Risk Factors for Intracranial Hemorrhage in Children with Sickle Cell Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1657-1657
Author(s):  
John J. Strouse ◽  
Michael R. DeBaun ◽  
James F. Casella
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Ischemic Stroke ◽  
Steady State ◽  
Sickle Cell ◽  
Intracranial Hemorrhage ◽  
Sickle Cell Anemia ◽  
Small Sample ◽  
Acute Chest Syndrome ◽  
Corticosteroid Administration

Background: Intracranial hemorrhage (ICH) is an uncommon, but devastating, complication of sickle cell disease (SCD) with mortality from 30 to 65%. Most reported cases are in adults; little is known about children. Proposed risk factors include previous ischemic stroke, aneurysms, low steady-state hemoglobin, high steady-state leukocyte count, acute chest syndrome, and hypertransfusion. Methods: Retrospective case-control study designed to characterize and evaluate risk factors for ICH among children with SCD age < 19 years hospitalized at Johns Hopkins Children’s Center from January 1979 to March 2004. Cases had SCD and ICH (intraparenchymal (IPH), subarachnoid (SAH), or intraventricular (IVH) hemorrhage confirmed by neuroimaging or analysis of cerebrospinal fluid; traumatic subdural and epidural hemorrhages were excluded). Controls had SCD and ischemic stroke (focal neurological deficits with corresponding cerebral infarcts by neuroimaging). Both were identified by searching the hospital discharge database using ICD-9 codes for acute stroke and SCD and reviewing the Division of Pediatric Hematology’s records. ACS was defined as a new pulmonary infiltrate and two of the following: chest or rib pain, dyspnea, fever, tachypnea, grunting, nasal flaring, or retractions. Blood pressure was adjusted for age, sex, and hemoglobin genotype. Results: We identified 7 cases (mean age=11.2 years, range 2 to 16 years) and 9 controls (mean age 6.2 years, range 2 to 8 years). As expected, cases were significantly older than controls (p<0.01). All cases and controls had sickle cell anemia. Cases presented with impaired mental status (5/7), bradycardia (5/7), headache (4/7), and emesis (3/7). They often had multiple sites of hemorrhage (5/7) and died during the initial hospitalization (4/7). Five had IPH involving the frontal, parietal, and/or temporal lobes (2 of the patients with IPH also had SAH, 1 had IVH and 1 had both SAH and IVH). Two additional patients had SAH (one also with IVH). Most cases and controls had elevated systolic blood pressure at the time of stroke (4/7 cases, 8/9 controls). Cases had lower steady-state hemoglobin (mean±SE 7.1±0.3 g/dl vs. 7.7±0.4 g/dl), lower steady-state blood pressures (systolic 104±9 vs. 117±5 mm Hg, diastolic 50±5 vs. 61±5 mm Hg) and higher steady-state leukocyte counts (16,590±2823/ul vs. 13,851±2184/ul) than controls, but these differences were not statistically significant. Mean hemoglobin concentration was increased 2.8 g/dl (39.9%) from steady-state at the time of stroke in cases and was unchanged in controls (p=0.08). Other events in the two weeks before ICH associated with increased odds of ICH included transfusion (simple in 5 cases, erythrocytapheresis in 1), ACS (3 cases), and corticosteroid administration (high-dose dexamethasone for ACS in 2, stress doses for possible adrenal insufficiency in 1). Conclusions: In this group of children with SCD, ICH was associated with antecedent events including transfusion and possibly corticosteroids. Mortality was similar to that of adults with SCD and ICH. Limitations of this study include the small sample size and the retrospective design. The contribution of antecedent events to ICH in children with SCD deserves further evaluation. Odds Ratios of Intracranial Hemorrhage For Events in the Last 14 Days Event Odds Ratio (95% CI) P-value Transfusion 48 (1.8-2469) <0.01 ACS 6 (0.3-33) 0.26 Corticosteroids ∞ (1.3- ∞) 0.06

Risk Factors for Primary Hemorrhagic Stroke in Adults with Sickle Cell Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3809-3809
Author(s):  
John J. Strouse ◽  
Joshua J. Field ◽  
Sophie Lanzkron
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hemorrhagic Stroke ◽  
Small Sample ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Elevated Systolic Blood Pressure

Abstract Primary hemorrhagic stroke is an uncommon but serious complication of sickle cell disease (SCD) with mortality from 20 to 65%. Proposed risk factors include previous ischemic stroke, aneurysms, low steady-state hemoglobin, high steady-state leukocyte count, acute chest syndrome, and transfusion. We performed a retrospective case-control study to evaluate risk factors for primary hemorrhagic stroke in adults (age &gt;19 years) with SCD hospitalized at Johns Hopkins Hospital from January 1989 to June 2007. Cases had SCD and intraparenchymal (IPH), subarachnoid (SAH), or intraventricular (IVH) hemorrhage confirmed by neuroimaging or analysis of cerebrospinal fluid; traumatic subdural and epidural hemorrhages were excluded. Controls had SCD and ischemic stroke (focal neurological deficits with corresponding cerebral infarcts by neuroimaging). Both were identified by searching the hospital discharge database using ICD-9 codes for acute stroke and SCD and reviewing divisional records. We compared continuous variables by Student’s t-test and calculated odds ratios with exact methods. We identified 7 cases (mean age 31 years, range 19 – 49, 29% male) and 9 controls (mean age 37 years, range 21 – 61, 11% male). All cases had sickle cell anemia (HbSS) and 17% had a prior overt stroke; Controls had HbSS (5/9) and HbSC (4/9) and 50% had a history of overt stroke. Cases presented with impaired mental status (5/6), headache (7/7) and seizure (5/7). Controls presented with hemiparesis (7/8) and rarely seizure (1/7). Three cases had IPH involving the frontal lobe, frontal and parietal lobes, or basal ganglia. Four patients had SAH with IVH (2) and frontal IPH (1). Cerebral angiography identified aneurysms in 3 cases. One case (14%) and no controls died during the initial hospitalization. About 50% of cases (3/6) and controls (4/9) had elevated systolic blood pressure at the time of stroke. Cases had lower steady-state hemoglobin (mean ± SEM 7.4 ± 1 g/dl vs. 9.3 ± 1.1 g/dl), lower steady-state blood pressures (systolic 120 ± 7 vs. 132 ± 11 mm Hg, diastolic 72 ± 7 vs. 73 ± 5 mm Hg) and higher steady-state leukocyte counts (12,912 ± 1007/ul vs. 11,097 ± 2520/ul) than controls, but these differences were not statistically significant. Mean hemoglobin concentration at the time of stroke increased 1.3 g/dl (22%) from steady-state in cases and 0.7 g/dl (10%) in controls. Three cases had simple transfusions (1, 4, and 11 days before their primary hemorrhagic stroke) in preparation for surgery (2) and for aplastic crisis (1). No controls were transfused, but a woman with HbSS had a hemoglobin of 14.5 g/dl at the time of stroke (from excessive erythropoietin administration). In this group of adults with SCD, primary hemorrhagic stroke was associated with genotype and antecedent transfusion. Mortality was lower than that previously described and may reflect improvements in medical care or random variation within a small sample. The contribution of antecedent events and other potentially modifiable risk factors for hemorrhagic stroke in adults with SCD deserves further evaluation. Table 1: Associations with Primary Hemorrhagic Stroke Variable Odds Ratio (95% CI) P-Value NC indicates not calculated Genotype (HbSS vs. Other) NC (1.1-∝) 0.09 Seizure (at presentation) 20 (1.0–1059) &lt;0.05 Transfusion in the last 14 days NC (1.1-∝) &lt;0.05 Surgery in the last 14 days 3.2 (0.1–212) 0.55

Antecedent Transfusion and Primary Hemorrhagic Stroke in Adults with Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1437-1437
Author(s):  
John J. Strouse ◽  
Joshua Field ◽  
Regina D. Crawford ◽  
Sophie Lanzkron
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hemorrhagic Stroke ◽  
Neurological Deficits ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Elevated Systolic Blood Pressure

Abstract Primary hemorrhagic stroke is an uncommon but serious complication of sickle cell disease (SCD) with mortality from 20 to 65%. Proposed risk factors include previous ischemic stroke, aneurysms, low steady-state hemoglobin, high steady-state leukocyte count, acute chest syndrome, and transfusion. We performed a retrospective case-control study to evaluate risk factors for primary hemorrhagic stroke in adults (age &gt;18 years) with SCD from Johns Hopkins and Barnes- Jewish Hospitals and Duke University Medical Center from January 1989 to April 2008. Cases had SCD and intraparenchymal (IPH), subarachnoid (SAH), or intraventricular (IVH) hemorrhage confirmed by neuroimaging or analysis of cerebrospinal fluid; traumatic hemorrhages and hemorrhagic conversion of ischemic strokes were excluded. Controls had SCD and ischemic stroke (focal neurological deficits with corresponding cerebral infarcts by neuroimaging). Both were identified by searching the hospital discharge database using ICD-9 codes for acute stroke and SCD and reviewing divisional records. We compared continuous variables by Student’s t-test and calculated odds ratios with exact methods. We identified 19 cases (mean age 29 years, range 18 – 66, 42% male) and 18 controls (mean age 34 years, range 19 – 61, 39% male). Most cases (14/18) had sickle cell anemia (HbSS) and 22% had a prior overt stroke; controls had HbSS (9/17), HbSB0thalassemia (1), or HbSC (7) and 41% had a history of overt stroke. Cases presented with headache (89%) and seizure (37%) and less frequently hemiparesis (27%). Controls presented with hemiparesis (78%), headache (57%), and rarely seizure (11%). Twelve cases had IPH including those with extension to the ventricles (1), subarachnoid (2) or both (2); six had SAH including ventricular extension (1). Potential causes of hemorrhagic stroke included moyamoya (4), aneurysms (3), anticoagulation (1) and ateriovenous malformation (1). Four cases (21%) and no controls died during the initial hospitalization. More cases (82%) than controls (44%, P&lt;0.05) had elevated systolic blood pressure at the time of stroke. At steady-state, cases had lower hemoglobin (mean ± SEM 8.5 ± 0.6 g/dl vs. 9.7 ± 0.6 g/dl), lower blood pressures (systolic 121 ± 4 vs. 127 ± 6 mm Hg, diastolic 71 ± 4 vs. 72 ± 9 mm Hg) and higher platelet counts (399,231 ± 74,024/ul vs. 362,200/ul ± 39,927/ul) than controls, but these differences were not statistically significant. Mean hemoglobin concentration at the time of stroke increased 1.3 g/dl (19%) from steady-state in cases and 0.01 g/dl (2%) in controls (p&lt;0.05). Seven cases had simple transfusions (between 1 and 11 days before their primary hemorrhagic stroke) in preparation for surgery (3), and for aplastic crisis (1), bacteremia (1), acute renal failure (1), or suspected acute chest syndrome (1). Only 1 control was transfused; and 1 with HbSS had a hemoglobin of 14.5 g/dl at the time of stroke (from excessive erythropoietin administration). In this group of adults with SCD, primary hemorrhagic stroke was associated with antecedent transfusion. Identifiable causes include moyamoya from obstructive cerebral vasculopathy, aneurysms and other vascular malformations, and rarely coagulopathy. Mortality was similar to that previously described. The association of recent transfusion and cerebral vasculopathy with hemorrhagic stroke suggests caution in the use of simple transfusion in adults with SCD and moyamoya or cerebral aneurysms. Table 1: Associations with Primary Hemorrhagic Stroke Variable Odds Ratio (95% CI) P-value Genotype (HbSS vs. other) 3 (0.6 – 17) NS Moyamoya 5 (0.4 – 260) NS Transfusion in the last 14 days 13 (1.3 – 630) &lt;0.02 NSAID in the last 14 days 2.9 (0.3 – 36) NS

Elevated Systolic Blood Pressure and Low Fetal Hemoglobin Are Risk Factors for Silent Cerebral Infarcts in Children with Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 262-262
Author(s):  
Sharada A. Sarnaik ◽  
James F. Casella ◽  
Bruce A Barton ◽  
Michele Afif ◽  
Gladstone Airewele ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Beta Thalassemia ◽  
Cerebral Infarcts ◽  
Hemoglobin F ◽  
Elevated Systolic Blood Pressure

Abstract Abstract 262 Introduction: The most common cause of neurological injury in sickle cell anemia is silent cerebral infarcts (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) cohort, we sought to identify risk factors associated with SCI. Patients and Methods: In this cross-sectional study, we evaluated the clinical history, baseline laboratory values and performed magnetic resonance imaging of the brain. For those children with SCI-like lesions, a pediatric neurologist examined the child and neuroradiology and neurology committees adjudicated the presence of SCI. Children between the ages of 5 and 15 years with hemoglobin SS or S-beta° thalassemia and no history of overt strokes or seizure were evaluated. Results: A total of 542 children were evaluated; 173 (31.9%) had SCI. The mean age of the children was 9.3 years, with 280 males (51.7%). In a multivariate logistic analysis, two covariates were significant: a single systolic blood pressure (SBP) obtained during a baseline well-visit, p = 0.015 and hemoglobin F (Hgb F) level obtained after three years of age, p = 0.038. Higher values of SBP and lower values of Hgb F increased the odds of SCI; Figure. Baseline values of white blood cell count, hemoglobin level, oxygen saturation, reticulocytes, pain, or ACS event rates were not associated with SCI. Conclusion: SBP and Hgb F level are two previously unidentified risk factors for SCI in children with sickle cell disease. Modulation of SBP and Hgb F levels might decrease the risk of SCI. Disclosures: No relevant conflicts of interest to declare.

Determinants of Inter-Procedure Interval in Patients with Sickle Cell Anemia Enrolled a Chronic Red Blood Cell Exchange Program

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4284-4284
Author(s):  
Alecia C. Nero ◽  
Theresa Nguyen Kinard ◽  
Beverley Adams-Huet ◽  
Karen Matevosyan ◽  
Ravindra Sarode
Keyword(s):  
Blood Cell ◽  
Multiple Regression ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Red Blood Cell ◽  
Small Sample ◽  
Blood Type ◽  
Acute Chest Syndrome ◽  
Intractable Pain ◽  
Post Procedure

Abstract Background: Sickle cell anemia (SCA) is a genetically inherited disorder that can lead to severe sequelae in any organ system. The most clinically devastating complications, e.g. stroke, are managed with chronic red blood cell (RBC) transfusions as curing the underlying SCA is often not an option. Chronic RBC exchange (RBCx), is an effective alternative to simple transfusions and often performed every 4-5 weeks. Isovolemic Hemodilution-Red Blood Cell Exchange (IHD-RBCx) is a modified RBCx method used at UT Southwestern Medical Center (UTSW) and increases the time interval between transfusions, i.e. inter-procedure interval (IPI), up to 9 weeks while maintaining the desired hemoglobin S targets at safe levels. This minimizes the overall lifetime procedures and blood exposures. The standard operating procedure for IHD-RBCx is published (Matevosyan et al, 2012). However, we observed IPI variability between patients in this chronic IHD-RBCx program. We sought to analyze hematologic characteristics in a cohort of adult SCA patients that may be associated with this noted variability. Methods: This IRB approved cross-sectional study evaluated medical and blood bank records of adult patients with SCA, i.e. hemoglobin SS or Sβ0 thalassemia genotypes, undergoing chronic IHD-RBCx at UTSW adult hospital sites between January 1, 2012 and December 31, 2013. Excluded participants were those with autoimmune disease, non-compliance with IHD-RBCx leading to delays > 7 days, or use of hydroxyurea or steroids within four months of the study period. Patients with < 5 exchanges were excluded as several procedures are needed to determine baseline IPIs. The primary indication for IHD-RBCx was secondary stroke prevention. Three subjects had alternative indications (i.e. recurrent severe acute chest syndrome that failed hydroxyurea therapy, intractable pain and severe anemia ineligible for iron chelation due to end-stage renal disease). Median values during the 2 year study were determined for the IPI, laboratory, and RBC properties for use in subsequent analyses. Correlation and multiple regression analyses were performed to determine variables predictive of IPI. Results: Twenty-four SCA patients in this chronic IHD-RBCx transfusion program met inclusion criteria of which 14 (58.3%) were female with age range 18-41 years. Three subjects had incomplete data. The median number of packed RBC (pRBC) units per IHD-RBCx was 8 (range: 6-11 units). The median volume per unit of pRBCs was 304.5 mL (range: 298.8-326.5 mL) with average age of the pRBCs 5.8 days ± 0.7 days. The median IPI was 55.8 days (range: 36.0-65.5 days). The strongest correlation with IPI was the change from the mid to post-procedure hemoglobin and hematocrit values, r=0.56, p=0.005 and r=0.57, p=0.003, respectively. Participants with documented direct antiglobulin test positivity (n=7), compared to those who remained negative (n=16), had 4.9 days increased IPI. This difference was not statistically significant, p=0.19. ABO differences in blood type also did not show statistical significant differences. However, A+ subjects had a 58 day interval compared to 51, 52, 53 days for B+, O+, O- respectively (Figure). In multiple regression models, log blood urea nitrogen (BUN) and post-procedure white blood cell count (WBC) were found to be independent predictors of IPI, beta=-11.3, p=0.04 and -2.1, p=0.03 respectively, with adjusted R2=0.31. Conclusions: Chronic IHD-RBCx effectively treats severe SCA complications. Discontinuing transfusions lead to repeat stroke events or the recurrence of disease manifestations making chronic transfusion programs an indefinite therapy. Outside of the expected correlation between the IPI and hemoglobin/hematocrit, WBC and BUN were found to have negative associations with IPIs. The decrease in WBCs is likely due to the direct clearing effect by the operating system. The association between BUN and IPI may imply relationship with renal function. Interestingly, association with creatinine was not statistically significant. The study is limited by the small sample size. Future studies of similar cohorts should prospectively evaluate target mechanisms which may lead to interventions that can minimize lifetime blood exposures given the growing demands for continued RBCx in severe SCA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Lung Function Impairment in Pediatric Subjects with Sickle Cell Anemia from Nigeria Is Associatede with Associated Low Steady Haemoglobin

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3659-3659
Author(s):  
Baba PD Inusa ◽  
Livingstone Gayus Dogara ◽  
Ramatu Zubair ◽  
Chiara Zuiani ◽  
Christoper Audu ◽  
...  
Keyword(s):  
Steady State ◽  
Lung Function ◽  
Lung Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Acute Chest Syndrome ◽  
Restrictive Lung Disease ◽  
Function Impairment ◽  
Z Scores ◽  
Lung Function Impairment

Abstract Low hemoglobin (Hb) level at steady state in subjects with sickle cell anemia (SCA) may indicate severe chronic hemolysis and might be related to a more severe course of disease. In this study we investigated the hypothesis that low hemoglobin at steady state may be associated with higher rate of lung function impairment in children and adolescents with SCA. Methods In this cross-sectional study black African subjects with SCA (Hb phenotype SS) aged 6 to 18 years followed at the Barau Dikko Teaching Hospital, Kaduna, Nigeria, underwent spirometry and anthropometry measures. A recent Hemoglobin level at steady state was recorded for each patient. Caregivers or patients were interviewed through a questionnaire investigating a history of asthma or acute chest syndrome (ACS) and frequency of pain crises in the last year that required analgesics for at least 24 hours. Exclusion criteria were: the lack of recorded complete blood count (CBC) performed in the last 6 months, respiratory symptoms or feeling unwell on the test day, SCA-related acute events (e.g., pain crises) in the last two weeks or a blood transfusion or an ACS episode in the last month. A portable Easy-on-PC spirometer (ndd, Zurich, Switzerland) was used. Data were included if at least two forced expiratory manoeuvres met the ATS/ERS acceptability and repeatability criteria adapted for children (Miller MR, ERJ 2005; Kirkby J, Pediatr.Pulmonol.2008). Spirometry z-scores and percentage of predicted for FEV1, FVC and FEV1/FVC were derived according to the GLI-2012 reference equations for African Americans (Quanjer PH, ERJ2012). Spirometry patterns were classified as normal, obstructive (zFVC ≥ 1.64 + zFEV1/FVC < -1.64), restrictive (zFVC < -1.64 + zFEV1/FVC ≥ -1.64) or mixed (zFVC < -1.64 + zFEV1/FVC < -1.64) and a FEV1 < 70% of predicted was considered indicative of lung end-organ disease (Kassim AA et al, Blood. 2015 Sep 24;126(13):1544-50). Group comparison between patients with Hb level < 7.5 g/dL versus Hb ≥7.5 g/dL were tested using unpaired t test, χ2 or Fisher's exact test as appropriate. The relationship between Hb values and spirometry outcomes was explored through logistic and linear regression models. P-value < 0.05 was adopted as representing a statistically significant difference. Analyses were conducted using the software STATA and Graphpad Prism 7. Results A total of 186 subjects with SCA were initially enrolled. Only one child was on hydroxyurea. After exclusions, data from 126 patients (mean ± SD age of 11.5 ± 3.1 yr., 53% boys) were retained for the final analysis. Mean ± SD Hb value was 7.8±0.9 g/dL (range 5.6 to 10.9). Frequency of low Hb (< 7.5 g/dL) at steady state was 30.9% (39/126). Mean FEV1 and FVC z-scores were lower and frequency of FEV1 < 70% of predicted was higher in patients in the low Hb group compared to those with Hb ≥7.5 g/dL though differences were not statistically significant (table 1). Prevalence of restrictive spirometry pattern, possibly suggesting restrictive lung disease, was significant higher in patients with Hb level < 7.5 g/dL (17/39, 43.5%) than in those with Hb ≥7.5 g/dL (20/87, 22.9%) (p = 0.01; table 1). The odds ratio for restrictive spirometry pattern in presence of Hb level <7.5 g/dL was 2.5 (95% CI 1.1 to 5.7; p = 0.03). In a linear regression model (figure 1) the FVC z-score resulted significantly related to the Hb level with an increase of 0.17 z-scores for each point of Hb (95% CI 0.01 to 0.34, p = 0.04; R2 = 0.03). Frequency of asthma, pain crises and previous acute chest syndrome did was similar between the two groups (data not showed) Conclusions In Nigerian pediatric patients with sickle cell anemia a hemoglobin level < 7.5 g/dL at steady state was associated with a 2.5 higher risk of presenting a restrictive spirometry pattern and with a higher frequency of end-organ lung disease (FEV1 < 70% of predicted). Low hemoglobin levels in wellbeing may depend on intense chronic haemolysis that could worsen microangiopathy, inflammation and ischemia and reperfusion injury in the lungs, potentially determining a precocious onset of restrictive lung disease. These preliminary data seem to indicate that a low Hb level at steady state in African pediatric patients with sickle cell anemia is associated with more severe lung impairment and should prompt respiratory assessment with lung function when found. Disclosures Inusa: Novartis plc: Honoraria, Research Funding, Speakers Bureau; Astrazeneca: Consultancy.

A Comparison Of Sickle Cell Anemia Between Patients From Nigeria and The United States

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 997-997
Author(s):  
Santosh L. Saraf ◽  
Bamidele O. Tayo ◽  
Titilola S. Akingbola ◽  
Babatunde L. Salako ◽  
Jennifer Layden ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Cell ◽  
Sickle Cell ◽  
White Blood Cell ◽  
Sickle Cell Anemia ◽  
The United States ◽  
Medical Attention ◽  
Acute Chest Syndrome ◽  
The University ◽  
The U.S

Abstract Sickle cell anemia (SCA) is among the most common monogenetic diseases worldwide and environmental and genetic factors are thought to contribute to variations in clinical presentation. We conducted a study to compare clinical and laboratory features between 214 SCA patients from the University of Ibadan, Nigeria and 200 SCA patients from the University of Illinois at Chicago, U.S. between the ages of 11 and 30 years old. Laboratory and clinical data were collected from clinic visits and comparisons between the two cohorts were adjusted for age, gender, and hydroxyurea use. SCA patients from Nigeria had lower median body weight, height, body mass index, systolic blood pressure, mean arterial pressure and pulse pressure (Table 1). Proportions of hydroxyurea use and vaccinations for streptococcus pneumoniae and influenza A were lower in SCA patients from Nigeria. Hematological indices showed that SCA patients from Nigeria had lower median values for hemoglobin F (HbF) percent, hemoglobin concentration and mean corpuscular volume but platelet and white blood cell counts were not significantly different compared to SCA patients from the U.S. In the white blood cell differential, lower granulocyte counts and higher lymphocyte and monocyte counts were observed in SCA patients from Nigeria. The proportion of patients with a history of ≥ 3 vaso-occlusive pain episodes requiring medical attention per year were similar between the Nigerian and U.S. cohorts but the proportions with histories of stroke, acute chest syndrome and > 5 lifetime transfusions were lower in the Nigerian versus U.S. cohort. On logistic regression analysis, male gender was independently associated with vaso-occlusive crises ≥ 3 per year in the Nigerian cohort (OR 1.9, 95% CI 1.1 – 3.4, p=0.04) and lower HbF concentration was associated with this pain category in the U.S. cohort (Hb F 1% decrement OR 1.1, 95% CI 1.0 – 1.1, p=0.02). A higher white blood cell count was independently associated with stroke history in both the Nigerian and U.S. cohorts (Nigeria: OR 1.1, 95% CI 1.0 - 1.3, p=0.03; US: OR 1.2, 95% CI 1.1 – 1.3, p=0.003). Additionally, a lower HbF concentration was independently associated with stroke history in the Nigerian cohort (Hb F 1% decrement OR 2.5, 95% CI 0.2 – 0.9, p=0.03). The lower height and low proportions of vaccination among the Nigerian SCA patients point to the need for improved nutrition and vaccination strategies, and the low utilization of hydroxyurea therapy highlights the need to investigate the appropriateness of this agent in the African context. On the other hand, the higher values for BMI and blood pressure in the UIC compared to Nigerian SCA patients parallel similar findings in non-sickle cell cohorts and raises the possibility that life-style factors may contribute to the higher rate of stroke in the UIC cohort. Whether the lower rate of complications in general in the Nigerian SCA patients reflects higher early mortality versus favorable genetic or environmental factors deserves further investigation. In summary, our study found both differences and similarities between patients with SCA from Nigeria and the U.S. and a better understanding of the genetic and environmental contributions may help guide future therapies for SCA in both settings. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease

Blood ◽  
1994 ◽  
Vol 84 (2) ◽  
pp. 643-649 ◽  
Author(s):  
O Castro ◽  
DJ Brambilla ◽  
B Thorington ◽  
CA Reindorf ◽  
RB Scott ◽  
...  
Keyword(s):  
Risk Factors ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Disease Incidence ◽  
National Study ◽  
Beta Thalassemia ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Age Related

Abstract The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients, is one of the most frequent causes of their morbidity and hospitalizations. Repeated ACS events may predict the development of chronic lung disease. ACS is reported as a frequent cause of death in these patients. We examine here the incidence and risk factors of ACS in 3,751 patients with sickle cell disease who were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs]) as part of a multicenter national study group. The ACS, defined by a new pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100 events). ACS incidence was higher in patients with homozygous sickle cell disease (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100 pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha-Thalassemia did not affect the rate of ACS incidence in SS patients. Within each Hb type the incidence was strongly but inversely related to age, being highest in children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of age), we documented an age-related within- person reduction in ACS attack rates. Adults with a higher ACS rate had a higher rate of mortality (from all causes) than those with low ACS rates. This increased rate of mortality might also have contributed to the decline in ACS rate with age. In multivariate analysis, other factors affecting incidence in SS patients were degree of anemia (lower ACS rates in patients with lower steady-state Hb levels) and fetal Hb (lower rates in patients with high fetal Hb). There was also a positive association between ACS rate and steady-state leukocyte count. The relationship of ACS rate to higher steady-state Hb levels in SS patients is unexplained but might be caused by increased blood viscosity.

scholarly journals The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease

Blood ◽  
1994 ◽  
Vol 84 (2) ◽  
pp. 643-649 ◽  
Author(s):  
O Castro ◽  
DJ Brambilla ◽  
B Thorington ◽  
CA Reindorf ◽  
RB Scott ◽  
...  
Keyword(s):  
Risk Factors ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Disease Incidence ◽  
National Study ◽  
Beta Thalassemia ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Age Related

The acute chest syndrome (ACS), a pneumonia-like illness in sickle cell patients, is one of the most frequent causes of their morbidity and hospitalizations. Repeated ACS events may predict the development of chronic lung disease. ACS is reported as a frequent cause of death in these patients. We examine here the incidence and risk factors of ACS in 3,751 patients with sickle cell disease who were observed prospectively for at least 2 years (19,867 patient-years [pt-yrs]) as part of a multicenter national study group. The ACS, defined by a new pulmonary infiltrate on x-ray, occurred at least once in 1,085 patients (2,100 events). ACS incidence was higher in patients with homozygous sickle cell disease (SS; 12.8/100 pt-yrs) and in patients with sickle cell-beta(0) -thalassemic (9.4/100 pt-yrs), and lower in patients with hemoglobin (Hb) SC disease (5.2/100 pt-yrs) and patients with sickle cell-beta(+) thalassemia (3.9/100 pt-yrs). alpha-Thalassemia did not affect the rate of ACS incidence in SS patients. Within each Hb type the incidence was strongly but inversely related to age, being highest in children 2 to 4 years of age (25.3/100 pt-yrs in SS) and decreasing gradually to its lowest value in adults (8.8/100 pt-yrs in SS). In SS children (< 10 years of age), we documented an age-related within- person reduction in ACS attack rates. Adults with a higher ACS rate had a higher rate of mortality (from all causes) than those with low ACS rates. This increased rate of mortality might also have contributed to the decline in ACS rate with age. In multivariate analysis, other factors affecting incidence in SS patients were degree of anemia (lower ACS rates in patients with lower steady-state Hb levels) and fetal Hb (lower rates in patients with high fetal Hb). There was also a positive association between ACS rate and steady-state leukocyte count. The relationship of ACS rate to higher steady-state Hb levels in SS patients is unexplained but might be caused by increased blood viscosity.

Daytime Steady-State Hemoglobin Desaturation Is a Risk Factor for Overt Stroke Children with Sickle Cell Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 431-431
Author(s):  
James W. Sargent ◽  
Charles T. Quinn
Keyword(s):  
Risk Factor ◽  
Ischemic Stroke ◽  
Steady State ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
Time Interval ◽  
Increased Risk ◽  
Nested Case Control ◽  
Control Study

Abstract Stroke is a serious complication of sickle cell anemia (SS). Steady-state hemoglobin (Hgb) desaturation, which is common in SS and often thought to be benign, could contribute to the risk of stroke because it perturbs endothelial function in SS (Lancet2003;362:1450) and might limit oxygen delivery to the brain. One previous study of SS patients found an association between nocturnal oxygen desaturation and strokes, transient ischemic attacks, and seizures (Lancet2001;357:1656). Nocturnal oxygen saturation is cumbersome to measure, and the association between daytime Hgb saturation and stroke has not been reported. We hypothesized that daytime steady-state Hgb desaturation was associated with and preceded overt stroke in children with SS. We performed a nested case-control study of the Dallas Newborn Cohort (Blood2004;103:4023). Cases were defined as cohort subjects with SS or sickle-β0-thalassemia (Sβ0) who had clinically overt ischemic strokes in the preceding 12 years. Controls were cohort subjects with SS or Sβ0 but without overt stroke who were reported previously (Br J Haematol2005;131:129). We collected mean steady-state oxygen saturations by pulse oximetry (SpO2) and mean steady-state hematologic data for cases (pre-stroke) and controls. For cases we also identified one SpO2 measurement and one blood count that was recorded closest to but preceding each stroke (the proximate pre-stroke values). We further calculated a predicted SpO2 for cases using a model that includes age, sex, and mean steady-state values of Hgb and reticulocyte count (Br J Haematol2005; 131:129) and calculated odds ratios for stroke by logistic regression. We identified 22 cases (100% SS; 68% male; mean age 7.9 years) and 390 controls (98% SS; 55% male; mean age 9.5 years). The steady-state SpO2 of cases (94.2%, standard deviation [SD] 3.0) was significantly lower than controls (96.3%, SD 3.0) (P=0.0014). The proximate pre-stroke SpO2 of cases (93.7% SD 3.8) was even lower than steady-state and significantly lower than controls (P=0.0006). The predicted steady-state SpO2 for cases was 95.2% (SD 1.4), meaning that the observed SpO2 of cases (94.2%) was lower than would be expected for SS patients without stroke given age, sex, and steady-state values of Hgb and reticulocyte count. The odds ratio for stroke was 1.32 (95% confidence interval 1.15 – 1.51) for each unit (1%) decrease in SpO2 while simultaneously controlling for age, sex, and steady-state values of Hgb and reticulocyte count (P<0.0001). In summary, we found that children with SS who develop a stroke have lower pre-stroke steady-state SpO2 values than children with SS who do not develop a stroke. Moreover, in children who develop stroke, the measured SpO2 value decreases as the time interval to stroke narrows. The odds of stroke increase as the SpO2 decreases. In conclusion, steady-state Hgb desaturation is a risk factor for ischemic stroke in children with SS. Decline in steady-state SpO2 over time further increases this risk. Hgb desaturation is an easily measured, potentially modifiable risk factor that could be used to identify children with SS who have an increased risk of overt ischemic stroke. Figure Figure

scholarly journals Associated risk factors for silent cerebral infarcts in sickle cell anemia: low baseline hemoglobin, sex, and relative high systolic blood pressure

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3684-3690 ◽  
Author(s):  
Michael R. DeBaun ◽  
Sharada A. Sarnaik ◽  
Mark J. Rodeghier ◽  
Caterina P. Minniti ◽  
Thomas H. Howard ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hemoglobin Concentration ◽  
Multivariable Logistic Regression Analysis ◽  
High Systolic Blood Pressure ◽  
Increased Risk ◽  
Baseline Hemoglobin

Abstract The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.

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