The effect of instrumentation and laboratory site on the accuracy of the APTT‐based heparin therapeutic range

Abstract

Summary Background Monitoring of unfractionated heparin therapy by activated partial thromboplastin time using the ex vivo method for determining the heparin therapeutic range (HTR) is the standard of practice. Many extrinsic and intrinsic factors influence accuracy of the HTR. This study investigates the affect of instrumentation and laboratory site on the accuracy of the ex vivo HTR method. Methods Patients on unfractionated heparin are used to determine the HTR by published guidelines. Various instruments and different laboratories are compared to investigate the affect of these variables on the HTR. Results The HTR is the same when the same model of instrument or even different models (same methodology) are used in the same laboratory. However, a significant clinical difference is observed when different hospital laboratories using same lot and instrument model are compared. Conclusions The ex vivo method for HTR is the best protocol currently available. The HTR should be determined and averaged on all of the same method instruments used in the laboratory. However, determination of the HTR in different laboratories should not be shared.

Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin Therapy: Issues and Recommendations

“…The poor correlation between APTT and antifactor Xa heparin assay may be attributed to several different variables. 1,[23][24][25][26][27] Biological (patient) variation among samples (increased acute phase proteins [factor VIII and fibrinogen], concurrent use of oral anticoagulants, pregnancy, and pathologic conditions) can contribute to this reduced correlation. 1,19,22,23 The observed discordance may also be due to preanalytical variables (drawing and processing of sample, time spent as whole blood or freezing the sample with residual platelets).…”

“…1,[23][24][25][26][27] Biological (patient) variation among samples (increased acute phase proteins [factor VIII and fibrinogen], concurrent use of oral anticoagulants, pregnancy, and pathologic conditions) can contribute to this reduced correlation. 1,19,22,23 The observed discordance may also be due to preanalytical variables (drawing and processing of sample, time spent as whole blood or freezing the sample with residual platelets). 1,19,[22][23][24][25][26] Analytical variables can also contribute to this poor correlation, including APTT reagent used, type of heparin assay, AT level in the patient's plasma, heparin calibrators used, or type of heparin molecules present in the blood.…”

“…1,19,22,23 The observed discordance may also be due to preanalytical variables (drawing and processing of sample, time spent as whole blood or freezing the sample with residual platelets). 1,19,[22][23][24][25][26] Analytical variables can also contribute to this poor correlation, including APTT reagent used, type of heparin assay, AT level in the patient's plasma, heparin calibrators used, or type of heparin molecules present in the blood. [27][28][29][30]…”

“…3). 23,31 This variability between lots may be seen with all commercial reagents so far evaluated. Therefore, the HTR must be redetermined or verified for each new lot of APTT.…”

Should we abandon the APTT for monitoring unfractionated heparin?

“…The sensitivity of APTT reagents to heparin varies and there is no system for normalizing this although local calibration can be performed. (9)(10)(11). APTT reagents from different manufacturers, and even different batches, show considerable and clinically important variation when heparin concentration by protamine assay is compared with APTT ratio (12).…”