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

Abstract 

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 (0–4.0µg/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 1.0μg/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.

Abbreviations: APTT, activated partial thromboplastin time, LA, lupus anticoagulant, ECA^®, ecarin chromogenic assay, Anti-FIIa, chromogenic Anti-Factor IIa assay, PiCT^®, prothrombinase-induced clotting time, dTT, plasma diluted thrombin time, DTI, direct thrombin inhibitor, HIT, heparin-induced thrombocytopenia, CPB, cardiopulmonary bypass surgery, INR, international normalized ratio, AT, antithrombin

Keywords: Direct thrombin inhibitor, Ecarin, Hirudin, Lupus anticoagulant, Oral anticoagulant