Comparative study and relevant exploration on methods for establishing unfractionated heparin therapeutic range (HTR) based on APTT.

BACKGROUND: Building heparin therapeutic range (HTR) to monitoring unfractionated heparin (UFH) is important, while the two methods for establishing HTR exhibit discrepancies and yield different HTR results. The manifestations and underlying factors contributing to these discrepancies remain areas of uncertainty.

METHODS: APTT, anti-Xa activity, and various coagulation factors, as well as FIB and AT, were measured in ex vivo samples from 41 patients receiving UFH treatment. The ex vivo curves were fitted using an exponential model, and HTR was calculated. Additionally, normal pooled plasma (NPP) from 38 healthy individuals and heparin sodium were used to prepare spiked samples in vitro, and calculate HTR in the same manner. Subsequent analyses of influencing factors followed a similar approach. Furthermore, three different APTT detection systems, comprising reagents and corresponding instruments from three manufacturers (Succeeder, HemosIL, and Stago), were used to test spiked heparinized samples and obtain the corresponding HTR results.

RESULTS: The HTR established using the ex vivo method was generally lower than that obtained with the in vitro method, with the discrepancy becoming more pronounced as UFH concentration increased. The levels of several coagulation factors in patient samples, particularly factor VIII and factor XII, significantly influenced HTR outcomes, with higher coagulation factor levels associated with lower HTR. Variability in coagulation factor levels among samples may be one of the factors contributing to the differences between the ex vivo and in vitro methods. Additionally, the interindividual variability observed within the therapeutic UFH range using the ex vivo method may also be related to specific coagulation factors. When establishing HTR using three different APTT detection systems in our laboratory, no substantial differences were observed. However, compared to the other two systems, the Stago group exhibited a relatively lower upper HTR limit and a narrower HTR range.

CONCLUSIONS: The difference between the ex vivo and in vitro methods may be influenced by variations in the levels of several coagulation factors, primarily factor VIII and factor XII. When making clinical decisions related to heparin monitoring, the distinct characteristics of the ex vivo and in vitro methods, as well as potential discrepancies caused by biases in patient samples, should be taken into account. Additionally, when switching detection reagents, it is important to recognize the potential impact of different reagent compositions on results and to establish an HTR that aligns with the new detection system in a timely manner.