Abstract

OBJECTIVES Iron overload is a common complication experienced by transfusion-dependent children with hemoglobin disorders. Chelators such as deferasirox (DFX) and deferiprone (DFP) are effective in overcoming this problem. We conducted this systematic review and meta-analysis to evaluate the effectiveness of DFX compared to DFP in treating iron overload amongst pediatric patients with hemoglobin disorders. MATERIAL AND METHODS PubMed and Cochrane Central were searched from their inception until Dec 21 2021, for randomized clinical trials (RCTs) and observational studies, which assessed the efficacy of DFX compared to DFP in the treatment of inherited hemoglobin disorders. The outcomes of interest included myocardial iron concentration (MRI T2*) at the end of the trial and change in mean serum ferritin (SF) levels at the 6 and 12 months mark. Weighted mean differences (WMDs) with their corresponding 95% confidence intervals (CIs) were calculated for continuous outcomes using random effects model. RESULTS A total of 5 studies comprising 607 children were included. The results of our analysis revealed no significant difference between DFX and DFP in MRI T2* at the end of treatment (WMD: -0.92;95% CI[-3.35,1.52]; p=0.46; I(2)=0). Moreover, there has been no significant difference noted in SF levels at both 6 months (WMD: 97.31; 95% CI[-236.16,430.77]; p=0.57; I(2)=0) and 12 months (WMD: 46.99; 95% CI[-191.42,285.40]; p=0.70; I(2)=0) respectively. CONCLUSION Our analysis shows no significant difference between the efficacy of DFX and DFP in the management of iron overload in children with inherited blood disorders. Future large-scale clinical trials are required to further validate our results.

Abstract

Hyperkalaemia following transfusion is widely reported in the literature. Our objective was to critically review recent evidence on hyperkalaemia in association with transfusion and to assess whether specific aspects of transfusion practice can affect the likelihood of developing hyperkalaemia. We searched 9 electronic databases (including MEDLINE, Embase, and Transfusion Evidence Library) using a predefined search strategy, from 2010 to April 8, 2021. Three reviewers performed dual screening, extraction, and risk of bias assessment. We used Cochrane risk of bias (ROB) 2 for assessment of RCTs, ROBINS-I for non-RCTs, and GRADE to assess the certainty of the evidence. We report 7 comparisons of interest in n = 3729 patients from 28 studies (11 RCTs, 4 prospective cohort studies, and 13 retrospective cohort studies): (1) age of blood, (2) washing, (3) filtration, (4) irradiation, (5) fluid type, (6) transfusion vs no transfusion, (7) blood volume/rate. Of the 28 studies included, 25 reported outcomes of potassium (K+) concentration, 17 the number developing hyperkalaemia, 13 mortality, 10 cardiac arrest, and 10 cardiac arrhythmia. Only 16 studies provided analysable data suitable for quantitative analysis. Evidence addressing our outcomes was of very low certainty (downgraded for incomplete outcome data, baseline imbalance, imprecision around the estimate, and small sample size). While 5 studies showed a difference in K+ concentration up to 6 hours posttransfusion for 3 comparisons (age of blood, washing, and transfusion volume/rate), and 3 studies showed a difference in the diagnosis of hyperkalaemia for 2 comparisons (age of blood, and transfusion volume/rate), the evidence was inconsistent across all included studies. There was no difference in any reported outcomes for 4 comparisons (filtration, irradiation, fluid type, or transfusion vs no transfusion). Overall, the reported evidence was too weak to support identification of groups most at risk of hyperkalaemia or to support recommendations on use of short-storage RBC. For other commonly used risk mitigations for hyperkalaemia in transfusion medicine, the (low certainty) evidence was either conflicting or not supportive.

Abstract

OBJECTIVES Sickle cell disease (SCD) is a complex, chronic condition that impairs health-related quality of life of affected individuals and their caregivers. As curative therapies emerge, comprehensive cost-effectiveness models will inform their value. These models will require descriptions of health states and their corresponding utility values that accurately reflect health-related quality of life over the disease trajectory. The objectives of this systematic review were to develop a catalog of health state utility (HSU) values for SCD, identify research gaps, and provide future directions for preference elicitation. METHODS Records were identified through searches of PubMed and Embase, Tufts Medical Center Cost-Effectiveness Analysis Registry, reference lists of relevant articles, and consultation with SCD experts (2008-2020). We removed duplicate records and excluded ineligible studies. For included studies, we summarized the study characteristics, methods used for eliciting HSUs, and HSU values. RESULTS Five studies empirically elicited utilities using indirect methods (EQ-5D) (n = 3) and Short Form-6 Dimension (n = 2); these represent health states associated with general SCD (n = 1), SCD complications (n = 2), and SCD treatments (n = 3). Additionally, we extracted HSUs from 7 quality-adjusted life-years-based outcome research studies. The HSU among patients with general SCD without specifying complications ranged from 0.64 to 0.887. Only 36% of the HSUs used in the quality-adjusted life-year-based outcomes research studies were derived from individuals with SCD. No study estimated HSUs in caregivers. CONCLUSIONS There is a dearth of literature of HSUs for use in SCD models. Future empirical studies should elicit a comprehensive set of HSUs from individuals with SCD and their caregivers.

Abstract

INTRODUCTION Iron chelation therapy (ICT) is essential to prevent complications of iron overload in patients with transfusion-dependent thalassaemia. However, there is currently no standard for how to best measure adherence to ICT, nor what level of adherence necessitates concern for poor outcomes, especially in paediatric patients. The objectives of this review are to identify rates of adherence to ICT, predictors of adherence, methods of measurement, and adherence-related health outcomes in children and adolescents. METHODS This review covers the literature published between 1980 and 2020 on ICT in thalassaemia that assessed adherence or compliance. Included studies reflect original research. The preferred reporting items of systematic reviews and meta-analyses (PRISMA) guidelines were followed for reporting results, and the findings were critically appraised with the Oxford Centre for Evidence-based Medicine criteria. RESULTS Of the 543 articles, 37 met the inclusion criteria. The most common methods of assessing adherence included patient self-report (n = 15/36, 41.7%), and pill count (n = 15/36, 41.7%), followed by subcutaneous medication monitoring (5/36, 13.8%) and prescription refills (n = 4/36, 11.1%). Study sizes ranged from 7 to 1115 participants. Studies reported adherence either in "categories" with different levels of adherence (n = 29) or "quantitatively" as a percentage of medication taken out of those prescribed (n = 7). Quantitatively, the percentage of adherence varied from 57% to 98.4% with a median of 89.5%. Five studies focussed on interventions, four of which were designed to improve adherence. Studies varied in sample size and methods of assessment, which prohibited performing a meta-analysis. CONCLUSIONS Due to a lack of clinical consensus on how adherence is defined, it is difficult to compare adherence to ICT in different studies. Future studies should be aimed at creating guidelines for assessing adherence and identifying suboptimal adherence. These future efforts will be crucial in informing evidence-based interventions to improve adherence and health outcomes in thalassaemia patients.Key messagesPredictive factors associated with ICT adherence in the paediatric population include age, social perception of ICT, social support, and side effects/discomfort.Increased adherence in the paediatric population is associated with decreased serum ferritin and improved cardiac, hepatic, and endocrine outcomes.Inadequate adherence to ICT is associated with increased lifetime health costs.There are few studies that focussed on interventions to increase adherence in the paediatric population, and the studies that do exist all focussed on different types of interventions; successful interventions focussed on consistent, long-term engagement with patients.

Abstract

BACKGROUND Myocardial iron deposition is a significant cause of morbidity and mortality in patients with transfusion-dependent thalassemia (TDT). Amlodipine, L-type calcium channel blocker with regular chelation therapy may reduce myocardial iron overload. Lack of randomized trials prompted this study to assess the effect of calcium channel blocker (amlodipine) in combination with iron chelation therapy on iron overload in patients with TDT. METHODS Sixty-four eligible patients were randomized to receive either amlodipine and chelation (group A) or chelation alone (group B) in double-blind placebo-controlled trial. Myocardial iron concentration (MIC) using T2* magnetic resonance imaging (MRI), liver iron concentration (LIC), left ventricular ejection fraction (LVEF), and serum ferritin were measured at baseline and 12 months. RESULTS In the amlodipine group, mean cardiac T2* value significantly increased from 18.11 ± 8.47 to 22.15 ± 7.61 (p = .002) at 12 months, whereas in control group, there was a nonsignificant increase (p = .62) in cardiac T2* value from 19.50 ± 8.84 to 20.03 ± 9.07. There was a significant decrease in MRI-derived MIC in the amlodipine group compared to control group (1.93 ± 1.61 to 1.29 ± 0.90, p = .01). Changes in the LVEF (p = .45), MRI-derived LIC (p = .09), and serum ferritin (p = .81) were not significant between the two groups. CONCLUSION Amlodipine is safe and when combined with chelation therapy appears to be more effective in reducing cardiac iron overload than chelation only in children and young adults with TDT.

Abstract

BACKGROUND Deferasirox has proved good efficacy and acceptable safety for the management of thalassaemia patients. However, some patients are unresponsive or intolerant to once-daily administration of deferasirox even at a high dose. The current study evaluated the effectiveness and tolerability of twice-daily dosing of deferasirox among transfusion-dependent paediatric beta-thalassaemia patients. METHODS This prospective randomized single-blinded parallel study included all transfusion-dependent paediatric beta-thalassaemia patients prescribed with deferasirox, who visit the study site for their regular blood transfusions and follow-up. The enrolled patients were randomized into intervention and control groups by using a simple block randomization method. In the intervention group, the once-daily dosing of deferasirox was changed to twice-daily dosing with the same total daily dose. Whereas, in the control group, the patients continued with the once-daily deferasirox dosing. The serum ferritin levels of both groups were determined on the enrolment day and after 6 months of follow-up. RESULTS Forty-one patients were included for analysis. A statistically significant mean decrease in serum ferritin levels was detected in the intervention group, while the serum ferritin levels of the control group significantly increased from baseline. The twice-daily dosing of deferasirox was better tolerated by the thalassaemia patients when compared to once-daily dosing. CONCLUSION This study concludes that twice-daily dosing of deferasirox with the same total daily dose significantly enhances the iron chelation efficacy and tolerability among transfusion-dependent paediatric beta-thalassaemia patients when compared to once-daily regimen.

Abstract

BACKGROUND AND OBJECTIVES There is a varied prevalence of red cell alloimmunization being reported from different parts of India. This study aimed to estimate the overall prevalence of alloimmunization in India by performing a systematic review of the literature and to establish the most suitable antigen-matching strategy to reduce the red blood cell (RBC) alloimmunization rate among transfusion recipients. MATERIALS AND METHODS A systematic search of all the original articles published in English on RBC alloimmunization among transfusion recipients from India in MEDLINE, SCOPUS, CINAHL and Google Scholar bibliographic databases was conducted. After screening the articles as per inclusion/exclusion criteria, data extraction was done independently by two sets of investigators. Meta-analysis was performed by the binary random-effects model using the restricted maximum likelihood method. RESULTS A total of 44 studies on RBC alloimmunization, with a cumulative sample size of 309,986 patients, were grouped into hospital-based and multiply-transfused patients, which yielded a prevalence of 0.5 (95% confidence interval; 0.3-0.8) and 4.8 (95% confidence interval; 3.9-5.7) per 100 patients, respectively. As many as 1992 alloantibodies were identified among the 1846 alloimmunized patients. The most common antibody identified was anti-E (127; 31.99%), followed by anti-c (75; 18.89%) in multiply-transfused patients. CONCLUSION The rate of alloimmunization was 0.5 per 100 patients tested for antibodies and 4.8 per 100 patients receiving transfusion. Considering E- and c-antigen-matched red cells along with ABO and RhD matching may significantly reduce the overall occurrence of alloimmunization among Indian population who are transfusion-dependent.

Abstract

BACKGROUND The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.

Abstract

BACKGROUND There are no international standards or normalizations for diagnosing and treating complications from blood transfusions. We comprehensively compared the incidence of adverse blood transfusions in children and adults. METHODS Available literature on blood transfusion adverse reactions in children and adults prior to November 27, 2021 was collected from several electronic databases. This meta-analysis was performed using Revman 5.2 and Stata 15.1. RESULTS The incidence of transfusion reactions is higher in children than in adults. Children transfused with red blood cells and platelets exhibited a higher incidence of transfusion reaction than that of adults. Moreover, the incidence of allergic and febrile non-hemolytic transfusion reactions was significantly higher in children than in adults. The incidence of some rare transfusion reactions was also significantly higher in children than in adults. CONCLUSION The incidence of transfusion reactions in children and adults is varied. Guidelines for children are necessary.

Abstract

The onset of respiratory distress and acute lung injury (ALI) following a blood transfusion is known as transfusion-related acute lung injury (TRALI), although its pathophysiology remains unknown. Even though sickle cell disease (SCD) has been studied for more than a century, few therapeutic and management strategies adequately address the emergence of TRALI. TRALI, an immune-mediated transfusion response that can result in life-threatening consequences, is diagnosed based on clinical signs and symptoms. Early detection and treatment increase the chances of survival and, in most cases, result in a complete recovery. Our objective is to provide a firm grasp of the present status of SCD-related TRALI care and therapy. After exploring multiple databases, this study offers evidence-based guidelines to aid clinicians and other healthcare professionals make decisions concerning transfusion assistance for SCD and the management of transfusion-related complications. Other risk factors for acute lung injury including sepsis aspiration should be ruled out throughout the diagnostic process. Several recent studies have shown that immunotherapy or immunological targets can effectively prevent these complications. Red cell transfusions, red cell antigen matching optimization, and iron chelation can also help reduce negative consequences. It is to be noted that poor clinical outcomes can be avoided by early detection and treatment of hemolytic transfusion reactions. Finally, preventing the onset of TRALI may be the most effective therapeutic strategy for SCD patients who rely on blood transfusions for survival.