Successful thrombolysis for acute ischaemic stroke in haemodialysis

NDT Plus (2010) 3: 576–578 doi: 10.1093/ndtplus/sfq154 Advance Access publication 24 August 2010 Case Report Successful thrombolysis for acute ischaemic stroke in haemodialysis Albert Power, Steven Moser and Neill Duncan Haemodialysis Research Group, Imperial College Kidney and Transplant Institute, West London Renal and Transplant Centre, Hammersmith Hospital, London, UK Abstract Stroke is a leading cause of death worldwide and is associated with significant morbidity in survivors. Early thrombolytic therapy in acute ischaemic stroke has been shown to dramatically improve patient outcomes. Although the age-adjusted incidence of stroke is 5–10 times greater in haemodialysis patients, the use of thrombolysis for this indication in this group of patients has not been described to date. We present a case where alteplase was used successfully for acute ischaemic stroke in a patient established on maintenance haemodialysis in the setting of an international randomized controlled trial and advocate caution with the use of systemic thrombolytics despite the favourable outcome seen with this case. Keywords: alteplase; haemodialysis; stroke Introduction Intravenous rtPA remains the only proven treatment for acute ischaemic stroke in the general population. Patients with end-stage renal disease (ESRD) on dialysis have a 5–10-fold higher incidence of stroke than the general population with an overall incidence rate of 13–33 per 1000 patient-years [1,2]. Haemorrhagic stroke subtype is more frequent in patients on dialysis (≥ 30%) [3]. This may reflect the bleeding diathesis of uraemia [4] as well as the effects of anticoagulation for vascular access and dialysis circuit patency, the prevalence and degree of hypertension, and the established ethnic variations. Patients with ESRD have been traditionally excluded from the large prospective randomized controlled trials that form the evidence base for treatment of vascular disease, including stroke, in the general population. The paradoxical effect of this apparent ‘renalism’ [5] is to potentially restrict access to beneficial therapies in a cohort that would have derived the greatest benefit. In addition, extrapolating outcome data derived from studies in the general population to patients on haemodialysis is not always fruitful. In one of the few adequately powered large prospective randomized controlled trials in haemodialysis (HD), atorvastatin did not reduce the incidence of stroke in stark contrast to studies in the general population [6]. At present, the use of thrombolytic therapy for acute ischaemic stroke in HD patients has not been described. Case report We present the case of a 73-year-old male of South Asian ethnicity. He had a prior diagnosis of progressive chronic kidney disease secondary to obstructive uropathy and recurrent urosepsis, and a hydronephrotic left kidney requiring insertion of a J-J ureteric stent in June 2009. In addition, he had type 2 diabetes mellitus, ischaemic heart disease (myocardial infarction March 2009) and a diagnosis of hypertension. He did not have a history of cardiac dysrhythmia, a prothrombotic diathesis or cerebrovascular disease. There was no family history of renal or cerebrovascular disease. He was not on maintenance antiplatelet agents or oral anticoagulants. He was a non-smoker and did not consume any alcohol. Following emergency admission to the intensive care unit with pulmonary oedema, oliguria and a serum creatinine of 10.2 mg/dL (899 μmol/L), he was established on maintenance thrice weekly HD via a right internal jugular tunnelled cuffed central venous catheter (TesioCath™, MedComp, Harleysville, PA, USA) 2.5-months prior to presentation with an acute stroke. He presented to his local emergency department with acute right hemiparesis and aphasia of a 90-min duration. He had undergone routine HD 24-h with no complications prior to presentation. On arrival, his blood pressure (BP) was 190/87 mmHg, capillary blood glucose was 86.5 mg/ dL (4.8 mmol/L) and his Glasgow Coma Score (GCS) was 15/15. He was in sinus rhythm on his electrocardiogram. An urgent CT scan of his brain revealed an acute ischaemic stroke affecting the superior parasagittal cortex of the left frontal lobe. There was no evidence of intracranial haemorrhage. At that point, he was transferred immediately to his local acute stroke centre. On arrival, his BP was 176/75 mmHg. Clinical examination revealed a mild right facial droop, evidence of a right hemiparesis (power 3/5 in the upper limb and power 0/5 in the lower limb) with increased muscle tone in the upper limb, lower limb hyperreflexia and an upgoing plantar response in the lower limb. © The Author 2010. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For permissions, please e-mail: Correspondence and offprint requests to: Albert Power; E-mail: , Successful thrombolysis for acute ischaemic stroke in haemodialysis Discussion rtPA (alteplase) is a glycoprotein that becomes activated on binding to fibrin, converting plasminogen to plasmin and leading to fibrinolysis. It is rapidly cleared from the circulation following administration undergoing predominantly hepatic clearance. When administered within 3-h of symptom onset in the seminal placebo-controlled National Institute of Neurological Disorders and Stroke (NINDS) rtPA study, it resulted in a significantly better neurological outcome at 3 months [7]. Analysis of pooled results of six randomized controlled trials of intravenous rtPA showed that Table 1. Laboratory tests at time of presentation Haemoglobin Total leucocyte count Platelet count Sodium Potassium Urea Creatinine Albumin Total cholesterol C-reactive protein INR APTT Fibrinogen 15.9 g/dL 7.5 × 109/mL 161 × 109/mL 136 mmol/L 4.7 mmol/L 12.2 mmol/L 462 μmol/L 44 g/L 2.2 mmol/L 2 mg/L 1.1 27.8 s 4.00 g/L Fig. 1. Single representative axial section through the brain postthrombolysis. Within the parasagittal cortex of the left frontal lobe in the anterior cerebral artery territory is an ischaemic infarct with a small amount of haemorrhagic transformation (area of increased attenuation marked with the arrow). the best outcomes occurred in patients treated within 2-h of symptom onset and suggested a benefit extending to 4.5-h. This was confirmed in a subsequent randomized controlled trial, ECASS III [8]. Although mortality did not differ between the two groups, 52.4% patients in the rtPA arm recovered with no disability after 90% vs 45.2% in the placebo arm (P = 0.04). There was, however, a higher rate of symptomatic intracerebral haemorrhage in the rtPA arm (2.4% vs 0.2%, P = 0.008) in keeping with prior studies. A Cochrane systematic review suggested a benefit associated with rtPA up to 6-h from symptom onset [9], and this is currently under study [10]. Use of rtPA is contraindicated in cases where there is a ‘known haemorrhagic diathesis’ or severe uncontrolled arterial hypertension (defined as 185/110 mm (...truncated)