Analysis of Anticoagulant Effect of Unfractionated Heparin by Using Thrombin Generation Assay in Vitro

Abstract

Unfractionated heparin (UFH) is widely used in the treatment and prophylaxis of thrombosis. The anticoagulant effect of UFH is monitored according to activated partial thromboplastin time (APTT). However, there are reports of cases in which hemorrhagic complications develop despite APTT being maintained within the therapeutic range. This indicates there are problems with the monitoring method using APTT during UFH treatment. To assess the actual anticoagulant effect in UFH therapy using APTT as a monitoring method, we investigated changes in APTT and thrombin generation (TG) potential in vitro with the addition of UFH to samples from 10 healthy adults. There were large individual differences in the degree of APTT prolongation with the addition of UFH to samples from healthy adults. Furthermore, individual differences in the degree of TG change exceeded those in APTT in 7 subjects with comparable APTT changes caused by UFH (coefficients of variation: 2–5% for APTT, 10–50% for TG potential). Thus, with UFH treatment, there are large individual differences in the degree of TG inhibition even when APTT is within the appropriate range for coagulation control. These findings provide invaluable information for resolving the problem of hemorrhagic complications during UFH treatment based on the current APTT method.