Evaluation of the activated partial thromboplastin time (APTT) sensitivityto heparin using five commercial reagents: Implications for therapeutic monitoring

Heparin is an effective drug for prevention and treatment of thromboembolic conditions. Although several biological assays have been proposed for moni toring unfractionated heparin therapy, the measurement of the activated par tial thromboplastin time (APTT) is the most widely employed test, and the o verall risk of thromboembolic episodes was markedly reduced by maintaining APTT ratios above 1.5. However, the adjustment of the heparin therapy on th e basis of APTT presents several questions which are still unresolved. Majo r discrepancies were found in APTTs performed using different reagents in b oth ex vivo and in vitro heparinized samples and occasionally with differen t lots of the same reagents; poor correlation was observed between APTT val ues and plasma heparin concentrations. In order to gain further insights in to this phenomenon, we analysed the sensitivity to heparin of five commerci al reagents for APTT measurement in 19 ex vivo heparinized samples. Differe nces were observed; correlation coefficients ranged from 0.820 to 0.985 and slopes of linear regressions from 0.26 to 1.14. Moreover, unsatisfactory c orrelations were obtained when APTT ratios were compared with heparin plasm a concentrations in the same patients' samples. In the heparin therapeutic range of 0.35 - 0.70 U/ml, reagent-dependent differences were observed in t he corresponding APTT values. These results point out a critical role of th e assay methodology in monitoring heparin therapy by APTT. We suggest that reference materials and methods should be urgently identified, a universall y agreed scale for reporting results should be established and reference ra nges for the unfractionated heparin therapy should be reconsidered taking o n account the reagent employed.