Pre-operative iron increases haemoglobin concentration before abdominal surgery: a systematic review and meta-analysis of randomized controlled trials
Scientific reports. 2022;12(1):2158
Professional surgical societies recommend the identification and treatment of pre-operative anaemia in patients scheduled for abdominal surgery. Our aim was to determine if pre-operative iron allows correction of haemoglobin concentration and decreased incidence of peri-operative blood transfusion in patients undergoing major abdominal surgery. MEDLINE, Embase and CENTRAL were searched for RCTs written in English and assessing the effect of pre-operative iron on the incidence of peri-operative allogeneic blood transfusion in patients undergoing major abdominal surgery. Pooled relative risk (RR), risk difference (RD) and mean difference (MD) were obtained using models with random effects. Heterogeneity was assessed using the Q-test and quantified using the I(2) value. Four RCTs were retained for analysis out of 285 eligible articles. MD in haemoglobin concentration between patients with pre-operative iron and patients without pre-operative iron was of 0.81 g/dl (3 RCTs, 95% CI 0.30 to 1.33, I(2): 60%, p = 0.002). Pre-operative iron did not lead to reduction in the incidence of peri-operative blood transfusion in terms of RD (4 RCTs, RD: - 0.13, 95% CI - 0.27 to 0.01, I(2): 65%, p = 0.07) or RR (4 RCTs, RR: 0.57, 95% CI 0.30 to 1.09, I(2): 64%, p = 0.09). To conclude, pre-operative iron significantly increases haemoglobin concentration by 0.81 g/dl before abdominal surgery but does not reduce the need for peri-operative blood transfusion. Important heterogeneity exists between existing RCTs in terms of populations and interventions. Future trials should target patients suffering from iron-deficiency anaemia and assess the effect of intervention on anaemia-related complications.
Patients undergoing major abdominal surgery (4 studies, n= 651).
Placebo or usual care.
Mean difference in haemoglobin concentration between patients with pre-operative iron and patients without pre-operative iron was of 0.81 g/dl. Pre-operative iron did not lead to reduction in the incidence of peri-operative blood transfusion in terms of risk difference (RD) or pooled relative risk (RR), (RD: - 0.13, RR: 0.57).
Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia
The New England journal of medicine. 2022;386(1):11-23
BACKGROUND A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).
Patients with severe aplastic anaemia (n= 197).
Immunosuppressive therapy plus eltrombopag (n= 96).
Immunosuppressive therapy (n= 101).
The percentage of patients who had a complete response at 3 months was 10% for patients in the immunosuppressive therapy group, and 22% for patients in the immunosuppressive therapy plus eltrombopag group. At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% for those receiving immunosuppressive therapy, and 68% for those receiving immunosuppressive therapy plus eltrombopag. The median times to the first response were 8.8 months (immunosuppressive therapy group) and 3.0 months (immunosuppressive therapy plus eltrombopag group). The incidence of severe adverse events was similar in all patients.
A Systematic review on diagnostic methods of red cell membrane disorders in Asia
International journal of laboratory hematology. 2022
Membranopathies are a group of inherited blood disorders where the diagnosis could form a challenge due to phenotype-genotype heterogeneity. In this review, the usage and limitations of diagnostic methods for membranopathies in Asian countries were evaluated. A systematic review was done using articles from PubMed, Google Scholar, and EBSCO from 2000 to 2020. Thirty-six studies conducted in seven Asian countries had used different diagnostic methods to confirm membranopathies. In 58.3% of studies, full blood count (FBC), reticulocyte count, and peripheral blood smear (PBS) were used in preliminary diagnosis. The combination of the above three with osmotic fragility (OF) test was used in 38.8%. The flowcytometric osmotic fragility (FC-OF) test was used in 27.7% where it showed high sensitivity (92%-100%) and specificity (96%-98%). The eosin-5-maleimide (EMA) assay was used in 68.1% with high sensitivity (95%-100%) and specificity (93%-99.6%). About 36.1% of studies had used sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) as a further diagnostic method to detect defective proteins. Genetic analysis to identify mutations was done using Sanger sequencing, next-generation sequencing (NGS), and whole-exome sequencing (WES) in 33.3%, 22.2%, and 13.8% of studies, respectively. The diagnostic yield of NGS ranged from 63% to 100%. Proteomics was used in 5.5% of studies to support the diagnosis of membranopathies. A single method could not diagnose all membranopathies. Next-generation sequencing, Sanger sequencing, and proteomics will supplement the well-established screening and confirmatory methods, but not replace them in hereditary hemolytic anemia assessment.
Erythropoietin in children with hemolytic uremic syndrome: a pilot randomized controlled trial
Pediatric nephrology (Berlin, Germany). 2022
BACKGROUND The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. METHODS We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. RESULTS Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. CONCLUSION In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.
Health Status Improvement with Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency
European journal of heart failure. 2022
AIM: Intravenous ferric carboxymaltose (FCM) has been shown to improve overall quality of life in iron-deficient heart failure with reduced ejection fraction (HFrEF) patients at a trial population level. This FAIR-HF and CONFIRM-HF pooled analysis explored the likelihood of individual improvement or deterioration in Kansas City Cardiomyopathy Questionnaire (KCCQ) domains with FCM vs placebo and evaluated the stability of this response over time. METHODS Changes vs baseline in KCCQ overall summary score (OSS), clinical summary score (CSS) and total symptom score (TSS) were assessed at weeks 12 and 24 in FCM and placebo groups . Mean between-group differences were estimated and individual responder analyses and analyses of response stability were performed. RESULTS Overall, 760 (FCM: 454) patients were studied. At week 12, the mean improvement in KCCQ OSS was 10.6 points with FCM vs 4.8 points with placebo (least-square mean difference [95% confidence interval (CI)]: 4.36 [2.14;6.59] points). A higher proportion of patients on FCM vs placebo experienced a KCCQ OSS improvement of ≥5 (58.3% vs 43.5%; odds ratio [95% CI]: 1.81 [1.30;2.51]), ≥10 (42.4% vs 29.3%; 1.73 [1.23;2.43]) or ≥15 (32.1% vs 22.6%; 1.46 [1.02;2.11]) points. Differences were similar at week 24 and for CSS and TSS domains. Of FCM patients with a ≥5-, ≥10- or ≥15-point improvement in KCCQ OSS at week 12, >75% sustained this improvement at week 24. CONCLUSION Treatment of iron-deficient HFrEF patients with intravenous FCM conveyed clinically relevant improvements in health status at an individual-patient level; benefits were sustained over time in most patients. This article is protected by copyright. All rights reserved.
Randomised open-label trial comparing intravenous iron and an erythropoiesis-stimulating agent versus oral iron to treat preoperative anaemia in cardiac surgery (INITIATE trial)
British journal of anaesthesia. 2022
BACKGROUND Preoperative anaemia is a risk factor for adverse postoperative outcomes after cardiac surgery. Iron deficiency is a frequent cause of low preoperative haemoglobin. An effective treatment for preoperative anaemia associated with iron deficiency has not been determined. METHODS We conducted a single-centre, open-label, pragmatic randomised trial, enrolling 156 elective cardiac surgery patients who had low preoperative haemoglobin (100-130 g L(-1)) with iron deficiency (serum ferritin <100 μg L(-1) or transferrin saturation <30%) to compare intravenous ferric derisomaltose 1000 mg and darbepoetin 200 μg subcutaneously (intervention group) with oral ferrous sulphate 600 mg daily (control group). The primary outcome was transfusion of at least one unit of allogeneic red cells during surgery and within the following 5 days. Secondary outcomes included the change in haemoglobin concentration between randomisation and surgery, red cell transfusion volume, postoperative blood loss, pre-specified postoperative complications, length of hospital stay, and in-hospital death. RESULTS The odds of red cell transfusion were lower in the intervention group compared with the control group (adjusted odds ratio=0.33; 95% confidence interval [CI], 0.15-0.75; P=0.008). Of the secondary outcomes, the only significant difference was the increase in haemoglobin between randomisation and surgery, intervention vs control 9.5 g L(-1) (95% CI, 6.8-12.2; P<0.001). CONCLUSIONS In patients with a low preoperative haemoglobin and iron deficiency, preoperative treatment with a single dose of ferric derisomaltose and darbepoetin decreased the proportion of participants who received a perioperative blood transfusion as a consequence of a greater increase in haemoglobin compared with treatment with oral ferrous sulphate. CLINICAL TRIAL REGISTRATION ISRCTN Number: 41421863; EUDRACT number: 2011-003695-36.
Safety of Ferric Carboxymaltose in Children: Report of a Case Series from Greece and Review of the Literature
Paediatric drugs. 2022
BACKGROUND Parenteral iron is generally considered safe in adults, and severe adverse events are extremely rare. Ferric carboxymaltose (FCM), a third-generation parenteral iron product, is not licensed for pediatric use. OBJECTIVE The aim of this study was to present our data on the safety of FCM in children with iron deficiency (ID) and/or iron deficiency anemia (IDA) and to investigate through a systematic literature review articles reporting on the safety of FCM use in children with ID/IDA. PATIENTS AND METHODS Safety data regarding children treated with FCM for ID/IDA from four pediatric departments in Greece over a 26-month period are presented. Additionally, a literature search was performed in PubMed, Scopus, and Google Scholar on December 4, 2021 for articles reporting on the use of FCM in children with ID/IDA. Review articles, guidelines, case reports/case series, and reports on the use of FCM for conditions other than ID/IDA were excluded. Identified articles were screened for all reported adverse events (AE) that were graded according to the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS In our cohort, 37 children with ID/IDA received 41 FCM infusions. All infusions were tolerated well. In addition, 11 articles reporting 1231 infusions of FCM in 866 children were identified in the literature. Among them, 52 (6%) children developed AE that were graded as mild or moderate (grades I-III). CONCLUSIONS Our patient cohort and this literature review provide further evidence for the good safety profile of FCM in children, although well-designed prospective clinical trials with appropriate safety endpoints are still required.
Efficacy and safety of intravenous iron with different frequencies for renal anaemia: A systematic review and meta-analysis
Journal of clinical pharmacy and therapeutics. 2022
WHAT IS KNOWN AND OBJECTIVE To evaluate the efficacy and safety of intravenous iron supplementation in patients with renal anaemia. METHODS We searched the PubMed, Embase, Cochrane Library, and Web of Science from their inception until 17 September 2021, for randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous iron at different frequencies. The observed efficacy indicators included transfer saturation (TSAT), serum ferritin (SF) and haemoglobin (HGB). Outcomes of interest included allergies, infections, all-cause mortality and cardiovascular events. RESULTS AND DISCUSSION Of the 751 eligible studies, 7 RCTs met the inclusion criteria. The RCTs showed that there were no significant differences between the low-frequency high-dose group (1-2 doses, >200 mg/dose) and the high-frequency low-dose group (4-5 doses, ≤200 mg/dose) in the increase in TSAT (WMD = 1.90; 95% CI = -2.04 to 5.84; I(2) = 0%), SF (WMD = 15.70; 95% CI = -32.20 to 70.61; I(2) = 0%) and HGB (WMD = -0.00; 95% CI = -0.43 to 0.42; I(2) = 0%). There was also no significant difference in the occurrence of outcome events, including allergies (RR = 1.84; 95% CI = 0.95 to 3.57; I(2) = 45%), infections (RR = 0.61; 95% CI = 0.20-1.86; I(2) = 0%), cardiovascular events (RR = 0.88; 95% CI = 0.67-1.15; I(2) = 48%) and all-cause mortality (RR = 0.74; 95% CI = 0.40-1.35; I(2) = 0%). WHAT IS NEW AND CONCLUSION Frequencies of intravenous iron supplementation with similar doses share similar safety and efficacy in patients with renal anaemia. However, a single dose or two doses of intravenous iron are more cost-effective and patient friendly. These findings may provide evidence for the clinical application of intravenous iron supplementation for patients with renal anaemia.
Efficacy and safety of ferric derisomaltose (FDI) compared with iron sucrose (IS) in patients with iron deficiency anemia after bariatric surgery
Obesity surgery. 2022
PURPOSE Iron deficiency is common following bariatric surgery, and treatment with intravenous iron is often required. This post hoc analysis of data from two randomized, open-label, multicenter trials evaluated the efficacy and safety of ferric derisomaltose (FDI; formerly iron isomaltoside 1000) versus iron sucrose (IS) over 4 weeks in adults with iron deficiency anemia (IDA) resulting from prior bariatric surgery. MATERIALS AND METHODS Data were pooled for participants who received FDI or IS in the PROVIDE or FERWON-IDA trials for the treatment of IDA post bariatric surgery. Efficacy outcomes included changes in hemoglobin (Hb) and iron parameters; safety outcomes included the incidence of adverse drug reactions (ADRs), serious or severe hypersensitivity reactions (HSRs), and hypophosphatemia. RESULTS The analysis included 159 patients. Mean (standard deviation) cumulative iron doses were 1199 (± 347) mg for FDI and 937 (± 209) mg for IS. Compared with IS, FDI resulted in a faster and more pronounced Hb response, and a higher proportion of responders (Hb level increase ≥ 2 g/dL from baseline) at all time points. The incidence of ADRs was similar with FDI and IS (15.1% and 18.2%, respectively), with no serious ADRs or serious or severe HSRs reported. The incidence of hypophosphatemia was low and similar in both treatment groups, with no cases of severe hypophosphatemia observed. CONCLUSIONS In patients with IDA resulting from bariatric surgery, FDI produced a faster and more pronounced Hb response than IS. Both FDI and IS were well tolerated.
Erythropoietin in Acute Kidney Injury (EAKI): a pragmatic randomized clinical trial
BMC nephrology. 2022;23(1):100
BACKGROUND Treatment with erythropoietin is well established for anemia in chronic kidney disease patients but not well studied in acute kidney injury. METHODS This is a multicenter, randomized, pragmatic controlled clinical trial. It included 134 hospitalized patients with anemia defined as hemoglobin < 11 g/dL and acute kidney injury defined as an increase of serum creatinine of ≥ 0.3 mg/dL within 48 h or 1.5 times baseline. One arm received recombinant human erythropoietin 4000 UI subcutaneously every other day (intervention; n = 67) and the second received standard of care (control; n = 67) during the hospitalization until discharge or death. The primary outcome was the need for transfusion; secondary outcomes were death, renal recovery, need for dialysis. RESULTS There was no statistically significant difference in transfusion need (RR = 1.05, 95%CI 0.65,1.68; p = 0.855), in renal recovery full or partial (RR = 0.96, 95%CI 0.81,1.15; p = 0.671), in need for dialysis (RR = 11.00, 95%CI 0.62, 195.08; p = 0.102) or in death (RR = 1.43, 95%CI 0.58,3.53; p = 0.440) between the erythropoietin and the control group. CONCLUSIONS Erythropoietin treatment had no impact on transfusions, renal recovery or mortality in acute kidney injury patients with anemia. The trial was registered on ClinicalTrials.gov (NCT03401710, 17/01/2018).