Ecarin Clotting Time is Sensitive to Heparinoids: Comparison of Two Different Techniques

Abstract

Ecarin clotting time (ECT) is currently developed for the specific monitoring of antithrombin drugs, such as hirudin, argatroban, and hirulog. Aqueous reagent and dry chemistry technology have become available for ECT monitoring of antithrombin agents. Currently, many heparinoids and heparinomimetic drugs are being developed. These agents activate heparin cofactor 11 (HCII) and primarily mediate their effects by inhibiting thrombin. Atthough the test is specific for antithrombin agents, heparin cofactor II-mediated thrombin inhibitors are capable of prolonging the ECT. In order to study the relative effects of some of these agents, ECT was measured in human plasma supplemented with PI-88 (a sutfated pentomanose ; Progen Industries Limited. Sydney, Australia), aprosulate, pentosan polysulfate, dermatan Sulfate, unfractionated heparin (UFH), and recombinant hirudin (r-hirtadin). All agents were supplemented to the citrited-pooled plasma prepared from 10 healthy volunteers at a graded dosage of 0 to 100 These techniques gave comparable results for all of the agents used (PI-88. r2 = 0.99; r-hirudin, r2= 0.98, UFH. r2 =0.98; dermatan sutfate, r2 = 0.95; aprosulate, r2 = 0.95; pentosan polysulfate, r2 = 0.94). The relative anticoagulant effects of various agents used on ECT varied widely, exhibiting their potency in the following order: r-hirudin = pentosan polysulfate > dermatan sulfate > PI-88 > aprosulate > UFH. The sensitivity of ECT was adjusted by varying the concentration of the ecarin reagent. The results suggest that HCIImediated inhibition of thrombin can be detected by using ECT reagents.