Background and Purpose: Patients with acute cardioembolic stroke frequently show hemorrhagic transformation (HTr). We attempted to identify predictors of symptomatic HTr in acute ischemic stroke with atrial fibrillation (AF). Methods: Of the consecutive acute ischemic stroke patients with AF at 12 hospitals in Korea, patients with posterior circulation stroke or thrombolytic therapy were excluded. Immediate anticoagulation was recommended to all patients, except those with: (1) large infarcts, 50% or more of the middle cerebral artery territory, (2) significant HTr on initial imaging, or (3) other safety concerns. Symptomatic HTr was defined as cerebral hemorrhage temporally related to neurological deterioration. Results: Of the 389 included patients (mean age 71 years), 260 (67%) were treated with anticoagulation within 1 week from the onset. Symptomatic HTr occurred in 4.6%. Large infarct (OR 6.38, 95% CI 1.16–35.14), previous hemorrhagic stroke (OR 10.67, 1.77–64.25), and low platelet count (OR per 104 increase 0.87, 0.79–0.97) were independent predictors of symptomatic HTr. hsCRP values tended to be higher in patients with symptomatic HTr (p = 0.055). Conclusions: Caution is needed in anticoagulation treatment of acute cardioembolic stroke patients with a large infarct, previous hemorrhagic stroke, low platelet count, or a high hsCRP level.

Keywords:
Acute ischemic stroke, Atrial fibrillation, Anticoagulation, Hemorrhagic transformation
1.
Paciaroni M, Agnelli G, Corea F, Ageno W, Alberti A, Lanari A, Caso V, Micheli S, Bertolani L, Venti M, Palmerini F, Biagini S, Comi G, Previdi P, Silvestrelli G: Early hemorrhagic transformation of brain infarction: rate, predictive factors, and influence on clinical outcome: results of a prospective multicenter study. Stroke 2008;39:2249–2256.
2.
Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, Brott T, Frankel M, Grotta JC, Haley EC Jr, Kwiatkowski T, Levine SR, Lewandowski C, Lu M, Lyden P, Marler JR, Patel S, Tilley BC, Albers G, Bluhmki E, Wilhelm M, Hamilton S: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials. Lancet 2004;363:768–774.
3.
Kerenyi L, Kardos L, Szasz J, Szatmari S, Bereczki D, Hegedus K, Csiba L: Factors influencing hemorrhagic transformation in ischemic stroke: a clinicopathological comparison. Eur J Neurol 2006;13:1251–1255.
4.
Berge E, Abdelnoor M, Nakstad PH, Sandset PM, HAEST Study Group: Low molecular-weight heparin versus aspirin in patients with acute ischaemic stroke and atrial fibrillation: a double-blind randomised study. Lancet 2000;355:1205–1210.
5.
Saxena R, Lewis S, Berge E, Sandercock PA, Koudstaal PJ: Risk of early death and recurrent stroke and effect of heparin in 3,169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial. Stroke 2001;32:2333–2337.
6.
Larrue V, von Kummer RR, Muller A, Bluhmki E: Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II). Stroke 2001;32:438–441.
7.
Montaner J, Molina CA, Monasterio J, Abilleira S, Arenillas JF, Ribo M, Quintana M, Alvarez-Sabin J: Matrix metalloproteinase-9 pretreatment level predicts intracranial hemorrhagic complications after thrombolysis in human stroke. Circulation 2003;107:598–603.
8.
Rodriguez-Yanez M, Castellanos M, Blanco M, Millan M, Nombela F, Sobrino T, Lizasoain I, Leira R, Serena J, Davalos A, Castillo J: Micro- and macroalbuminuria predict hemorrhagic transformation in acute ischemic stroke. Neurology 2006;67:1172–1177.
9.
Kidwell CS, Saver JL, Carneado J, Sayre J, Starkman S, Duckwiler G, Gobin YP, Jahan R, Vespa P, Villablanca JP, Liebeskind DS, Vinuela F: Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis. Stroke 2002;33:717–724.
10.
Bang OY, Saver JL, Liebeskind DS, Starkman S, Villablanca P, Salamon N, Buck B, Ali L, Restrepo L, Vinuela F, Duckwiler G, Jahan R, Razinia T, Ovbiagele B: Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis. Neurology 2007;68:737–742.
11.
Kim EY, Na DG, Kim SS, Lee KH, Ryoo JW, Kim HK: Prediction of hemorrhagic transformation in acute ischemic stroke: role of diffusion-weighted imaging and early parenchymal enhancement. Am J Neuroradiol 2005;26:1050–1055.
12.
Gilligan AK, Markus R, Read S, Srikanth V, Hirano T, Fitt G, Arends M, Chambers BR, Davis SM, Donnan GA: Baseline blood pressure but not early computed tomography changes predicts major hemorrhage after streptokinase in acute ischemic stroke. Stroke 2002;33:2236–2242.
13.
Lee SH, Kang BS, Kim N, Roh JK: Does microbleed predict haemorrhagic transformation after acute atherothrombotic or cardioembolic stroke? J Neurol Neurosurg Psychiatry 2008;79:913–916.
14.
The NINDS t-PA Stroke Study Group: Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. Stroke 1997;28:2109–2118.
15.
Ay H, Furie KL, Singhal A, Smith WS, Sorensen AG, Koroshetz WJ: An evidence-based causative classification system for acute ischemic stroke. Ann Neurol 2005;58:688–697.
16.
Sharma JC, Hasson MS, Butcher C: How well does the Oxfordshire Community Stroke Project classification predict the site and size of infarct of brain imaging? J Neurol Neurosurg Psychiatry 2001;70:567.
17.
Hacke W, Kaste M, Fieschi C, et al: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: the European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017–1025.
18.
Lee BC, Roh JK: International experience in stroke registries: Korean Stroke Registry. Am J Prev Med 2006;31:S243–S245.
19.
Brott T, Adams HP Jr, Olinger CP, et al: Measurements of acute cerebral infarction: a clinical examination scale. Stroke 1989;20:864–870.
20.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA: MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. Am J Roentgenol 1987;149:351–356.
21.
Di Napoli M, Schwaninger M, Cappelli R, Ceccarelli E, Di Gianfilippo G, Donati C, Emsley HC, Forconi S, Hopkins SJ, Masotti L, Muir KW, Paciucci A, Papa F, Roncacci S, Sander D, Sander K, Smith CJ, Stefanini A, Weber D: Evaluation of C-reactive protein measurement for assessing the risk and prognosis in ischemic stroke: a statement for health care professionals from the CRP Pooling Project members. Stroke 2005;36:1316–1329.
22.
O’Donnell MJ, Berge E, Sandset PM: Are there patients with acute ischemic stroke and atrial fibrillation that benefit from low molecular weight heparin? Stroke 2006;37:452–455.
23.
Terruzzi A, Valente L, Mariani R, Moschini L, Camerlingo M: C-reactive protein and aetiological subtypes of cerebral infarction. Neurol Sci 2008;29:245–249.
24.
Eikelboom JW, Hankey GJ, Baker RI, McQuillan A, Thom J, Staton J, Cole V, Yi Q: C-reactive protein in ischemic stroke and its etiologic subtypes. J Stroke Cerebrovasc Dis 2003;12:74–81.
25.
McColl BW, Rothwell NJ, Allan SM: Systemic inflammation alters the kinetics of cerebrovascular tight junction disruption after experimental stroke in mice. Neurobiol Dis 2008;28:9451–9462.
26.
Fan YH, Zhang L, Lam WW, Mok VC, Wong KS: Cerebral microbleeds as a risk factor for subsequent intracerebral hemorrhages among patients with acute ischemic stroke. Stroke 2003;34:2459–2462.
27.
Stroke Prevention in Atrial Fibrillation Investigators: Design of a multicenter randomized trial for the Stroke Prevention in Atrial Fibrillation Study. Stroke 1990;21:538–545.
28.
Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, Murray E: Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet 2007;370:493–503.
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2010
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