Comparison of monitoring methods for lepirudin: Impact of warfarin and lupus anticoagulant

Introduction: Appropriate monitoring methods are needed for lepirudin, a direct thrombin inhibitor, as activated partial thromboplastin time (APTT) may under- or overestimate lepirudin. We compared APTT with thrombin-specific methods, also in the presence of warfarin and lupus anticoagulant (LA). Materials and Methods: Lepirudin i.v. was assessed in five patients (35 samples) and in vitro spiked plasma pools: normal control and plasma containing warfarin and LA. Wide dose-responses to lepirudin (0-4.0 mu g/ml) were studied with APTT (Actin FSL (R)), Ecarin Chromogenic Assay (ECA (R)), chromogenic Anti-Factor IIa (Anti-FIIa, Hirudin Activity Assay (R)), Prothrombinase-induced Clotting Time (PiCT (R)), and plasma diluted Thrombin Time (dTT). Results: APTT both under- and overestimated in vivo lepirudin doses according to ECA (R) and Anti-FIIa, which matched completely in various plasma pools at all lepirudin doses (r=0.99). APTT and PiCT (R) underestimated high lepirudin concentrations in normal plasma, and in LA-positive plasma they were invalid. In all plasma pools, dTT (1:16) indicated lepirudin well up to 1.0 mu g/ml. Conclusions: ECA (R) or Anti-FIIa are preferable for lepirudin monitoring, because neither warfarin nor LA, interfered with them, and they were the most precise methods even for supratherapeutic doses. PiCT (R) reflected co-inhibition of FIIa and FXa, but was disturbed, like APTT, by LA and high lepirudin. Further experience of laboratory monitoring is valuable in this era of new anticoagulants. (C) 2010 Elsevier Ltd. All rights reserved.