"Overview of the causes of venous thrombosis" and "Evaluating adult patients with established venous thromboembolism for acquired and inherited risk factors".) Other causes Other defined traditional stroke mechanisms may be present in patients with SCD. Management is reviewed separately: Small vessel disease (see "Lacunar infarcts") Large vessel atherosclerosis (see "Management of symptomatic carotid atherosclerotic disease" and "Intracranial large artery atherosclerosis: Treatment and prognosis") Cardiogenic embolism (see "Stroke in patients with atrial fibrillation") Role of antiplatelet agents and anticoagulation Antiplatelet agents The efficacy of antiplatelet agents has not been studied for acute treatment or secondary prevention of SCD-associated TIA or ischemic stroke in children or adults [15]. In the general population, aspirin or short-term dual antiplatelet therapy (DAPT) are indicated for most adults with acute TIA or acute ischemic stroke, and antiplatelet therapy may be appropriate for adults with SCD who have an acute TIA or ischemic stroke, particularly if they have traditional stroke risk factors, especially intracranial atherosclerosis. (See "Early antithrombotic treatment of acute ischemic stroke and transient ischemic attack".) https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 13/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Antiplatelet therapy may also be appropriate for secondary stroke prevention in adults with SCD who have traditional stroke risk factors, similar to the general population [16]. (See "Long-term antithrombotic therapy for the secondary prevention of ischemic stroke".) Anticoagulation We generally do not use anticoagulation for ischemic stroke in patients with SCD. However, SCD is a hypercoagulable state, and prophylactic dose anticoagulation may be appropriate for venous thromboembolism (VTE) prophylaxis in those admitted with an acute medical illness, especially adults and those with decreased mobility. (See 'Supportive care' above and "Prevention and treatment of venous thromboembolism in patients with acute stroke".) Anticoagulation may be appropriate for: CVT (see "Cerebral venous thrombosis: Treatment and prognosis") Increased probability of thromboembolic disease, after the immediate risk of hemorrhagic conversion has receded (see "Stroke in patients with atrial fibrillation" and "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome") Administration and adverse events are discussed separately. (see "Venous thromboembolism: Initiation of anticoagulation" and "Venous thromboembolism: Anticoagulation after initial management") INTRACRANIAL HEMORRHAGE MANAGEMENT Intracranial hemorrhage (ICH), also called hemorrhagic stroke, accounts for approximately one- third of cerebrovascular events in patients with SCD and is more common in older individuals [17]. (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Incidence' and "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Risk factors: Hemorrhagic stroke'.) Urgent interventions In addition to acute stabilization of the patient as described above (see 'Immediate evaluation and management' above), the following should be done immediately ( algorithm 1): Discontinue all anticoagulants and antiplatelet agents, unless the benefits of continuing are thought to outweigh their risks for that patient, such as in the setting of CVST and hemorrhagic venous infarction or a prosthetic heart valve where anticoagulation might be held briefly for stabilization and then restarted. https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 14/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate For patients receiving an anticoagulant, decide whether a reversal agent is needed. For those who have received a short-acting anticoagulant for which several half-lives have passed, reversal may not be required. For patients with thrombocytopenia, administer platelet transfusions as necessary to maintain the platelet count 100,000/microL. Obtain neurosurgical consultation if a procedure may be required to reduce intracranial pressure or to treat a bleeding aneurysm. Obtain imaging such as CT- or MR-angiography to guide further therapy in most cases. Management of ICH and subarachnoid hemorrhage (SAH) in the general population is discussed separately. (See "Spontaneous intracerebral hemorrhage: Acute treatment and prognosis" and "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Nonaneurysmal subarachnoid hemorrhage".) Additional therapy according to type of bleed Hemorrhagic transformation of arterial ischemic stroke Hemorrhagic transformation of an ischemic stroke should be managed as with other causes of hemorrhagic stroke, including stopping and reversing any anticoagulation, correcting any coagulopathy, and transfusing platelets as needed. Transfusion is appropriate. (See 'Transfusion' above.) Cerebral venous sinus thrombosis (CVST) Management is similar to individuals without SCD. (See "Cerebral venous thrombosis: Treatment and prognosis".) SAH from aneurysmal bleeding Initial treatment of SAH includes intensive care monitoring, analgesia, and close attention to blood pressure control; as well as ventriculostomy for those with increased intracranial pressure. Aneurysm repair should be attempted if possible. Details are presented separately. (See "Aneurysmal subarachnoid hemorrhage: Treatment and prognosis" and "Treatment of cerebral aneurysms" and "Nonaneurysmal subarachnoid hemorrhage".) Patients with SAH who are undergoing surgery should have exchange transfusion if possible prior to surgery, to reduce sickle hemoglobin to <30 percent of total hemoglobin; ideally surgery is performed within a week of exchange transfusion. (See "Red blood cell transfusion in sickle cell disease: Indications and transfusion techniques", section on 'Prophylactic preoperative transfusion'.) https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 15/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Intraventricular hemorrhage (IVH) IVH may occur when subarachnoid or intraparenchymal hemorrhage extends into the ventricles [18]. Patients with prior ischemic stroke may be at risk for IVH and intraparenchymal hemorrhage, even months to years later [19]. Hemorrhage into the third ventricle or cerebral aqueduct confers a high risk for late deterioration. Patients may be awake and alert immediately following the bleed and become comatose over the ensuing 48 hours because of obstructive hydrocephalus and ventricular dilation. Emergency ventricular drainage may be necessary [20]. Management is discussed separately. (See "Intraventricular hemorrhage".) Despite these interventions, mortality from ICH in SCD is as high as 24 to 30 percent [14,17]. Deaths generally occur within the first two weeks, many on the first day [17]. Some individuals have moderate to severe residual disability [21]. FOLLOW-UP AFTER THE ACUTE EVENT Repeat imaging If the initial magnetic resonance imaging (MRI) study does not show ischemic injury and clinically the patient seemed to have a stroke or transient ischemic attack (TIA), we perform a repeat MRI of the brain two to four weeks after the initial presentation, since diffusion weighted images of the brain may rarely be negative upon presentation and may still demonstrate very small areas of ischemic injury upon subsequent imaging [22]. Secondary stroke prevention Secondary stroke prevention is critical, typically involving chronic transfusions. (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Prevention of recurrent ischemic stroke (secondary stroke prophylaxis)' and "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Prevention of hemorrhagic strokes'.) Cognitive or behavioral dysfunction (See "Prevention of stroke (initial or recurrent) in sickle cell disease", section on 'Management of cognitive and behavioral dysfunction'.) Motor deficits (See "Overview of geriatric rehabilitation: Patient assessment and common indications for rehabilitation", section on 'Stroke' and "Overview of ischemic stroke prognosis in adults", section on 'Interventions that improve outcomes'.) SOCIETY GUIDELINE LINKS https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 16/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sickle cell disease and thalassemias" and "Society guideline links: Stroke in children".) PATIENT PERSPECTIVE TOPIC Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Sickle cell disease".) SUMMARY AND RECOMMENDATIONS Presentation Acute ischemic stroke due to cerebral vaso-occlusion is the first consideration in patients with sickle cell disease (SCD) who present with new neurologic findings or severe headache. Hemorrhagic stroke accounts for one-third of events. It is important not to overlook other potential causes of neurologic deterioration, including transient ischemic attack (TIA), cerebral venous thrombosis (CVT), seizure, infection, and other stroke mimics. (See 'Presentation' above.) Immediate measures Management involves initial stabilization by clinicians with expertise in stroke and SCD, supplemental oxygen to maintain saturation >95 percent, rapid clinical assessment and baseline laboratory testing, and simple transfusion, followed by neuroimaging ( algorithm 1). Patients with fever should receive empiric broad- spectrum antibiotics and antipyretics. (See 'Immediate evaluation and management' above.) Neuroimaging Brain and neurovascular imaging is essential to differentiate ischemia from hemorrhage, exclude stroke mimics, and assess large cervical and intracranial arteries. Magnetic resonance imaging (MRI) is generally preferred. (See 'Neuroimaging' above.) Transfusion For patients with SCD who have a suspected or confirmed stroke (ischemic or hemorrhagic) or TIA, we suggest exchange transfusion (Grade 2C). The goal is to lower the percentage of sickle hemoglobin to <30 percent of total hemoglobin (typically to 15 to 20 percent) without raising the total hemoglobin >10 g/dL and causing hyperviscosity. Simple transfusion is used as a temporizing measure until exchange transfusion can be instituted. (See 'Transfusion' above.) https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 17/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Reperfusion Adults with SCD and acute ischemic stroke should be evaluated for intravenous thrombolysis and mechanical thrombectomy. (See 'Reperfusion therapy' above.) Mechanism-specific treatment The following is appropriate in addition to immediate assessment, stabilization, and other standard acute stroke management ( algorithm 1): Ischemic stroke or TIA Antiplatelet therapy may be appropriate for adults with SCD who have an acute TIA or ischemic stroke, particularly if they have traditional stroke risk factors. (See 'Role of antiplatelet agents and anticoagulation' above.) Intracranial hemorrhage Neurosurgical evaluation and angiography to guide therapy. Additional interventions for specific types of hemorrhagic stroke are discussed above. (See 'Intracranial hemorrhage management' above.) Moyamoya syndrome Some clinicians start antiplatelet therapy. (See 'Moyamoya syndrome' above.) CVT Heparin anticoagulation, even if hemorrhagic transformation occurs. (See 'Cerebral venous thrombosis' above.) Follow-up Secondary stroke prevention is critical. Repeat imaging, cognitive assistance, and rehabilitation services may be appropriate. (See 'Follow-up after the acute event' above.) ACKNOWLEDGMENTS UpToDate acknowledges ZoAnn Dreyer, MD, who contributed to earlier versions of this topic review. The UpToDate editorial staff also acknowledge the extensive contributions of Donald H Mahoney, Jr, MD to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Kassim AA, Galadanci NA, Pruthi S, DeBaun MR. How I treat and manage strokes in sickle cell disease. Blood 2015; 125:3401. https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 18/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate 2. Ovbiagele B, Kidwell CS, Saver JL. Epidemiological impact in the United States of a tissue- based definition of transient ischemic attack. Stroke 2003; 34:919. 3. Lehman LL, Watson CG, Kapur K, et al. Predictors of Stroke After Transient Ischemic Attack in Children. Stroke 2016; 47:88. 4. Easton JD, Saver JL, Albers GW, et al. Definition and evaluation of transient ischemic attack: a scientific statement for healthcare professionals from the American Heart Association/American Stroke Association Stroke Council; Council on Cardiovascular Surgery and Anesthesia; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; and the Interdisciplinary Council on Peripheral Vascular Disease. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. Stroke 2009; 40:2276. 5. DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv 2020; 4:1554. 6. Hulbert ML, Scothorn DJ, Panepinto JA, et al. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia. J Pediatr 2006; 149:710. 7. Giles MF, Rothwell PM. Risk of stroke early after transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol 2007; 6:1063. 8. Guilliams KP, Fields ME, Ragan DK, et al. Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia. Blood 2018; 131:1012. 9. Juttukonda MR, Lee CA, Patel NJ, et al. Differential cerebral hemometabolic responses to blood transfusions in adults and children with sickle cell anemia. J Magn Reson Imaging 2019; 49:466. 10. https://www.nhlbi.nih.gov/sites/default/files/media/docs/Evd-Bsd_SickleCellDis_Rep2014.pd f (Accessed on July 20, 2018). 11. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA 2014; 312:1033. 12. Alakbarzade V, Maduakor C, Khan U, et al. Cerebrovascular disease in sickle cell disease. Pract Neurol 2023; 23:131. 13. Adams RJ, Cox M, Ozark SD, et al. Coexistent Sickle Cell Disease Has No Impact on the Safety or Outcome of Lytic Therapy in Acute Ischemic Stroke: Findings From Get With The Guidelines-Stroke. Stroke 2017; 48:686. https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 19/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate 14. Strouse JJ, Lanzkron S, Urrutia V. The epidemiology, evaluation and treatment of stroke in adults with sickle cell disease. Expert Rev Hematol 2011; 4:597. 15. Guilliams KP, Kirkham FJ, Holzhauer S, et al. Arteriopathy Influences Pediatric Ischemic Stroke Presentation, but Sickle Cell Disease Influences Stroke Management. Stroke 2019; 50:1089. 16. Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke 2021; 52:e364. 17. Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood 1998; 91:288. 18. Adams RJ, Nichols FT. Sickle cell anemia, sickle cell trait and thalassemia. In: Handbook of Cli nical Neurology, Vascular Disease Part III, Vinken PJ, Bruyn GW, Klawans HL (Eds), Elsevier, A msterdam 1989. p.503. 19. Powars D, Adams RJ, Nichols FT, et al. Delayed intracranial hemorrhage following cerebral infarction in sickle cell anemia. J Assoc Acad Minor Phys 1990; 1:79. 20. Adams RJ. Neurologic complications. In: Sickle Cell Disease: Basic Principles and Clinical Prac tice, Embury SH, Robert P, Hebbel RP, et al (Eds), Raven Press, Ltd, New York 1994. p.599. 21. Oyesiku NM, Barrow DL, Eckman JR, et al. Intracranial aneurysms in sickle-cell anemia: clinical features and pathogenesis. J Neurosurg 1991; 75:356. 22. Makin SD, Doubal FN, Dennis MS, Wardlaw JM. Clinically Confirmed Stroke With Negative Diffusion-Weighted Imaging Magnetic Resonance Imaging: Longitudinal Study of Clinical Outcomes, Stroke Recurrence, and Systematic Review. Stroke 2015; 46:3142. Topic 5926 Version 52.0 https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 20/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate GRAPHICS Cerebrovascular complications with their locations in sickle cell disease Cerebrovascular complications of the large and small vessels of the brain and their corresponding territories are shown. The most common complications are cerebral infarcts in major vessels and "borderzone" infarctions. Borderzone infarctions are most common in the areas between the middle and anterior cerebral arteries, and between the middle and posterior cerebral arteries. Fat embolism and venous side abnormalities are the least common lesions. Small white matter lesions visualized on magnetic resonance imaging can be seen in asymptomatic patients. Multiple cerebral aneurysms can be present within the branches of the circle of Willis. ICA: internal carotid artery; MCA: middle cerebral artery; ACA: anterior cerebral artery; MRI: magnetic resonance imaging; BA: basilar artery. https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 21/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Modi ed from: Adams RJ. Neurologic complications. In: Sickle Cell Disease: Basic Principles and Clinical Practice, Embury SH, Robert P, Hebbel RP, et al (Eds), Raven Press, New York 1994. Graphic 50288 Version 4.0 https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 22/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Management of acute stroke in sickle cell disease SCD: sickle cell disease; IV: intravenous; Hb: hemoglobin; RBC: red blood cell; TIA: transient ischemic attack; I magnetic resonance angiography; CTA: CT angiography; CBC: complete blood count; PT: prothrombin time; a DBP: diastolic blood pressure; ICH: intracerebral hemorrhage; SAH: subarachnoid hemorrhage; MAP: mean a resonance venography; CT: computed tomography. Initial stabilization with a rapid clinical assessment should occur simultaneously with prompt RBC transfusi transfusion are sent while rapid neuroimaging is ordered. https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 23/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate IVT can proceed concurrently with RBC transfusion but should not replace or delay transfusion. Importantl IVT is administered. Graphic 140156 Version 1.0 https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 24/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Eligibility criteria for the treatment of acute ischemic stroke with intravenous thrombolysis (recombinant tissue plasminogen activator or tPA) Inclusion criteria Clinical diagnosis of ischemic stroke causing measurable neurologic deficit Onset of symptoms <4.5 hours before beginning treatment; if the exact time of stroke onset is not known, it is defined as the last time the patient was known to be normal or at neurologic baseline Age 18 years Exclusion criteria Patient history Ischemic stroke or severe head trauma in the previous three months Previous intracranial hemorrhage Intra-axial intracranial neoplasm Gastrointestinal malignancy Gastrointestinal hemorrhage in the previous 21 days Intracranial or intraspinal surgery within the prior three months Clinical Symptoms suggestive of subarachnoid hemorrhage Persistent blood pressure elevation (systolic 185 mmHg or diastolic 110 mmHg) Active internal bleeding Presentation consistent with infective endocarditis Stroke known or suspected to be associated with aortic arch dissection Acute bleeding diathesis, including but not limited to conditions defined under 'Hematologic' Hematologic 3 Platelet count <100,000/mm * Current anticoagulant use with an INR >1.7 or PT >15 seconds or aPTT >40 seconds* Therapeutic doses of low molecular weight heparin received within 24 hours (eg, to treat VTE and ACS); this exclusion does not apply to prophylactic doses (eg, to prevent VTE) Current use (ie, last dose within 48 hours in a patient with normal renal function) of a direct thrombin inhibitor or direct factor Xa inhibitor with evidence of anticoagulant effect by laboratory tests such as aPTT, INR, ECT, TT, or appropriate factor Xa activity assays Head CT Evidence of hemorrhage https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 25/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Extensive regions of obvious hypodensity consistent with irreversible injury Warnings Only minor and isolated neurologic signs or rapidly improving symptoms Serum glucose <50 mg/dL (<2.8 mmol/L) Serious trauma in the previous 14 days Major surgery in the previous 14 days History of gastrointestinal bleeding (remote) or genitourinary bleeding Seizure at the onset of stroke with postictal neurologic impairments Pregnancy** Arterial puncture at a noncompressible site in the previous seven days Large ( 10 mm), untreated, unruptured intracranial aneurysm Untreated intracranial vascular malformation Additional warnings for treatment from 3 to 4.5 hours from symptom onset Age >80 years Oral anticoagulant use regardless of INR Severe stroke (NIHSS score >25) Combination of both previous ischemic stroke and diabetes mellitus ACS: acute coronary syndrome; aPTT: activated partial thromboplastin time; ECT: ecarin clotting time; INR: international normalized ratio; PT: prothrombin time; NIHSS: National Institutes of Health Stroke Scale; tPA: intravenous alteplase; TT: thrombin time; VTE: venous thromboembolism. Although it is desirable to know the results of these tests, thrombolytic therapy should not be delayed while results are pending unless (1) there is clinical suspicion of a bleeding abnormality or thrombocytopenia, (2) the patient is currently on or has recently received anticoagulants (eg, heparin, warfarin, a direct thrombin inhibitor, or a direct factor Xa inhibitor), or (3) use of anticoagulants is not known. Otherwise, treatment with intravenous tPA can be started before availability of coagulation test results but should be discontinued if the INR, PT, or aPTT exceed the limits stated in the table, or 3 if platelet count is <100,000 mm . With careful consideration and weighting of risk-to-benefit, patients may receive intravenous alteplase despite one or more warnings. Patients who have a persistent neurologic deficit that is potentially disabling, despite improvement of any degree, should be treated with tPA in the absence of other contraindications. Any of the following should be considered disabling deficits: Complete hemianopia: 2 on NIHSS question 3, or Severe aphasia: 2 on NIHSS question 9, or Visual or sensory extinction: 1 on NIHSS question 11, or Any weakness limiting sustained effort against gravity: 2 on NIHSS question 5 or 6, or Any deficits that lead to a total NIHSS >5, or https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 26/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Any remaining deficit considered potentially disabling in the view of the patient and the treating practitioner using clinical judgment Patients may be treated with intravenous alteplase if glucose level is subsequently normalized. The potential risks of bleeding with alteplase from injuries related to the trauma should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. The increased risk of surgical site bleeding with alteplase should be weighed against the anticipated benefits of reduced stroke-related neurologic deficits. There is a low increased risk of new bleeding with alteplase in the setting of past gastrointestinal or genitourinary bleeding. However, alteplase administration within 21 days of gastrointestinal bleeding is not recommended. Alteplase is reasonable in patients with a seizure at stroke onset if evidence suggests that residual impairments are secondary to acute ischemic stroke and not to a postictal phenomenon. * Alteplase can be given in pregnancy when the anticipated benefits of treating moderate or severe stroke outweigh the anticipated increased risks of uterine bleeding. The safety and efficacy of administering alteplase is uncertain for these relative exclusions. Although these were exclusions in the trial showing benefit in the 3 to 4.5 hour window, intravenous alteplase appears to be safe and may be beneficial for patients with these criteria, including patients taking oral anticoagulants with an INR <1.7. Adapted from: 1. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med 2008; 359:1317. 2. Del Zoppo GJ, Saver JL, Jauch EC, et al. Expansion of the time window for treatment of acute ischemic stroke with intravenous tissue plasminogen activator. A science advisory from the American Heart Association/American Stroke Association. Stroke 2009; 40:2945. 3. Re-examining Acute Eligibility for Thrombolysis (TREAT) Task Force:, Levine SR, Khatri P, et al. Review, historical context, and clari cations of the NINDS rt-PA stroke trials exclusion criteria: Part 1: rapidly improving stroke symptoms. Stroke 2013; 44:2500. 4. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al. Scienti c rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2016; 47:581. 5. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50:e344. Graphic 71462 Version 26.0 https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 27/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Indications for mechanical thrombectomy to treat patients with acute ischemic IV: intravenous; tPA: tissue plasminogen activator (alteplase or tenecteplase); CTA: computed tomography an artery occlusion; MT: mechanical thrombectomy; ASPECTS: Alberta Stroke Program Early CT Score; NIHSS: Na tomography; MRI: magnetic resonance imaging; mRS: modified Rankin Scale; MCA: middle cerebral artery; IC recovery. Patients are not ordinarily eligible for IV tPA unless the time last known to be well is <4.5 hours. However, im that is diffusion positive and FLAIR negative) is an option at expert stroke centers to select patients with wake associated UpToDate topics for details. Usually assessed with MRA or CTA, less often with digital subtraction angiography. There is intracranial arterial occlusion of the distal ICA, middle cerebral (M1/M2), or anterior cerebral (A1/A2 MT may be a treatment option for patients with acute ischemic stroke caused by occlusion of the basilar ar stroke centers, but benefit is uncertain. [1] Based upon data from the Aurora study . Reference: https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 28/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate 1. Albers GW, Lansberg MG, Brown S, et al. Assessment of Optimal Patient Selection for Endovascular Thrombectomy Beyond 6 Hou Neurol 2021; 78:1064. Graphic 117086 Version 3.0 https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 29/30 7/6/23, 12:22 PM Acute stroke (ischemic and hemorrhagic) in children and adults with sickle cell disease - UpToDate Contributor Disclosures Alex George, MD, PhD Grant/Research/Clinical Trial Support: Forma Pharmaceuticals [Sickle cell disease]. Consultant/Advisory Boards: Agios Pharmaceuticals [Sickle cell disease]; Chiesi USA [Transfusional iron overload]; GBT Pharmaceuticals [Sickle cell disease]. Speaker's Bureau: GBT Pharmaceuticals [Sickle cell disease]. All of the relevant financial relationships listed have been mitigated. Lori Jordan, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Douglas R Nordli, Jr, MD No relevant financial relationship(s) with ineligible companies to disclose. Michael R DeBaun, MD, MPH Consultant/Advisory Boards: Forma therapeutics [Sickle cell disease]; Global Blood Therapeutics [Sickle cell disease]; Novartis [Priapism in sickle cell disease]; Vertex/CRISPR Therapeutics [Sickle cell disease, beta thalassemia]. All of the relevant financial relationships listed have been mitigated. Jennifer S Tirnauer, MD No relevant financial relationship(s) with ineligible companies to disclose. John F Dashe, MD, PhD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/acute-stroke-ischemic-and-hemorrhagic-in-children-and-adults-with-sickle-cell-disease/print 30/30