Mini-Review A review of the effects of the oral direct thrombin inhibitor ximelagatran on coagulation assays Stefan C. Carlsson a, * , Christer Mattsson a , Ulf G. Eriksson a , Troy C. Sarich b , Karin Wa ˚hlander a ,A ˚ sa Eliasson a , Bjo ¨rn W. Karlson a , Sunita B. Sheth b , Peter Held a a AstraZeneca R&D Mo¨lndal, Mo¨lndal, Sweden b AstraZeneca LP, Wilmington, DE, USA Received 5 May 2004; received in revised form 30 June 2004; accepted 1 July 2004 Available online 14 August 2004 Introduction Ximelagatran is the first oral agent in the new anticoagulant drug class of direct thrombin inhibitors (DTIs) 1 and has been clinically developed using fixed dosing without the use of coagulation monitoring. While coagulation monitoring is not required with ximelagatran, effects on various coagulation assays have been studied. This paper describes the effects of melagatran, the active form of ximelagatran, on different coagulation assays and considers their possible use in special clinical situations. Ximelagatran has been evaluated in a range of potential indications, including the prevention of venous thromboembolism (VTE) in orthopaedic surgery patients [1—4], the prevention of stroke associated with atrial fibrillation [5—7], the treatment [8] and long-term secondary preven- tion [9] of VTE, and prevention of major cardiovascular events following acute myocardial infarction [10]. In all indications, fixed-dose regimens of ximelagatran have provided effective 0049-3848/$ - see front matter D 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2004.07.001 KEYWORDS Activated clotting time; Activated partial thromboplastin time; Blood coagulation tests; Ecarin clotting time; Oral direct thrombin inhibitors; Prothrombin time; Thrombin clotting time; Ximelagatran Abbreviations: ACT, activated clottingtime; APTT, activated partial thromboplastin time; DTI, direct thrombin inhibitor; ECT, ecarin clotting time; FV, factor V; IC 50 , plasma concentration of anticoagulant agent that doubles the clotting time compared with anticoagulant-free plasma; INR, International Normalized Ratio; ISI, International Sensitivity Index; LC, liquid chromatog- raphy; LMWH, low-molecular-weight heparin; PiCT, prothrombi- nase-induced clotting time; PT, prothrombin time; PTC, prothrombin complex; TT, thrombin clotting time; UFH, unfrac- tionated heparin; VTE, venous thromboembolism. * Corresponding author. Integrative Pharmacology, DISCOV- ERY, SE431 83 Mo ¨lndal, Sweden. Tel.: +46 31 776 20 17; fax: +46 31 776 37 66. E-mail address: Stefan.c.carlsson@astrazeneca.com (S.C. Carlsson). 1 [World Health Organization Anatomical Therapeutic Chem- ical (ATC) classification: ximelagatran B01AE05; melagatran B01AE04]. Thrombosis Research (2005) 115, 9---18 intl.elsevierhealth.com/journals/thre