ABC | Volume 114, Nº4, Suplement, April 2020

Case Report Adar et al. Dabigatran and massive pleuropericardial effusion Arq Bras Cardiol 2020; 114(4Suppl.1):13-15 chain reaction (PCR) and microorganisms ( Mycobacterium tuberculosis ). There was no pericardial effusion on repeat echocardiography performed on the following day after pericardiocentesis (Figure 1C). According to the modified Light criteria, pericardial effusion had exudative characteristics. Thoracentesis was then performed, and 2 L of pleural fluid was drained out. Biochemical tests were again consistent with exudative fluid. Inflammatory, rheumatological, infection and cancer screening markers were all negative. Renal functions improved after fluid replacement, pericardiocentesis, and discontinuation of indomethacin therapy. His overall status improved significantly, and no other complications were noticed. On the 8 th day of hospitalization, he was discharged with subcutaneous enoxaparin. Discussion This is the first reported case of massive pleuropericardial effusion associated with concomitant use of dabigatran and indomethacin. For the following reasons, we thought that dabigatran toxicity was the most plausible cause of pleuropericardial effusion in the present case. (1) Presence of hemorrhagic pleuropericardial effusion, (2) development of effusions after development of acute renal failure, (3) high APTT (91.4 seconds) and INR (2.5) levels at presentation, 2 and, finally, (4) no other reasons to explain hemorrhagic pleuropericardial effusion. Dabigatran is an active metabolite derived from the hydrolysis of dabigatran etexilate. It inhibits both free and clot-bound thrombin. The half-life of dabigatran is 12–14 hours and it is largely excreted via the kidneys. 3 Current guidelines recommend regular follow-up of kidney function in these patients. 4 In the present case, the patient experienced acute renal failure after initiation of indomethacin, a nephrotoxic agent, during dabigatran therapy. We found 12 cases of hemopericardium associated with dabigatran toxicity. 1,5-9 Indication for dabigatran was stroke prevention in atrial fibrillation for all reported cases. Consistent with our findings, 7 (58%) (,7,10-13 of these cases had acute renal failure at presentation and 4 (33%) 5,7-9 experienced hemopericardium two months after initiation of dabigatran. The absorption of dabigatran etexilate is mediated by the p-glycoprotein (P-gp). Gastrointestinal tract-based P-gb interactions may interfere with the absorption of dabigatran. Ye CG et al. reported that indomethacin may inhibit P-gp by decreasing its expression and/or direct inhibition of its activity. 14 Thus, co-administration with indomethacin may have contributed to dabigatran toxicity in our case. Idarucizumab, a humanized monoclonal antibody fragment which binds to dabigatran with high affinity without increasing thrombotic events, is used for reversing the anticoagulant effect of dabigatran in patients with life-threatening bleeding conditions. 15 The effect of dabigatran was successfully reversed with idarucizumab in the present case. Two hours after initiating idarucizumab, the APPT value was found to fall from 91.4 seconds to 44 seconds. In addition, no bleeding or thrombotic complications occurred after pericardiocentesis. Conclusion Pleuropericardial effusion shouldbe considered inpatientswith newly developed dyspnea who are under dabigatran treatment. The risk of major bleeding may increase when indomethacin is used concomitantly with dabigatran. When prescribing dabigatran, all patients should be informed about the potential interactions with other drugs. Potential risks of concomitant nephrotoxic medications should be considered in all patients receiving dabigatran and, if possible, these agents should be avoided, particularly in patients with multiple risk factors for bleeding. Finally, patients who develop bleeding under treatment with dabigatran should be investigated for co-medications. Author contributions Conception and design of the research: Adar A, Onalan O; Acquisition of data and Analysis and interpretation of the data: Adar A, Onalan O, Cakan F; Writing of the manuscript: Adar A, Cakan F; Critical revision of the manuscript for intellectual content: Onalan O. Figure 2 – Blood-red non-coagulating pericardial fluid. 14