Thrombophilic DNA Mutations As Independent Risk Factors for Stroke and Avascular Necrosis in Sickle Cell Anemia

Hematology ◽  
2001 ◽  
Vol 6 (5) ◽  
pp. 347-353 ◽  
Author(s):  
Sherri A. Zimmerman ◽  
Thad A. Howard ◽  
Matthew R. Whorton ◽  
Wendell F. Rosse ◽  
Andra H. James ◽  
...  
Keyword(s):  
Risk Factors ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Dna Mutations ◽  
Independent Risk Factors

G6PD deficiency, absence of α-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4314-4317 ◽  
Author(s):  
Françoise Bernaudin ◽  
Suzanne Verlhac ◽  
Sylvie Chevret ◽  
Martine Torres ◽  
Lena Coic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
G6pd Deficiency ◽  
Odds Ratio ◽  
Multivariate Logistic Regression Analysis ◽  
Multivariate Logistic Regression ◽  
Alpha Thalassemia ◽  
Independent Risk Factors ◽  
First Time

AbstractStroke is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). This study aimed at defining predictive factors for abnormally high velocities (≥ 2 m/sec) based on the Créteil pediatric sickle cell anemia (SCA) cohort composed of 373 stroke-free SCA children. α genes and β-globin haplotypes were determined. Biologic parameters were obtained at baseline. α-thalassemia was present in 155 of 325 and G6PD deficiency in 36 of 325 evaluated patients. TCD was abnormal in 62 of 373 patients. Multivariate logistic regression analysis showed that G6PD deficiency (odds ratio [OR] = 3.36, 95% confidence interval [CI] 1.10-10.33; P = .034), absence of alpha-thalassemia (OR = 6.45, 95% CI 2.21-18.87; P = .001), hemoglobin (OR per g/dL = 0.63, 95% CI 0.41-0.97; P = .038), and lactate dehydrogenase (LDH) levels (OR per IU/L = 1.001, 95% CI 1.000-1.002; P = .047) were independent risk factors for abnormally high velocities. This study confirms the protective effect of alpha-thalassemia and shows for the first time that G6PD deficiency and hemolysis independently increase the risk of cerebral vasculopathy.

High LDH Level, G6PD Deficiency and Absence of alpha-Thalassemia Are Significant Independent Risk Factors of Abnormally High Cerebral Velocities in Patients with Sickle Cell Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 430-430 ◽  
Author(s):  
Francoise Bernaudin ◽  
Suzanne Verlhac ◽  
Lena Coïc ◽  
Cecile Arnaud ◽  
Annie Kamdem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
G6pd Deficiency ◽  
Intensive Therapy ◽  
Univariate Analysis ◽  
Beta Globin ◽  
Alpha Thalassemia ◽  
Cerebral Mri ◽  
Independent Risk Factors

Abstract Background Predicting the severity of sickle cell anemia (SCA) is important for providing better informed genetic counseling and for better targeting of intensive therapies. Stroke is the most severe complication in children with SCA and is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). We attempted to define the risk factors associated with high velocities. Methods This study concerned the Créteil pediatric SCA cohort, composed of newborn patients, screened and followed at our Center since birth, and of patients secondarily referred to the Center because of the severity of their disease. Time-averaged mean of maximum velocities (TAMMX) higher than 200 cm/sec were considered as abnormal, resulting in initiation of a transfusion program initiated</DEL>. Cerebral MRI/MRA was done after the age of 5 years or earlier in case of abnormal TCD. Alpha </DEL>genes and beta-globin haplotypes were determined. Baseline biological parameters (G6PD activity; WBC, PMN, Reticulocytes, Platelets counts; Hemoglobin, Hematocrit, HbF, LDH levels; MCV; SpO2) were obtained a minimum of 3 months away from a transfusion, one month from a painful episode, after 18 months of age and, before intensive therapy. Results SS children (390; 189 F, 201 M) were annually explored by TCD (n=2286) since 1992, and followed for a total of 1962 patient-years. The follow-up before initiation of intensive therapy was 1032 patient-years. Nineteen patients experienced an overt stroke. TCD was abnormal in 65 of 390 patients (17%). MRI (n=850) was performed in 268 patients, was abnormal in 86 cases and showed silent infarcts in 67 of 249 patients (27%). Silent infarcts were seen in 33% of patients with abnormal TCD. Alpha genes study, available in 336 patients, demonstrated alpha-thalassemia in 158 patients (47%): 31 had a deletion of 2 genes (7.9%) and 127 of 1 gene (32.6%). G6PD deficiency was present in 26 of 228 evaluated patients (11%). Beta-globin haplotypes studied in 316 patients were Car/Car in 125 (40%), Ben/Ben in 76 (24%), Sen/Sen in 30 (9%) and, “other” in 85 (27%). Univariate analysis showed that the risk of abnormally high velocities was not related to sex, beta-globin haplotypes, pain and acute chest syndrom rates, WBC, PMN, platelets counts, HbF level and SpO2 but was significantly associated with the absence of alpha-thalassemia (p< 0.001), G6PD deficiency (p=0.012), low Hb and Ht levels (p< 0.001), high reticulocyte count (p=0.008), high MCV (p=0.004) and high LDH level (p<0.001). Multivariate logistic regression analysis showed that absence of alpha-thalassemia [OR= 14.5, 95% CI (2.6–79.7)], (p=0.002); G6PD deficiency [OR=6.7, 95% CI (1.7–26.1)], (p=0.006) and, LDH > 1200 UI/L [OR=4.5, 95% CI (1.5–13.5)], (p=0.007) were independent risk factors of abnormally high velocities. Conclusion This study confirms that the risk of high velocities in patients with SCA is significantly decreased by the presence of alpha-thalassemia. It shows for the first time that hemolysis is a more significant risk factor than the degree of anemia and that absence of alpha-thalassemia, G6PD deficiency and hemolysis are significant independent risk factors of cerebral vasculopathy in patients with SCA.

scholarly journals Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia

Blood ◽  
2015 ◽  
Vol 125 (10) ◽  
pp. 1653-1661 ◽  
Author(s):  
Françoise Bernaudin ◽  
Suzanne Verlhac ◽  
Cécile Arnaud ◽  
Annie Kamdem ◽  
Manuela Vasile ◽  
...  
Keyword(s):  
Risk Factors ◽  
Carotid Stenosis ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Internal Carotid ◽  
Cerebral Infarcts ◽  
Acute Anemia ◽  
Key Points ◽  
Independent Risk Factors ◽  
Baseline Hemoglobin

Key PointsBaseline hemoglobin levels lower than 7 g/dL, acute anemia, and extracranial internal carotid stenosis are significant and independent risk factors for SCI in SCA.

scholarly journals Clinical and Biomarker Predictors for Avascular Necrosis in Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3091-3091
Author(s):  
Michael Rabaza ◽  
Maria Armila Ruiz ◽  
Liana Posch ◽  
Faiz Ahmed Hussain ◽  
Franklin Njoku ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Research Funding ◽  
Medical Attention ◽  
Cell Disease ◽  
Advisory Committees ◽  
Early Management

Abstract Introduction Sickle cell disease (SCD) affects 1 in 365 African Americans and approximately 25 million people world-wide. A common skeletal system complication is avascular necrosis (AVN), which can cause substantial pain and a reduced quality of life. While early management of AVN is focused on increasing range of motion with physical therapy and pain relief, there are no clear predictors for who is more likely to develop AVN and earlier institution of these preventive measure could help decrease disease progression. Vascular endothelial growth factor (VEGF) is a biomarker of endothelial injury and may indicate reduced vascular supply to the femoral or humeral head. Here we describe potential risk factors and biologic pathways for AVN in SCD, as understanding these may lead to improvements in future monitoring, early detection, and early intervention practices. Methods We investigated clinical and laboratory risk factors associated with AVN in a cohort of 435 SCD patients from our center. Blood samples, clinical, and laboratory data were collected at the time of enrollment during a clinic visit. Genotyping for alpha thalassemia was performed by PCR and the serum concentration of VEGF was measured by ELISA. AVN status was confirmed by review of the medical record and available imaging. We conducted a cross-sectional analysis comparing categorical and linear variables by AVN status using the chi-square and Kruskal-Wallis test, respectively. The independent association of the clinical and laboratory variables with AVN status was determined by logistic regression analysis. The initial model included variables with a P-value &lt; 0.1 on univariate analysis and the final model was ascertained by stepwise forward and backward selection. Median values and interquartile range (IQR) are provided. Results The median age of the cohort was 32 (IQR, 24 - 43) years, 57% (250/435) were female, and 46% (198/435) were on hydroxyurea. AVN was observed in 34% (149/435) of SCD patients. SCD patients with AVN were older, had more frequent vaso-occlusive crises requiring medical attention, and had a higher body mass index (Table I) (P ≤ 0.002). We measured VEGF in 241 of the SCD patients with serum samples available at the time of enrolment. Serum VEGF concentrations trended higher in SCD patients with versus without AVN (420 vs. 359 pg/mL, respectively; P = 0.078). In the multivariate analysis model, AVN was independently associated with increased number of vaso-occlusive crises (OR 1.1, 95% CI: 1.0 - 1.14; P = 0.02), AST concentration (natural log OR 0.5, 95% CI: 0.2 - 0.9; P = 0.03), VEGF concentration (natural log OR 1.4, 95% CI: 1.0 - 1.9; P = 0.047), and tobacco use (OR 1.9, 95% CI: 0.9 - 3.7; P = 0.078). Discussion In conclusion, we demonstrate a high prevalence of AVN in an adult cohort of SCD patients. The presence of AVN was independently associated with a greater frequency of vaso-occlusive pain episodes, which may demonstrate a shared pathophysiology between AVN and vaso-occlusion that merits further investigation. We demonstrate that serum VEGF concentrations are higher in SCD patients with AVN and may be a clinical tool to identify those at high-risk and for earlier intervention for this complication. Figure 1 Figure 1. Disclosures Gordeuk: Modus Therapeutics: Consultancy; Novartis: Research Funding; Incyte: Research Funding; Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CSL Behring: Consultancy. Saraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia

2017 ◽  
Vol 32 (9) ◽  
pp. 1565-1573 ◽  
Author(s):  
Jeffrey D. Lebensburger ◽  
Gary R. Cutter ◽  
Thomas H. Howard ◽  
Paul Muntner ◽  
Daniel I. Feig
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Pediatric Patients

scholarly journals Abnormal Pulmonary Function and Associated Risk Factors in Children and Adolescents With Sickle Cell Anemia

2014 ◽  
Vol 36 (3) ◽  
pp. 185-189 ◽  
Author(s):  
Manuel Arteta ◽  
Andrew Campbell ◽  
Mehdi Nouraie ◽  
Sohail Rana ◽  
Onyinye C. Onyekwere ◽  
...  
Keyword(s):  
Risk Factors ◽  
Pulmonary Function ◽  
Children And Adolescents ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Associated Risk Factors ◽  
Abnormal Pulmonary Function

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

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.

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