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BMJ Case Reports Jun 2017A 39-year-old man with a history of sickle cell disease (SCD) presented with left leg weakness. He had a normal CT head and CT angiogram, but MRI head showed multiple...
A 39-year-old man with a history of sickle cell disease (SCD) presented with left leg weakness. He had a normal CT head and CT angiogram, but MRI head showed multiple acute bilateral cortical infarcts including in the right precentral gyrus. The MRI findings were more in keeping with an embolic source rather than stroke related to SCD, although it could not be ruled out. He also had an echocardiogram which revealed a patent foramen ovale. He was treated with antiplatelet therapy and also had red blood cell exchange transfusion. His symptoms improved significantly and he was discharged with follow-up as an outpatient and a cardiology review.
Topics: Adult; Anemia, Sickle Cell; Echocardiography; Embolism; Erythrocyte Transfusion; Foramen Ovale, Patent; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Platelet Aggregation Inhibitors; Stroke; Uncertainty
PubMed: 28645902
DOI: 10.1136/bcr-2016-218358 -
Haematologica Nov 2020
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Betacoronavirus; COVID-19; Child; Child, Preschool; Coronavirus Infections; Female; Hemoglobinopathies; Humans; Infant; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2; Surveys and Questionnaires; Young Adult
PubMed: 33054122
DOI: 10.3324/haematol.2020.259440 -
Balkan Medical Journal Jul 2023Hemoglobinopathies are the most common inherited diseases in humans resulting from impaired globin chain synthesis of hemoglobin. The progression of thalassemia rates is...
BACKGROUND
Hemoglobinopathies are the most common inherited diseases in humans resulting from impaired globin chain synthesis of hemoglobin. The progression of thalassemia rates is prevented with prenatal screening methods.
AIMS
To evaluate the hematological parameters of α- and β-thalassemia and normal fetuses aged 17-25 weeks of gestation.
STUDY DESIGN
A cross-sectional study.
METHODS
Pregnant women who underwent cordocentesis in the second trimester because of the risk of having a baby with thalassemia were included in the study. Hematological indices and molecular DNA methods were analyzed from the cord blood samples of 129 women who were 17-25 weeks into pregnancy. The HPLC method was used for Hb fraction analysis. Amplification refractory mutation system, restriction enzyme analysis, multiplex polymerase chain reaction, and sequencing methods were used for the molecular analysis. Maternal contamination was eliminated by the short tandem repeat method.
RESULTS
In total, 112 of the fetuses carry α- and β-thalassemia heterozygous or homozygous (α: 37, β: 58, mixed: 17) and 17 fetuses had a normal genotype for thalassemia. Significant differences in adult hemoglobin (HbA), fetal hemoglobin (HbF), Hb Barts, MCV, MCH, and RDW were detected in three groups compared with the normal group (p < 0.001, except for RBC, Hb, HCT, and MCHC). Differences in HbF, Hb Barts, MCV, MCH, and RDW were observed in the α-thalassemia groups compared with the normal group (p < 0.001). Among the five β-thalassemia subgroups, only HbA and RDW were different from the normal group (p < 0.001).
CONCLUSION
This study could be a good reference for future studies and prenatal diagnostic applications in emphasizing the importance of changes in the blood parameters of fetuses before molecular genotyping. These hematological data give valuable information to clinicians about the fetus to enlighten families in making appropriate decisions during prenatal diagnosis.
Topics: Female; Pregnancy; Humans; beta-Thalassemia; Pregnancy Trimester, Second; Fetal Blood; Cross-Sectional Studies; alpha-Thalassemia; Genotype; Fetus
PubMed: 37154826
DOI: 10.4274/balkanmedj.galenos.2023.2023-1-86 -
Trials Apr 2020Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD...
BACKGROUND
Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD during pregnancy. Serial prophylactic exchange blood transfusion (SPEBT) has been shown to be effective in treating SCD outside pregnancy, but evidence is lacking regarding its use during pregnancy. The aim of this study is to assess the feasibility and acceptability of conducting a future phase 3 randomised controlled trial (RCT) to establish the clinical and cost effectiveness of SPEBT in pregnant women with SCD.
METHODS
The study is an individually randomised, two-arm, feasibility trial with embedded qualitative and health economic studies. Fifty women, 18 years of age and older, with SCD and a singleton pregnancy at ≤ 18 weeks' gestation will be recruited from six hospitals in England. Randomisation will be conducted using a secure online database and minimised by centre, SCD genotype and maternal age. Women allocated to the intervention arm will receive SPEBT commencing at ≤ 18 weeks' gestation, performed using automated erythrocytapheresis every 6-10 weeks until the end of pregnancy, aiming to maintain HbS% or combined HbS/HbC% below 30%. Women in the standard care arm will only receive transfusion when clinically indicated. The primary outcome will be the recruitment rate. Additional endpoints include reasons for refusal to participate, attrition rate, protocol adherence, and maternal and neonatal outcomes. Women will be monitored throughout pregnancy to assess maternal, sickle, and foetal complications. Detailed information about adverse events (including hospital admission) and birth outcomes will be extracted from medical records and via interview at 6 weeks postpartum. An embedded qualitative study will consist of interviews with (a) 15-25 trial participants to assess experiences and acceptability, (b) 5-15 women who decline to participate to identify barriers to recruitment and (c) 15-20 clinical staff to explore fidelity and acceptability. A health economic study will inform a future cost effectiveness and cost-utility analysis.
DISCUSSION
This feasibility study aims to rigorously evaluate SPEBT as a treatment for SCD in pregnancy and its impact on maternal and infant outcomes.
TRIAL REGISTRATION
NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
Topics: Adolescent; Adult; Anemia, Sickle Cell; Blood Transfusion; Cost-Benefit Analysis; England; Feasibility Studies; Female; Follow-Up Studies; Humans; Middle Aged; Multicenter Studies as Topic; Pregnancy; Pregnancy Complications; Prenatal Care; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32312326
DOI: 10.1186/s13063-020-4212-8 -
Haematologica Apr 2017Sickle cell disease is an increasing global health burden. This inherited disease is characterized by a remarkable phenotypic heterogeneity, which can only partly be...
Sickle cell disease is an increasing global health burden. This inherited disease is characterized by a remarkable phenotypic heterogeneity, which can only partly be explained by genetic factors. Environmental factors are likely to play an important role but studies of their impact on disease severity are limited and their results are often inconsistent. This study investigated associations between a range of environmental factors and hospital admissions of young patients with sickle cell disease in London and in Paris between 2008 and 2012. Specific analyses were conducted for subgroups of patients with different genotypes and for the main reasons for admissions. Generalized additive models and distributed lag non-linear models were used to assess the magnitude of the associations and to calculate relative risks. Some environmental factors significantly influence the numbers of hospital admissions of children with sickle cell disease, although the associations identified are complicated. Our study suggests that meteorological factors are more likely to be associated with hospital admissions for sickle cell disease than air pollutants. It confirms previous reports of risks associated with wind speed (risk ratio: 1.06/standard deviation; 95% confidence interval: 1.00-1.12) and also with rainfall (1.06/standard deviation; 95% confidence interval: 1.01-1.12). Maximum atmospheric pressure was found to be a protective factor (0.93/standard deviation; 95% confidence interval: 0.88-0.99). Weak or no associations were found with temperature. Divergent associations were identified for different genotypes or reasons for admissions, which could partly explain the lack of consistency in earlier studies. Advice to patients with sickle cell disease usually includes avoiding a range of environmental conditions that are believed to trigger acute complications, including extreme temperatures and high altitudes. Scientific evidence to support such advice is limited and sometimes confusing. This study shows that environmental factors do explain some of the variations in rates of admission to hospital with acute symptoms in sickle cell disease, but the associations are complex, and likely to be specific to different environments and the individual's exposure to them. Furthermore, this study highlights the need for prospective studies with large numbers of patients and standardized protocols across Europe.
Topics: Adolescent; Adult; Aged; Anemia, Sickle Cell; Child; Child, Preschool; Disease Progression; Environment; Environmental Exposure; Hospitalization; Humans; London; Middle Aged; Odds Ratio; Paris; Public Health Surveillance; Risk Factors; Young Adult
PubMed: 27909222
DOI: 10.3324/haematol.2016.154245 -
Blood Apr 2022Excessive intravascular release of lysed cellular contents from damaged red blood cells (RBCs) in patients with sickle cell anemia (SCA) can activate the inflammasome, a... (Randomized Controlled Trial)
Randomized Controlled Trial
Excessive intravascular release of lysed cellular contents from damaged red blood cells (RBCs) in patients with sickle cell anemia (SCA) can activate the inflammasome, a multiprotein oligomer promoting maturation and secretion of proinflammatory cytokines, including interleukin-1β (IL-1β). We hypothesized that IL-1β blockade by canakinumab in patients with SCA would reduce markers of inflammation and clinical disease activity. In this randomized, double-blind, multicenter phase 2a study, patients aged 8 to 20 years with SCA (HbSS or HbSβ0-thalassemia), history of acute pain episodes, and elevated high-sensitivity C-reactive protein >1.0 mg/L at screening were randomized 1:1 to received 6 monthly treatments with 300 mg subcutaneous canakinumab or placebo. Measured outcomes at baseline and weeks 4, 8, 12, 16, 20, and 24 included electronic patient-reported outcomes, hospitalization rate, and adverse events (AEs) and serious AEs (SAEs). All but 1 of the 49 enrolled patients were receiving stable background hydroxyurea therapy. Although the primary objective (prespecified reduction of pain) was not met, compared with patients in the placebo arm, patients treated with canakinumab had reductions in markers of inflammation, occurrence of SCA-related AEs and SAEs, and number and duration of hospitalizations as well as trends for improvement in pain intensity, fatigue, and absences from school or work. Post hoc analysis revealed treatment effects on weight, restricted to pediatric patients. Canakinumab was well tolerated with no treatment-related SAEs and no new safety signal. These findings demonstrate that the inflammation associated with SCA can be reduced by selective IL-1β blockade by canakinumab with potential for therapeutic benefits. This trial was registered at www.clinicaltrials.gov as #NCT02961218.
Topics: Anemia, Sickle Cell; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biomarkers; Child; Double-Blind Method; Humans; Inflammation; Young Adult
PubMed: 35226723
DOI: 10.1182/blood.2021013674 -
European Heart Journal. Quality of Care... May 2022To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low-middle-income country (LMIC) and using the result to guide...
AIMS
To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low-middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients.
METHODS AND RESULTS
A prospective UK-India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results. Participants were recruited by the local patient advocate charity, who organized the patient medical camps. The average scanning time was 11.3 ± 2.5 min at the baseline and 9.8 ± 2.4 min (P < 0.001) at follow-up. The baseline visit was attended by 103 patients (mean age 25 years) and 83% attended the second assessment. At baseline, 29% had a cardiac T2* < 20 ms, which represents significant iron loading, and 12% had left ventricular ejection fraction <60%, the accepted lower limit in this population. Only 3% were free of liver iron (T2* ≥ 17 ms). At 13 months, more patients were taking intensified dual chelation therapy (43% vs. 55%, P = 0.002). In those with cardiac siderosis (baseline T2* < 20 ms), there was an improvement in T2*-10.9 ± 5.9 to 13.5 ± 8.7 ms, P = 0.005-and fewer were classified as having clinically important cardiac iron loading (T2* < 20 ms, 24% vs. 16%, P < 0.001). This is the first illustration in an LMIC that incorporating CMR results into patient management plans can improve cardiac iron loading.
CONCLUSION
For thalassaemia patients in an LMIC, a simplified CMR protocol linked to therapeutic recommendation via the patient camp model led to enhanced chelation therapy and a reduction in cardiac iron in 1 year.
Topics: Adult; Chelation Therapy; Cohort Studies; Humans; Iron; Magnetic Resonance Imaging; Prospective Studies; Stroke Volume; Thalassemia; Ventricular Function, Left; beta-Thalassemia
PubMed: 34849707
DOI: 10.1093/ehjqcco/qcab089 -
Orphanet Journal of Rare Diseases Jul 2021Thalassaemia, a hereditary haemoglobin disorder, is a major public health concern in some parts of the world. Although Bangladesh is in the world's thalassaemia belt,...
BACKGROUND
Thalassaemia, a hereditary haemoglobin disorder, is a major public health concern in some parts of the world. Although Bangladesh is in the world's thalassaemia belt, the information on this disease is scarce. Additionally, the awareness of this life threatening, but potentially preventable disease is surprisingly poor. However, mass awareness is pivotal for the development of an effective preventive strategy. In this context, the understanding of parental perspectives is essential to grasp the magnitude of the problem. Therefore, this study aimed to investigate the parental knowledge gaps and perceptions regarding thalassemia, the barriers confronted by the parents for caring for their thalassaemic children and their attitude to prenatal screening and prenatal diagnosis.
METHODS
This cross-sectional study was conducted between January 2018 and December 2018 at a dedicated thalassemia hospital located in Dhaka. A structured questionnaire was used for face-to-face interviews with parents of thalassaemic children. Descriptive statistics were used to analyse data.
RESULTS
Of 365 respondents, nearly all respondents (97%) had not heard about the term, 'thalassemia' before the disease was diagnosed in their children; all (100%) were unscreened for carrier status prior to marriage. Mean knowledge scores were significantly higher in respondents with higher income and education. Most respondents (~ 91%) had a guilty feeling for not undergoing premarital screening. Only around 36% of them had heard about prenatal diagnosis. Approximately 25% participants would consider prenatal diagnosis in a future pregnancy, while 70% of them were unsure and only ~ 5% would decline prenatal diagnosis. Only 9.3% mothers had prenatal diagnosis in a previous pregnancy. Nearly 80% of the parents faced difficulty for obtaining blood donors regularly and a similar proportion (~ 81%) of them did not receive support from any organized blood clubs. More than 40% of the parents reported they felt socially stigmatized.
CONCLUSION
This study suggests poor parental knowledge regarding thalassaemia including prenatal diagnosis and the challenges faced while caring for their children. These findings would be of paramount importance in planning and devising effective prevention and intervention strategies in Bangladesh as well as other countries with similar sociocultural setting.
Topics: Bangladesh; Child; Cross-Sectional Studies; Emotions; Female; Health Knowledge, Attitudes, Practice; Humans; Parents; Pregnancy; Prenatal Diagnosis; Thalassemia
PubMed: 34271949
DOI: 10.1186/s13023-021-01947-6 -
BMC Nephrology Sep 2017Early detection and interventions have enabled patients with sickle cell disease (SCD) to live well into adulthood. Consequently, the chronicity of SCD allows for the...
BACKGROUND
Early detection and interventions have enabled patients with sickle cell disease (SCD) to live well into adulthood. Consequently, the chronicity of SCD allows for the insidious manifestation of multisystem complications, including renal damage. Cystic renal lesions are commonly incidentally discovered on ultrasound and computerised tomography (CT) imaging of the abdomen. Most are benign simple cysts, however, difficulties may be encountered if infection, rupture, haemorrhage or cancerous changes develop. We aimed to determine whether patients with SCD have a higher prevalence of simple renal cysts compared to non-SCD individuals.
METHODS
Data for a group of 223 patients with SCD who had undergone an ultrasound and/or CT imaging of the abdomen were extracted for comparison with 180 control patients (haemoglobin genotype unknown), matched for age and ethnicity. Scans were evaluated for 198 SCD patients and 180 controls.
RESULTS
Renal cysts were found in 58% of the SCD group and 20% of the controls (OR 5.4 (CI 2.6-11.0), RR 2.8 (CI 1.9-4.2)). Bilateral renal cysts were found in 28% of the SCD participants in comparison with 5% of the control group. In those who had one or more cysts identified, the average number of cysts was 3.76 for the SCD group and 1.94 for the controls. Men with SCD were more likely to develop cysts than women (66% vs 53%), as were men without SCD (22% vs 17%).
CONCLUSIONS
Simple renal cysts occur more frequently, are more abundant and develop at a younger age in patients with SCD than ethnically-matched controls. Further study of the mechanism underlying cyst formation may shed light on both sickle cell nephropathy and other cystic renal diseases.
Topics: Adolescent; Adult; Anemia, Sickle Cell; Cross-Sectional Studies; Female; Humans; Kidney Diseases, Cystic; Male; Middle Aged; Prevalence; Tomography, X-Ray Computed; Ultrasonography; Young Adult
PubMed: 28934953
DOI: 10.1186/s12882-017-0714-3 -
British Journal of Haematology Oct 2019A brief measure of patient satisfaction with treatment for pain is needed to help improve the treatment of painful episodes caused by sickle cell disease (SCD),...
A brief measure of patient satisfaction with treatment for pain is needed to help improve the treatment of painful episodes caused by sickle cell disease (SCD), especially during and after the transition from paediatric to adult care. Focus groups of 28 adolescent and adult patients were consulted about the content, clarity and relevance of 30 potential items, resulting in an 18-item version. This was validated by analysing questionnaire responses from 120 patients aged 12-53 years. Confirmatory factor analysis and item analysis indicated five subscales with high internal reliability: 'Communication and Involvement' (6 items, α = 0·87); 'Respect and Dignity' (3 items, α = 0·82); 'Pain Control' (3 items, α = 0·91); 'Staff Attitudes and Behaviour' (4 items, α = 0·88); and 'Overall Satisfaction' (2 items, α = 0·85) plus a Total Satisfaction score (18 items, α = 0·96). High negative correlations with the Picker Patient Experience Questionnaire, a measure of problem experiences, indicated good convergent validity. Lower satisfaction scores among patients aged over 18 years, those admitted via the emergency department, those treated by non-specialist hospital staff, and those reporting more breakthrough pain indicated good concurrent validity. The questionnaire provides a convenient brief measure that can be used to inform and evaluate improvements in healthcare for adolescent and adult patients with SCD, and could potentially be adapted for other painful conditions.
Topics: Acute Pain; Adolescent; Adult; Anemia, Sickle Cell; Child; England; Female; Focus Groups; Hospitalization; Humans; Male; Middle Aged; Pain Management; Patient Satisfaction; Psychometrics; Reproducibility of Results; Surveys and Questionnaires; Transition to Adult Care; Young Adult
PubMed: 31230352
DOI: 10.1111/bjh.16015