Insufficient anticoagulation with dabigatran in a patient with short bowel syndrome

http://dx.doi. org/10.1160/TH14-02-0104 Thromb Haemost 2014; 112: 419–420 Dear Sirs, In the past years, several novel oral anticoagulants (NOACs) with direct mechanisms of action were introduced into clinical practice. While the amount of information on their efficacy compared to vitamin K antagonists in different indications is currently exponentially growing (1), there are still several areas of uncertainty regarding their use in specific clinical settings including patients with short bowel syndrome (SBS). An 81-year-old Caucasian female patient was admitted to our hospital with acute onset dysarthria and left sided central facial palsy. The patient had a long history of arterial hypertension and heart failure with preserved ejection fraction and had been treated with lercanidipine, clonidine, metoprolol, triamterene, hydrochlorothiazide, furosemide, isosorbide mononitrate, and pantoprazole for several years. Three moths before admission she had suffered a mesenteric ischaemia with ileal gangrene and diffuse peritonitis. Consequently, her small intestine had to be partially removed, leaving 90 cm jejunum and 10 cm ileum in situ. The aetiology of the ischaemia was related to a systemic embolism into the superior mesenteric artery secondary to atrial fibrillation (AF), which had been unknown until that point. Subsequently, oral anticoagulation with the direct thrombin inhibitor dabigatran etexilate was initiated (CHA2DS2-VASc score 7) (2). Due to the advanced age of the patient, a dosage of 110 mg administered twice daily was chosen. Computed tomography of the brain on the day of admission showed no signs of acute ischaemia or intracranial bleeding. Duplex sonography revealed no haemodynamically relevant arterial stenosis, and 24-hour (h) electrocardiography confirmed AF. Despite the inconspicuous brain imaging, the distinct clinical symptoms combined with proven AF led to the diagnosis of acute cardioembolic stroke of the right middle cerebral artery territory. Kidney function as estimated by the CockcroftGault equation (3) was decreased (range 37 ml/min to 43 ml/min) during the stay at hospital. Before the intake of dabigatran etexilate, i.e. at trough, the international normalised ratio (INR) and activated partial thromboplastin time were within normal range. In order to elucidate the stroke aetiology, peak and trough plasma concentrations of dabigatran were measured with the HEMOCLOT thrombin inhibitor assay (4) 2 h (peak) and 12 h (trough) after witnessed medication intake. The anticoagulant therapy was changed from dabigatran etexilate to the direct factor Xa inhibitor rivaroxaban. Because of the history and high risk of the patient we decided to use the higher standard dose of 20 mg administered once daily. After showing continuous improvement of her neurological symptoms, the patient was uneventfully discharged on day 5. As both peak and trough plasma concentrations of dabigatran were low (▶ Table 1), we subsequently analysed three single nucleotide polymorphisms (SNPs) that were recently significantly linked to plasma concentrations and pharmacokinetics of dabigatran in patients with AF (5). As shown in ▶ Table 2, the patient was a heterozygote carrier of minor alleles