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

IntroductionAppropriate 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 MethodsLepirudin 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 µg/ml) were studied with APTT (Actin FSL®), Ecarin Chromogenic Assay (ECA®), chromogenic Anti-Factor IIa (Anti-FIIa, Hirudin Activity Assay®), Prothrombinase-induced Clotting Time (PiCT®), and plasma diluted Thrombin Time (dTT).ResultsAPTT both under- and overestimated in vivo lepirudin doses according to ECA® and Anti-FIIa, which matched completely in various plasma pools at all lepirudin doses (r = 0.99). APTT and PiCT® 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 μg/ml.ConclusionsECA® 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® 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.