Dabigatran etexilate, a direct thrombin inhibitor, was recently introduced in clinical use to prevent thromboembolic events in patients with risk factors (such as non-valvular atrial fibrillation or deep vein thrombosis). Dabigatran is not recommended in patients with creatinine clearance below 30 mL/min. More than 85% of the drug is eliminated by the renal route while the remaining part via the enteral route. Acute renal failure can result in an unexpected increase in serum levels of Dabigatran. In elderly, renal dysfunction, co-morbidity, and concomitant intake of different drugs could make the dosage of Dabigatran challenging. We present a case of an elderly man who suffered a severe accidental dabigatran intoxication with acute liver toxicity recovered after dialytic treatment and Idarucizumab.

BACKGROUND: Pulmonary vein antrum isolation has proven to be a useful strategy for radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) worldwide. Anticoagulation therapies are necessary to avoid thromboembolic events before, during, and after RFCA of AF. During the RFCA procedure for AF, it is recommended that the activated coagulation time be maintained between 300 s and 400 s using heparin as an anticoagulation therapy.
METHODS: An 81-year-old man with symptomatic and drug-refractory paroxysmal AF underwent RFCA. We found that he had a severe heparin resistance during the RFCA procedure, and heparin had little effect on him. Thus, a direct thrombin inhibitor, Argatroban Hydrate®, was used instead of heparin for anticoagulation therapy during the procedure. Finally, the AF was successfully treated by RFCA without any complications. With a post-procedural inspection, we found that he had a Type-1 antithrombin III (AT-III) deficiency.
CONCLUSIONS: Atrial fibrillation is the most common clinical arrhythmia and is associated with significant clinical morbidity and increased mortality. An AT-III deficiency is a well-known autosomal dominant hereditary disease and congenital blood coagulation abnormality occurring in about 1:500-5000 live births that may sometimes cause thrombophilia. Thus, the physicians may occasionally come across patients with an AT-III deficiency in real-world clinical practice, even though they have no history of thrombophilia. Argatroban Hydrate® may be effective and feasible for anticoagulation therapy during the RFCA procedure of AF in patients with heparin resistance such as in this present case.

BACKGROUND: Dabigatran etexilate, was found to be effective for stroke prevention in patients with non-valvular atrial fibrillation. Given its predictable pharmacodynamics, laboratory monitoring is not required. Moreover, the risks of overall bleeding, intracranial bleeding, and life-threatening hemorrhage from dabigatran were found to be lower than warfarin. However, a higher risk of gastrointestinal (GI) bleeding caused by dabigatran from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial has raised the concern regarding clinical outcomes of patients with GI bleeding caused by dabigatran compared with warfarin.
METHODS: We retrospectively studied patients who were hospitalized for GI bleeding from dabigatran compared with warfarin with therapeutic anticoagulation monitoring during 2009 to 2012. Initial laboratory findings at presentation, number of transfused packed red blood cells (PRBCs), acute kidney injury, clinical outcomes (e.g., hypotension, tachycardia), length of stay, and death were compared.
RESULTS: Thirteen patients taking dabigatran and 26 patients who were on warfarin with therapeutic international normalized ratio (INR) were hospitalized during the study period. Demographic data and baseline parameters between the two groups were not significantly different except for concurrent aspirin use (84.6% vs. 50%, P=0.036). Fifty-four percent of patients taking dabigatran did not have activated partial thromboplastin time (aPTT) level performed at presentation (7/13). The patients with GI bleeding from warfarin received significantly more PRBC transfusions compared with the dabigatran group (1.92±2.2 vs. 0.69±1.1 units, P=0.024). After controlling for initial hemoglobin and history of chronic kidney disease by using multivariate analysis, the patients in the warfarin group were likely to receive more PRBC. Hypotension at presentation was more common in GI bleeding caused by warfarin than dabigatran but the P value was insignificant (30.8% vs. 7.7%, P=0.11). Nevertheless, no differences in clinical outcomes or length of stay were found between the two groups.
CONCLUSIONS: From our data, the patients with GI bleeding from dabigatran were likely to receive fewer PRBC transfusions; however, clinical outcomes and length of stay were comparable to GI bleeding caused by warfarin. Our sample generalizes to an elderly population (mean age of 77.9±10 years old) with creatinine clearance (CrCl) >30 mL/min who experience GI bleeding during chronic anticoagulation.