Reactions Weekly | 2021
Dabigatran etexilate
Abstract
Bleeding disorders accompanied by acute kidney injury secondary to nephropathy: case report A 71-year-old man experienced epistaxis, haemoptysis and acute kidney injury (AKI) secondary to anticoagulant-related nephropathy (ARN) during anticoagulant therapy with dabigatran etexilate for atrial fibrillation. The man was hospitalised due to severe AKI accompanied by multiple overt bleedings (current presentation). He had multiple morbidities, including atrial fibrillation following pacemaker implantation due to atrioventricular block in May 2017, for which he had been receiving oral dabigatran etexilate [dabigatran] 150mg twice a day. Of note, his renal function had been normal at dabigatran etexilate initiation. Later, in March 2018, he developed persistent fatigue following a flu-like syndrome, with occasional episodes of epistaxis, haemoptysis and haematuria. Blood tests performed following admission, on 26 March 2018, revealed anaemia with haemoglobin (Hb) levels of 9.4 g/dL, as well as severe renal failure with serum creatinine (sCr) levels of 5.12 mg/dL. Hence, he was urgently referred to emergency service. On 29 March 2018, in the emergency room, laboratory analyses revealed the following: sCr 6.4 mg/dL, activated partial thromboplastin time 70 seconds, INR 2.3 and Hb 8 g/dL. The man was administered idarucizumab as an antidote to over-anticoagulation with dabigatran etexilate. Chest CT scan demonstrated bilateral localised ground glass lesions with partly pseudonodular pattern. Abdominal sonography revealed no significant abnormalities. Rapidly progressive glomerulonephritis with a lung-kidney syndrome was suspected; hence, tests for antiglomerular membrane antibodies (anti-GBMAb) and antineutrophil cytoplasmic antibodies (ANCA) were urgently performed. Soon after ELISA confirmation of positivity for anti-myeloperoxidase antibodies (anti-MPO titre of 61.4 RU/mL), he was transferred to the nephrology unit on 30 March 2018, with a hypothesis of new onset ANCA-associated vasculitis (AAV). Based on this hypothesis, he received empirical therapy with methylprednisolone on 5 April 2018 and the day after. Renal ultrasound revealed normal-sized kidneys with increased cortical echogenicity, and a slight reduction in corticomedullary differentiation. Since the chest images were not entirely suggestive for haemorrhagic alveolitis, and given the absence of systemic signs and symptoms, as well as the negativity of anti-GBMAb and low levels of inflammatory markers (CRP 9 mg/L), the hypothesis of AAV was revised. The morphology of urine RBCs confirmed glomerular haematuria. A renal biopsy was performed on 6 April 2018, when sCr peaked at 7.9 mg/dL and coagulopathy was reversed safely. After a few hours, he developed loin pain, accompanied by a large self-limiting perirenal haematoma. Biopsy findings revealed complex features: prominent acute tubular injury with several obstructive RBC casts, mesangial matrix expansion and hypercellularity at glomerulus, interstitium with blood extravasation and moderate inflammation, arteriolar hyalinosis and arteriosclerosis. Immunofluorescence demonstrated 4+positivity for IgA; hence, AAV was excluded, and he was diagnosed with underlying IgA nephropathy (Oxford score M1, E1, S1, T0 and C0) with possibly iatrogenic acute tubularinterstitial damage. In order to promote a ’flushing’ effect within tubules, he received mannitol on 9 April 2018, with a rapid and progressive decrease in sCr. Twenty-four hours urinary output persistently remained above 1.5–1.8L, since his admission. Sodium bicarbonate was added due to metabolic acidosis (arterial blood gas analysis revealed the following: pH 7.34, pCO2 38mm Hg, pO2 85mm Hg, HCO3 20 mmol/L and BE -4 mmol/L), and subsequently maintained to force alkaline diuresis (urinary pH increased from 5.0 to 8.0 prior to discharge), and to prevent occurrence of protein (haemoglobin) casts. A prednisone taper was added. He was discharged with sCr of 3.3 mg/dL, glomerular proteinuria 3.1 g/24 hours, and plenty of erythrocytes per high power field (HPF) at urine sediment. Dabigatran etexilate was replaced with enoxaparin sodium [enoxaparin], until he underwent percutaneous closure of his left atrial appendage in June 2018. His renal function progressively improved over time, with a remarkable decrease in proteinuria and haematuria. Prednisone was discontinued in September 2018, when his sCr was 1.2 mg/dL, proteinuria was 0.9 g/24h and 1–5 RBC per HPF were detectable. The development of epistaxis, haemoptysis and AKI secondary to ARN were thus attributed to anticoagulant therapy with dabigatran etexilate.