In reply
There are 2 major issues concerning heparin monitoring. As stated in our article and reemphasized by Mungall, the first is the ability to generalize results from previous trials. This requires the ability to achieve degrees of anticoagulation similar to those reported in earlier studies. The second issue involves optimizing heparin therapy.
Mungall references studies that used the activated partial thromboplastin time (aPTT) ratio to adjust heparin therapy as evidence to support this method of heparin monitoring. This presumes that an aPTT ratio adequately adjusts for the variability of different reagents. Of the 5 studies Mungall cites that used an aPTT ratio 1.5 to 2.5 times that of controls,1- 5 3 of these actually used an aPTT ratio of 1.5 to 2.0 with no evidence provided by the authors2- 4 that the aPTT ratio was established using heparin levels. The study by Hull et al5 used an aPTT ratio of 1.57 to 2.14, which was determined by protamine titration to correspond to heparin levels of 0.2 to 0.4 U/mL. As noted by Hirsh,6 "Because the slopes of the lines describing the relation between the aPTT and heparin levels with different reagents may not be parallel, responsiveness may not be standardized by expressing the aPTT result as a ratio." Brill-Edwards et al7 reported therapeutic aPTT ratios for 4 reagents corresponding to therapeutic heparin levels of 0.2 to 0.4 U/mL by protamine titration. These ratios were 2.3 to 3.0, 2.0 to 2.6, 1.8 to 2.5, and 1.9 to 2.5, respectively. Given this variation in aPTT ratios for different reagents, one cannot be certain that the degree of anticoagulation achieved in an individual patient is the same as that achieved in a reported trial based on the aPTT ratios.