Therapeutic ranges and laboratory monitoring of heparin using the APTT

Unfractionated heparin (UFH) therapy is used for many medical treatment protocols including venous thromboembolism. Therapeutic levels must be reached rapidly and maintained within defined ranges. The activated partial thromboplastin time (aPTT) is the most common laboratory test used to monitor UFH therapy, but is known to have considerable variability so that establishing heparin therapeutic ranges (HTR) is problematic. This study analyses different methodologies to determine UFH aPTT therapeutic ranges and assist in laboratory implementation of optimised protocols. A total of 73 samples were obtained from patients receiving UFH therapy at one hospital site. The HTR was determined using three methods: (a) calibration of the aPTT to 0.3-0.7IU/mL of anti-factor Xa activity (ex vivo method); (b) application of 1.5 - 2.5 times median control aPTT and (c) using normal pooled plasma spiked with heparin (in vitro method). Different aPTT reagents were also evaluated, and results were compared with ex vivo results from another hospital site. Discordance was noted between the three HTRs and different aPTT reagents showed varying sensitivity to UFH. The therapeutic status of patients was most discordant using the 1.5 - 2.5 times HTR, whilst the spiked curve approach revealed a falsely elevated HTR. It can be concluded that ex vivo methods using the aPTT and the anti-factor Xa HTR equivalent to 0.3-0.7IUmL, whilst yielding variability, showed the best concordance with the current HTR for the same lot number of aPTT reagent. The variability between the sensitivity of aPTT reagents supports the recommendation that HTRs be re-evaluated for reagent and lot. The 1.5 - 2.5 x aPTT and in vitro spiked curve HTRs are not suitable substitutes to the ex vivo method.