scholarly journals Would the (too?) normal adaptation to exercise in sickle cell trait carrier be a reflection of preventive mechanisms against potential myocardial and muscle injury?

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
S Antoine-Jonville ◽  
K Reminy ◽  
ET N"go Sock ◽  
P Cherubin ◽  
O Hue ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Muscle Injury ◽  
Sickle Cell Trait ◽  
Clinical Signs ◽  
Electrolyte Imbalance ◽  
Moderate Intensity ◽  
Exercise Participation ◽  
Warm Environment ◽  
Increased Risk ◽  
Exercise Induced

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission, Region Guadeloupe Background. Sickle cell trait (SCT) is an inherited red blood cell condition without medical consequence in most cases. However, its strong association with increased risk of exercise-induced sudden death (independent of pre-existing disease) or exertional collapse has been demonstrated in athletes, military recruits and firefighters. The mechanisms potentially leading to cardiac arrest during or after exercise in SCT have not been fully elucidated although contributing factors have been identified (the main one being rhabdomyolysis) or suspected. Warm environment (even without dehydration) can contribute to the occurrence of fatal events. Purpose. The aims of this study were to 1) compare the biomarkers of myocardial and muscle injury response (and their determinants) to exercise in SCT carriers and controls performing a hard bout of exercise 2) identify the potential deleterious role of warmth during exercise and recovery in SCT and non-SCT. Methods. Nine otherwise healthy 21 ± 3yo male students with SCT and 11 non-SCT (comparable in physical fitness, regular exercise participation and body mass index) were included. The volunteers performed in a randomized order 3 sessions: cycling exercise in a control (21°C) and warm (31°C) environment followed by recovery in a room at 21°C, and both exercise and recovery in a warm environment. The exercise was as follows: 18-min rectangular moderate intensity period + maximal incremental test + 3 30-s supramaximal sprints spaced with 20-s resting intervals. Recovery and hydration were planned between each exercise part. The ECG was monitored throughout exercise. Blood was sampled before and at the end of the exercise but also during the recovery including a meal up to 130-min after the end of exercise. Results. No evidence of severe cardiac injury (ECG and biomarkers), rhabdomyolysis or occlusive events (clinical signs and biomarkers), infection (complete blood count), inflammation (biomarkers) or electrolyte imbalance (ionogram) was observed in the SCT carriers of this study: indices were comparable between SCT and non-SCT carriers, with normal exercise-related evolutions and normal recovery. Interestingly, some indices however converge towards a profile with lower complication risk in SCT. The lactate concentrations tended to be lower in SCT than non-SCT during exercise (p = 0.062) and were significantly lower during the recovery in particular after exercising at 31°C but not at 21°C. The leukocytes count was lower in SCT than non-SCT (p = 0.043) and increased in a greater extent with exercise in the later (p = 0.041). The exercise-induced increase in cortisol and glucose concentrations observed in non-SCT did not occur in SCT carriers (interactions p and p = 0.040 and p = 0.033). Conclusions. Although these results do not evidence pathophysiological mechanisms, they feed the hypothesis of "storm" against which protective mechanisms could have developed and that may fail under particular conditions.

scholarly journals Sickle Cell Trait and Renal Function in Hispanics in the United States: the Northern Manhattan Study

2017 ◽  
Vol 27 (1) ◽  
pp. 11 ◽  
Author(s):  
Nicole D. Dueker ◽  
David Della-Morte ◽  
Tatjana Rundek ◽  
Ralph L. Sacco ◽  
Susan H. Blanton
Keyword(s):  
United States ◽  
Chronic Kidney Disease ◽  
African Americans ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
The United States ◽  
Genetic Mutation ◽  
Single Mutation ◽  
Increased Risk

<p class="Pa7">Sickle cell anemia (SCA) is a common hematological disorder among individu­als of African descent in the United States; the disorder results in the production of abnormal hemoglobin. It is caused by homozygosity for a genetic mutation in HBB; rs334. While the presence of a single mutation (sickle cell trait, SCT) has long been considered a benign trait, recent research suggests that SCT is associated with renal dysfunction, including a decrease in estimated glomerular filtration rate (eGFR) and increased risk of chronic kidney disease (CKD) in African Americans. It is currently unknown whether similar associations are observed in Hispanics. Therefore, our study aimed to determine if SCT is associated with mean eGFR and CKD in a sample of 340 Dominican Hispanics from the Northern Manhattan Study. Using regression analyses, we tested rs334 for association with eGFR and CKD, adjusting for age and sex. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equa­tion and CKD was defined as eGFR &lt; 60 mL/min/1.73 m2. Within our sample, there were 16 individuals with SCT (SCT carriers). We found that SCT carriers had a mean eGFR that was 12.12 mL/min/1.73m2 lower than non-carriers (P=.002). Additionally, SCT carriers had 2.72 times higher odds of CKD compared with non-carriers (P=.09). Taken together, these novel results show that Hispanics with SCT, as found among African Americans with SCT, may also be at increased risk for kidney disease.</p><p class="Pa7"><em>Ethn Dis. </em>2017; 27(1)<strong>:</strong>11-14; doi:10.18865/ed.27.1.11.</p><p class="Pa7"> </p>

Sickle Cells and Anesthesia

PEDIATRICS ◽  
1974 ◽  
Vol 53 (3) ◽  
pp. 446-446
Author(s):  
Herbert T. Abelson
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Sickle Cells ◽  
Risk Of Death ◽  
Increased Risk

The implication by McGarry and Duncan that sickle cell trait carries an increased risk of death following anesthesia should be carefully weighed against their proffered evidence. In two of their five cases, a hematologic diagnosis was not established, but rather implied by postmortem findings. These two cases could therefore represent an additional, mixed, sickle hemoglobinopathy. In addition, postmortem sickling can hardly serve as an indicator of premortem pathophysiology. Since previous firm documentation of anesthetic deaths associated with sickle cell trait are not available, the following questions would seem to be pertinent: (1) what is the overall incidence of anesthetic deaths in the authors' institution and (2) over what period of time were these cases collected?

Sickle cell trait and the risk of venous thromboembolism among blacks

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 908-912 ◽  
Author(s):  
Harland Austin ◽  
Nigel S. Key ◽  
Jane M. Benson ◽  
Cathy Lally ◽  
Nicole F. Dowling ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Odds Ratio ◽  
Sickle Cell Trait ◽  
Coagulation System ◽  
Cell Disease ◽  
Hemoglobin C ◽  
Increased Risk ◽  
S Allele

Abstract People with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, but it is unknown whether they experience an increased risk of venous thromboembolism. We conducted a case–control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics. All subjects were assayed for hemoglobin S and hemoglobin C genotypes. The prevalence of the S allele was 0.070 and 0.032 for case patients and controls, respectively (P < .001). The odds that a patient had sickle cell trait were approximately twice that of a control, indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype (odds ratio = 1.8 with 95% confidence interval, 1.2-2.9). The odds ratio for pulmonary embolism and sickle cell trait was higher, 3.9 (2.2-6.9). The prevalence of sickle cell disease was also increased among case patients compared with controls. We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7%.

scholarly journals Cardiovascular Outcomes in African Americans with Sickle Cell Trait and Chronic Kidney Disease

2019 ◽  
Vol 49 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Kabir O. Olaniran ◽  
Nwamaka D. Eneanya ◽  
Andrew S. Allegretti ◽  
Sophia H. Zhao ◽  
Maureen M. Achebe ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
African American ◽  
Cardiovascular Risk ◽  
African Americans ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Increased Risk ◽  
The Mean

Background: Sickle cell trait (SCT) is common among African Americans and has been historically considered to be benign. Recently, SCT has been associated with an increased risk for chronic kidney disease (CKD) and cardiovascular disease in the general population. Our understanding of SCT has been extrapolated largely from data of patients with sickle cell disease (SCD). Notably, in SCD, the outcomes differ by sex. The effect of SCT on cardiovascular risk in the African American CKD population is unknown, and the interaction between SCT and sex on cardiovascular risk has not been investigated. Methods: We performed a 2-center retrospective cohort study of all African American patients with SCT using international classification of disease diagnosis codes and CKD (using the 2012 Kidney Disease Improving Global Outcomes criteria) with at least 1 year of follow-up between January 2005 and December 2017. A reference group of ­African American CKD patients without SCT was used as a comparator during the same period. SCT patients and the reference patients were matched at baseline for age, sex, comorbidities, and proteinuria. Primary outcomes were incident coronary artery disease (CAD), incident stroke, and all-cause mortality. Analysis of effect modification between sex and SCT on primary outcomes was performed. Results: We identified 621 African American CKD patients, 217 SCT patients, and 404 reference patients. The mean age was 56 ± 13 years and 66% were female. The mean estimated glomerular filtration rate was 69 ± 30 mL/min. The mean follow-up time was 8 ± 4 years. There were no significant differences in the primary outcomes comparing SCT patients to matched controls. The interaction term between SCT and sex, however, was significant in the CAD model (p < 0.01). Stratification by sex showed no increased risk in females but a significantly increased risk for CAD in male SCT patients (hazard ratio [HR] 2.14; 95% CI 1.18–3.86), which persisted after multivariable analysis (HR 2.13; 95% CI 1.17–3.86). Conclusion: SCT is associated with an increased risk for CAD in African American males with CKD. The excess risk in males with SCT appears to follow the same pattern as risk in males with SCD. Larger studies are needed to confirm these findings.

scholarly journals Sickle Cell Trait and Risk of Ischemic Stroke in Young Adults

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
Author(s):  
Rebecca V. Zhang ◽  
Kathleen A. Ryan ◽  
Haley Lopez ◽  
Marcella A. Wozniak ◽  
Michael S. Phipps ◽  
...  
Keyword(s):  
Young Adults ◽  
Ischemic Stroke ◽  
Sickle Cell ◽  
Early Onset ◽  
Odds Ratio ◽  
Sickle Cell Trait ◽  
Smoking Status ◽  
Population Based ◽  
Logistic Regression Models ◽  
Increased Risk

Background and Purpose: Approximately 8% of Blacks have sickle cell trait (SCT), and there are conflicting reports from recent cohort studies on the association of SCT with ischemic stroke (IS). Most prior studies focused on older populations, with few data available in young adults. Methods: A population-based case-control study of early-onset IS was conducted in the Baltimore-Washington region between 1992 and 2007. From this study, 342 Black IS cases, ages 15 to 49, and 333 controls without IS were used to examine the association between SCT and IS. Each participant’s SCT status was established by genotyping and imputation. For analysis, χ 2 tests and logistic regression models were performed with adjustment for potential confounding variables. Results: Participants with SCT (n=55) did not differ from those without SCT (n=620) in prevalence of hypertension, previous myocardial infarction, diabetes mellitus, and current smoking status. Stroke cases had increased prevalence in these risk factors compared with controls. We did not find an association between SCT and early-onset IS in our overall population (odds ratio=0.9 [95% CI, 0.5–1.7]) or stratified by sex in males (odds ratio=1.26 [95% CI, 0.56–2.80]) and females (odds ratio=0.67 [95% CI, 0.28–1.69]). Conclusions: Our data did not find evidence of increased risk of early-onset stroke with SCT.

Exercise-induced death in sickle cell trait: role of aging, training, and deconditioning

1996 ◽  
Vol 28 (5) ◽  
pp. 541-544
Author(s):  
DANIEL LE GALLAIS ◽  
ALPHONSE BILÉ ◽  
JACQUES MERCIER ◽  
MARC PASCHEL ◽  
JEAN LOUIS TONELLOT ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Exercise Induced

ID: 139: PROGRESSIVE GLOMERULAR DAMAGE IN SICKLE CELL TRAIT AND SICKLE CELL ANEMIA MOUSE MODELS

2016 ◽  
Vol 64 (4) ◽  
pp. 957.2-958
Author(s):  
SL Saraf ◽  
JR Sysol ◽  
JA Arruda ◽  
RF Machado ◽  
VR Gordeuk ◽  
...  
Keyword(s):  
Gene Expression ◽  
African Americans ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Sickle Cell Trait ◽  
Linear Trend ◽  
Mesangial Expansion ◽  
Urine Protein ◽  
Increased Risk

The hemoglobin S mutation, a glutamic acid to valine substitution in the β-globin chain, results in hemoglobin polymerization under hypoxic conditions and leads to vaso-occlusion and hemolysis. Homozygous inheritance (Hb SS; sickle cell anemia) affects 1 in 500 African Americans and is consistently associated with an increased risk for kidney disease which may be due to cell-free hemoglobin toxicity, ischemic injury, or hyperfiltration-mediated damage to the kidney. Heterozygous inheritance (Hb AS; sickle cell trait) affects 1 in 8 African Americans and has also been associated with an increased risk for kidney disease, although not in all cohorts and the mechanisms are not well understood.We investigated whether inheritance of the Hb S mutation resulted in incremental kidney damage in Hb AS and Hb SS mice compared to Hb AA mice by histology, proteinuria, and candidate gene expression using transgenic sickle mice ≥6 months of age (Townes model, Jackson Laboratory). Values are presented as mean±standard error and analyses are adjusted for age.Using Masson trichrome stained sections of the kidney, progressive patterns of mesangial expansion were observed in age-matched Hb AS and Hb SS mice versus Hb AA mice by renal pathologists blinded to the hemoglobin genotype (figure 1). Hb AS mice had diffuse (>50% of the glomeruli per slide being involved) mesangial expansion while Hb SS mice had diffuse and global (>50% of the individual glomerulus being involved) mesangial expansion. Glomerular perimeters were measured using NanoZoomer Whole Slide Imaging in 26 randomly selected glomeruli from 2 age-matched mice per genotype. Using the upper quartile as the definition for an enlarged glomerulus, the proportion of enlarged glomeruli progressively increased from Hb AA (15%) to Hb AS (31%) to Hb SS mice (58%) (Cochran's test of linear trend, P=0.001) (figure 2). Progressively higher kidney weights were also observed from Hb AA (429±28 mg, n=8) to Hb AS (446±27 mg, n=18) to Hb SS (567±19 mg, n=5) mice (Test for linear trend, P=0.047). We then measured urine protein and urine creatinine concentrations using the Bio-Rad dye method and Jaffé reaction, respectively. Progressively higher urine protein-to-creatinine ratios were observed from Hb AA to Hb AS to Hb SS mice (figure 3) (Test for linear trend, P=0.09). Gene expression of candidate genes (TGFB1, IL6, MMP9, Klotho, HMOX1, and SHROOM3) was determined by rt-PCR from kidneys of age-matched, female Hb AA and Hb AS mice (n=5). Increased expression of Klotho (P=0.09) was observed in Hb AS mice (figure 4). Klotho is a β-glucoronidase that is highly expressed in the kidney and acts as a cofactor that increases the affinity of the FGF23 ligand for the FGF receptor.In conclusion, we observed progressive glomerular injury, determined by mesangial expansion, proportion of enlarged glomeruli, and urine protein concentrations in Hb AS and Hb SS mice compared to Hb AA mice. Klotho was upregulated in Hb AS mice and may play a role in the pathophysiology of kidney damage in Hb AS which will require further investigation.Abstract ID: 139 Figure 1

Role of Exercise-Induced Oxidative Stress in Sickle Cell Trait and Disease

2015 ◽  
Vol 46 (5) ◽  
pp. 629-639 ◽  
Author(s):  
Erica N. Chirico ◽  
Camille Faës ◽  
Philippe Connes ◽  
Emmanuelle Canet-Soulas ◽  
Cyril Martin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Exercise Induced

scholarly journals Risk of Pregnancy-Related Venous Thromboembolism in Black Women with Sickle Cell Trait

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2044-2044
Author(s):  
Tijesunimi Oni ◽  
Manuela Plazas Montana ◽  
Mamie Myo Thant ◽  
Sarah Baghdadi ◽  
Jaanvi Mahesh ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Black Women ◽  
Sickle Cell ◽  
Research Funding ◽  
Sickle Cell Trait ◽  
Post Partum ◽  
Search Term ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Privately Held

Abstract Background: Select inherited thrombophilias have been shown to potentiate the risk of venous thromboembolism (VTE) during pregnancy and the post-partum period. Sickle cell trait (SCT) is associated with an increased risk of VTE in the general Black population; however, prior studies investigating the risk of pregnancy-related VTE among women with SCT have been limited by an overall low number of VTE events. We, therefore, designed a retrospective cohort enriched for pregnancy-related VTE events among Black women at Johns Hopkins Hospital to address this question. Methods: We generated a cohort enriched for pregnancy-related VTE at Johns Hopkins or affiliate hospitals from 2009-2019 by using EPIC and an internal ObGyn database to identify Black women ≥18 years with at least 1 pregnancy encounter in addition to at least 1 VTE-related ICD-10 diagnosis code or comprehensive VTE-related search term. All charts were manually reviewed to confirm hemoglobinopathy status and to verify the presence or absence of a VTE event during pregnancy or 6 weeks post-partum. Individuals with sickle cell disease, history of VTE prior to index pregnancy, catheter-related or superficial vein thrombosis only, or unknown pregnancy VTE outcome were excluded. Results: A total of 418 women were included for analysis. The mean age at pregnancy was 30 years (range 18-48), and the prevalence of SCT was 6.7%, which is similar to the prevalence in the general Black American population. Thirty-seven women (8.9%) were confirmed to have a pregnancy-related VTE event. Among those with VTE, SCT carriers demonstrated a higher proportion of pulmonary embolism (PE), unusual vein thrombosis, and antepartum VTE events compared to women with HbAA (Table 1), though numbers were small. After adjusting for age, the risk of VTE was 2.9-fold (95% CI 1.1-7.9) higher among pregnant Black women with SCT compared to those without. Conclusions: In this enriched cohort, SCT was associated with an increased risk of pregnancy-related VTE among Black women. The pattern of pregnancy-related VTE was different in individuals with SCT compared to those with HbAA, with SCT demonstrating a higher proportion of PE and antepartum events. The higher risk of PE compared to isolated DVT is similar to the pattern observed in prior population-based studies of SCT. Because the prevalence of SCT is high and the overall risk of VTE in pregnancy is low, future studies are needed to determine whether routine thromboprophylaxis is warranted for select high-risk pregnant women with SCT. Figure 1 Figure 1. Disclosures Lanzkron: Novartis: Research Funding; CSL Behring: Research Funding; Shire: Research Funding; Novo Nordisk: Consultancy; Imara: Research Funding; Bluebird Bio: Consultancy; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; GBT: Research Funding. Naik: Rigel: Research Funding.

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