Abstract
Although the activated partial thromboplastin time (aPTT) remains the most widely used method for monitoring unfractionated heparin (UFH) therapy, it is affected by a number of preanalytic, analytic, and biological variables, which undermine both its accuracy and precision. In an effort to improve the accuracy and precision of laboratory monitoring of UFH, the College of American Pathologists (CAP) and the American College of Chest Physicians (ACCP) have issued guidelines recommending that the therapeutic range of the aPTT be defined in each laboratory through correlation with a direct measurement of heparin activity such as the factor Xa inhibition assay (anti-FXa). Whether and to what extent this approach enhances the precision of UFH monitoring has not been reported. We conducted a cross-validation study among 4 CAP-accredited coagulation laboratories to assess the interlaboratory precision of the anti-FXa-correlation method. An aPTT and anti-FXa were performed in each laboratory on plasma samples from 44 inpatients receiving UFH. Interlaboratory precision of the anti-FXa-correlation method was compared to that of the traditional 1.5–2.5 times the upper limit of normal (ULN) method for defining the therapeutic aPTT range. Modest to poor intralaboratory correlation between the aPTT and anti-FXa was observed in each of the 4 laboratories. The coefficients of determination (R2) ranged from 0.1962 to 0.6964. In accordance with CAP guidelines, the anti-FXa-derived therapeutic aPTT range was defined by linear regression corresponding to a range of anti-FXa activity of 0.3 – 0.7 units/ml. In each laboratory, the range defined by this method was broader than that defined using the ULN method. In 3 of the laboratories, the therapeutic range defined by the anti-FXa-correlation method extended more than 20 seconds beyond the upper limit of the therapeutic range defined by the ULN approach. Based on the laboratory-specific therapeutic ranges defined by both methods, samples were segregated into therapeutic category [i.e. below therapeutic (BT), therapeutic (T), or above therapeutic (AT)]. Using the ULN method, there was agreement among all 4 laboratories regarding the therapeutic category in 22 (50%) samples, whereas consensus was achieved in only 7 (16%) samples with the anti-FXa-correlation method. Furthermore, 3 (7%) samples were simultaneously determined to be BT and AT in different laboratories by the anti-FXa-correlation method, suggesting that the dose of UFH might be increased in one center and decreased in another for the same patient encounter. This striking discrepancy was not observed with the ULN method. In conclusion, the anti-FXa-correlation method for defining the therapeutic range of the aPTT does not enhance the interlaboratory precision of UFH laboratory monitoring and may be inferior to the ULN method in this regard. Clinical studies are needed to assess the impact of these findings on patient safety.
Design and Implementation of an Anti–Factor Xa Heparin Monitoring Protocol
