Background: The Hemorrhage after Thrombolysis (HAT) score has recently been introduced as a practical scale for risk stratification of intracranial hemorrhage (ICH) in patients receiving intravenous tissue plasminogen activator (tPA). We aimed to externally validate and evaluate the predictive ability of the HAT score in patients with proximal arterial occlusions (PAO) enrolled into randomized clinical trials of sonothrombolysis. Methods: The HAT score (range 0, minimum risk, to 5, maximum risk) was retrospectively calculated for each patient using clinical trial data (baseline NIHSS, extent of hypodensity on CT, history of diabetes mellitus and serum glucose). Symptomatic ICH (sICH) was defined as imaging evidence of ICH with clinical worsening (NIHSS ≧4) within 72 h from stroke onset. The predictive ability of the HAT score for sICH and any ICH (both asymptomatic and symptomatic) was calculated using c statistics. Results: A total of 161 tPA-treated patients (mean age 68 ± 13 years, 58% men, median NIHSS 16, interquartile range 9) with PAO were randomized in TUCSON (n = 35) and CLOTBUST (n = 126). sICH occurred in 9 (5.6%) cases, and 6 had asymptomatic ICH. The rates of sICH for the corresponding HAT scores were: HAT 0–1: 3%; 2: 9%; 3: 14%; 4–5: 14%. The risk of sICH (c statistic 0.72, 95% CI: 0.58–0.86; p = 0.027) and any ICH (c statistic 0.70, 95% CI: 0.58–0.82; p = 0.011) increased with higher HAT scores. Higher HAT scores were also associated with higher likelihood of persisting occlusion (c statistic 0.63, 95% CI: 0.54–0.72; p = 0.004). Conclusions: The HAT score has reasonable external validity for predicting the risk of sICH following intravenous thrombolysis in patients with PAO. Moreover, higher HAT scores appear to be associated with higher likelihood of persisting occlusion in tPA-treated patients.

1.
Derex L, Nighoghossian N: Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update. J Neurol Neurosurg Psychiatry 2008;79:1093–1099.
2.
Khatri P, Wechsler LR, Broderick JP: Intracranial hemorrhage associated with revascularization therapies. Stroke 2007;38:431–440.
3.
Lou M, Safdar A, Mehdiratta M, Kumar S, Schlaug G, Caplan L, Searls D, Selim M: The HAT Score: a simple grading scale for predicting hemorrhage after thrombolysis. Neurology 2008;71:1417–1423.
4.
Alexandrov AV, Molina CA, Grotta JC, Garami Z, Ford SR, Alvarez-Sabin J, Montaner J, Saqqur M, Demchuk AM, Moyé LA, Hill MD, Wojner AW; CLOTBUST Investigators: Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke. N Engl J Med 2004;351:2170–2178.
5.
Molina CA, Barreto AD, Tsivgoulis G, Sierzenski P, Malkoff MD, Rubiera M, Gonzales N, Mikulik R, Pate G, Ostrem J, Singleton W, Manvelian G, Unger EC, Grotta JC, Schellinger PD, Alexandrov AV: Transcranial ultrasound in clinical sonothrombolysis (TUCSON) trial. Ann Neurol 2009;66:28–38.
6.
Demchuk AM, Burgin WS, Christou I, Felberg RA, Barber PA, Hill MD, Alexandrov AV: Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator. Stroke 2001;32:89–93.
7.
Burgin WS, Malkoff M, Felberg RA, Demchuk AM, Christou I, Grotta JC, Alexandrov AV: Transcranial Doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke. Stroke 2000;31:1128–1132.
8.
Alexandrov AV, Burgin WS, Demchuk AM, El-Mitwalli A, Grotta JC: Speed of intracranial clot lysis with intravenous TPA therapy: sonographic classification and short term improvement. Circulation 2001;103:2897–2902.
9.
Chernyshev OY, Garami Z, Calleja S, Song J, Campbell MS, Noser EA, Shaltoni H, Chen CI, Iguchi Y, Grotta JC, Alexandrov AV: The yield and accuracy of urgent combined carotid-transcranial ultrasound testing in acute cerebral ischemia. Stroke 2005;36:32–37.
10.
Tsivgoulis G, Sharma VK, Lao AY, Malkoff MD, Alexandrov AV: Validation of transcranial Doppler with computed tomography angiography in acute cerebral ischemia. Stroke 2007;38:1245–1249.
11.
Saqqur M, Tsivgoulis G, Molina CA, Demchuk AM, Shuaib A, Alexandrov AV; CLOTBUST Investigators: Residual flow at the site of intracranial occlusion on transcranial Doppler predicts response to intravenous thrombolysis: a multi-center study. Cerebrovasc Dis 2009;27:5–12.
12.
Saqqur M, Tsivgoulis G, Molina CA, Demchuk AM, Siddiqui M, Alvarez-Sabín J, Uchino K, Calleja S, Alexandrov AV; CLOTBUST Investigators: Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: a multicenter study. Neurology 2008;71:1304–1312.
13.
The NINDS rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–1587.
14.
Alexandrov AV, Grotta JC: Arterial reocclusion in stroke patients treated with intravenous tissue plasminogen activator. Neurology 2002;59:862–867.
15.
Alexandrov AV, Wojner AW, Grotta JC: CLOTBUST: design of a randomized trial of ultrasound-enhanced thrombolysis for acute ischemic stroke. J Neuroimaging 2004;14:108–112.
16.
Barreto AD, Sharma VK, Lao AY, Schellinger PD, Amarenco P, Sierzenski P, Alexandrov AV, Molina CA: Safety and dose-escalation study design of Transcranial Ultrasound in Clinical SONolysis for acute ischemic stroke: the TUCSON Trial. Int J Stroke 2009;4:42–48.
17.
Wahlgren N, Ahmed N, Dávalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G; SITS-MOST investigators: Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet 2007;369:275–282.
18.
Lewis JR, Sauro J: When 100% really isn’t 100%: improving the accuracy of small-sample estimates of completion rates. J Usability Stud 2006;1:136–150.
19.
de la Ossa NP, Castellanos M, Jimenez M, Lopez-Cancio B, Dorado L, Guerrero C, Millan M, Serena J, Davalos A: Validation of the HAT-score scale as a predictor of hemorrhagic transformation in a large cohort of acute stroke patients treated with intravenous tPA. Stroke 2010;41:e30.
20.
Tsivgoulis G, Saqqur M, Sharma VK, Lao AY, Hill MD, Alexandrov AV: Association of pretreatment blood pressure with tissue plasminogen activator-induced arterial recanalization in acute ischemic stroke. Stroke 2007;38:961–966.
21.
Ribo M, Molina C, Montaner J, Rubiera M, Delgado-Mederos R, Arenillas JF, Quintana M, Alvarez-Sabín J: Acute hyperglycemia state is associated with lower tPA-induced recanalization rates in stroke patients. Stroke 2005;36:1705–1709.
22.
Martini SR, Hill MD, Alexandrov AV, Molina CA, Kent TA: Outcome in hyperglycemic stroke with ultrasound-augmented thrombolytic therapy. Neurology 2006;67:700–702.
23.
Tsivgoulis G, Saqqur M, Sharma VK, Lao AY, Hoover SL, Alexandrov AV; CLOTBUST Investigators: Association of pretreatment ASPECTS scores with tPA-induced arterial recanalization in acute middle cerebral artery occlusion. J Neuroimaging 2008;18:56–61.
24.
Ibrahim MM, Sebastian J, Hussain M, Al-Hussain F, Uchino K, Molina C, Khan K, Demchuk AM, Alexandrov AV, Saqqur M; CLOTBUST Investigators: Does current oral antiplatelet agent or subtherapeutic anticoagulation use have an effect on tissue-plasminogen-activator-mediated recanalization rate in patients with acute ischemic stroke? Cerebrovasc Dis 2010;30:508–513.
25.
Molina CA, Alexandrov AV, Demchuk AM, Saqqur M, Uchino K, Alvarez-Sabín J; CLOTBUST Investigators: Improving the predictive accuracy of recanalization on stroke outcome in patients treated with tissue plasminogen activator. Stroke 2004;35:151–156.
26.
Nordt TK, Klassen KJ, Schneider DJ, Sobel BE: Augmentation of synthesis of plasminogen activator inhibitor type-1 in arterial endothelial cells by glucose and its implications for local fibrinolysis. Arterioscler Thromb 1993;13:1822–1828.
27.
Tsivgoulis G, Alexandrov AV, Sloan MA: Advances in transcranial Doppler ultrasonography. Curr Neurol Neurosci Rep 2009;1:46–54.
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