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

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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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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Discontinuation of long-term transfusion therapy in patients with sickle cell disease and stroke

The Journal of Pediatrics ◽

10.1016/s0022-3476(97)70108-2 ◽

1997 ◽

Vol 131 (5) ◽

pp. 757-760 ◽

Cited By ~ 31

Author(s):

Sohail Rana ◽

Patricia E. Houston ◽

Narita Surana ◽

Eglal I. Shalaby-Rana ◽

Oswaldo L. Castro

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Transfusion Therapy

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

Blood ◽

10.1182/blood-2010-01-261123 ◽

2011 ◽

Vol 117 (3) ◽

pp. 772-779 ◽

Cited By ~ 154

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.

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

Pediatric Blood & Cancer ◽

10.1002/pbc.21338 ◽

2008 ◽

Vol 50 (3) ◽

pp. 599-602 ◽

Cited By ~ 3

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

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Silent Cerebral Infarcts and Cerebral Aneurysms Are Prevalent in Adults with Sickle Cell Disease

Blood ◽

10.1182/blood.v124.21.2712.2712 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2712-2712

Author(s):

Adetola A. Kassim ◽

Sumit Pruthi ◽

Matthew Day ◽

Michael R. DeBaun ◽

Lori C. Jordan

Keyword(s):

Sickle Cell Disease ◽

Cerebral Aneurysm ◽

Sickle Cell ◽

Cerebral Aneurysms ◽

Cell Disease ◽

Cerebral Infarcts ◽

Transfusion Therapy ◽

History Of ◽

The Brain ◽

Saccular Aneurysms

Abstract Introduction: Neurologic complications are a major cause of morbidity in sickle cell disease (SCD). The cumulative cerebral risk for neurological complications in sickle cell anemia has been estimated around 50% by age 14 (Bernaudin et. al, 2011;Blood 4:1130-40). Silent cerebral infarcts (SCI), is the most commonly recognized cause of neurological injury, associated with cognitive difficulties (King et al, Am J Hematol 2014;89:162-7) found in 20-40% of children with SCD, more common in genotype SS or Sβ0 thalassemia. The prevalence of SCI has not been well studied in adults. The prevalence of intracranial saccular aneurysms by radiographic and autopsy series is estimated to be 3.2% in a population without comorbidity, a mean age of 50 years, and a 1:1 gender ratio. (Valk et al, Lancet Neurol 2011; 10: 626–36) while other investigators found a 1.8% prevalence and no increased incidence with age (Vernooij et al NEJM 2007;357:1821-8). The goal of this study was to assess the prevalence of neurologic morbidity, including SCI, overt stroke, and cerebral aneurysm, in a large cohort of adults with SCD. We hypothesized the SCI would be more prevalent in adults compared to children with SCD. Methods: Due to the high prevalence of cerebral infarcts in children with SCD, we elected to obtain as part of routine clinical practice, a MRI and magnetic resonance angiography (MRA) of the brain in adults with SCD in our Hematology clinic. As standard care if SCIs are seen, neurocognitive testing is recommended, and based on this testing and MRI results, appropriate patients are referred for vocational rehabilitation service. All MRIs and MRAs were reviewed by 2 board certified neuroradiologists and consensus findings were recorded including presence of cerebral infarcts, intracerebral hemorrhage, aneurysms and cerebralvasculopathy. All adults with SCD were followed by a single hematologist and were asked about neurological symptoms. Medical records were reviewed to see if stroke like symptoms had been reported. If no symptoms were reported and no abnormalities were documented on neurological examination, then infarcts were judged to be silent. Results: The study population included 94 adults with SCD (80% HbSS or Hb Sβ0 thalassemia; 11% HbSC, and 9% other), 51% males, median age 26 years, interquartile range (22-36 years) who had MRI of the brain and 88 had MRA of the brain. Of these, 91 MRIs were of sufficient quality to assess for the presence or absence of infarcts. Infarcts were present in 58% (53 individuals) with multiple infarcts in 40% (37 patients); infarcts were overt/symptomatic in 13% (12) and silent in 45% (41). Hemorrhages were present in 8 patients (9%) and of these, 7 of 8 also had infarcts present on MRI. MRI and MRA of the brain were felt of adequate quality to assess for vascular disease or aneurysm in 79 patients. Of these 7.5% (6 of 79 patients) had moyamoya vasculopathy and 7.5% (6 of 79 patients) had saccular aneurysms with no overlap between groups. All of the adults with moyamoya vasculopathy had overt strokes. The aneurysms were incidental findings and all were <5mm in size. Patients were referred to Neurosurgery for evaluation of aneurysmal lesions. Amongst the 12 adults with a history of overt stroke, 67% were on therapy (50% on hydroxyurea therapy; 17% on chronic blood transfusion therapy), 42% (5 of 12) received aspirin for stroke and 1 patient was already on warfarin for history of systemic thrombosis at the time of stroke. Conclusions: Silent cerebral infarctions are common in adults with SCD. Silent cerebral infarcts were present in 45% and over strokes had occurred in 13% of adults with SCD. Our aneurysm prevalence of 7.5% in a younger cohort (median age 26 years) suggests that adults with SCD may have a higher prevalence of cerebral aneurysms than the general population. Further study is warranted to assess whether SCD should be considered a comorbidity that confers a higher risk of cerebral aneurysm in adults. The optimal strategies for primary and secondary stroke prevention and to mitigate against the progressive cerebral vasculopathy in adults with SCD are still being debated. Disclosures No relevant conflicts of interest to declare.

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Hypertransfusion Therapy in Sickle Cell Disease in Nigeria

Advances in Hematology ◽

10.1155/2014/923593 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Ademola Samson Adewoyin ◽

Jude Chike Obieche

Keyword(s):

Health Status ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Blood Component ◽

Transfusion Medicine ◽

Cell Disease ◽

Transfusion Therapy ◽

Careful Patient ◽

Prevention And Treatment

Introduction. Hypertransfusion refers to chronic blood transfusion therapy aimed at ameliorating disease complications in various haemopathies particularly the haemoglobinopathies. In sickle cell disease, hypertransfusion is aimed at maintaining patient’s haemoglobin level at 10 to 11 g/dL using haemoglobin AA blood and its resultant dilutional effect on sickle haemoglobin is sustained by intermittent long-term transfusions.Aim and Objective. This paper highlights hypertransfusion and its privileged position as a secondary measure in prevention and treatment of sickle cell disease, especially in the Nigerian context.Materials and Methods. Relevant literatures were searched on PubMed, Google Scholar and standard texts in haematology and transfusion medicine. Keywords used in the search are hypertransfusion, sickle cell disease, chronic transfusion, and Nigeria. Literatures gathered were reviewed, summarized, and presented in this paper.Result. Immense clinical benefit is associated with hypertransfusion therapy including prevention of stroke and amelioration of severe sickle cell disease especially in transplant ineligible patients. Careful patient selections, appropriate blood component, and prevention of transfusion hazards as well as oversight function of an experienced haematologist are pertinent to a successful hypertransfusion therapy.Conclusion. Improved knowledge of the benefits and practice of hypertransfusion will effectively translate into improved health status even among Nigerian sickle cell disease patients.

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Increased blood requirements during long-term transfusion therapy for sickle cell disease

The Journal of Pediatrics ◽

10.1016/s0022-3476(05)82155-9 ◽

1991 ◽

Vol 118 (3) ◽

pp. 405-407 ◽

Cited By ~ 9

Author(s):

Alan R. Cohen ◽

George R. Buchanan ◽

Marie Martin ◽

Kwaku Ohene-Frempong

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

Transfusion Therapy

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Hydroxyurea for the Prevention of Stroke and Other Vasoocclusive Complications in Children with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3792.3792 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3792-3792 ◽

Cited By ~ 1

Author(s):

Markus Schmugge ◽

Karin Zurbriggen ◽

Manuela Albisetti ◽

Marlies Schmid ◽

Ralf W. Baumgartner ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Stroke Prevention ◽

Stroke Recurrence ◽

Healthy Children ◽

Cell Disease ◽

Therapeutic Alternative ◽

Stop Trial ◽

Hydroxyurea Treatment

Abstract Due to the immigration of families of Mediterranean, Asian and African origins to Switzerland an increasing number of children with Sickle Cell Disease (SCD) are being followed in our centers. The Swiss Pediatric Sickle Cell Disease Registry is aimed to study prognostic aspects and the outcome of different therapeutic approaches. Particularly, indications for hydroxyurea treatment and the effects of its long-term use are assessed. The risk of stroke in children with sickle cell disease (SCD) is approximately 200–300-fold greater compared to healthy children. 10% of children with SCD have a specially high risk for stroke with an incidence of 1 in 100 children per year. The US stroke prevention (STOP) trial has demonstrated the benefit of regular red cell transfusions for stroke prevention; however hemochromatosis is frequent and blood-borne infections can occur. Hydroxyurea (HU) can be a therapeutic alternative for the prevention of stroke in children with SCD and other severe vasoocclusive complications (VOC). From 52 children in our centers with SCD or with compound hemoglobinopathies 27 (median age 10.5, range 3.8–19 y) are treated with HU and were followed for 9–101 (mean 47) months. 16 received HU for recurrent VOC, including 4 children with chest syndrome. Two children recieved HU for silent cerebral infarctions and after stroke, respectively (Jehovas Witness). In 9 children HU was commenced for pathological transcranial dopppler ultrasonography (TCD) results according to the STOP trial criteria. TCDs were performed in all SCD patients once a year, in children with conditional TCDs every 6 months, and every 3 months in patients with pathological TCD results. Upon observation of two pathological TCDs at 2–3 months interval, HU was initiated with 10 to maximally 30 mg/kg/day. HU was well tolerated in all patients and no leuko- or neutropenia was observed. No stroke, stroke recurrence, chest syndrome or splenic sequestration was observed during HU treatment and the average number of hospital days/y before (9d) and after 12 months of HU (3d) were reduced significantly (P=0.002). However after 12–24 months, abnormal lung function and growth retardation did not improve significantly. Laboratory studies documented a significant increase in total Hb (mean 79 to 93 g/l; P=0.03), HbF (9 to 23%; P=0.0001) and MCV (83 to 94 fl; P=0.001) and a significant decrease of HbS (86 to 71%; P<0.0001), WBC (7,8 to 5.4; P<0.05) and bilirubin (54 to 36 umol/l; P<0.05) after 12 months of HU. In children that had received HU for pathological TCDs the increase of HbF resulted in a reduction of the middle cerebral arteries blood flow velocities as soon as after 5–7 months. We conclude that HU is a promising therapeutic alternative for the prevention of stroke and other VOC in SCD. Safety and efficacy of this treatment in children has to be assessed by further long-term studies.

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