Blood transfusion therapy is feasible in a clinical trial setting in children with sickle cell disease and silent cerebral infarcts

Abstract Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.

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Encephaloduroarteriosynangiosis (EDAS) For Patients With Sickle Cell Disease

Blood ◽

10.1182/blood.v122.21.999.999 ◽

2013 ◽

Vol 122 (21) ◽

pp. 999-999

Author(s):

Jeffrey D. Lebensburger ◽

Christina J. Bemrich-Stolz ◽

Christoph Griessenauer ◽

Lee Hilliard ◽

Thomas H. Howard ◽

...

Keyword(s):

Clinical Trial ◽

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Stroke Prevention ◽

Case Series ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Transfusion Therapy ◽

Indirect Revascularization

Abstract Introduction Regular blood transfusion therapy is the standard care for secondary prevention of strokes in sickle cell disease (SCD). Despite regular blood transfusion therapy approximately 45% of the children with strokes will have progressive neurological disease (overt strokes or new silent cerebral infarcts) with an incidence of overt strokes of 3.2 events/100 patient-years (95% confidence interval, 1.3-6.5) (Hulbert, Blood 2011). Limited additional therapeutic options exist for these patients. Encephaloduroarteriosynangiosis (EDAS) is a neurosurgical procedure to improve cerebral blood flow by transposing scalp arteries onto the surface of the brain. Five previously published series reported a total of 41 EDAS or indirect revascularization procedures on patients with SCD aged 3-22 yrs. Three of 41 patients (7%) had a stroke at 24 hours, 5 days and three weeks following EDAS/indirect revascularization. Additionally, one patient developed TIA 12 months later, two patients developed intracranial hemorrhage, and one patient died from a pulmonary embolus during an episode of acute chest syndrome 48 months post-EDAS. To date, the incidence of complications and efficacy of EDAS procedure in stroke prevention has not been well established. Objectives To examine the incidence of overt stroke pre and post-EDAS for patients on chronic transfusion. Methods We studied a pediatric cohort with history of HbSS and SB0 thalassemia on chronic transfusion for CNS injury who underwent EDAS at the University of Alabama at Birmingham. The incidence of overt stroke pre- and post-EDAS was reviewed. All pre-transfusion hemoglobin and percent Hemoglobin S levels were recorded from the time of their first recorded abnormal MRI. To determine the acute complications of EDAS, we reviewed the peri-operative hospital records at the time of EDAS, post-EDAS emergency room visits and chronic transfusion clinic visits post EDAS. Results A total of 13 patients on chronic transfusion for secondary stroke prevention underwent 17 EDAS procedures for recurrent stroke, progressive vascular disease, or neurologic change including psychosis and decline in neuropsychometric scores. The mean time to EDAS was 80 months (median 56) from their first abnormal MRI in the medical records. The patients’ mean pre-transfusion hemoglobin level was 9.4 g/dL and mean HbS was 29.5%. All participants (n=13) maintained a mean pre-transfusion HbS < 40%; 62% (8/13) participants maintained a mean HbS <30% (two patients with elevated HbS were transitioned to hydroxyurea as part of a clinical trial). Prior to EDAS, three patients had a new overt stroke during 81 patient years.(3.7 strokes per 100 pt yrs) One of 17 EDAS procedures was complicated by an acute stroke one month after the procedure. No additional strokes occurred in these patients during 34 patient years.(3 strokes per 100 pt yrs) One child developed a chronic subdural hematoma one month post-EDAS requiring burr hole drainage; this patient had a complete recovery. Conclusion This case series represents the largest cohort of EDAS procedures for children with SCD, and in combination with the literature, suggests that patients with progressive CNS disease may benefit from EDAS. A multicenter retrospective case series should be completed to identify risk factors for progression status post an EDAS procedure followed by a clinical trial to determine the effectiveness of the procedure versus regular blood transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

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Abstract TP402: Sickle Cell Disease in Pediatric Stroke - Inpatient Resource Utilization in the Decade Following STOP

Stroke ◽

10.1161/str.48.suppl_1.tp402 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

J. Michael Taylor ◽

Paul Horn ◽

Heidi Sucharew ◽

Todd A Abruzzo ◽

Jane Khoury

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Care Utilization ◽

Cell Disease ◽

Common Procedure ◽

Transfusion Therapy ◽

Stroke Population ◽

Clinical Classification Software ◽

Inpatient Database

Background: Sickle cell disease (SCD) is an important risk factor for stroke in children. Natural history studies demonstrate that greater than 10% of hemoglobin SS patients suffered ischemic stroke prior to age 20 years. In 1998, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) successfully demonstrated the role for routine transfusion therapy in reducing stroke in at risk SCD patients. Fullerton and colleagues then found that first time stroke in SCD decreased in Californian children in the 2 years following STOP. We investigated the stroke rate and health care utilization of children with SCD for two calendar years in the decade following publication of the STOP trial using a national inpatient database. Methods: The 2000 and 2009 Kids’ Inpatient Database (KID) were used for analysis. SCD and stroke cases were identified by ICD-9 codes 282.6x, 430, 431, 432.9, 434.X1, 434.9, 435.9. We queried the KID procedural clinical classification software for utilization of services pertinent to SCD and stroke; transfusion, MRI, and cerebral angio. Results: In 2000, SCD was a discharge diagnosis in 34,294 children and 158 (0.46%) children had SCD and stroke. By 2009, discharges with SCD rose to 37,082 children with 212 (0.57%) children carrying both diagnoses. In 2000 and 2009, AIS is the most common stroke type at 83%, males account for 53% of stroke and black race was reported by 92% of SCD and stroke subjects. Procedure utilization is higher in the SCD and stroke population than in SCD without stroke (Figure 1). Blood transfusion is the most common procedure in both study years, significantly higher in stroke subjects. Conclusion: For pediatric inpatients with SCD, blood transfusion and diagnostic cerebrovascular procedures were significantly more common in the cohort with comorbid stroke. In the decade after STOP, children hospitalized with SCD and stroke represented less than 0.6% of the total inpatient SCD population.

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Retinal microvascular analysis using Fundus Fluorescein Angiography in Egyptian sickle cell disease patients

QJM ◽

10.1093/qjmed/hcab113.067 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Nayera H El Sherif ◽

Mahmoud A Kenny ◽

Waheed S Elhalfawy

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Fluorescein Angiography ◽

Sickle Cell ◽

Large Sample Size ◽

Cell Disease ◽

Fundus Fluorescein Angiography ◽

Transfusion Therapy ◽

Hydroxyurea Treatment ◽

Trans Cranial Doppler

Abstract Background Sickle cell disease can affect retina of eye via vaso-occulsive changes that occur in micro-vessels of retina which could be analysed by using Fundus Fluorescein Angiography. Aim To analyze macular microvascular alternation in patients with SCD by Fundus Fluorescein Angiography (FFA) and to assess the role of potentially contributory Clinico-pathological factors including Trans-Cranial Doppler, genotypes, hydroxyurea, transfusion therapy and finally iron overload state on the development of macular alterations. Method This was across-sectional study which included 30 Sickle cell disease patients randomly recruited from the Paediatric Haematology clinic, children Hospital, Ain Shams University, Cairo, Egypt. Complete blood count (CBC), Trans-Cranial Doppler (TCD) and Fundus Fluorescein Angiography. Results In our study, there were 30 patients with mean age (14.1± 4.02), 5 patients had abnormal/conditional Trans-Cranial, 15 patients had Vaso-occlusive crises, 11 patients were on regular simple blood transfusion; all 30 studied sickle cell disease patients had normal Fundus Fluorescein Angiography and eye examination and only one patient hadabnormal visual acuity;A 29 years oldgirl who had five attacks of cerebral strokes last year, on regular simple blood transfusion and Hydroxyurea treatment with abnormal TCD and recurrent Vaso-occlusive crises in last two years, Although her vision is hand movement yet Fundus Fluorescein Angiography was normal. Conclusion we didn’t find any Retinal microvascular alternation in our studied SCD patients using Fundus Fluorescein Angiography, we related our results to the fact that our studied SCD patients were young and all our studied patients were on hydroxyurea therapy with fair compliance, further studies using large sample size are warranted in order to illustrate the utility of Fundus Fluorescein Angiography (FFA) as a tool for better detection of sickle retinopathy.

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Automated exchange compared to manual and simple blood transfusion attenuates rise in ferritin level after 1 year of regular blood transfusion therapy in chronically transfused children with sickle cell disease

Transfusion ◽

10.1111/trf.15982 ◽

2020 ◽

Vol 60 (11) ◽

pp. 2508-2516

Author(s):

Shannon Kelly ◽

Mark Rodeghier ◽

Michael R. DeBaun

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Ferritin Level ◽

Cell Disease ◽

Transfusion Therapy

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How I treat and manage strokes in sickle cell disease

Blood ◽

10.1182/blood-2014-09-551564 ◽

2015 ◽

Vol 125 (22) ◽

pp. 3401-3410 ◽

Cited By ~ 64

Author(s):

Adetola A. Kassim ◽

Najibah A. Galadanci ◽

Sumit Pruthi ◽

Michael R. DeBaun

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Exchange Transfusion ◽

Management Strategies ◽

Cell Disease ◽

Transfusion Therapy ◽

Hematopoietic Stem ◽

Neuro Imaging

Abstract Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD.

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Chronic Blood Transfusion Therapy Practices to Treat Strokes in Children with Sickle Cell Disease

Journal of the American Academy of Nurse Practitioners ◽

10.1111/j.1745-7599.2005.0046.x ◽

2005 ◽

Vol 17 (7) ◽

pp. 277-282 ◽

Cited By ~ 8

Author(s):

Terianne Lindsey ◽

Nutrena Watts-Tate ◽

Elaine Southwood ◽

Julie Routhieaux ◽

Janice Beatty ◽

...

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Cell Disease ◽

Transfusion Therapy

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Strokes in children with sickle cell disease at the National Hospital Abuja Nigeria

Nigerian Journal of Paediatrics ◽

10.4314/njp.v40i2.10 ◽

2013 ◽

Vol 40 (2) ◽

pp. 158-164

Author(s):

O Oniyangi ◽

P Ahmed ◽

OT Otuneye ◽

J Okon ◽

HA Aikhionbare ◽

...

Keyword(s):

Sickle Cell Disease ◽

Brain Imaging ◽

Clinical Features ◽

Sickle Cell ◽

Stroke Recurrence ◽

Cell Disease ◽

Cerebral Infarcts ◽

National Hospital ◽

Transfusion Therapy

Background: Strokes occur in sickle cell disease (SCD), and are associated with significant morbidity and mortality.Objectives: To determine the prevalence of strokes amongst childrenwith SCD, and document the major clinical features, complications, effect of treatment with chronic transfusion therapy (CTT) and outcome.Methods: A descriptive retrospective study of SCD children with strokes seen at the National Hospital Abuja, Nigeria over a 2.5 year period from January 2009 – June 2012. Data was collected by scrutinizing case files obtained from the hospital medical records unit. Information obtained included demographic data, clinical features, packed cell volume (PCV), brain imaging, long term neurologic deficits, effect of CTT, stroke recurrence and outcome.Results: There were 31 children with strokes among 596 children with SCD documented in the register, giving a prevalence of 5.2%. Twenty six (26) case notes were retrieved. There were 12 males and 14 females, M: F ratio of 0.9:1; mean age was 6.4 years (SD 3.4) range: 1 year 7 months – 14 years; mean PCV at the time of strokes was 21.1% (SD 3.9) range 14 –29%. All (100%) had Haemoglobin SS on electrophoresis. Presentationswere convulsions 18, inability to use limbs 11, weakness of limbs 10; long term neurological deficits were hemiplegia 11, cognition loss 11. Three (3) children had no deficits. Brain imaging (Computed Tomography Scan and Magnetic Resonance Imaging) done in 16 (61.5%) children showed cerebral atrophy in 10, acute cerebral infarcts in 9, chronic cerebral infarcts in 6, acute intra cranial haemorrhage in 1 and normal imagings in 4 children. Twelve (12) children (46.2%) children had recurrences of stroke ranging in number from 1 to 4, which occurred 6 months to 3 years afterthe initial stroke. There were no statistical significant differences between the children with recurrences of stroke compared to those without regarding the age, sex, weight or PCVs p > 0.05. Fifteen (15) children (57.7%) wereenrolled in CTT. Two (2) out of 7 children (28.6%) that had regular CTT had stroke recurrence; compared to 5 out of 11 children (45.4%) with no CTT (p > 0.05). Four (4) out of 6 (66.7%) children with irregular CTT and 1 of 2 children who stopped CTT had stroke recurrence.Outcome: 17 children were alive, 7 were lost to follow up, 1 died and 1 was referred to another center.Conclusion: Strokes were an important cause of morbidity in Nigerianchildren with SCD, with major long term neurologic deficits. CTT appearedbeneficial in preventing stroke recurrences. Primary prevention strategy by Trans Cranial Doppler ultrasound studies of the cerebral arteries, with the aim of promptly initiating appropriate preventive therapy for stroke is strongly advocated.Key words: Sickle cell disease, Stroke, Children, Chronic Transfusion Therapy

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Central nervous system complications and management in sickle cell disease

Blood ◽

10.1182/blood-2015-09-618579 ◽

2016 ◽

Vol 127 (7) ◽

pp. 829-838 ◽

Cited By ~ 110

Author(s):

Michael R. DeBaun ◽

Fenella J. Kirkham

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Sickle Cell Disease ◽

Blood Transfusion ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Stroke Prevention ◽

High Income ◽

Cell Disease ◽

Cerebral Infarcts

Abstract With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ∼11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA (3% and 10%, respectively). In high-income countries, RCTs (Stroke Prevention in Sickle Cell Anemia [STOP], STOP II) have demonstrated that regular blood transfusion therapy (typically monthly) achieves primary stroke prevention in children with SCA and high transcranial Doppler (TCD) velocities; after at least a year, hydroxycarbamide may be substituted (TCD With Transfusions Changing to Hydroxyurea [TWiTCH]). Also in high-income countries, RCTs have demonstrated that regular blood transfusion is the optimal current therapy for secondary prevention of infarcts for children with SCA and strokes (Stroke With Transfusions Changing to Hydroxyurea [SWiTCH]) or silent cerebral infarcts (Silent Infarct Transfusion [SIT] Trial). For adults with SCD, CNS complications continue to be a major cause of morbidity and mortality, with no evidence-based strategy for prevention.

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