The APTT Monitoring of Heparin - The ISTH/ICSH Collaborative Study

Summary

In an international collaborative study three candidate reference and the local APTT reagent have been tested with lyophilized plasmas containing heparin added in vitro and fresh plasmas from heparinized patients to determine whether it was possible to standardize APTT heparin monitoring.

The APTT responses of patients with thrombosis were much less to the same concentrations of heparin so only these plasmas were used to calibrate the reagents.

A calibration constant (b) was determined for each local APTT system from the orthogonal regression slope of the patients’ and normals’ plasmas. Although the calibration was based on relatively limited numbers of patients’ plasmas the results gave no consistent indication that this method of analysis with the reference preparations was incorrect. Two of the three candidate reference reagents performed almost equally well and one of these reagents is recommended as the APTT reference preparation. Use of a single b value for a brand of reagent for all laboratories is not advised. Each laboratory must perform its own local calibration. The adoption of a reference APTT reagent together with the use of orthogonal regression analysis would be a useful step to initiate APTT heparin monitoring standardization and to develop safe and effective local therapeutic ranges.

• References

• 1 Triplett DA. Heparin: Clinical use and monitoring. In: Laboratory Evaluation of Coagulation. Triplett DA. ed. American Society of Clinical Pathologists; Chicago, IL: 1982. pp 271-313
• 2 Thomson JM. The control of heparin therapy by the activated partial thromboplastin time: sensitivity of various thromboplastins to heparin. In: Standardization of Coagulation Assays: an overview. Triplett DA. ed. College of American Pathologists; Skokie, IL: 1982. pp 195-206
• 3 Poller L, Thomson JM. The partial thromboplastin (Cephalin) time test. J Clin Pathol 1972; 25: 1038-1042
• 4 Koepke J. The partial thromboplastin time in the CAP survey programme. Amer J Clin Path 1975; 63: 990-994
• 5 Refsum N, Abildgaard U. “Cephotest” in monitoring heparin therapy. Evaluation of a standardized activated partial thromboplastin time (APTT) test Farmakoterapi 1976; 1-2: 27-35
• 6 Shapiro GA, Huntzinger SW, Wilson JE. Variations among commercial activated partial thromboplastin time reagents in response to heparin. Am J Clin Pathol 1977; 67: 477-480
• 7 Barrowcliffe TW, Gray E. Studies of phospholipid reagents used in coagulation II: factors influencing their sensitivity to heparin. Thromb Haemost 1981; 46 (02) 634-637
• 8 Brandt JT, Triplett DA. Laboratory monitoring of heparin. Effect of reagents and instruments on the activated partial thromboplastin time Amer J Clin Path 1981; 76: 530-537
• 9 Mannucci PM. A multicentre evaluation of partial thromboplastin time reagents in the detection of mild haemophiliacs. In: Standardization of Coagulation Assays: an overview. Triplett DA. ed. College of American Pathologists; Skokie, IL: 1982. pp 165-177
• 10 Van den Besselaar AM H P, Meeuwisse-Braun J, Jansen-Gruter R, Bertina RM. Monitoring heparin therapy by the activated partial thromboplastin time - The effect of pre-analytical conditions. Thromb Haemost 1987; 57: 226-231
• 11 Basu D, Gallis A, Hirsh J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time. N Engl J Med 1972; 287: 324-327
• 12 Kirkwood TB L. Calibration of reference thromboplastins. Thromb Haemost 1983; 49: 238-244
• 13 Hermans J, Van den Besselaar AM H P, Loeliger EA, Van der Velde EA. A collaborative calibration study of reference materials for thromboplastins. Thromb Haemost 1983; 50: 712-717
• 14 Poller L, Thomson JM, Taberner DA, Clarke DK. The correction of coagulometer effects on international normalized ratios: a multicentre evaluation. Brit J Haemat 1984; 86: 112-117
• 15 Poller L, Triplett DA, Hirsh J, Carroll J, Clarke K. The value of plasma calibrants in correcting coagulometer effects on International Normalized Ratios - An International Multicentre Study. Amer J Clin Path. (in press)
• 16 Patefield WM. On the information matrix in the linear functional relationship problem. Applied Statistics 1977; 26: 69-70
• 17 Van der Velde EA. Orthogonal regression equation. Thromboplastin calibration and oral anticoagulant control. Ed: Van den Besselaar AM H P, Gralnick HR, Lewis SM. 1984: 25-39 Marinus Nijhoff Publishers; The Hague: