Two trade names of deferasirox (Osveral® and Exjade®) in reduction of iron overload parameters in major beta-thalassemia patients: A randomized open labeled clinical trial
Caspian journal of internal medicine. 2022;13(1):61-69
BACKGROUND Beta-thalassemia major patients typically require chronic transfusion and iron-chelating agents to reduce serum iron overload. Osveral(®) is an available Iranian brand name of deferasirox used by majority of thalassemic patients. The aim of this study was to compare the efficacy of Osveral(®) vs. Exjade(®) in major beta- thalassemia patients. METHODS In this randomized clinical trial, all patients received a single daily dose of 30 mg/kg either of Osveral(®) or Exjade(®) for 6 months. Primary outcome was the mean of bimonthly changes in serum ferritin concentration and secondary outcomes included mean changes of heart and liver MRI T2* after a year. RESULTS Finally, 80 patients completed the study. The mean serum ferritin level at the end of sixth month significantly decreased in Osveral(®) and Exjade(®) groups (p<0.01). After a year, means cardiac MRI T2* in Osveral(®) group were changed from 25.9±9.6 ms to 25.4±9.7 ms and in Exjade(®) group from 24.8±9.2 ms to 26.9±5.9 ms, with no significant difference (P=0.43). Mean liver MRI T2* for Osveral(®) and Exjade(®) groups were 8.6±6.4 ms (baseline 6.3±4.7) and 6.3±4 ms (baseline 4.9±3.5), respectively and there was no significant difference between two study arms (P=0.1). CONCLUSION Osveral(®) decreased significantly the serum ferritin level and improved heart and liver iron overload as efficient as Exjade(®). It can be a suitable cost-effective alternative agent in beta-thalassemia major patients.
A systematic review of adherence to iron chelation therapy among children and adolescents with thalassemia
Annals of medicine. 2022;54(1):326-342
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.
A Systematic Review on the Management of Transfusion-Related Acute Lung Injury in Transfusion-Dependent Sickle Cell Disease
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.
Blood transfusions may adversely affect survival outcomes of patients with lung cancer: a systematic review and meta-analysis
Translational lung cancer research. 2021;10(4):1700-1710
BACKGROUND Despite common use in clinical practice, the impact of blood transfusions on prognosis among patients with lung cancer remains unclear. The purpose of the current study is to perform an updated systematic review and meta-analysis to evaluate the influence of blood transfusions on survival outcomes of lung cancer patients. METHODS We searched PubMed, Embase, Cochrane Library, and Ovid MEDLINE for publications illustrating the association between blood transfusions and prognosis among people with lung cancer from inception to November 2019. Overall survival (OS) and disease-free survival (DFS) were the outcomes of interest. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the random-effects model. Study heterogeneity was evaluated with the I(2) test. Publication bias was explored via funnel plot and trim-and-fill analyses. RESULTS We included 23 cohort studies with 12,175 patients (3,027 cases and 9,148 controls) for meta-analysis. Among these records, 22 studies investigated the effect of perioperative transfusions, while one examined that of transfusions during chemotherapy. Two studies suggested the possible dose-dependent effect in accordance with the number of transfused units. In pooled analyses, blood transfusions deleteriously influenced both OS (HR=1.35, 95% CI: 1.14-1.61, P<0.001, I(2)=0%) and DFS (HR=1.46, 95% CI: 1.15-1.86, P=0.001, I(2)=0%) of people with lung cancer. No evidence of significant publication bias was detected in funnel plot and trim-and-fill analyses (OS: HR=1.26, 95% CI: 1.07-1.49, P=0.006; DFS: HR=1.35, 95% CI: 1.08-1.69, P=0.008). CONCLUSIONS Blood transfusions were associated with decreased survival of patients with lung cancer.
Back to base pairs: What is the genetic risk for red bloodcell alloimmunization?
Blood reviews. 2021;:100794
Red blood cell (RBC) alloimmunization is a serious complication of blood transfusions, challenging selection of compatible units for future transfusions. Genetic characteristics may be associated with the risk of RBC alloimmunization and may therefore serve to identify high-risk patients. The aim of this systematic review was to summarize the available evidence on genetic risk factors for RBC alloimmunization. Electronic databases were searched up to April 2020 for studies (Search terms included transfusion, alloimmunization and genetic). A total of 2581 alloimmunized cases and 26,558 controls were derived from 24 studies. The alleles that were most frequently studied and that demonstrated significant associations in a meta-analysis with alloimmunization to the Duffy(a) antigen were HLA-DRB1*04 (Odds Ratio 7.80 (95%CI 4.57-13.33)), HLA-DRB1*15 (OR 3.76 (95%CI 2.14-6.59)), and HLA-DRB1*03 (OR 0.12 (95%CI 0.05-0.29)). Furthermore, significant associations with anti-K formation was found for the alleles HLA-DRB1*10 (OR 2.64 (95%CI 1.41-4.95)), HLA*DRB1*11 (OR 2.11, (95%CI 1.34-3.32)), and HLA-DRB1*13 (OR 1.71 (95%CI 1.26-2.33)). Overall, the available evidence was of moderate to low quality, hampering interpretation of reported results. There is an urgent need for high quality evidence on genetic risk factors for RBC alloimmunization.
Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label, noninferiority study
Blood advances. 2021
Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload and requires chelation therapy. The iron chelator deferiprone is often used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study (NCT02041299) assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76, 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia.
Patients with sickle cell disease or other anaemias receiving chronic transfusion therapy (n= 228).
Oral deferiprone (n= 152).
Subcutaneous deferoxamine (n= 76).
The least squares mean (standard error) change in liver iron concentration was -4.04 (0.48) mg/g dry weight for deferiprone vs. -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance. Non-inferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Treatment-related adverse events (AEs), serious AEs, and AEs leading to withdrawal did not differ significantly between the groups.
Liberal blood transfusion strategies and associated infection in orthopedic patients: A meta-analysis
OBJECTIVE It remains unclear whether transfusion strategies during orthopedic surgery and infection are related. The purpose of this study is to evaluate whether liberal blood transfusion strategies contribute to infection risk in orthopedic patients by analyzing randomized controlled trials (RCTs). METHODS RCTs with liberal versus restrictive red blood cell (RBC) transfusion strategies were identified by searching PubMed, Embase, the Cochrane Central Register of Controlled Trials from their inception to July 2019. Ten studies with infections as outcomes were included in the final analysis. According to the Jadad scale, all studies were considered to be of high quality. RESULTS Ten trials involving 3938 participants were included in this study. The pooled risk ratio (RR) for the association between liberal transfusion strategy and infection was 1.34 (95% confidence intervals [CI], 0.94-1.90; P = .106). The sensitivity analysis indicated unstable results, and no significant publication bias was observed. CONCLUSION This pooled analysis of RCTs demonstrates that liberal transfusion strategies in orthopedic patients result in a nonsignificant increase in infections compared with more restrictive strategies. The conclusions are mainly based on retrospective studies and should not be considered as recommendation before they are supported by larger scale and well-designed RCTs.
Effects of stored autotransfusion on electrolytes and postoperative complications in patients undergoing elective orthopedic surgery
American journal of translational research. 2021;13(6):7200-7206
OBJECTIVE To ivestigate the effect of stored autotransfusion on the electrolytes and postoperative complications in patients undergoing elective orthopedic surgery. METHODS A total of 76 cases of patients undergoing elective orthopedic surgery were randomly divided into an observation group (38 cases, taking stored autotransfusion) and a control group (38 cases, taking allogeneic blood transfusion) according to a random number table method. The intraoperative-related indexes (intraoperative blood loss, autologous or allogeneic blood transfusion volume, urine volume, and length of hospital stay), electrolyte levels before and 48 hours after the operation, routine blood and coagulation function were compared between the two groups, and the postoperative complications related to blood transfusion were recorded. RESULTS The length of hospital stay of the observation group was significantly lower than that of the control group (P<0.05). The concentrations of K(+) and Na(+) in the control group 48 h after the operation were higher than those before the operation and than those in the observation group, while the concentration of Ca(2+) was lower than that before the operation and that in the observation group (all P<0.05). The levels of Hb, RBC, and HCT in the control group 48 h after the operation were lower than those before the operation and those in the observation group (all P<0.05). The levels of WBC in the two groups 48 h after the operation were significantly higher, but those in the observation group were lower than those in the control group (all P<0.05). There were no significant changes in Pt, APTT, D-D, and FIB levels between the two groups. There were no significant changes in Pt, APTT, D-D, and FIB levels 48 hours after the operation compared with those before the operation (P>0.05). The incidence of postoperative complications caused by blood transfusion in the observation group was lower than that in the control group (P<0.05). CONCLUSION Storage autotransfusion can effectively balance the electrolyte level and reduce the incidence of complications in patients undergoing elective orthopedic surgery. This is worthy of clinical application.
Total hip arthroplasty in sickle cell disease: a systematic review
EFORT Open Rev. 2020;5(3):180-188
Total hip arthroplasty (THA) in sickle cell disease (SCD) patients can be a challenging procedure.This systematic review evaluated the revision rate, functional outcomes and complications of THA in sicklers.A systematic search was conducted according to the PRISMA guidelines, using four search engines from inception to May 2019.Fifteen studies with 971 THAs were included. There were 437 cemented and 520 uncemented THAs.There were 164 revision THAs (16.8%); 52 uncemented and 105 cemented THAs.Forty-two infections were recorded; 16 infections for cemented and 23 for uncemented THAs.Fifty-seven cups, 26 stems, eight cup/stem with aseptic loosening that were more frequently cemented were reported. The 28 unspecified aseptic loosening cases were more frequently uncemented THAs.All studies demonstrated the functional improvement of patients.There were 109 medical complications (14.3%). Sickle cell crises (SCC) and transfusion reactions were most usually recorded.Forty-six intraoperative complications (4.7%) were reported; 18 femoral fractures, four acetabular and 18 femoral perforations. Seventeen femoral fractures occurred during uncemented THA.THA in SCD is still related to a high risk of complications. The outcomes in properly selected sicklers have been improved. Perioperative adequate hydration, warming, oxygen supply and transfusion protocols are mandated to prevent SCC and transfusion reactions. The surgeon must be prepared to deal with a high rate of intraoperative fractures and have different implant options readily available. No definite conclusion can be made regarding the best fixation mode. Cemented implants demonstrated a higher revision rate and uncemented implants a higher risk for intraoperative complications. Cite this article: EFORT Open Rev 2020;5:180-188. DOI: 10.1302/2058-5241.5.190038.
N-acetylcysteine Restored Heart Rate Variability and Prevented Serious Adverse Events in Transfusion-dependent Thalassemia Patients: a Double-blind Single Center Randomized Controlled Trial
Int J Med Sci. 2020;17(9):1147-1155
Regular blood transfusions in transfusion-dependent thalassemia (TDT) patients can lead to iron overload, causing oxidative stress and sympathovagal imbalance, resulting in increased cardiac complications. We hypothesized that administrating of N-acetylcysteine (NAC) prevents serious adverse events including cardiac complications in TDT patients by reducing systemic oxidative stress and balancing cardiac sympathovagal control. This study was double-blind, randomized control trial, investigating in 59 Thai TDT patients. After randomization, the participants were divided into two groups. The control group received standard care of TDT patient plus placebo, whereas the intervention group received 600 mg of NAC orally for six months. Serum 8-isoprostane, TNF-alpha, IL-10, 24-hour ECG monitoring, echocardiograms and the incidence of thalassemia-related complications were collected. At baseline, no significant difference in any parameters between the control and the intervention groups. At the end of intervention, the incidence of serious adverse events (i.e. infection, worsening thalassemia) was significantly higher in the control group when compared with the intervention group (24.1% vs. 3.3%, p=0.019) (Chi-square test; absolute risk reduction=20.8%, number needed to treat=4.8). The control group also had significantly lower time-dependent HRV parameters, compared with the intervention group (p=0.025 and 0.030, independent t-test). Treatment with NAC restored HRV and reduced serious adverse event in TDT patients, however, no difference in cardiac complications could be demonstrated. NAC could prevent serious adverse events in TDT patients. The proposed mechanism might be the balancing of sympathovagal control.