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Lamotrigine triggers the contact phase of coagulation Volume 14, issue 2, June 2012

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epd.2012.0503

Auteur(s) : Thomas W Stief thstief@med.uni-marburg.de

Institute of Laboratory Medicine and Pathobiochemistry, University Hospital, Baldingerstr, D-35043 Marburg, Germany

To the editor,

Lamotrigine has been described to be able to prolong activated partial thromboplastin time (aPTT) and produce skin eruption (Yeom et al., 2011). Lamotrigine is a trigger of the contact phase of coagulation, the intrinsic system of coagulation (Stief, 2012); plasma concentrations of about 2 mg/L lamotrigine, via folding of factor 12 into activated factor 12 (figure 1), enhance the recalcified intrinsic thrombin generation two-fold. This is of particular pathophysiological importance if the respective patient suffers from liver insufficiency, because the hepatocytes normally clear activated factors of the contact phase out of the circulation (Loureiro-Silva et al., 1993). Prolongation of aPTT together with skin eruptions is typical of massive activation of the contact phase, characterised by consumption of contact factors and systemically circulating kallikrein, an important pro-inflammatory compound (Tomita et al., 2012) that could cause the observed skin eruptions. Patients who are susceptible to lamotrigine-induced contact activation could be identified by performing an ultra-specific, ultra-sensitive thrombin generation assay, such as the RECA (recalcified coagulation activity assay) and by checking liver sufficiency (bilirubin, ALT, and γGT) before exposure to the drug. Lamotrigine in such susceptible patients should be combined with prophylactic concentrations of low-molecular-weight heparin (Stief, 2011).