RESUMO
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 (0-4.0microg/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). RESULTS: APTT 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 1.0microg/ml. CONCLUSIONS: ECA 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.