scholarly journals Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease

Blood ◽  
2011 ◽  
Vol 117 (3) ◽  
pp. 772-779 ◽  
Author(s):  
Monica L. Hulbert ◽  
Robert C. McKinstry ◽  
JoAnne L. Lacey ◽  
Christopher J. Moran ◽  
Julie A. Panepinto ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Secondary Stroke Prevention ◽  
Cell Disease ◽  
Cerebral Infarcts ◽  
Eligibility Criteria ◽  
Transfusion Therapy

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.

scholarly journals Central nervous system complications and management in sickle cell disease

Blood ◽  
2016 ◽  
Vol 127 (7) ◽  
pp. 829-838 ◽  
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.

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

2008 ◽  
Vol 50 (3) ◽  
pp. 599-602 ◽  
Author(s):  
Allison A. King ◽  
Michael Noetzel ◽  
Desirée A. White ◽  
Robert C. McKinstry ◽  
Michael R. DeBaun
Keyword(s):  
Clinical Trial ◽  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Cell Disease ◽  
Cerebral Infarcts ◽  
Transfusion Therapy ◽  
Clinical Trial Setting ◽  
Trial Setting

Encephaloduroarteriosynangiosis (EDAS) For Patients With Sickle Cell Disease

Blood ◽  
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.

scholarly journals Chronic Manual Exchange Transfusions Compared with Erythrocytapheresis in Children and Teens with Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4927-4927
Author(s):  
Debbie Woods ◽  
Robert J. Hayashi ◽  
Melanie E. Fields ◽  
Monica L. Hulbert
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Secondary Stroke Prevention ◽  
Cell Disease ◽  
Double Lumen ◽  
Transfusion Therapy ◽  
Catheter Complications ◽  
Hb S

Abstract Background: Children and young adults with sickle cell disease (SCD) are at high risk of strokes and are frequently treated with red blood cell (RBC) transfusions. RBCs may be given by simple transfusion, manual exchange transfusion (ME), or erythrocytapheresis (ECP) with a goal of suppressing hemoglobin (Hb) S while minimizing transfusion-induced iron overload. There have been no formal comparisons of these modalities, and practices for transfusion management vary among institutions. We compared transfusion therapy outcomes among patients with SCD undergoing transfusion therapy for primary or secondary stroke prevention, hypothesizing that children would be more likely to achieve Hb S suppression and ferritin goals while receiving ECP. We also compared complications of transfusion therapy across transfusion modalities. Methods: This is a single-institution retrospective cohort study of 38 patients with SCD who received chronic transfusion therapy for primary or secondary stroke prevention from 1/1/2008 through 12/31/2012. Per institutional practice, younger patients receive ME for stroke prevention; they are offered ECP when their size is adequate for a large-bore double-lumen implantable port, but may choose to continue ME. The pre-transfusion Hb S goal is <30% for at least 2 years, then may be liberalized to <50% for subjects without either abnormal transcranial Doppler ultrasound or infarct recurrence. Hb S percentage and ferritin were measured prior to each transfusion. Patients on transfusion therapy for 6 or more months were included; one child who had a stroke after brain tumor biopsy was excluded. Subjects were censored at last date of follow-up or date of hematopoietic stem cell transplant. The following factors were evaluated: duration and mode of transfusion therapy, achievement of Hb S suppression goal, ferritin levels, and catheter complications. Categorical variables were compared with Fisher’s exact test and medians with the Mann-Whitney U-test in SPSS version 21 (IBM, Armonk, NY). Results: During the study period, 38 subjects (42% male) met all inclusion criteria. Of these, 5 received exclusively ECP, 17 received exclusively ME, and 16 received both modalities during the study period. For the most recent 12-month period of data for each participant, 13 received ECP and 25 received ME. There was no association between modality of transfusion and the proportion of visits during which subjects achieved their pre-transfusion Hb S goal during the 12-month period. The median proportion of visits achieving the Hb S goal was 0.80 for ECP (IQR 0.40-1.0) versus 0.50 for ME (IQR 0.28-0.90) (p=0.27). Furthermore, there was no significant difference in ferritin concentrations between transfusion modalities: median 875 ng/ml for ECP (IQR 578-2659) versus median 1527 ng/ml for ME (IQR 731-2568) (p=0.56). Children who had ever received ECP had a significantly longer total duration of transfusion therapy (median 97 months, IQR 51.5-134) than those receiving ME only (median 28 months, IQR 12.5-47) (p<0.001). Among 21 subjects who had ever received ECP, 15 (71.4%) experienced one or more catheter complications, including infection, thrombosis, catheter leakage, or venous stenosis, compared with 1/17 subjects (5.8%) who had never received ECP (OR for catheter complications 40 for subjects who had ever received ECP, 95% CI 4.29, 372.4, p <0.001). Five subjects switched from ECP to ME due to stenosis of the great vessels that precluded double-lumen port replacement. Conclusions: Children with SCD receiving ECP and ME for stroke prevention in this cohort had similar achievement of Hb S suppression goals and iron overload management. Additional patient-specific factors may be responsible for variations in pre-transfusion Hb S and ferritin concentrations. Catheter complications were significantly more common in children and adolescents receiving ECP compared with ME, likely due to the large-bore double-lumen port utilized for ECP at our center. Disclosures No relevant conflicts of interest to declare.

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

Stroke ◽  
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.

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

QJM ◽  
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.

scholarly journals How I treat and manage strokes in sickle cell disease

Blood ◽  
2015 ◽  
Vol 125 (22) ◽  
pp. 3401-3410 ◽  
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.

Financial analysis of chronic transfusion for stroke prevention in sickle cell disease

Blood ◽  
2000 ◽  
Vol 96 (7) ◽  
pp. 2369-2372 ◽  
Author(s):  
Alan S. Wayne ◽  
Steve E. Schoenike ◽  
Charles H. Pegelow
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Financial Analysis ◽  
Allogeneic Bone Marrow Transplantation ◽  
Financial Impact ◽  
Red Blood Cell Transfusion ◽  
Allogeneic Bone ◽  
Cell Disease ◽  
Transfusion Therapy

Abstract Chronic red blood cell transfusion can prevent many of the manifestations of sickle cell disease. The medical costs of chronic transfusion and management of associated side effects, especially iron overload, are considerable. This study was undertaken to evaluate the financial impact of chronic transfusion for stroke prevention in patients with sickle cell anemia. Outpatient charges pertaining to hospital-based Medicare uniform bill (UB-92) codes, professional fees, and iron chelation were evaluated. Data were collected on 21 patients for a total of 296 patient months (mean, 14; median, 14 months/patient). Charges ranged from $9828 to $50 852 per patient per year. UB-92, chelation, and physician-related charges accounted for 53%, 42%, and 5% of total charges, respectively. Of UB-92 charges, 58% were associated with laboratory fees and 16% were related to the processing and administration of blood. Charges for patients who required chelation therapy ranged from $31 143 to $50 852 per patient per year (mean, $39 779; median, $38 607). Deferoxamine accounted for 71% of chelation-related charges, which ranged from $12 719 to $24 845 per patient per year (mean, $20 514; median, $21 381). The financial impact of chronic transfusion therapy for sickle cell disease is substantial with charges approaching $400 000 per patient decade for patients who require deferoxamine chelation. These data should be considered in reference to cost and efficacy analyses of alternative therapies for sickle cell disease, such as allogeneic bone marrow transplantation.

Sign in / Sign up

Export Citation Format

Share Document