American Journal of Emergency Medicine 33 (2015) 307.e1–307.e4
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Readministration of intravenous alteplase in acute ischemic stroke patients: case series and systematic review Abstract Background: Because of a high risk of recurrence of ischemic events, some patients may be candidates for readministration of intravenous (IV) alteplase. Methods: We performed a single-center review and performed a search on PubMed from January 1966 to April 2014 for cases of readministration of alteplase. Favorable outcome was defined by a modified Rankin scale of 0 to 2 at discharge or at 1 to 3 months, improvement of greater than or equal to 4 points within 24 hours in the National Institutes of Health Stroke Scale score, or as a major improvement in the 72-hour National Institutes of Health Stroke Scale score. Results: Four ischemic stroke patients underwent readministration of IV alteplase in our single-center review. None of the patients had symptomatic or asymptomatic intracerebral hemorrhage. In 2 patients, IV alteplase had been administered for a previous acute ischemic stroke, 6 and 49 days before the index ischemic stroke. At discharge, both patients had a favorable outcome. A total of 22 cases of readministration of alteplase for ischemic stroke have been reported in literature. The mean interval between the 2 administrations of alteplase was 428 days (range, 3 hours to 2280 days). Asymptomatic postthrombolytic intracerebral hemorrhages were seen in 2 patients. Favorable outcome was seen in 16 patients. A total of 9 underwent readministration of IV alteplase within 3 months for recurrent ischemic stroke. Favorable outcome was seen in 5 of these 9 patients. Conclusions: We observed a relatively high rate of favorable outcomes and a small rate of adverse events after readministration of IV alteplase in ischemic stroke patients. Because of a high risk of recurrence of ischemic events [1-3], some patients may be candidates for readministration of intravenous (IV) alteplase (Activase; Genentech, San Francisco, CA). Previous studies excluded ischemic stroke patients if they had another stroke within the preceding 3 months, but did not specify previous use of alteplase [4,5]. The package insert for alteplase reports that readministration of alteplase should be undertaken with caution [6]. We performed this study to determine the adverse events and response of readministration of IV alteplase in patients with acute ischemic stroke. Ischemic stroke patients were identified from search for encounters, in Enterprise Data Warehouse, with 2 or more separate performances of thrombolysis using the International Classification of Disease, Ninth Revision, Clinical Modification procedure code 99.10 [7]. The time interval between initial use and readministration of alteplase was ascertained. We recorded admission, 24-hour posttreatment, and 7-day National Institutes of Health Stroke Scale (NIHSS) scores, and any occurrence of postalteplase intracerebral hemorrhage (ICH). Outcome at time of discharge was assessed using modified Rankin Scale (mRS). 0735-6757/© 2014 Elsevier Inc. All rights reserved.
We performed a PubMed search from January 1966 to April 2014 with the key words “retreatment”, and “tpa” or “Activase” or “Alteplase,” “thrombolysis for recurrent stroke,” and “repeat tpa and ischemic stroke.” We performed 2 other searches: one, using the key words “thrombolysis for recurrent stroke”; second one, using “repeat tpa” and “ischemic stroke.” A total of 7 pertinent articles were identified [8-14]. Favorable outcome was defined by documentation of mRS of 0 to 2 at discharge or at 1 to 3 months, improvement of greater than or equal to 4 points within 24 hours in the NIHSS score, or as a major improvement in the 72-hour NIHSS score. Four ischemic stroke patients underwent alteplase readministration (Table). All were on aspirin before the index ischemic stroke. In 2 patients, aged 73 and 54 years, IV alteplase had been administered for a previous acute ischemic stroke, 6 and 49 days before the index ischemic stroke. In patients 1 and 2, the initial NIHSS scores were 6 and 2 at time of index ischemic stroke, respectively. Both patients received IV alteplase in doses of 73.4 mg and 100 mg, respectively. At discharge, both patients had no deficits (mRS of 0). In 2 other patients, aged 91 and 78 years, IV alteplase had been administered for a previous femoral-popliteal thrombosis, 448 and 127 days before the index ischemic stroke (see the Table). Both patients received IV alteplase in doses of 63.3 mg and 74.7 mg, respectively. At discharge, patient 3 had mRS of 5, and the fourth patient died after withdrawal of care. None of the 4 patients had symptomatic or asymptomatic ICH, allergic reaction, angioneurotic edema, or anaphylaxis. A total of 22 cases of readministration of alteplase for ischemic stroke have been reported in literature. The mean interval between the 2 administrations of alteplase was 428 days (range, 3 hours to 2280 days) for these patients. The median NIHSS score at readministration was 15 (range, 2-27). Postthrombolytic ICH was seen in 2 patients; it was considered symptomatic ICH in none of the 2 patients. Allergic reaction was reported on second exposure in one of 22 patients. This patient had also had an allergic reaction on first exposure. Favorable outcome was seen in 16 patients. A total of 9 received IV alteplase for ischemic stroke within 3 months before readministration of alteplase for recurrent ischemic stroke. The mean interval between the 2 administrations of alteplase was 38 days (range, 3 hours to 90 days). Postthrombolytic asymptomatic ICH was seen in 2 patients, and favorable outcome was seen in 5 patients. We did not notice any adverse events in the 4 acute ischemic stroke patients who had previously received IV alteplase. In 9 of the 22 patients identified in literature, second administration of IV alteplase was preceded by a previous administration for prior ischemic stroke within the last 3 months. Although IV alteplase is identical to endogenous tissue-type plasminogen activator, serious reactions (anaphylactoid reactions) have been observed during thrombolytic therapy with IV alteplase [15-17]. Another concern is that the region
307.e2
Table Demographic, clinical and neuroimaging findings, and clinical outcomes associated with readministration of IV alteplase in acute ischemic stroke patients Age/Sex
Cardiovascular risk factors
Initial Initial CT NIHSS scan score
Duration since last alteplase use (d)
Dose of alteplase at Indication for readministration first alteplase (mg)
Location of index stroke
24-h 7-d ICH Any major mRS NIHSS NIHSS on CT bleeding score score scan episode
IA alteplase Mechanical administration thrombectomy
1
73/M
HTN, HL
6
No ICH
6
73.44
Ischemic stroke
0
0
No
No
0
No
No
2
54/M
Unknown
2
49
100
Left middle cerebral artery ischemic stroke
2
0
No
No
0
Yes
Yes
3
91/W
23
448
63.27
No
No
5
No
No
74.70
24
Died
No
No
Died No
Yes
64/W
19
Small vessel 127 white matter ischemic change NA 690
Central pontine infarct Left middle cerebral artery
32
78/M
Acute left foot ischemia Left leg arterial occlusion
32
4
Aortic stenosis, AF, CHF, HTN, diabetes CHF, arteriosclerotic heart disease, HL NA
Hypodensity parasagittal left frontal lobe; previous infarct No ICH
Right internal carotid artery Left middle cerebral artery
Middle cerebral artery NA
NA
No
No
4
No
No
6
84/W
NA
12
NA
90
NA
Middle cerebral artery NA
NA
No
No
2
No
No
7
76/M
NA
6
NA
210
NA
Middle cerebral artery NA
NA
No
No
1
No
No
8
72/M
NA
6
NA
270
NA
Middle cerebral artery NA
NA
No
No
0
No
No
9
83/W
NA
18
NA
720
NA
Middle cerebral artery NA + anterior cerebral artery
NA
No
No
3
Yes
No
10
64/M
NA
7
NA
540
NA
Middle cerebral artery NA
NA
No
No
2
No
No
11
54/W
NA
27
NA
240
NA
Basilar artery
NA
NA
No
No
1
No
No
12
68/W
NA
22
NA
1440
NA
Middle cerebral artery NA
NA
No
No
6
No
No
13 13
63/M 65/Mc
NA NA
5 7
NA NA
300 780
NA NA
Middle cerebral artery infarct Posterior cerebral artery infarct Middle cerebral artery infarct Middle cerebral artery infarct Middle cerebral artery + anterior cerebral artery infarct Middle cerebral artery infarct Middle cerebral artery infarct Basilar artery infarct Middle cerebral artery infarct
NA NA
No No
No No
0 1
No No
No No
50/W
None/unknown
18
NA
6
0.9 mg/kg
Middle cerebral artery NA Posterior cerebral NA artery Left internal carotid NA artery
NA
No
No
0
No
Yes
15
70/M
HTN
13
NA
180
0.9 mg/kg
NA
NA
No
No
4
Yesa
Yes
16
73/W
Diabetes mellitus
12
NA
90
0.9 mg/kg
NA
NA
No
No
0
No
No
17
74/W
HTN
22
NA
480
0.9 mg/kg
NA
NA
No
No
0
No
Yes
18
56/M
HTN, diabetes
15
NA
2280
0.9 mg/kg
Right middle cerebral artery Left middle cerebral artery Left middle cerebral artery Right middle cerebral artery Left middle cerebral artery Right middle cerebral artery Right middle cerebral artery
NA
NA
No
No
1
Yesa a
5
14
Current study
Sauer et al [8]
Yoo et al [9]
22
NA
19
67/M
HTN, diabetes
19
NA
1410
0.9 mg/kg
20
75/W
HL
15
NA
1110
0.9 mg/kg
50/M
None/unknown
10
Previous right 4 middle cerebral infarct
21
Topakian et al [10]
50
Right internal carotid artery infarct Left middle cerebral artery infarct Left middle cerebral artery infarct Left middle cerebral artery infarct Right middle cerebral artery infarct Right middle cerebral artery infarct Left middle cerebral artery infarct Right middle cerebral artery infarct
No
NA
NA
No
No
0
Yes
NA
NA
No
No
4
No
Yes
6
NA
No
No
1
No
No
Yes
A.I. Qureshi et al. / American Journal of Emergency Medicine 33 (2015) 307.e1–307.e4
No. Study
0.9 mg/kg 0.125 No ICH 15
0.9 mg/kg 70 No ICH 4
Cappellari 75/W et al [14] 27
HTN, smoking, coronary artery disease, HL HTN, PAF 87/M 26
Abbreviations: AF, atrial fibrillation; CHF, congestive heart failure; CT, computed tomography; HL, hyperlipidemia; HTN, hypertension; IA, intraarterial; M, man; NA, not available; PAF, paroxysmal atrial fibrillation; W, woman; NIHSS, National Institutes of Health Stroke Scale. a Intraarterial urokinase. b Seventy-two hour NIHSS. c Second readministration of IV alteplase.
No No 0 Left middle cerebral artery
1
No
No
NA
No No NA Right middle cerebral artery
NA
No
No
1
No No 5 NA 0.9 mg/kg 70 No ICH 9 Coronary artery disease, smoking 83/M 25
23 81/W Alhazzaa et al [13] 24
AF
21 Megadolichobasilar ectasia Cambron et al [12] 23
69/M
Right middle cerebral artery
NA
No
No
No 5 NA 0.9 mg/kg
Right middle cerebral artery infarct Right middle cerebral artery infarct Right middle cerebral artery infarct Ischemic stroke
Right middle cerebral artery
NA
Yes
No
No
No No NA NA NA
Basilar artery infarct Basilar artery
0b
No
No
No Died No No Yes NA 16 Left middle cerebral artery Right middle cerebral artery infarct 0.9 mg/kg
4 Previous right lenticular infarct Mural 365 thrombus in basilar artery No ICH 6 22 76/W Sposato et al [11] 22
HTN, HL, PAF, CHF
Age/Sex No. Study
Table (continued)
Cardiovascular risk factors
Initial Initial CT NIHSS scan score
Duration since last alteplase use (d)
Dose of alteplase at Indication for readministration first alteplase (mg)
Location of index stroke
24-h 7-d ICH Any major mRS NIHSS NIHSS on CT bleeding score score scan episode
IA alteplase Mechanical administration thrombectomy
A.I. Qureshi et al. / American Journal of Emergency Medicine 33 (2015) 307.e1–307.e4
307.e3
of recent ischemic stroke may be vulnerable to postthrombolytic ICH. However, the rates of postthrombolytic ICHs were low in patients with recent silent ischemic events on magnetic resonance imaging [18,19] and those presenting with acute stroke within 3 months of previous stroke [13]. The circulating alteplase is rapidly degraded in the hepatic system (initial half-life of 5 minutes and a terminal half-life of 72 minutes) [20], and thus, the possibility of accumulation of drug with repeated administration is nonexistent. Our report supports readministration of alteplase for ischemic stroke in the absence of standard exclusion criteria as outlined in the American Stroke Association guidelines [21]. Adnan I. Qureshi, MD⁎ Ahmed A. Malik, MD Zeenat Qureshi Stroke Institute, 519 2nd St N, St Cloud, MN 56303 ⁎Corresponding author. Department of Cerebrovascular Diseases and Interventional Neurology, CentraCare Health System 1406 6th Ave N St Cloud, MN 56303 Tel.: + 1 320 281 5545; fax: +1 320 281 5547. E-mail addresses: [email protected] (A.I. Qureshi), [email protected] (A.A. Malik) Melissa Freese, RN Michelle J. Thompson, CAGNP CentraCare Health System, Department of Cerebrovascular Diseases and Interventional Neurology, St Cloud Hospital 1406 6th Ave N, St Cloud, MN 56303 E-mail addresses: [email protected] (M. Freese), [email protected] (M. Thompson) Asif A. Khan, MD M. Fareed K. Suri, MD Zeenat Qureshi Stroke Institute, 519 2nd St N, St Cloud, MN 56303 E-mail addresses: [email protected] (A. Khan), [email protected] (M.F.K. Suri) http://dx.doi.org/10.1016/j.ajem.2014.07.020 References [1] Pennlert J, Eriksson M, Carlberg B, Wiklund PG. Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase. Stroke 2014;45(6):1839–41. [2] Prencipe M, Culasso F, Rasura M, Anzini A, Beccia M, Cao M, et al. Long-term prognosis after a minor stroke: 10-year mortality and major stroke recurrence rates in a hospital-based cohort. Stroke 1998;29(1):126–32. [3] Hankey GJ, Jamrozik K, Broadhurst RJ, Forbes S, Burvill PW, Anderson CS, et al. Long-term risk of first recurrent stroke in the Perth Community Stroke Study. Stroke 1998;29(12):2491–500. [4] Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333(24):1581–7. [5] Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359(13):1317–29. [6] Activase; Alteplase: A Tissue Plasminogen Avtivator. cited 2014 06/06/2014, Available from: http://www.gene.com/download/pdf/activase_prescribing.pdf. [7] Qureshi AI, Harris-Lane P, Siddiqi F, Kirmani JF. International classification of diseases and current procedural terminology codes underestimated thrombolytic use for ischemic stroke. J Clin Epidemiol 2006;59(8):856–8. [8] Sauer R, Huttner HB, Breuer L, Engelhorn T, Schellinger PD, Schwab S, et al. Repeated thrombolysis for chronologically separated ischemic strokes: a case series. Stroke 2010;41(8):1829–32. [9] Yoo HS, Kim YD, Lee HS, Song D, Song TJ, Kim BM, et al. Repeated thrombolytic therapy in patients with recurrent acute ischemic stroke. J Stroke 2013;15(3):182–8. [10] Topakian R, Gruber F, Fellner FA, Haring HP, Aichner FT. Thrombolysis beyond the guidelines: two treatments in one subject within 90 hours based on a modified magnetic resonance imaging brain clock concept. Stroke 2005;36(11):e162–4. [11] Sposato LA, Salutto V, Beratti DE, Monti P, Riccio PM, Mazia C. Adverse outcome of early recurrent ischemic stroke secondary to atrial fibrillation after repeated systemic thrombolysis. Case Rep Vasc Med 2013;2013:371642. [12] Cambron M, Van Hooff RJ, Nieboer K, De Keyser J, Brouns R. Successful repetitive intravenous thrombolysis in a patient with recurrent brainstem infarctions due to megadolichobasilar ectasia. JAMA Neurol 2013;70(4):520–1. [13] Alhazzaa M, Sharma M, Blacquiere D, Stotts G, Hogan M, Dowlatshahi D. Thrombolysis despite recent stroke: a case series. Stroke 2013;44(6):1736–8.
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A.I. Qureshi et al. / American Journal of Emergency Medicine 33 (2015) 307.e1–307.e4
[14] Cappellari M, Tomelleri G, Carletti M, Bovi P, Moretto G. Intravenous thrombolysis on early recurrent cardioembolic stroke: 'Dr Jekyll' or 'Mr Hyde'? Blood Coagul Fibrinolysis 2012;23(1):78–81. [15] Hill MD, Barber PA, Takahashi J, Demchuk AM, Feasby TE, Buchan AM. Anaphylactoid reactions and angioedema during alteplase treatment of acute ischemic stroke. CMAJ 2000;162(9):1281–4. [16] Zarar A, Khan AA, Adil MM, Qureshi AI. Anaphylactic shock associated with intravenous thrombolytics. Am J Emerg Med 2014;32(1):113 e3-5. [17] Pancioli A, Brott T, Donaldson V, Miller R. Asymmetric angioneurotic edema associated with thrombolysis for acute stroke. Ann Emerg Med 1997;30(2):227–9. [18] Tisserand M, Le Guennec L, Touze E, Hess A, Charbonnier C, Devauchelle AD, et al. Prevalence of MRI-defined recent silent ischemia and associated bleeding risk with thrombolysis. Neurology 2011;76(15):1288–95.
[19] Gaillard N, Schmidt C, Costalat V, Bousquet JP, Heroum C, Milhaud D, et al. Hemorrhagic risk of recent silent cerebral infarct on prethrombolysis MR imaging in acute stroke. AJNR Am J Neuroradiol 2012;33(2):227–31. [20] Xavier AR, Siddiqui AM, Kirmani JF, Hanel RA, Yahia AM, Qureshi AI. Clinical potential of intra-arterial thrombolytic therapy in patients with acute ischaemic stroke. CNS Drugs 2003;17(4):213–24. [21] Adams Jr HP, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38(5):1655–711.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
Readministration of intravenous alteplase in acute ischemic stroke patients: case series and systematic review Abstract Background: Because of a high risk of recurrence of ischemic events, some patients may be candidates for readministration of intravenous (IV) alteplase. Methods: We performed a single-center review and performed a search on PubMed from January 1966 to April 2014 for cases of readministration of alteplase. Favorable outcome was defined by a modified Rankin scale of 0 to 2 at discharge or at 1 to 3 months, improvement of greater than or equal to 4 points within 24 hours in the National Institutes of Health Stroke Scale score, or as a major improvement in the 72-hour National Institutes of Health Stroke Scale score. Results: Four ischemic stroke patients underwent readministration of IV alteplase in our single-center review. None of the patients had symptomatic or asymptomatic intracerebral hemorrhage. In 2 patients, IV alteplase had been administered for a previous acute ischemic stroke, 6 and 49 days before the index ischemic stroke. At discharge, both patients had a favorable outcome. A total of 22 cases of readministration of alteplase for ischemic stroke have been reported in literature. The mean interval between the 2 administrations of alteplase was 428 days (range, 3 hours to 2280 days). Asymptomatic postthrombolytic intracerebral hemorrhages were seen in 2 patients. Favorable outcome was seen in 16 patients. A total of 9 underwent readministration of IV alteplase within 3 months for recurrent ischemic stroke. Favorable outcome was seen in 5 of these 9 patients. Conclusions: We observed a relatively high rate of favorable outcomes and a small rate of adverse events after readministration of IV alteplase in ischemic stroke patients. Because of a high risk of recurrence of ischemic events [1-3], some patients may be candidates for readministration of intravenous (IV) alteplase (Activase; Genentech, San Francisco, CA). Previous studies excluded ischemic stroke patients if they had another stroke within the preceding 3 months, but did not specify previous use of alteplase [4,5]. The package insert for alteplase reports that readministration of alteplase should be undertaken with caution [6]. We performed this study to determine the adverse events and response of readministration of IV alteplase in patients with acute ischemic stroke. Ischemic stroke patients were identified from search for encounters, in Enterprise Data Warehouse, with 2 or more separate performances of thrombolysis using the International Classification of Disease, Ninth Revision, Clinical Modification procedure code 99.10 [7]. The time interval between initial use and readministration of alteplase was ascertained. We recorded admission, 24-hour posttreatment, and 7-day National Institutes of Health Stroke Scale (NIHSS) scores, and any occurrence of postalteplase intracerebral hemorrhage (ICH). Outcome at time of discharge was assessed using modified Rankin Scale (mRS). 0735-6757/© 2014 Elsevier Inc. All rights reserved.
We performed a PubMed search from January 1966 to April 2014 with the key words “retreatment”, and “tpa” or “Activase” or “Alteplase,” “thrombolysis for recurrent stroke,” and “repeat tpa and ischemic stroke.” We performed 2 other searches: one, using the key words “thrombolysis for recurrent stroke”; second one, using “repeat tpa” and “ischemic stroke.” A total of 7 pertinent articles were identified [8-14]. Favorable outcome was defined by documentation of mRS of 0 to 2 at discharge or at 1 to 3 months, improvement of greater than or equal to 4 points within 24 hours in the NIHSS score, or as a major improvement in the 72-hour NIHSS score. Four ischemic stroke patients underwent alteplase readministration (Table). All were on aspirin before the index ischemic stroke. In 2 patients, aged 73 and 54 years, IV alteplase had been administered for a previous acute ischemic stroke, 6 and 49 days before the index ischemic stroke. In patients 1 and 2, the initial NIHSS scores were 6 and 2 at time of index ischemic stroke, respectively. Both patients received IV alteplase in doses of 73.4 mg and 100 mg, respectively. At discharge, both patients had no deficits (mRS of 0). In 2 other patients, aged 91 and 78 years, IV alteplase had been administered for a previous femoral-popliteal thrombosis, 448 and 127 days before the index ischemic stroke (see the Table). Both patients received IV alteplase in doses of 63.3 mg and 74.7 mg, respectively. At discharge, patient 3 had mRS of 5, and the fourth patient died after withdrawal of care. None of the 4 patients had symptomatic or asymptomatic ICH, allergic reaction, angioneurotic edema, or anaphylaxis. A total of 22 cases of readministration of alteplase for ischemic stroke have been reported in literature. The mean interval between the 2 administrations of alteplase was 428 days (range, 3 hours to 2280 days) for these patients. The median NIHSS score at readministration was 15 (range, 2-27). Postthrombolytic ICH was seen in 2 patients; it was considered symptomatic ICH in none of the 2 patients. Allergic reaction was reported on second exposure in one of 22 patients. This patient had also had an allergic reaction on first exposure. Favorable outcome was seen in 16 patients. A total of 9 received IV alteplase for ischemic stroke within 3 months before readministration of alteplase for recurrent ischemic stroke. The mean interval between the 2 administrations of alteplase was 38 days (range, 3 hours to 90 days). Postthrombolytic asymptomatic ICH was seen in 2 patients, and favorable outcome was seen in 5 patients. We did not notice any adverse events in the 4 acute ischemic stroke patients who had previously received IV alteplase. In 9 of the 22 patients identified in literature, second administration of IV alteplase was preceded by a previous administration for prior ischemic stroke within the last 3 months. Although IV alteplase is identical to endogenous tissue-type plasminogen activator, serious reactions (anaphylactoid reactions) have been observed during thrombolytic therapy with IV alteplase [15-17]. Another concern is that the region
307.e2
Table Demographic, clinical and neuroimaging findings, and clinical outcomes associated with readministration of IV alteplase in acute ischemic stroke patients Age/Sex
Cardiovascular risk factors
Initial Initial CT NIHSS scan score
Duration since last alteplase use (d)
Dose of alteplase at Indication for readministration first alteplase (mg)
Location of index stroke
24-h 7-d ICH Any major mRS NIHSS NIHSS on CT bleeding score score scan episode
IA alteplase Mechanical administration thrombectomy
1
73/M
HTN, HL
6
No ICH
6
73.44
Ischemic stroke
0
0
No
No
0
No
No
2
54/M
Unknown
2
49
100
Left middle cerebral artery ischemic stroke
2
0
No
No
0
Yes
Yes
3
91/W
23
448
63.27
No
No
5
No
No
74.70
24
Died
No
No
Died No
Yes
64/W
19
Small vessel 127 white matter ischemic change NA 690
Central pontine infarct Left middle cerebral artery
32
78/M
Acute left foot ischemia Left leg arterial occlusion
32
4
Aortic stenosis, AF, CHF, HTN, diabetes CHF, arteriosclerotic heart disease, HL NA
Hypodensity parasagittal left frontal lobe; previous infarct No ICH
Right internal carotid artery Left middle cerebral artery
Middle cerebral artery NA
NA
No
No
4
No
No
6
84/W
NA
12
NA
90
NA
Middle cerebral artery NA
NA
No
No
2
No
No
7
76/M
NA
6
NA
210
NA
Middle cerebral artery NA
NA
No
No
1
No
No
8
72/M
NA
6
NA
270
NA
Middle cerebral artery NA
NA
No
No
0
No
No
9
83/W
NA
18
NA
720
NA
Middle cerebral artery NA + anterior cerebral artery
NA
No
No
3
Yes
No
10
64/M
NA
7
NA
540
NA
Middle cerebral artery NA
NA
No
No
2
No
No
11
54/W
NA
27
NA
240
NA
Basilar artery
NA
NA
No
No
1
No
No
12
68/W
NA
22
NA
1440
NA
Middle cerebral artery NA
NA
No
No
6
No
No
13 13
63/M 65/Mc
NA NA
5 7
NA NA
300 780
NA NA
Middle cerebral artery infarct Posterior cerebral artery infarct Middle cerebral artery infarct Middle cerebral artery infarct Middle cerebral artery + anterior cerebral artery infarct Middle cerebral artery infarct Middle cerebral artery infarct Basilar artery infarct Middle cerebral artery infarct
NA NA
No No
No No
0 1
No No
No No
50/W
None/unknown
18
NA
6
0.9 mg/kg
Middle cerebral artery NA Posterior cerebral NA artery Left internal carotid NA artery
NA
No
No
0
No
Yes
15
70/M
HTN
13
NA
180
0.9 mg/kg
NA
NA
No
No
4
Yesa
Yes
16
73/W
Diabetes mellitus
12
NA
90
0.9 mg/kg
NA
NA
No
No
0
No
No
17
74/W
HTN
22
NA
480
0.9 mg/kg
NA
NA
No
No
0
No
Yes
18
56/M
HTN, diabetes
15
NA
2280
0.9 mg/kg
Right middle cerebral artery Left middle cerebral artery Left middle cerebral artery Right middle cerebral artery Left middle cerebral artery Right middle cerebral artery Right middle cerebral artery
NA
NA
No
No
1
Yesa a
5
14
Current study
Sauer et al [8]
Yoo et al [9]
22
NA
19
67/M
HTN, diabetes
19
NA
1410
0.9 mg/kg
20
75/W
HL
15
NA
1110
0.9 mg/kg
50/M
None/unknown
10
Previous right 4 middle cerebral infarct
21
Topakian et al [10]
50
Right internal carotid artery infarct Left middle cerebral artery infarct Left middle cerebral artery infarct Left middle cerebral artery infarct Right middle cerebral artery infarct Right middle cerebral artery infarct Left middle cerebral artery infarct Right middle cerebral artery infarct
No
NA
NA
No
No
0
Yes
NA
NA
No
No
4
No
Yes
6
NA
No
No
1
No
No
Yes
A.I. Qureshi et al. / American Journal of Emergency Medicine 33 (2015) 307.e1–307.e4
No. Study
0.9 mg/kg 0.125 No ICH 15
0.9 mg/kg 70 No ICH 4
Cappellari 75/W et al [14] 27
HTN, smoking, coronary artery disease, HL HTN, PAF 87/M 26
Abbreviations: AF, atrial fibrillation; CHF, congestive heart failure; CT, computed tomography; HL, hyperlipidemia; HTN, hypertension; IA, intraarterial; M, man; NA, not available; PAF, paroxysmal atrial fibrillation; W, woman; NIHSS, National Institutes of Health Stroke Scale. a Intraarterial urokinase. b Seventy-two hour NIHSS. c Second readministration of IV alteplase.
No No 0 Left middle cerebral artery
1
No
No
NA
No No NA Right middle cerebral artery
NA
No
No
1
No No 5 NA 0.9 mg/kg 70 No ICH 9 Coronary artery disease, smoking 83/M 25
23 81/W Alhazzaa et al [13] 24
AF
21 Megadolichobasilar ectasia Cambron et al [12] 23
69/M
Right middle cerebral artery
NA
No
No
No 5 NA 0.9 mg/kg
Right middle cerebral artery infarct Right middle cerebral artery infarct Right middle cerebral artery infarct Ischemic stroke
Right middle cerebral artery
NA
Yes
No
No
No No NA NA NA
Basilar artery infarct Basilar artery
0b
No
No
No Died No No Yes NA 16 Left middle cerebral artery Right middle cerebral artery infarct 0.9 mg/kg
4 Previous right lenticular infarct Mural 365 thrombus in basilar artery No ICH 6 22 76/W Sposato et al [11] 22
HTN, HL, PAF, CHF
Age/Sex No. Study
Table (continued)
Cardiovascular risk factors
Initial Initial CT NIHSS scan score
Duration since last alteplase use (d)
Dose of alteplase at Indication for readministration first alteplase (mg)
Location of index stroke
24-h 7-d ICH Any major mRS NIHSS NIHSS on CT bleeding score score scan episode
IA alteplase Mechanical administration thrombectomy
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307.e3
of recent ischemic stroke may be vulnerable to postthrombolytic ICH. However, the rates of postthrombolytic ICHs were low in patients with recent silent ischemic events on magnetic resonance imaging [18,19] and those presenting with acute stroke within 3 months of previous stroke [13]. The circulating alteplase is rapidly degraded in the hepatic system (initial half-life of 5 minutes and a terminal half-life of 72 minutes) [20], and thus, the possibility of accumulation of drug with repeated administration is nonexistent. Our report supports readministration of alteplase for ischemic stroke in the absence of standard exclusion criteria as outlined in the American Stroke Association guidelines [21]. Adnan I. Qureshi, MD⁎ Ahmed A. Malik, MD Zeenat Qureshi Stroke Institute, 519 2nd St N, St Cloud, MN 56303 ⁎Corresponding author. Department of Cerebrovascular Diseases and Interventional Neurology, CentraCare Health System 1406 6th Ave N St Cloud, MN 56303 Tel.: + 1 320 281 5545; fax: +1 320 281 5547. E-mail addresses: [email protected] (A.I. Qureshi), [email protected] (A.A. Malik) Melissa Freese, RN Michelle J. Thompson, CAGNP CentraCare Health System, Department of Cerebrovascular Diseases and Interventional Neurology, St Cloud Hospital 1406 6th Ave N, St Cloud, MN 56303 E-mail addresses: [email protected] (M. Freese), [email protected] (M. Thompson) Asif A. Khan, MD M. Fareed K. Suri, MD Zeenat Qureshi Stroke Institute, 519 2nd St N, St Cloud, MN 56303 E-mail addresses: [email protected] (A. Khan), [email protected] (M.F.K. Suri) http://dx.doi.org/10.1016/j.ajem.2014.07.020 References [1] Pennlert J, Eriksson M, Carlberg B, Wiklund PG. Long-Term Risk and Predictors of Recurrent Stroke Beyond the Acute Phase. Stroke 2014;45(6):1839–41. [2] Prencipe M, Culasso F, Rasura M, Anzini A, Beccia M, Cao M, et al. Long-term prognosis after a minor stroke: 10-year mortality and major stroke recurrence rates in a hospital-based cohort. Stroke 1998;29(1):126–32. [3] Hankey GJ, Jamrozik K, Broadhurst RJ, Forbes S, Burvill PW, Anderson CS, et al. Long-term risk of first recurrent stroke in the Perth Community Stroke Study. Stroke 1998;29(12):2491–500. [4] Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995; 333(24):1581–7. [5] Hacke W, Kaste M, Bluhmki E, Brozman M, Davalos A, Guidetti D, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008;359(13):1317–29. [6] Activase; Alteplase: A Tissue Plasminogen Avtivator. cited 2014 06/06/2014, Available from: http://www.gene.com/download/pdf/activase_prescribing.pdf. [7] Qureshi AI, Harris-Lane P, Siddiqi F, Kirmani JF. International classification of diseases and current procedural terminology codes underestimated thrombolytic use for ischemic stroke. J Clin Epidemiol 2006;59(8):856–8. [8] Sauer R, Huttner HB, Breuer L, Engelhorn T, Schellinger PD, Schwab S, et al. Repeated thrombolysis for chronologically separated ischemic strokes: a case series. Stroke 2010;41(8):1829–32. [9] Yoo HS, Kim YD, Lee HS, Song D, Song TJ, Kim BM, et al. Repeated thrombolytic therapy in patients with recurrent acute ischemic stroke. J Stroke 2013;15(3):182–8. [10] Topakian R, Gruber F, Fellner FA, Haring HP, Aichner FT. Thrombolysis beyond the guidelines: two treatments in one subject within 90 hours based on a modified magnetic resonance imaging brain clock concept. Stroke 2005;36(11):e162–4. [11] Sposato LA, Salutto V, Beratti DE, Monti P, Riccio PM, Mazia C. Adverse outcome of early recurrent ischemic stroke secondary to atrial fibrillation after repeated systemic thrombolysis. Case Rep Vasc Med 2013;2013:371642. [12] Cambron M, Van Hooff RJ, Nieboer K, De Keyser J, Brouns R. Successful repetitive intravenous thrombolysis in a patient with recurrent brainstem infarctions due to megadolichobasilar ectasia. JAMA Neurol 2013;70(4):520–1. [13] Alhazzaa M, Sharma M, Blacquiere D, Stotts G, Hogan M, Dowlatshahi D. Thrombolysis despite recent stroke: a case series. Stroke 2013;44(6):1736–8.
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