Lack of Cost-Effectiveness of Preoperative Erythropoiesis-Stimulating Agents and/or Iron Therapy in Anaemic, Elective Surgery Patients: A Systematic Review and Updated Analysis
OBJECTIVES For anaemic elective surgery patients, current clinical practice guidelines weakly recommend the routine use of iron, but not erythrocyte-stimulating agents (ESAs), except for short-acting ESAs in major orthopaedic surgery. This recommendation is, however, not based on any cost-effectiveness studies. The aim of this research was to (1) systematically review the literature regarding cost effectiveness of preoperative iron and/or ESAs in anaemic, elective surgery patients and (2) update existing economic evaluations (EEs) with recent data. METHODS Eight databases and registries were searched for EEs and randomized controlled trials (RCTs) reporting cost-effectiveness data on November 11, 2020. Data were extracted, narratively synthesized and critically appraised using the Philips reporting checklist. Pre-existing full EEs were updated with effectiveness data from a recent systematic review and current cost data. Incremental cost-effectiveness ratios were expressed as cost per (quality-adjusted) life-year [(QA)LY] gained. RESULTS Only five studies (4 EEs and 1 RCT) were included, one on intravenous iron and four on ESAs + oral iron. The EE on intravenous iron only had an in-hospital time horizon. Therefore, cost effectiveness of preoperative iron remains uncertain. The three EEs on ESAs had a lifetime time horizon, but reported cost per (QA)LY gained of 20-65 million (GBP or CAD). Updating these analyses with current data confirmed ESAs to have a cost per (QA)LY gained of 3.5-120 million (GBP or CAD). CONCLUSIONS Cost effectiveness of preoperative iron is unproven, whereas routine preoperative ESA therapy cannot be considered cost effective in elective surgery, based on the limited available data. Future guidelines should reflect these findings.
Elective surgery patients with anaemia (5 studies).
Erythrocyte-stimulating agents (ESAs) and oral iron.
The economic evaluation on intravenous iron only had an in-hospital time horizon. Cost effectiveness of preoperative iron remained uncertain. The three economic evaluations on ESAs had a lifetime time horizon, but reported cost per (QA)LY gained of 20-65 million (GBP or CAD). Updating these analyses with current data confirmed ESAs to have a cost per (QA)LY gained of 3.5-120 million (GBP or CAD).
Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis
Transfusion medicine reviews. 2021
Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence).
Dental care as a risk factor for transfusion transmissible infections in blood donors: a systematic review and meta-analysis
International journal of evidence-based healthcare. 2020
BACKGROUND AND OBJECTIVES The deferral policy for blood donation after dental care is based on the precautionary principle. The aim of this systematic review is to give an overview of the scientific evidence concerning the risk of transfusion transmissible infections (TTIs) after dental care. MATERIALS AND METHODS Four databases were searched: Medline, the Cochrane Library, Embase and Web of Science. Screening was independently performed by two reviewers. The quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development and Evaluation principle. A meta-analysis was performed to assess the association between dental treatment and TTI markers. RESULTS A total of 22 studies were included. Meta-analysis of 16 studies showed an increased association of TTIs with dental treatment, however with large heterogeneity. Subgroup analysis revealed a significant increased association of hepatitis B virus (HBV) with dental treatment [odds ratio 1.79, 95% confidence interval (1.48; 2.18)]. There was conflicting evidence concerning the risk of hepatitis C virus (HCV). One study could not demonstrate a statistically significant increased association of human T-lymphotropic virus type I with dental treatment. Three studies showed a significant increased association of HCV with tooth extraction [odds ratio 1.48, 95% confidence interval (1.11; 1.97)]. Finally, there is conflicting evidence concerning the risk of HBV or HCV after dental cleaning. One study could not demonstrate an association between HIV and dental cleaning. All evidence is of very low certainty and results cannot be considered precise. CONCLUSION Studies of high quality concerning the risk of TTI after dental care in blood donors are scarce. An association of HBV after dental treatment and HCV after tooth extraction was demonstrated but evidence is of very low certainty. The currently identified studies are of too low certainty to make any suggestions regarding the value of deferral or deferral times.
Iron supplementation limits the deleterious effects of repeated blood donation on endurance sport performance but not on iron status
Blood transfusion = Trasfusione del sangue. 2020;18(5):334-347
BACKGROUND Every day, blood banks worldwide face the challenge of ensuring an adequate blood supply. Iron deficiency is by far the most common cause of deferral of blood donors. The aim of the present study was to determine the effect of iron supplementation after repeated blood donation on iron status and physiological performance. MATERIALS AND METHODS Forty-four moderately trained and iron-replete subjects were randomly divided into a whole blood donation (n=36) and a placebo donation (n=8) group. One third of the donation group received no iron supplementation, whereas one third received 20 mg iron and one third received 80 mg iron daily for 28 days. The subjects were intended to make three donations 3 months apart, and recovery of endurance capacity, assessed by an incremental maximal cycling test, and haematological parameters was monitored up to 28 days after each donation. RESULTS Negative effects of repeated blood donation were found for markers of iron storage, markers of functional iron and/or iron metabolism regulation, and physiological markers. Iron supplementation did not affect iron storage but did limit, at the highest dose of 80 mg, the effect of blood donations on functional iron and/or iron metabolism regulation, and at both 20 and 80 mg the negative effects on maximal power output and peak oxygen consumption. DISCUSSION Iron supplementation limited the deleterious effects of repeated blood donation on endurance sport performance but not on decline in iron status in iron-replete young men. These results underline the importance of iron supplementation to minimise the deleterious effects of blood donation on physiological functions, and the necessity to optimise the supplementation strategy to preserve iron status.
Is sexual risk behaviour associated with an increased risk of transfusion-transmissible infections in blood donors from Western and Pacific countries? A systematic review and meta-analysis
Vox sanguinis. 2019
BACKGROUND AND OBJECTIVES The donor medical questionnaire is designed to aid blood establishments in supporting a safe blood supply. According to blood donor deferral policies, sexual risk behaviour (SRB) leads to a (temporary) deferral from blood donation. This systematic review aimed to scientifically underpin these policies by identifying the best available evidence on the association between SRB and the risk of transfusion transmissible infections (TTIs). MATERIALS & METHODS Studies from three databases investigating the link between SRB (excluding men who have sex with men (MSM)) and TTIs (HBV, HCV, HIV, Treponema pallidum) in donors from Western and Pacific countries were obtained and assessed on eligibility by two reviewers independently. The association between SRB and TTIs was expressed by calculating pooled effect measures via meta-analyses. The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS We identified 3750 references and finally included 15 observational studies. Meta-analyses showed that there is a significant (P < 0.05) positive association between the following SRB and HBV and/or HCV infection: having sex with an intravenous drug user (high-certainty evidence), receiving money or goods for sex (moderate-high certainty evidence), having a sex partner with hepatitis/HIV (moderate-certainty evidence) and paid for sex or anal sex (low-certainty evidence). CONCLUSION Sexual risk behaviour (including having sex with an intravenous drug user, receiving money or goods for sex or having a sex partner with hepatitis/HIV) is probably associated with an increased risk of HBV/HCV infection in blood donors from Western and Pacific countries.
Is there a risk of transfusion-transmissible infections after percutaneous needle treatments in blood donors? A systematic review and meta-analysis
Vox sanguinis. 2019
BACKGROUND AND OBJECTIVES The donor medical questionnaire identifies a blood donor's history of known blood safety risks. Current Australian, Canadian, European and USA legislation temporarily defers blood donors who received different percutaneous needle treatments (i.e. tattooing, acupuncture and piercing) from blood donation. This systematic review aimed to scientifically underpin these deferrals by identifying the best available evidence on the association between percutaneous needle treatments and the risk of transfusion-transmissible infections (TTIs). MATERIALS AND METHODS Studies from three databases investigating the link between percutaneous needle treatments and TTIs (HBV, HCV and HIV infection) in blood donors were retained and assessed on eligibility by two reviewers independently. The association between percutaneous needle treatments and TTIs was expressed by conducting meta-analyses and calculating pooled effect measures (odds ratios (ORs) and 95% CIs). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS We identified 1242 references and finally included 21 observational studies. Twenty studies assessed the link between percutaneous needle treatments and HCV infection and found that blood donors receiving these treatments had an increased risk of HCV infection (tattooing: pooled OR 5.28, 95% CI [4.33, 6.44], P < 0.00001 (low-quality evidence); acupuncture: pooled OR 1.56, 95% CI [1.17, 2.08], P = 0.03 (very low-quality evidence); and piercing: pooled OR 3.25, 95% CI [1.68, 6.30], P = 0.0005 (low-quality evidence)). CONCLUSION Percutaneous needle treatments may be associated with an increased HCV infection risk. Further high-quality studies are required to formulate stronger evidence-based recommendations on percutaneous needle treatments as a blood donor deferral criterion.
The effect of a standard whole blood donation on oxygen uptake and exercise capacity: a systematic review and meta-analysis
BACKGROUND Blood is a life-saving product for many people worldwide. Voluntary blood donation serves the demand for blood but there are concerns among potential donors about the impact of blood loss on exercise performance. This systematic review aimed to collect the best available evidence of the effect of a standard whole blood donation on aerobic exercise performance. STUDY DESIGN AND METHODS Studies from six databases dealing with a standard whole blood donation (400-500 mL) followed by (sub)maximal exercise were retained. The outcomes included exercise-related blood variables (hemoglobin [Hb] concentration, hematocrit, and red blood cell count) and endurance exercise variables ((sub)maximal oxygen uptake, peak work rate, and time to exhaustion). Overall effects at different time points postdonation were investigated by performing meta-analyses and calculating mean differences (and 95% confidence intervals). The GRADE methodology (Grades of Recommendation, Assessment, Development, and Evaluation) was used to assess the quality of evidence. RESULTS We identified 6237 references and finally included 18 before-after studies of low quality. Twenty-four to 48 hours after a blood donation, 1) Hb concentration was reduced (7% decrease) until 14 days after the blood donation (4% decrease), 2) maximal oxygen uptake (VO2max ) was lower (7% decrease), and 3) a reduction in maximal exercise capacity (10% decrease) was present. CONCLUSION The best available evidence indicates that a standard whole blood donation (400-500 mL) leads to small but potentially physiologically important reductions in Hb levels, VO2max , and maximal exercise capacity in the first 2 days after the blood donation.
Methodologic quality assessment of red blood cell transfusion guidelines and the evidence base of more restrictive transfusion thresholds
BACKGROUND Recent literature suggests that more restrictive red blood cell (RBC) transfusion practices are equivalent or better than more liberal transfusion practices. The methodologic quality of guidelines recommending more restrictive transfusion thresholds and their underlying scientific evidence is unclear. Therefore, we aimed to evaluate the quality of the development process of RBC transfusion guidelines and to investigate the underlying evidence of guidelines recommending a more restrictive hemoglobin (Hb) threshold. STUDY DESIGN AND METHODS Via systematic literature screening of relevant databases (NGC, GIN, Medline, and Embase), RBC transfusion guidelines recommending a more restrictive Hb level (<6, <7, or <8 g/dL) were included. Four assessors independently evaluated the methodologic quality by scoring the rigor of development domain (AGREE II checklist). The level of evidence served as a reference for the quality of the underlying evidence. RESULTS The methodologic quality of 13 RBC transfusion guidelines was variable (18%-72%) but highest for those developed by Advancing Transfusion and Cellular Therapies Worldwide (72%), the Task Force of Advanced Bleeding Care in Trauma (70%), and the Dutch Institute for Healthcare Improvement (61%). A Hb level of less than 7 g/dL (intensive care unit patients) or less than 8 g/dL (postoperative patients) were the only thresholds based on high-quality evidence. Only four of 32 recommendations had a high-quality evidence base. CONCLUSION Methodologic quality should be guaranteed in future RBC transfusion guideline development to ensure that the best available evidence is captured when recommending restrictive transfusion strategies. More high-quality trials are needed to provide a stronger scientific basis for RBC transfusion guidelines that recommend more restrictive transfusion thresholds.
Is having sex with other men a risk factor for transfusion-transmissible infections in male blood donors in Western countries? A systematic review
PLoS ONE [Electronic Resource]. 2015;10((4):):e0122523.
BACKGROUND Although increased prevalence of transfusion transmissible infections (TTI) among "men who have sex with men" (MSM) has been well documented, the exclusion of MSM as blood donors is contested. The aim of this systematic review is to find studies that describe the risk of TTI in MSM blood donors. METHODS We searched MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, Cinahl, and Web of Science, and used GRADE for determining evidence quality. We included studies comparing MSM and non-MSM blood donors (or people eligible to give blood), living in areas most relevant for our Blood Service. RESULTS Out of 18 987 articles, 14 observational studies were included. Two studies directly compared MSM with non-MSM donors showing that MSM donors have a statistically significant higher risk of HIV-1 infections. In one of these studies it was shown that this was related to recent (< 12 months) MSM contact. In two additional studies no evidence was shown in favour of a certain deferral period for MSM. Ten studies, applying permanent deferral for MSM, compared infected versus non-infected donors. One study found that MSM is a statistically significant risk factor for HIV-1 infection in blood donors. For other TTI such as HBV or HCV, an increased risk of infection could not be demonstrated, because the precision of the results was affected by the low numbers of donors with MSM as risk factor, or because of risk of bias in the included studies. All studies included low level evidence, because of risk of bias and imprecision of the results. CONCLUSIONS High-quality studies investigating the risk of TTI in MSM who donate blood are scarce. The available evidence suggests a link between MSM blood donors and HIV-1 infection, but is too limited to be able to unambiguously/clearly recommend a certain deferral policy.
The effect of pre-donation hypotension on whole blood donor adverse reactions: a systematic review
Journal of the American Society of Hypertension. 2014;8((6):):429-36.
Blood services are reliant upon healthy blood donors to provide a safe and adequate supply of blood products. Inappropriate variables contained within blood donor exclusion criteria can defer potentially appropriate donors. The aim of this systematic review was to examine the effect of low pre-donation blood pressure, as compared with normal blood pressure, on adverse events in allogeneic whole blood donors. A systematic review was performed using highly sensitive search strategies within five databases (Cochrane Central Register of Controlled Trials, CINAHL, Embase, MEDLINE, and Web of Science) from inception date until April 12, 2013. Out of 8305 records, 10 observational studies were identified that addressed the question. Five of these studies (with a combined total of 1,482,020 donations and 2903 donors) included either a statistical analysis or an appropriate study design that controlled for possible confounding factors. Based on the currently available evidence, hypotension has not been shown to be an independent predictive factor for donor complications. However, the overall quality of evidence was rather limited and rated 'low,' using the GRADE approach. In conclusion there is currently no evidence that hypotensive blood donors have a greater risk for donor adverse events compared with their normotensive counterparts. Copyright 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.