Effect of Phenprocoumon on Monitoring of Lepirudin, Argatroban, Melagatran and Unfractionated Heparin with the PiCT Method

Abstract

Prothrombinase-induced clotting time (PiCT) is a clotting-time test for heparins and direct thrombin inhibitors to reduce drawbacks of aPTT. Effects of the direct thrombin inhibitors lepirudin, argatroban, melagatran and of unfractionated heparin (UFH) were investigated in normal and oral anticoagulant plasma samples. Lepirudin showed potentiating interferences with phenprocoumon effects. Melagatran, argatroban and UFH delivered distinct linear additive effects in both plasma sample groups. PiCT ratio reduces differences between both groups with UFH, and argatroban inhibitor-receptor-binding mode plays a role in interaction patterns.

Prothrombinase-Induced Clotting Time Assay for Determination of the Anticoagulant Effects of Unfractionated and Low-Molecular-Weight Heparins, Fondaparinux, and Thrombin Inhibitors

“…34 The effect of warfarin on the PiCT was examined previously by Fenyvesi et al 33 Warfarin pretreatment had only a minor effect on the monitoring of UFH using PiCT. In contrast, prothrombin inhibition by recombinant hirudin or other substances led to considerably prolonged clotting times in warfarin-pretreated subjects compared with "normal" subjects.…”

“…33 Recently, it was also shown that PiCT may be used for newer compounds such as sulfaminoheparosans 39 and direct FXa inhibitors. 34 For the latter, however, it may be advantageous to perform PiCT …”

“…[32][33][34] However, a detailed evaluation of its main components and an overview of its applications has not been published.…”

Anticoagulation With Argatroban for Elective Percutaneous Coronary Intervention: Population Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Relationship of Coagulation Parameters

“…The activated partial thromoplastin time (aPTT) is an accepted coagulation parameter suitable to monitor argatroban in most other clinical applications with the lower doses 6 , 11 . However, the ecarin time (ECA‐T) is a more specific monitoring parameter for DTIs, although it is not yet standardized for routine clinical practice 11 , 12 . The prothrombinase‐induced clotting time (PiCT) is also prolonged by argatroban and has been suggested as an alternative coagulation parameter to monitor argatroban therapy 12 .…”

'Argatroban' Monitoring in Human Plasma: aPTT and PiCT Studies on QCM-D vs 'Gold Standard'

“…They are easy bioavailable, and they have longer plasma half-life and a more predictable anticoagulant response. Furthermore, they have less adverse after- for monitoring all anticoagulants 3,4 and to reduce the flaws of aPTT [5][6][7][8][9][10] .…”