. Robust tests for equality of variance. In: Contributions to Probability and Statistics. Olkin I. (ed.) Stanford Univ Press; Palo Alto, CA: 1960: 278-292
• 12 Loeliger EA. Laboratory control, optimal therapeutic ranges and therapeutic quality control in oral anticoagulation. Acta Haematol 1985; 74: 125-131
• 13 WHO Expert Committee on Biological Standardization. Twenty-eighth Report. Technical Report Series 610. WHO; Geneva: 1977
• 14 WHO Expert Committee on Biological Standardization. Thirtieth Report. Technical Report Series 638. WHO; Geneva: 1979
• 15 WHO Expert Committee on Biological Standardization. Thirty-third Report. Technical Report Series 687. WHO; Geneva: 1983
• 16 WHO Expert Committee on Biological Standardization. Thirty-fourth Report. Technical Report Series 700. WHO; Geneva: 1984
• 17 Thomson JM, Stevenson KJ, Tomenson JA. Report on proposed second WHO international reference thromboplastin, human, plain, to replace the WHO international reference preparations, human, combined. WHO; Geneva: 1983
• 18 Loeliger EA, van den Besselaar AM H P, Hermans J, van der Velde EA. Certification of three reference materials for thromboplastins, BCR information. Commission of the European Communities; Brussels: 1981
• 19 Italian (C.I.S.M.E.L.) Study Group. Activated partial thromboplastin time. A multicenter evaluation of 17 reagents in the screening of mild haemophilia A Scand J Haematol 1980; 25: 308-317
• 20 Marlar AR, Bauer JP, Endres-Brooks LJ, Montgomery RR, Miller MC, Schanen MM. Comparison of the sensitivity of commercial APTT reagents in the detection of mild coagulopathies. Am J Clin Pathol 1984; 82: 436-439
• 21 Van den Besselaar AM H P, Evatt BL, Brogan DR, Triplett DA. Proficiency testing and standardization of prothrombin time: effect of thromboplastin, instrumentation, and plasma. Am J Clin Pathol 1984; 82: 688-699
• 22 Loeliger EA, Van der Hoeff-van HalemR, Van Halem-Visser LP. Thromboplastin calibration. Experience of the Dutch Reference Laboratory for Anticoagulant Control Thromb Haemostas 1978; 40: 272-287
• 23 Van den Besselaar AM H P, van Halem-Visser LP, Hoekstra-Schuman M, Van der Marel-van NieuwkoopW, Loeliger EA. Simplified thromboplastin calibration. Further experience of the Dutch Reference Laboratory for Anticoagulant Control Thromb Haemostas 1980; 43: 53-57
• 24 Loeliger EA, Lewis SM. Progress in laboratory control of oral anticoagulants. Lancet 1982; 2: 318-320
• 25 Andrews J, Sonquist J, Klem L. Multiple Classification Analysis. A report on a computer program for multiple regression using categorical predictors. Institute for Social Research, University of Michigan; Ann Arbor, MI: 1967. 2. 21-22