Comparison of monitoring methods for lepirudin: impact of warfarin and lupus anticoagulant.
BACKGROUND
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).


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.
Salmela
Birgitta
B
Coagulation Disorders, Division of Hematology, Department of Internal Medicine, Finland.
Joutsi-Korhonen
Lotta
L
Saarela
Ellen
E
Lassila
Riitta
R
D002863:Chromogenic Compounds; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors; D016903:Drug Monitoring / Q000379:methods*; D010450:Endopeptidases; D005343:Fibrinolytic Agents; D006629:Hirudins / Q000493:pharmacokinetics*; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000494:pharmacology*; D008666:Metalloendopeptidases; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D014859:Warfarin / Q000494:pharmacology*
D002863:Chromogenic Compounds; D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D006629:Hirudins; D016682:Lupus Coagulation Inhibitor; D011994:Recombinant Proteins; D014859:Warfarin; D010450:Endopeptidases; C478420:FIIa; D008666:Metalloendopeptidases; C020097:ecarin; C083544:lepirudin