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

Blood ◽  
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.

Sickle Cell Anemia

2017 ◽  
Author(s):  
Eboni I Lance ◽  
Andrew W. Zimmerman
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Blood Cells ◽  
Marrow Transplant ◽  
Neurologic Complications ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Hematological Disorder ◽  
History Of ◽  
Underlying Mechanisms

Sickle cell disease is a genetic hematological disorder involving red blood cells that become deformed when stressed. Patients with homozygous hemoglobin SS disease often have multiple systemic and neurologic complications, particularly stroke. Intellectual disability is commonly seen in the population, in patients with and without a history of stroke, attributed to different underlying mechanisms of brain injury. Autism is rare and not described in sickle cell disease in the literature to date. Many treatments (chronic transfusion therapy, hydroxyurea, bone marrow transplant) are in trials at this time to see if risk of stroke and other neurologic complications can be reduced (ClinicalTrials.gov identifiers: NCT01425307, NCT01389024, NCT00152113).

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

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

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 A cautionary note regarding hydroxyurea in sickle cell disease

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1124-1128
Author(s):  
EP Vichinsky ◽  
BH Lubin
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Course ◽  
Fetal Hemoglobin ◽  
Organ Damage ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
History Of ◽  
Hbf Level

Hydroxyurea can increase fetal hemoglobin (HbF) and improve the clinical course of sickle cell disease (SCD) patients. However, several issues of hydroxyurea therapy remain unresolved, including differences in patients' drug clearance, predictability of drug response, reversibility of sickle cell disease-related organ damage by hydroxyurea, and the efficacy of elevated HbF. We treated two patients with hydroxyurea for periods of 1 to 4 years, monitoring clinical course and laboratory parameters at regular intervals. The first patient (patient A) had a history of chronic pain and extensive hospitalizations. The second patient (patient B) had a history of stroke and refused to continue with chronic transfusion therapy and chelation. Both patients showed a fivefold to tenfold increase in HbF (5% to 25%, 3% to 31%). However, patient A developed an acute chest syndrome, despite an HbF level of 20%. After red blood cell transfusions for hypoxia, the HbF level decreased to 5%. When hydroxyurea dosage was increased, pancytopenia developed and was not resolved until 2 months after hydroxyurea was discontinued; Patient B developed a cerebral hemorrhage on hydroxyurea; he died shortly thereafter. His HbF level was 21% before death. We noted an increase in HbF and a general improvement in the two patients. However, both experienced major SCD-related complications despite HbF levels over 20%. Our findings also suggest that the progressive vascular changes associated with SCD are unlikely to be dramatically affected by increased HbF levels. Because neither the efficacy nor the toxicity of hydroxyurea have been thoroughly investigated, physicians should be cautious in prescribing hydroxyurea for patients with SCD before completion of the National Clinical Trial.

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

Moyamoya Disease Predicts Progression of Cerebral Vasculopathy in Patients with Sickle Cell Disease Despite Chronic Transfusion Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2071-2071 ◽  
Author(s):  
Alyssa M Schlenz ◽  
Michael U Antonucci ◽  
Rebecca Cafiero ◽  
Nina-Serena Burkett ◽  
Julie Kanter
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Moyamoya Disease ◽  
Stroke Prevention ◽  
Conflicts Of Interest ◽  
The Body ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Moya Moya Disease ◽  
History Of

Abstract Introduction: Patients with sickle cell disease (SCD) develop multi-organ complications due to hemolysis, inflammation, and vascular occlusion that results in small vessel obstruction throughout the body. In the brain, however, large cerebral vessels are also damaged resulting in occlusion or stenosis and subsequent development of abnormal collateral vasculature and moyamoya disease. Chronic red cell transfusion (CRCT) therapy significantly reduces the risk of stroke in children with abnormal transcranial doppler (TCD) studies and is also effective in reducing stroke recurrence in those with a history of overt or silent stroke; however, it is unclear if CRCT halts or reverses the progression of vasculopathy. The present study evaluated cerebrovascular stenosis and moya moya disease as risk factors for progression of vasculopathy over time in a cohort of patients with SCD who were started on CRCT therapy as children for stroke prevention. Methods: A retrospective cohort study (with IRB approval) was used to evaluate cerebrovascular changes in patients on CRCT.Patients were included in the study if they had received CRCT for stroke prevention for at least 12 months and had at least two serial magnetic resonance imaging and angiography (MRI/MRA) studies for review. For the imaging analysis, the patient's MRI/MRA closest to the initiation of CRCT (i.e. baseline imaging) was compared to the most recent imaging available by a neuro radiologist who was blind to the patient's clinical history. Additional demographic information included the patient's current age, gender, indication for CRCT, years on CRCT, and laboratory results for pre-transfusion % hemoglobin S (HbS). Results: Forty patients with SCD (current age: M = 16.48, SD = 5.10; 23 male, 17 female) were included. Average duration of CRCT therapy was 9.96 years (SD = 5.67) and average pre-transfusion HbS levels were 42.52% (SD = 9.88). Patients were initiated on therapy due to: overt stroke (n = 19), silent stroke (n = 2), and abnormal TCD (n = 20). Of the 20 patients initiated on therapy due to abnormal TCD, 7 were found to have abnormal MRI at baseline consistent with silent stroke. One of these patients was also found to have co-occurring moyamoya disease, despite no evidence of prior overt stroke. At baseline, 45% (n = 18) of patients had abnormal MRA and 25% (n = 10) had moyamoya disease. Progression of vasculopathy occurred in 15% (n = 6) of patients, all of whom had a history of moya moya disease at baseline (5 patients with overt stroke and 1 with silent stroke). Of the remaining 3 patients with moya moya disease at baseline, 2 remained stable with no improvement and 1 demonstrated improvement on MRA. For patients with abnormal MRA, but no history of moya moya disease (n = 9), 5 demonstrated improvement (2 patients with silent stroke and 3 with overt stroke). Conclusions: Progression of vasculopathy was common among patients with baseline moyamoya disease despite CRCT. Also notable, however, was improvement in vasculopathy (as defined by reduction of stenosis) in 6 patients, the majority of whom had not developed moyamoya prior to the initiation of CRCT suggesting that more mild vasculopathy can be reversed with early intervention. Patients with moya moya disease warrant ongoing annual assessment as they may require vascular bypass to prevent further worsening. Future large, multi-site investigations are needed to identify improved biomarkers and further understand characteristics of patients who demonstrate improvement versus progression of vasculopathy on CRCT. Disclosures No relevant conflicts of interest to declare.

scholarly journals A cautionary note regarding hydroxyurea in sickle cell disease

Blood ◽  
1994 ◽  
Vol 83 (4) ◽  
pp. 1124-1128 ◽  
Author(s):  
EP Vichinsky ◽  
BH Lubin
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Course ◽  
Fetal Hemoglobin ◽  
Organ Damage ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
History Of ◽  
Hbf Level

Abstract Hydroxyurea can increase fetal hemoglobin (HbF) and improve the clinical course of sickle cell disease (SCD) patients. However, several issues of hydroxyurea therapy remain unresolved, including differences in patients' drug clearance, predictability of drug response, reversibility of sickle cell disease-related organ damage by hydroxyurea, and the efficacy of elevated HbF. We treated two patients with hydroxyurea for periods of 1 to 4 years, monitoring clinical course and laboratory parameters at regular intervals. The first patient (patient A) had a history of chronic pain and extensive hospitalizations. The second patient (patient B) had a history of stroke and refused to continue with chronic transfusion therapy and chelation. Both patients showed a fivefold to tenfold increase in HbF (5% to 25%, 3% to 31%). However, patient A developed an acute chest syndrome, despite an HbF level of 20%. After red blood cell transfusions for hypoxia, the HbF level decreased to 5%. When hydroxyurea dosage was increased, pancytopenia developed and was not resolved until 2 months after hydroxyurea was discontinued; Patient B developed a cerebral hemorrhage on hydroxyurea; he died shortly thereafter. His HbF level was 21% before death. We noted an increase in HbF and a general improvement in the two patients. However, both experienced major SCD-related complications despite HbF levels over 20%. Our findings also suggest that the progressive vascular changes associated with SCD are unlikely to be dramatically affected by increased HbF levels. Because neither the efficacy nor the toxicity of hydroxyurea have been thoroughly investigated, physicians should be cautious in prescribing hydroxyurea for patients with SCD before completion of the National Clinical Trial.

Limitations of Clinical Trials in Sickle Cell Disease: A Case Study of the Multi-center Study of Hydroxyurea (MSH) Trial and the Stroke Prevention (STOP) Trial

Hematology ◽  
2007 ◽  
Vol 2007 (1) ◽  
pp. 482-488 ◽  
Author(s):  
Michael R. DeBaun ◽  
Joshua J. Field
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Stop Trial ◽  
History Of ◽  
Secondary Analyses ◽  
Multi Center Study ◽  
Center Study

AbstractIn the past two decades, two landmark randomized controlled trials (RCT) have been completed among individuals with sickle cell disease (SCD), the Multi-center Study of Hydroxyurea (MSH) trial and the Stroke Prevention (STOP) trial. The MSH trial tested the hypothesis that hydroxyurea will reduce the frequency of painful episodes for adults with hemoglobin SS who had a history of 3 or more painful episodes per year. The STOP trial tested the hypothesis that among children with hemoglobin SS and an elevated transcranial Doppler (TCD) velocity measurement, blood transfusion therapy would decrease the risk of an initial stroke. After completion, both trials have defined standard care for individuals with hemoglobin SS. The purpose of this review is to examine the limitations of the MSH and STOP trials. In the context of these trials, we will examine the effects of narrow inclusion criteria that primarily include participants with hemoglobin SS and secondary analyses that are prone to false-positive results. In addition, we describe how after publication of these two trials use of hydroxyurea and TCD assessment has drifted towards a standard practice without evidence of therapeutic efficacy among groups that were excluded from the trials. Finally, we suggest that rigorously conducted RCTs or at the minimum multicenter observation studies with strong methodology should be performed in these excluded subgroups to confirm a benefit of hydroxyurea or TCD measurement.

Nocturnal Hypertension Associated with Stroke and Silent Cerebral Infarcts in Children with Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Kaitlin Strumph ◽  
Michael Hafeman ◽  
Saritha Ranabothu ◽  
William Gomes ◽  
Steven Benitez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Ambulatory Blood Pressure ◽  
Masked Hypertension ◽  
Cell Disease ◽  
Cerebral Infarcts ◽  
Nocturnal Hypertension ◽  
History Of ◽  
Blood Pressures

Background: Strokes and silent cerebral infarcts (SCIs) lead to significant morbidity and mortality in children with sickle cell disease (SCD). Discovering modifiable risk factors is paramount to decreasing the incidence and progression of these devastating cerebrovascular outcomes. Higher systolic blood pressures have previously been shown to increase risk for stroke and SCIs however patients with SCD often have lower clinic blood pressures than the general population. 24 hour ambulatory blood pressure monitoring (ABPM) allows for more robust examination of blood pressure values. Previous studies have investigated associations with abnormal ABPM parameters and end-organ dysfunction, mainly SCD nephropathy. Associations with cerebrovascular events have not yet been investigated. This study aimed to determine if there is an association between blood pressure abnormalities on ABPM with stroke and silent cerebral infarcts. Methods: A cross-sectional study was performed. Children with SCD were enrolled and completed a 24-hour ABPM. Of this cohort, children with HbSS or HbSβ0 with a documented MRI brain within a year of the ABPM were included in the analysis. SCIs were defined as discrete, infarct-like T2 hyperintense lesions measuring at least 3mm in diameter on two orthogonal imaging sequences. Bivariate analyses were performed to identify the association between ambulatory blood pressure parameters with cerebrovascular outcomes specifically SCI or history of stroke. Results: A final cohort of 42 children with a median age of 13 years (10, 17) was included in the analysis. Seven (17%) had a history of stroke, 7 (17%) had documented SCIs, and the remaining 28 (67%) had no history of stroke or SCIs. Masked hypertension was seen in 5% of subjects and nocturnal hypertension was seen in 25%. Abnormal overnight dipping noted in 85% of subjects. The presence of nocturnal hypertension was significantly higher in the SCI/stroke group (55% vs 12%, p = 0.01). Sensitivity analyses were performed to determine if blood pressure abnormalities continued to show an association with cerebrovascular findings when stroke patients were removed. Nocturnal hypertension remained significantly associated with the presence of SCIs (p = 0.006). The median systolic load (percentage of blood pressures above the 95th percentile on ABPM), while below the cutoff for hypertension in both cohorts, was higher in the stroke/SCI group (18.6) compared to the group without SCIs or stroke (6.1), but did not meet statistical significance (p = 0.07). Conclusions: This study reveals an association between nocturnal hypertension and a higher prevalence of SCI and stroke in children with SCD. Our findings also confirm the high prevalence of nocturnal hypertension and impairment of nocturnal dipping seen in this population. Adequately powered, prospective cohorts of ABPM in SCD patients are needed to further evaluate causation between nocturnal hypertension and cerebrovascular outcomes. Disclosures No relevant conflicts of interest to declare.

Increased Pre-Transfusion Reticulocytosis Among Chronically Transfused Sickle Cell Disease Patients Is Associated With More Severe Cerebral Vasculopathy

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1163-1163
Author(s):  
Megha Kaushal ◽  
Ross M. Fasano ◽  
Colleen Byrnes ◽  
Naomi L.C. Luban ◽  
Emily Riehm Meier ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Sickle Cell Disease ◽  
Magnetic Resonance Angiography ◽  
Sickle Cell ◽  
Control Group ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Blood Samples ◽  
History Of ◽  
The Mean

Abstract Chronic red blood cell transfusion therapy is indicated for primary and secondary stroke prevention in children with sickle cell disease (SCD). The main transfusion goal is achievement of pre-transfusion sickle hemoglobin (HbS) levels of 30%. Unfortunately, there continues to be a population of patients with a history of stroke who have progressive vasculopathy and/or secondary stroke, despite chronic transfusion therapy. Predictive markers for vasculopathy and cerebral events are needed to identify patients at risk for disease progression. Increased reticulocytosis was previously associated with other sickle cell disease complications, and adherent reticulocytes may contribute to the vascular pathology. The objective of this study was to explore the hypothesis that pre-transfusion reticulocytosis may serve as a disease severity marker for cerebral vasculopathy among chronically transfused children with sickle cell disease. After obtaining consent and assent, reticulocytosis was studied in a cohort of pediatric sickle cell patients treated with chronic transfusions (n=33, ages 2-17 years). The group was stratified into three groups: group 1 with an abnormal transcranial doppler (TCD) study in the absence of magnetic resonance angiography (MRA) detected vasculopathy [TCD(+), MRA(-), n=14], group 2 with a history of a stroke in the absence of MRA-detected vasculopathy [Stroke(+), MRA(-), n=5], and group 3 with a history of abnormal TCD or stroke and more severe vasculopathy detected by magnetic resonance angiography [MRA(+), n=14]. Pre-transfusion blood samples were analyzed within 72 hours of collection. Steady-state blood samples were also examined from a control group of pediatric SCD patients (>6 years of age) with normal TCD studies who were receiving supportive care in the absence of chronic transfusions or hydroxyurea (n=7). Hematologic data, including automated complete blood counts, absolute reticulocyte counts (ARC) with reticulocyte maturity were obtained. In addition, a flow cytometric approach was developed to further examine and quantitate reticulocyte subsets based upon staining with thiazole orange combined with CD36, CD45, CD49d, CD71, and CD235. The pre-transfusion HbS levels were not statistically different among the three transfused groups ([TCD(+), MRA(-)]: 30.2 ± 11.8%; [Stroke(+), MRA(-)]: 28.4 ± 3.3%; [MRA(+)]: 33.3 ± 9%, p>0.3). The high levels of reticulocytosis in the pre-transfusion samples were similar to those measured in the control group (ARC: 451 ± 126 K/uL in the chronically transfused cohort; ARC: 369 ± 94 K/uL in the control group, p=0.11). Pre-transfusion reticulocytosis was detected in every chronically transfused subject (ARC range 151-701 K/ul). The mean ARC in the [TCD(+), MRA(-)] group was not significantly different from the [Stroke(+), MRA(-)] group (411 ± 135 K/uL and 396 ± 97 K/uL respectively, p=0.82). However, the mean ARC in the [MRA(+)] group (512 ± 107 K/uL) was significantly higher than the control group, the [TCD(+), MRA(-)] group and the [Stroke(+), MRA(-)] group (p<0.05). The increased ARC in the MRA(+) group included higher absolute numbers of circulating reticulocytes at all stages of maturation including the immature reticulocyte subset [CD36(+), CD71(+)] that was detected in every sample. These data suggest that reticulocytosis with the release of immature CD36(+), CD71(+) cells into the peripheral blood remains as a characteristic feature of pediatric SCD even among chronically transfused patients. More severe vasculopathy, detected by MRA, was associated with significantly higher levels of pre-transfusion reticulocytosis. As such, reticulocytosis should be explored further as a marker or a potential contributor to more severe vasculopathy among chronically transfused children with SCD. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document