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Preoperative Transfusion in Sickle Cell Disease Children Undergoing Adenotonsillectomy
Kanotra, S., Muller, S. H., Kanotra, J., Gardner, R., Kanotra, S. P.
Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India. 2023;75(2):227-235
Abstract
OBJECTIVE To perform a systematic review and meta-analysis comparing two pre-operative transfusion regimens (conservative versus aggressive) in children with sickle cell disease(SCD) undergoing adenotonsillectomy in terms of post-operative complications, complications related to SCD and transfusion related complications. DATA SOURCES AND REVIEW METHODS A literature review was performed through PubMed, EMBASE, Cochrane, and Ovid databases using the following phrases: (Adenotonsillectomy OR Tonsillectomy) AND (Sickle Cell Disease OR Sickle Cell Trait). Using predetermined inclusion and exclusion criteria, seven articles were selected for systemic review and two control trials were included in meta-analysis. RESULTS Out of a total of 3,146 results, seven articles were selected for review and two controlled trials were included in the meta-analysis. There was no statistically significant difference in the rate of primary and secondary hemorrhage between the aggressive and conservative transfusion regimens (RR = 3.1, CI = 0.84-11.4, p-value = 0.089). The rate of sickle cell disease related complications including vaso-occlusive crisis and acute chest syndrome was also not statistically significant between the two transfusion groups (RR = 1.4, CI = 0.7-2.8, p-value = 0.339). Even though, the transfusion related complications did not reach statistical significance, there was a higher complication rate in the group receiving aggressive blood transfusion. CONCLUSION In SCD children undergoing adenotonsillectomy, an aggressive transfusion regimen that focuses on reducing the Hemoglobin S ratio to below 30% has not been shown to be more effective in reducing post-operative complications when compared to a conservative transfusion regimen. Therefore, it is reasonable to utilize a conservative transfusion regimen, thereby reducing the transfusion-associated risks.
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Interventions for chronic kidney disease in people with sickle cell disease
Roy, N. B., Carpenter, A., Dale-Harris, I., Dorée, C., Estcourt, L. J.
The Cochrane database of systematic reviews. 2023;8(8):Cd012380
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Editor's Choice
Abstract
BACKGROUND Sickle cell disease (SCD), one of the commonest severe monogenic disorders, is caused by the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD. Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD. Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, with increased prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. This is an update of a review first published in 2017. OBJECTIVES To assess the effectiveness of any intervention for preventing or reducing kidney complications or chronic kidney disease in people with sickle cell disease. Possible interventions include red blood cell transfusions, hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination. SEARCH METHODS We searched for relevant trials in the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, CENTRAL, MEDLINE, Embase, seven other databases, and two other trials registers. SELECTION CRITERIA Randomised controlled trials (RCTs) comparing interventions to prevent or reduce kidney complications or CKD in people with SCD. We applied no restrictions related to outcomes examined, language, or publication status. DATA COLLECTION AND ANALYSIS Two review authors independently assessed trial eligibility, extracted data, assessed the risk of bias, and assessed the certainty of the evidence (GRADE). MAIN RESULTS We included three RCTs with 385 participants. We rated the certainty of the evidence as low to very low across different outcomes according to GRADE methodology, downgrading for risk of bias concerns, indirectness, and imprecision. Hydroxyurea versus placebo One RCT published in 2011 compared hydroxyurea to placebo in 193 children aged nine to 18 months. We are unsure if hydroxyurea compared to placebo reduces or prevents progression of kidney disease assessed by change in glomerular filtration rate (mean difference (MD) 0.58 mL/min /1.73 m(2), 95% confidence interval (CI) -14.60 to 15.76; 142 participants; very low certainty). Hydroxyurea compared to placebo may improve the ability to concentrate urine (MD 42.23 mOsm/kg, 95% CI 12.14 to 72.32; 178 participants; low certainty), and may make little or no difference to SCD-related serious adverse events, including acute chest syndrome (risk ratio (RR) 0.39, 99% CI 0.13 to 1.16; 193 participants; low certainty), painful crisis (RR 0.68, 99% CI 0.45 to 1.02; 193 participants; low certainty); and hospitalisations (RR 0.83, 99% CI 0.68 to 1.01; 193 participants; low certainty). No deaths occurred in either trial arm and the RCT did not report quality of life. Angiotensin-converting enzyme inhibitors versus placebo One RCT published in 1998 compared an ACEI (captopril) to placebo in 22 adults with normal blood pressure and microalbuminuria. We are unsure if captopril compared to placebo reduces proteinuria (MD -49.00 mg/day, 95% CI -124.10 to 26.10; 22 participants; very low certainty). We are unsure if captopril reduces or prevents kidney disease as measured by creatinine clearance; the trial authors stated that creatinine clearance remained constant over six months in both groups, but provided no comparative data (very low certainty). The RCT did not report serious adverse events, all-cause mortality, or quality of life. Angiotensin-converting enzyme inhibitors versus vitamin C One RCT published in 2020 compared an ACEI (lisinopril) with vitamin C in 170 children aged one to 18 years with normal blood pressure and microalbuminuria. It reported no data we could analyse. We are unsure if lisinopril compared to vitamin C reduces proteinuria in this population: the large drop in microalbuminuria in both arms of the trial after only one month on treatment may have been due to an overestimation of microalbuminuria at baseline rather than a true effect. The RCT did not report serious adverse events, all-cause mortality, or quality of life. AUTHORS' CONCLUSIONS We are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. We are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. We are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria. No RCTs assessed red blood cell transfusions or any combined interventions to prevent or reduce kidney complications. Due to lack of evidence, we cannot comment on the management of children aged over 18 months or adults with any known genotype of SCD. We have identified a lack of adequately designed and powered studies, although we found four ongoing trials since the last version of this review. Only one ongoing trial addresses renal function as a primary outcome in the short term, but such interventions have long-term effects. Trials of hydroxyurea, ACEIs or red blood cell transfusion in older children and adults are urgently needed to determine any effect on prevention or reduction of kidney complications in people with SCD.
PICO Summary
Population
Children and adults with sickle cell disease (3 randomised controlled trials, n= 385).
Intervention
Interventions to prevent or reduce kidney complications or chronic kidney disease, including: hydroxyurea, and angiotensin-converting enzyme inhibitors (ACEIs), either alone or in combination.
Comparison
Placebo.
Outcome
This systematic review is an update of a review first published in 2017. The authors rated the certainty of the evidence as low to very low across different outcomes. The authors are unsure if hydroxyurea improves glomerular filtration rate or reduces hyperfiltration in children aged nine to 18 months, but it may improve their ability to concentrate urine and may make little or no difference to the incidence of acute chest syndrome, painful crises, and hospitalisations. The authors are unsure if ACEI compared to placebo has any effect on preventing or reducing kidney complications in adults with normal blood pressure and microalbuminuria. The authors are unsure if ACEI compared to vitamin C has any effect on preventing or reducing kidney complications in children with normal blood pressure and microalbuminuria.
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Overview of current progress and challenges in diagnosis, and management of pediatric sickle cell disease in Democratic Republic of the Congo
Kasai ET, Alworong'a Opara JP, Ntokamunda Kadima J, Kalenga M, Batina Agasa S, Marini Djang'eing'a R, Boemer F
Hematology (Amsterdam, Netherlands). 2022;27(1):132-140
Abstract
OBJECTIVES Sickle cell disease (SCD) encompasses health complications, primarily affecting the hematologic system and leading to high death rates in childhood. As a rule, the World Health Organisation (WHO) stepwise gold-standard about the strategies for prevention, diagnosis, and treatment of SCD must be multidimensional. This overview aimed to highlight current advances and challenges linked to strategic issues, diagnosis, the prevalence, and treatment of pediatric cases in Sub-Saharan Africa, particularly the Democratic Republic of the Congo. METHODS We searched data on Google Scholar, Medline, PubMed, Science Direct, Scopus, and ResearchGate. RESULTS The laboratory diagnosis of SCD has progressed from conventional electrophoresis to rapid point-of-care tests that allows early neonate screening. HemoTypeSC(TM) is an affordable test for neonatal screening in DRC. The pediatric SCD prevalence in Sub-Saharan Africa lay within 1-7.7% of homozygous(SS) and 15-40% of the heterozygous(AS) forms of SCD, depending on the method used and the ethnic population tested. Various supportive management protocols for comorbidities and complications exist, but they are not standardized in the Region. CONCLUSION Notwithstanding some progress accomplished, the disease is still challenging in Sub-Saharan Africa due to limited early diagnostic testing and a lack of specific medications. There is a need for harmonizing therapeutic protocols and conducting controlled valid clinical trials.
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Health related quality of life in children with sickle cell disease: A systematic review and meta-analysis
Stokoe M, Zwicker HM, Forbes C, Abu-Saris Nelh, Fay-McClymont TB, Désiré N, Guilcher GMT, Singh G, Leaker M, Yeates KO, et al
Blood reviews. 2022;:100982
Abstract
This review had three aims: 1) describe the measures used to assess health-related quality of life (HRQL) in pediatric patients diagnosed with sickle cell disease (SCD); 2) document the biopsychosocial factors related to HRQL in pediatric patients diagnosed with SCD; and 3) complete a meta-analysis comparing HRQL in pediatric patients diagnosed with SCD to healthy controls. Included studies were published in English, quantitatively assessed HRQL as a primary aim, in both SCD and controls, and included participants between 0 and 21 years of age. The final review included 66 articles, with a total of 8642 participants with SCD, 4 months-21 years of age, and 62,458 controls, 5-27 years of age. HRQL was predominately measured using the Pediatric Quality of Life Inventory Generic Core and Sickle Cell Disease Module. Meta-analyses revealed children with SCD had significantly worse HRQL compared to healthy controls (standardized mean difference = -0.93, 95% CI = -1.25, -0.61, p < 0.00001). Worse HRQL was associated with more severe SCD, female sex, and pain. The findings indicate that children with SCD are at risk for worse HRQL compared to their healthy peers and their HRQL may be impacted by several biopsychosocial factors. Future research is needed to examine how sociocultural factors uniquely impact this population and their overall quality of life.
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Blood transfusions for treating acute chest syndrome in people with sickle cell disease
Dolatkhah R, Dastgiri S
The Cochrane database of systematic reviews. 2020;1:Cd007843
Abstract
BACKGROUND Sickle cell disease is an inherited autosomal recessive blood condition and is one of the most prevalent genetic blood diseases worldwide. Acute chest syndrome is a frequent complication of sickle cell disease, as well as a major cause of morbidity and the greatest single cause of mortality in children with sickle cell disease. Standard treatment may include intravenous hydration, oxygen as treatment for hypoxia, antibiotics to treat the infectious cause and blood transfusions may be given. This is an update of a Cochrane Review first published in 2010 and updated in 2016. OBJECTIVES To assess the effectiveness of blood transfusions, simple and exchange, for treating acute chest syndrome by comparing improvement in symptoms and clinical outcomes against standard care. SEARCH METHODS We searched The Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. Date of the most recent search: 30 May 2019. SELECTION CRITERIA Randomised controlled trials and quasi-randomised controlled trials comparing either simple or exchange transfusion versus standard care (no transfusion) in people with sickle cell disease suffering from acute chest syndrome. DATA COLLECTION AND ANALYSIS Both authors independently selected trials and assessed the risk of bias, no data could be extracted. MAIN RESULTS One trial was eligible for inclusion in the review. While in the multicentre trial 237 people were enrolled (169 SCC, 42 SC, 15 Sbeta(0)-thalassaemia, 11Sbeta(+)-thalassaemia); the majority were recruited to an observational arm and only ten participants met the inclusion criteria for randomisation. Of these, four were randomised to the transfusion arm and received a single transfusion of 7 to 13 mL/kg packed red blood cells, and six were randomised to standard care. None of the four participants who received packed red blood cells developed acute chest syndrome, while 33% (two participants) developed acute chest syndrome in standard care arm. No data for any pre-defined outcomes were available. AUTHORS' CONCLUSIONS We found only one very small randomised controlled trial; this is not enough to make any reliable conclusion to support the use of blood transfusion. Whilst there appears to be some indication that chronic blood transfusion may play a roll in reducing the incidence of acute chest syndrome in people with sickle cell disease and albeit offering transfusions may be a widely accepted clinical practice, there is currently no reliable evidence to support or refute the perceived benefits of these as treatment options; very limited information about any of the potential harms associated with these interventions or indeed guidance that can be used to aid clinical decision making. Clinicians should therefore base any treatment decisions on a combination of; their clinical experience, individual circumstances and the unique characteristics and preferences of adequately informed people with sickle cell disease who are suffering with acute chest syndrome. This review highlights the need of further high quality research to provide reliable evidence for the effectiveness of these interventions for the relief of the symptoms of acute chest syndrome in people with sickle cell disease.
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Etiology and therapeutic management of neonatal jaundice in Iran: a systematic review and meta-analysis
Zahed Pasha Y, Alizadeh-Tabari S, Zahed Pasha E, Zamani M
World journal of pediatrics : WJP. 2020
Abstract
BACKGROUND Jaundice is a life-threatening disorder in the neonates. In the present study, we aimed to assess systematically available evidence on causes and management of jaundice in Iranian newborn patients. METHODS We searched the databases of PubMed, Web of Sciences, Scopus and Google Scholar for English articles published since inception until May 2019. A search was also done for Persian articles in Magiran and Scientific Information Database. Studies were evaluated based on predefined criteria by two reviewers. Data analysis was performed by STATA software. RESULTS A total of 33 articles were finally included. The overall pooled prevalence of causes of jaundice among Iranian neonates was as follows: ABO blood groups incompatibility, 16.9% [95% confidence interval (CI) 10.9-22.8]; Rh blood group incompatibility, 4% (95% CI 2.5-5.5); ABO and Rh blood groups incompatibility, 3.6% (95% CI 0-7.7); glucose-6-phosphate dehydrogenase (G6PD) deficiency, 6.3% (95% CI 5.1-7.5); infection, 6.6% (95% CI 5.2-8.1); hypothyroidism, 4.2% (95% CI 0.1-8.3); infant of diabetic mother: 2.3% (95% CI 0.1-4.5); unknown, 50.7% (95% CI 33.4-68); cephalohematoma, 0.6% (95% CI 0.3-0.9). Regarding treatment of icterus, seven and eight articles were found on phototherapy and exchange transfusion, respectively. In five studies, all patients underwent phototherapy, but rate of exchange transfusion use was between 6.6% and 50.9%. CONCLUSIONS According to the results, unknown factors were the most common causes of icterus in Iranian neonates, followed by ABO blood groups incompatibility, infections and G6PD deficiency. By the way, phototherapy and exchange transfusion were found as therapeutic choices of neonatal jaundice.
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Hydroxyurea can be used in children with sickle cell disease and cerebral vasculopathy for the prevention of chronic complications? A meta-analysis
Nunez RM, Figueroa CAP, Garcia-Perdomo HA
Journal of child health care : for professionals working with children in the hospital and community. 2019;:1367493518814922
Abstract
We conducted a systematic review for evaluating the impact of hydroxyurea and chronic blood transfusion in children with sickle cell disease (SCD). A search was done in four databases from inception to 2017. Trials enrolling pediatric patients with SCD and cerebral vasculopathy with or without previous episode of stroke and that reported outcomes of occurrence of stroke and other events were included. Trained reviewers determined eligibility, risk of bias, and abstracted data. Random-effects meta-analysis was conducted. We found that the primary outcome was the occurrence of stroke. We found two trials that recruited 254 patients. No difference was found for confirmed stroke occurrence (risk difference 0.04 [95% CI: -0.03 to 0.03]) and for new-onset neurological deficit (risk difference 0.11 [95% CI: -0.00 to 0.21]). Transfusions provided a significant lower risk of vaso-occlussive crisis (risk difference 0.10 [95% CI: 0.001 to 0.20]). Finally, transfusions provided a lower risk of having high concentrations of abnormal hemoglobin S (mean difference 37.94 [95% CI: 27.55 to 48.32]). As a conclusion, transfusions plus chelation therapy might be used instead of hydroxyurea in children with SCD. There is a lack of high-quality research in the care of children with SCD, and therefore a call for action is needed.
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8.
Impact of Red Blood Cell Antigen Matching on Alloimmunization and Transfusion Complications in Patients with Sickle Cell Disease: A Systematic Review
Fasano RM, Meyer EK, Branscomb J, White MS, Gibson RW, Eckman JR
Transfusion Medicine Reviews. 2018;33((1):):12-23.
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Editor's Choice
Abstract
Red blood cells (RBC) transfusion is critical in managing acute and chronic complications in sickle cell disease (SCD); however, it is complicated by RBC alloimmunization, iron overload, transfusion reactions and infection. Several reports documented an increased incidence of alloantibodies in transfused individuals with SCD, especially for Rh and Kell antigens. As a result, the National Institutes of Health Expert Panel and British Society for Haematology guidelines recommend primary matching for C/c, E/e and K antigens in addition to ABO/RhD for RBC transfusions. However, the evidence supporting these recommendations was cited as limited and understanding of alloimmunization in SCD is evolving. To examine the limitations of the evidence, we undertook a systematic review of evidence behind recommendations for limited and extended serologic and genotypic RBC antigen matching to reduce alloimmunization, autoimmunization and transfusion reactions. Searches of PubMed, Embase, Cochrane, and Web of Science databases using MeSH index and free text terms between 1976 through October 2015 and papers and captured through July 2016 through review references in papers, word of mouth, and ongoing Google Scholar and Medline Alerts identified 303 unique articles. Nineteen articles met inclusion criteria and were classified by the Oxford Centre Evidence Based levels of evidence. Strengthening the Reporting of Observational Studies in Epidemiology checklists were completed for 18 of the 19 studies. There were no prospective randomized controlled trials. Sixteen of the articles were cohort studies, two were cross-sectional studies, and one decision tree model examining costs. Low-quality evidence from observational cohort studies supports that alloimmunization prevalence can be decreased by extending serological RBC antigen matching. Transfusion reactions are generally poorly and inconsistently reported. There was no evidence reporting the effect prophylactic genotypic matching has on alloimmunization, autoimmunization or transfusion reactions. There were no studies comparing prophylactic genotypic matching to serologic matching. High-quality evidence was lacking to support clinical decision making regarding best transfusion practices. Multicenter prospective randomized clinical trials are needed to determine best strategies for reducing the rate of alloimmunization using serologic and genotypic matching.
PICO Summary
Population
Children and adults with sickle cell disease (19 studies, 0 RCTs).
Intervention
Limited (C/c, E/e, K) or extended (C/c, E/e, K, Jka/b, Fya/b, +/-S/s) serologic matching.
Comparison
Standard ABO and RhD matching alone.
Outcome
This systematic reviewed included 16 cohort studies, 2 cross-sectional studies, and 1 decision tree model examining costs. Low-quality evidence from observational cohort studies supported that alloimmunization prevalence can be decreased by extending serological red blood cell antigen matching. Transfusion reactions were generally poorly and inconsistently reported. There was no evidence reporting the effect prophylactic genotypic matching has on alloimmunization, autoimmunization or transfusion reactions. There were no studies comparing prophylactic genotypic matching to serologic matching. High-quality evidence supporting clinical decision making regarding best transfusion practices was lacking.
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Red blood cell transfusion to treat or prevent complications in sickle cell disease: an overview of Cochrane reviews
Fortin PM, Hopewell S, Estcourt LJ
The Cochrane Database of Systematic Reviews. 2018;((8)):CD012082.
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Editor's Choice
Abstract
BACKGROUND Globally, sickle cell disease (SCD) is one of the commonest severe monogenic disorders, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Red blood cell (RBC) transfusions are used to treat complications of SCD, e.g. acute chest syndrome (ACS) (this often involves a single transfusion episode), or they can be part of a regular long-term transfusion programme to prevent SCD complications. OBJECTIVES To summarize the evidence in Cochrane Reviews of the effectiveness and safety of RBC transfusions versus no transfusion, or restrictive (to increase the total haemoglobin) versus liberal (to decrease the haemoglobin S level below a specified percentage) transfusion, for treating or preventing complications experienced by people with SCD. METHODS We included Cochrane Reviews of randomised or quasi-randomised controlled trials published in the Cochrane Database of Systematic Reviews, that addressed various SCD complications and had RBC transfusion as an intervention or comparator. We assessed the methodological quality of included reviews according to the AMSTAR quality assessment. MAIN RESULTS We included 15 Cochrane Reviews, 10 of which had no included studies with an RBC transfusion intervention (five reported RCTs with other interventions; and five contained no studies). Five of the 15 reviews included participants randomised to RBC transfusion, but in one of these reviews only 10 participants were randomised with no usable data. Four reviews (nine trials with 1502 participants) reported data comparing short- or long-term RBC transfusions versus standard care, disease-modifying agents, a restrictive versus a liberal transfusion strategy and long-term RBC transfusions versus transfusions to treat complications. All reviews were of high quality according to AMSTAR quality assessment, however, the quality of the included trials was highly variable across outcomes. Trials were downgraded according to GRADE methodology for risk of bias, indirectness (most trials were conducted in children with HbSS), and imprecision (outcomes had wide confidence intervals).In all four reviews and all comparisons there was little or no difference in the risk of death (very low-quality evidence). There were either no deaths or death was a rare event.Short-term RBC transfusion versus standard care (one review: two trials, 434 participants, GRADE very low- to low-quality evidence)In people undergoing low- to medium-risk surgery, RBC transfusions may decrease the risk of acute chest syndrome (ACS) in people with African haplotypes compared to standard care (low-quality evidence), but there was little or no difference in people with the Arabic haplotype (very-low quality evidence). There was also little or no difference in the risk of other SCD-related or transfusion-related complications (very-low quality evidence).Long-term RBC transfusion versus standard care (two reviews: three trials, 405 participants, very low- to moderate-quality evidence)In children and adolescents at high risk of stroke (abnormal transcranial doppler (TCD) velocities or silent cerebral infarct (SCI)), long-term RBC transfusions probably decrease the risk of stroke (moderate-quality evidence) and may decrease the risk of ACS and painful crisis compared to standard care (low-quality evidence). Long-term RBC transfusions may also decrease the risk of SCI in children with abnormal TCD velocities (low-quality evidence), but there may be little or no difference in the risk of SCI in children with normal TCD velocities and previous SCI (low-quality evidence).In children and adolescents already receiving long-term RBC transfusions for preventing stroke, in comparison to standard care, continuing long-term RBC transfusions may reduce the risk of SCI (low-quality evidence) but we do not know whether there is a difference in the risk of stroke (very-low quality evidence). In children with normal TCD velocities and SCI there was little
PICO Summary
Population
Children and adults with sickle cell disease (15 reviews).
Intervention
Red blood cell (RBC) transfusions. RBC transfusions plus standard care. Restrictive RBC transfusion strategy.
Comparison
No RBC transfusions. Standard care. Disease-modifying drug therapy. Liberal RBC transfusion strategy.
Outcome
In people undergoing low- to medium-risk surgery, RBC transfusions may decrease the risk of acute chest syndrome (ACS) in people with African haplotypes compared to standard care (low-quality evidence), but there was little or no difference in people with the Arabic haplotype (very-low quality evidence). In children and adolescents at high risk of stroke (abnormal transcranial doppler (TCD) velocities or silent cerebral infarct (SCI)), long-term RBC transfusions probably decrease the risk of stroke (moderate-quality evidence) and may decrease the risk of ACS and painful crisis compared to standard care (low-quality evidence). Long-term RBC transfusions may also decrease the risk of SCI in children with abnormal TCD velocities (low-quality evidence), but there may be little or no difference in the risk of SCI in children with normal TCD velocities and previous SCI (low-quality evidence). In children with normal TCD velocities and SCI there was little or no difference in the risk of alloimmunisation or transfusion reactions, but RBC transfusions may increase the risk of iron overload (low-quality evidence).
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10.
Interventions for chronic kidney disease in people with sickle cell disease
Roy NB, Fortin PM, Bull KR, Doree C, Trivella M, Hopewell S, Estcourt LJ
The Cochrane Database of Systematic Reviews. 2017;((7)):CD012380.
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Editor's Choice
Abstract
BACKGROUND Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta-globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Kidney disease is a frequent and potentially severe complication in people with SCD.Chronic kidney disease is defined as abnormalities of kidney structure or function, present for more than three months. Sickle cell nephropathy refers to the spectrum of kidney complications in SCD.Glomerular damage is a cause of microalbuminuria and can develop at an early age in children with SCD, and increases in prevalence in adulthood. In people with sickle cell nephropathy, outcomes are poor as a result of the progression to proteinuria and chronic kidney insufficiency. Up to 12% of people who develop sickle cell nephropathy will develop end-stage renal disease. OBJECTIVES To assess the effectiveness of any intervention in preventing or reducing kidney complications or chronic kidney disease in people with SCD (including red blood cell transfusions, hydroxyurea and angiotensin-converting enzyme inhibitor (ACEI)), either alone or in combination with each other. SEARCH METHODS We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 05 April 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 13 April 2017. SELECTION CRITERIA Randomised controlled trials comparing interventions to prevent or reduce kidney complications or chronic kidney disease in people with SCD. There were no restrictions by outcomes examined, language or publication status. DATA COLLECTION AND ANALYSIS Two authors independently assessed trial eligibility, extracted data and assessed the risk of bias. MAIN RESULTS We included two trials with 215 participants. One trial was published in 2011 and included 193 children aged 9 months to 18 months, and compared treatment with hydroxyurea to placebo. The second trial was published in 1998 and included 22 adults with normal blood pressure and microalbuminuria and compared ACEI to placebo.We rated the quality of evidence as low to very low across different outcomes according to GRADE methodology. This was due to trials having: a high or unclear risk of bias including attrition and detection bias; indirectness (the available evidence was for children aged 9 months to 18 months in one trial and a small and select adult sample size in a second trial); and imprecise outcome effect estimates of significant benefit or harm. Hydroxyurea versus placebo We are very uncertain if hydroxyurea reduces or prevents progression of kidney disease (assessed by change in glomerular filtration rate), or reduces hyperfiltration in children aged 9 to 18 months, mean difference (MD) 0.58 (95% confidence interval (CI) -14.60 to 15.76 (mL/min per 1.73 m(2))) (one study; 142 participants; very low-quality evidence).In children aged 9 to 18 months, hydroxyurea may improve the ability to concentrate urine, MD 42.23 (95% CI 12.14 to 72.32 (mOsm/kg)) (one study; 178 participants; low-quality evidence).Hydroxyurea may make little or no difference to SCD-related serious adverse events including: incidence of acute chest syndrome, risk ratio (RR) 0.39 (99% CI 0.13 to 1.16); painful crisis, RR 0.68 (99% CI 0.45 to 1.02); and hospitalisations, RR 0.83 (99% CI 0.68 to 1.01) (one study, 193 participants; low-quality evidence).No deaths occurred in the trial. Quality of life was not reported. ACEI versus placeboWe are very uncertain if ACEI reduces proteinuria in adults with SCD who have normal blood pressure and microalbuminuria, MD -49.00 (95% CI -124.10 to 26.10 (mg per day)) (one study; 22 participants; very low-quality evidence). We are very uncertain if ACEI reduce or prevent kidney disease as measured by creatinine clearance. The authors state that creatinine clearance remained constant ove
PICO Summary
Population
Children and adults with sickle cell disease (SCD), (2 studies, n= 215).
Intervention
Red blood cell transfusions, hydroxyurea and angiotensin‐converting enzyme inhibitor (ACEI), either alone or in combination with each other.
Comparison
Placebo, or usual care.
Outcome
Hydroxyurea vs. placebo: Authors were very uncertain if hydroxyurea reduced or prevented progression of kidney disease (assessed by change in glomerular filtration rate), or reduced hyperfiltration in children aged 9 to 18 months, mean difference (MD) 0.58 (mL/min per 1.73 m2). ACEI vs. placebo: Authors were very uncertain if ACEI reduced proteinuria in adults with SCD who have normal blood pressure and microalbuminuria, MD -49.00 (mg per day). Authors were very uncertain if ACEI reduced or prevented kidney disease as measured by creatinine clearance.