Efficacy and safety of darbepoetin alpha in patients with myelodysplastic syndromes: a systematic review and meta‐analysis

We conducted a systematic review and meta‐analysis to estimate the efficacy of darbepoetin alpha (DA) for treatment of myelodysplastic syndrome (MDS)‐related anaemia. Eligible studies were prospective, interventional, and reported World Health Organization, French‐American‐British, or International Prognostic Scoring System (IPSS) criteria. Outcomes included erythroid response rate (primary); haemoglobin response; change in haemoglobin, transfusion status, and quality‐of‐life (QoL); and safety. Ten studies (N = 647) were analysed. Erythroid response rate range was 38–72%; median response duration range was 12–51+ months. Patients with erythropoietin (EPO) <100 iu/l had 35% [95% confidence interval (CI): 22–48%; P < 0·001) better response than patients with EPO >100 iu/l. Erythropoesis‐stimulating agent (ESA)‐naïve patients had 17% (95% CI: 3–32%; P = 0·022) greater response rate than those previously treated with ESA. Nonetheless, previously treated patients had response rates of 25–75%. Higher baseline haemoglobin levels, higher dose, transfusion‐independence and low‐risk IPSS status were reported by several studies to be associated with better response. QoL, transfusion rates and haemoglobin levels improved with treatment. Hypertension, thromboembolism and progression to acute myeloid leukaemia were reported in 2%, 1% and 1% of patients, respectively. This meta‐analysis suggests that DA treatment can be useful for improving erythroid response in MDS patients with anaemia, even among patients previously treated with ESA.     

Red cell transfusion thresholds in myelodysplastic syndromes: a clinician survey to inform future clinical trials

Optimal red cell transfusion thresholds in myelodysplastic syndrome are not established. In this survey of 110 Australasian haematologists’ practice in myelodysplastic syndrome‐related anaemia, 92% of respondents set transfusion thresholds, and would typically transfuse at a haemoglobin <80 g/L aiming for a post‐transfusion haemoglobin 90–100 g/L, reflecting a restrictive transfusion strategy. Higher thresholds were typically used for patients with cardiovascular disease or anaemia symptoms. These results will inform the design of clinical trials comparing transfusion thresholds.     

Radiation recall following cisplatin chemotherapy

The decision to transfuse a neonate can be approached by addressing a series of questions that cover the cause of anaemia, alternatives to transfusion, the need for transfusion and the risks. Recent clinical trials of red cell transfusions have started to inform evidence‐based transfusion practice, but have raised uncertainties about neurological outcomes when policies advocating use of fewer red cell transfusions at lower haemoglobin concentration (Hb) thresholds were tested. Red cell transfusions should be considered when the Hb <120 g/l for premature neonates requiring mechanical ventilation support, with lower thresholds applying for oxygen‐dependent neonates not requiring ventilation or for late anaemia (Hb <70–100 g/l, depending on gestational and post‐natal age). There is no recent high quality evidence to inform thresholds for prophylactic platelet transfusions in stable non‐bleeding premature neonates with platelet count levels of 50 × 10⁹/l, although common practice has become more restrictive, using lower safe thresholds for platelet transfusion between 20 and 30 × 10⁹/l. A more appropriate transfusion strategy for fresh frozen plasma (FFP) in neonates is one that emphasizes the therapeutic use of FFP in the face of bleeding, rather than prophylactic use in stable non‐bleeding neonates who often have mild to moderate apparent abnormalities of standard coagulation tests, after allowing for appropriate reference ranges.     

Expanding restrictive transfusion evidence in surgical practice: a multicentre,prospective cohort study

BackgroundFindings of observational studies investigating the impact of transfusions are at odds with those of randomised controlled trials, raising concern that observational studies may be inappropriate to inform transfusion decisions. We examined whether observational data could replicate evidence from randomised controlled trials on restrictive transfusion in cardiac and orthopaedic surgery, and be generalised to broader specialties as well as to a lower haemoglobin transfusion threshold (7 g/dL).Material and methodsA multicentre, prospective cohort study was performed at three representative regional hospitals in China between 2015 and 2016. Participants were surgical inpatients (≥18 years; hospital stay ≥24 h) in six specialties: cardiac, cerebral, vascular (CCV), and orthopaedic, general, thoracic (non-CCV). Patients with a stable haemoglobin (7–10 g/dL) constituted the primary analytic sample, while patients with ≥500 mL intra-operative bleeding were analysed separately to avoid haemoglobin instability. The association of transfusion with surgical outcomes (death, in-hospital complications) was evaluated.ResultsThe transfusion rate was 10.7% in 36,607 patients (mean age, 52.5±14.3 years; 52.3% female). After restriction, stratification, and propensity score matching to reduce patients’ heterogeneity, transfusion was unrelated to death (CCV: odds ratio [OR]=0.74, 95% confidence interval [CI]: 0.16–3.39; non-CCV: OR 0.83, 95% CI: 0.36–1.94) and the composite complication (CCV: OR 1.31, 95% CI: 0.63–2.72; non-CCV: OR=1.24, 95% CI: 0.81–1.90). The results were consistent in subgroups (elderly, coronary heart disease, malignant tumour, severe illness) and applicable to patients with significant bleeding after restoration of a stable haemoglobin.DiscussionTransfusion at a stable haemoglobin concentration of 7–10 g/dL did not alter surgical outcomes. Our results show the feasibility of observational data to expand restrictive transfusion to broader specialties and a lower transfusion threshold in surgical practice.     

Using longitudinal data from the Health Survey for England to resolve discrepancies in thresholds for haemoglobin in older adults

Anaemia increases with age and is common among older people. Due to its relationship with morbidity and mortality, accurate diagnosis is important. Thresholds defining the diagnosis of anaemia have been the subject of considerable scientific debate, with both higher and lower cut‐offs proposed. High haemoglobin is also a health risk in some but not all studies. Using nationally representative data of 5,329 adults aged 65 + years (Health Survey for England 1998, 2005, 2006), linked to administrative mortality data, this paper describes the relationship between haemoglobin levels and mortality, adjusted for age and other confounders. Among men, a reverse J shaped relationship was observed: relative to the modal group (140–149 g/l), those with ‘mild anaemia’ of 120–129 g/l haemoglobin had a 56% (95% confidence interval 24–96%) greater mortality hazard, and those with ‘severe anaemia’, haemoglobin <120 g/l, had an 87% (39–153%) greater hazard. At the other end of the range, those with haemoglobin ≥160 g/l had 32% (2–70%) greater mortality hazard. Haemoglobin levels in women showed a similar but smaller, non‐significant pattern: hazard ratio 1·32 (0·91–1·92) for severe anaemia (<110 g/l), and 1·30 (0·95–1·79) for high haemoglobin (≥150 g/l). This research supports the use of the World Health Organization thresholds (130 g/l for men, 120 g/l for women).     

Silent myocardial ischaemia and haemoglobin concentration: a randomized controlled trial of transfusion strategy in lower limb arthroplasty

BACKGROUND AND OBJECTIVES: Red cell transfusion is commonly used in orthopaedic surgery. Evidence suggests that a restrictive transfusion strategy may be safe for most patients. However, concern has been raised over the risks of anaemia in those with ischaemic cardiac disease. Perioperative silent myocardial ischaemia (SMI) has a relatively high incidence in the elderly population undergoing elective surgery. This study used Holter monitoring to compare the effect of a restrictive and a liberal red cell transfusion strategy on the incidence of SMI in patients without signs or symptoms of ischaemic heart disease who were undergoing lower limb arthroplasty. MATERIALS AND METHODS: We performed a multicentre, controlled trial in which 260 patients undergoing elective hip and knee replacement surgery were enrolled and randomized to transfusion triggers that were either restrictive (8 g/dl) or liberal (10 g/dl). Participants were monitored with continuous ambulatory electrocardiogram (ECG) (Holter monitoring), preoperatively for 12 h and postoperatively for 72 h. The tapes were analysed for new ischaemia by technicians blinded to treatment. The total ischaemia time in minutes was divided by the recording time in hours and an ischaemic load in min/h was calculated. Haemoglobin levels were measured preoperatively, postoperatively in the recovery room, and on days one, three and five after surgery. RESULTS: The mean postoperative haemoglobin concentration was 9.87 g/dl in the restrictive group and 11.09 g/dl in the liberal group. In the restrictive group, 34% were transfused a total of 89 red cell units, and in the liberal group 43% were given a total of 119 red cell units. A postoperative episode of silent ischaemia was experienced by 21/109 (19%) patients in the restrictive group and by 26/109 (24%) patients in the liberal group [mean difference -4.6%; 95% confidence interval (CI): -15.5% to 6%, P = 0.41). There was no significant difference (P = 0.53) between the overall ischaemic load in the restrictive group (median 0 min/h, range 0-4.18) and the liberal group (median 0 min/h, range 0-19.48). In those patients who did experience postoperative SMI, the mean ischaemic load was 0.48 min/h in the restrictive group and 1.51 min/h in the liberal group (ratio 0.32, 95% CI: 0.14-0.76, P = 0.011). The median postoperative length of hospital stay in the restrictive group was 7.3 days [range 5-11; interquartile range (IQR) 6-8] compared with 7.5 days (range 5-13; IQR 7-8) in the liberal group. The numbers were not large enough to conclude equivalence. CONCLUSIONS: In patients without preoperative evidence of myocardial ischaemia undergoing elective hip and knee replacement surgery, a restrictive transfusion strategy seems unlikely to be associated with an increased incidence of SMI. A proportion of these patients experience moderate SMI, regardless of the transfusion trigger. Use of a restrictive transfusion strategy did not increase length of hospital stay, and use of this strategy would lead to a significant reduction in red cell transfusion in orthopaedic surgery. Our data did not indicate any potential for harm in employing such a strategy in patients with no prior evidence of cardiac ischaemia who were undergoing elective orthopaedic surgery.     

Monitoring compliance with transfusion guidelines in hospital departments by electronic data capture

Background

The practice of transfusing red blood cells is still liberal in some centres suggesting a lack of compliance with guidelines recommending transfusion of red blood cells at haemoglobin levels of 6–8 g/dL in the non-bleeding patient. Few databases provide ongoing feedback of data on pre-transfusion haemoglobin levels at the departmental level. In a tertiary care hospital, no such data were produced before this study. Our aim was to establish a Patient Blood Management database based on electronic data capture in order to monitor compliance with transfusion guidelines at departmental and hospital levels.

Materials and methods

Hospital data on admissions, diagnoses and surgical procedures were used to define the populations of patients. Data on haemoglobin measurements and red blood cell transfusions were used to calculate pre-transfusion haemoglobin, percentage of transfused patients and transfusion volumes.

Results

The model dataset include 33,587 admissions, of which 10% had received at least one unit of red blood cells. Haemoglobin measurements preceded 96.7% of the units transfused. The median pre-transfusion haemoglobin was 8.9 g/dL (interquartile range 8.2–9.7) at the hospital level. In only 6.5% of the cases, transfusion was initiated at 7.3 g/dL or lower as recommended by the Danish national transfusion guideline. In 27% of the cases, transfusion was initiated when the haemoglobin level was 9.3 g/dL or higher, which is not recommended. A median of two units was transfused per transfusion episode and per hospital admission. Transfusion practice was more liberal in surgical and intensive care units than in medical departments.

Discussion

We described pre-transfusion haemoglobin levels, transfusion rates and volumes at hospital and departmental levels, and in surgical subpopulations. Initial data revealed an extensive liberal practice and low compliance with national transfusion guidelines, and identified wards in need of intervention.     

Rationalizing blood transfusion in cardiac surgery: the impact of a red cell volume‐based guideline on blood usage and clinical outcome

Background and Objectives Cardiac surgery is currently considered one of the heaviest users of red blood cells. An explanation may be found, in part, in considering the effect of the heavy clear fluid load associated with cardiopulmonary bypass. This may result in the artificial depression of haemoglobin concentration, overestimating the requirement for red cell transfusion if this is the sole parameter considered. To address this issue, we examined the impact of a red cell volume‐based transfusion guideline on transfusion requirement. Materials and Methods This was a single‐centre, randomized controlled trial. The cohort of 86 patients was allocated to receive red cells as per the red cell volume guideline (group RCV) or standard haemoglobin concentration‐based departmental policy (group C). Outcome measures were red cell transfusion and clinical outcome. Results All preoperative data were comparable between the two groups. A significantly fewer percentage of patients in group RCV were transfused red cells (RCV = 32·6% vs. C = 53·5%, P = 0·05). No significant difference was found between any of the outcome measures with the exception of median hospital stay (RCV = 5·9 days vs. C = 6·8 days, P = 0·02). Conclusion In elective cardiac surgery patients, considering haemoglobin concentration alone may overestimate the requirement for red cell transfusion. More research is required to determine the impact of restrictive transfusion policies on clinical outcome following cardiac surgery.     

Red cell transfusion for iron-deficiency anaemia: a retrospective audit at a tertiary hospital

BACKGROUND AND OBJECTIVES: The role of red cell transfusion in the management of iron-deficiency anaemia is controversial. This audit was undertaken to monitor the overall transfusion practices of patients admitted to a 600-bed acute tertiary hospital with confirmed severe iron deficiency. MATERIALS AND METHODS: Data from 615 consecutive patients with iron deficiency and no evidence of iron therapy during the period from 1 March 2001 to 30 September 2005 were retrospectively reviewed. RESULTS: Of the 615 iron-deficient patients, 39.2% were transfused. Overall transfused patients were significantly older (mean 73 years old vs. 53 years old; P < 0.0001) with more comorbidities than those not transfused. The pretransfusion haemoglobin (Hb) was < 90 g/l in 92.5% compared to 15.4% of patients not transfused. The post-transfusion Hb was > or = 100 g/l in 75.0% of patients and > or = 110 g/l in 44.2%. Although currently rare (2.5% patients) our speculative data suggest that single red cell transfusions may be appropriate in < or = 29% of patients if restrictive thresholds were adopted. CONCLUSION: Red cell transfusions are commonly administered to elderly patients with severe iron-deficiency anaemia. They may be necessary to alleviate severe morbidity until the time at which iron therapy becomes clinically effective. However, greater emphasis should be given to restrictive transfusion strategies and dosing. Transfusion of single red cell units followed by clinical assessment will determine the need for subsequent units and ensure that this valuable resource is appropriately used.     

Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of ≥120 g/L with darbepoetin alfa ± filgrastim or erythrocyte transfusions

Objective: Anaemia in low‐risk myelodysplastic syndromes (MDS) is associated with reduced quality of life (QoL). Response to treatment with erythropoietin ± granulocyte colony‐stimulating factor (G‐CSF) is associated with improved QoL, but whether transfusion therapy with higher haemoglobin (Hb) target levels has similar effects is unknown. The objective for this prospective phase II Nordic multicentre trial was to assess QoL, response rate and physical function in elderly anaemic MDS patients treated to a target Hb level of >120 g/L. Methods: Thirty‐six elderly patients with low‐ and intermediate‐1 risk MDS received darbepoetin (DA) 300 μg/wk, with the addition of G‐CSF if no response. If the Hb target was reached at 16 wk, treatment was maintained until week 26. Remaining patients were transfused to reach the target level for at least 8 wk. Results: Twenty‐seven patients completed the study. Response rate to DA ± G‐CSF was 67% in evaluable patients and 56% according to intention to treat. Eighteen patients reached the target Hb level according to protocol. QoL scores for fatigue, dyspnoea, constipation, and physical, role and social functioning improved significantly during study, with similar results for transfused and untransfused patients. Maintaining Hb >120 g/L did not confer a higher transfusion rate, once the target was reached. In two of fourteen patients, magnetic resonance imaging T2* indicated cardiac iron overload, however, without association with ferritin levels. Conclusions: In elderly anaemic MDS patients, an increment in haemoglobin is associated with improved QoL, whether induced by growth factor treatment or transfusion therapy.     

A randomized comparison of once weekly epoetin alfa to extended schedule epoetin or darbepoetin in chemotherapy‐associated anemia

Erythropoiesis‐stimulating agents (ESAs) epoetin alfa (EA) and darbepoetin alfa (DA) increase hemoglobin (Hb) levels and reduce red blood cell (RBC) transfusion requirements in patients with cancer chemotherapy‐associated anemia (CAA). Extended‐interval ESA dosing (administration less than once weekly) is common with DA, but previous studies suggested that EA might also be administered less often than weekly. In this multicenter prospective trial, 239 CAA patients with Hb <10.5 g/dL were randomized to receive EA 40,000 U subcutaneously once weekly (“40K” arm), EA 80,000 U every 3 weeks (“80K”), EA 120,000 U every 3 weeks (“120K” arm), or DA 500 mcg every 3 weeks (“DA”), for 15 weeks. The primary endpoint was the proportion of patients achieving Hb ≥ 11.5 g/dL or increment of Hb > 2.0 g/dL from baseline without transfusion. Secondary endpoints included transfusion requirements, adverse events (AEs), and patient‐reported outcomes (PROs). There were no significant differences between treatment arms in the proportion of patients achieving Hb response (68.9% for 40K, 61.7% for 80K, 65.5% for 120K, and 66.7% for DA; P > 0.41 for all comparisons) or requiring RBC transfusion, but the median Hb increment from baseline was higher in the 40K and DA arms compared to the two extended dosing EA arms, and Hb response was achieved soonest in the weekly EA arm. There were no differences in PROs or AEs. The FDA‐approved schedules tested—weekly EA 40,000 U, and every 3 week DA 500 mcg—are reasonable standards for CAA therapy. Am. J. Hematol. 90:877–881, 2015. © 2015 Wiley Periodicals, Inc.     

Iron‐chelating therapy with deferasirox in transfusion‐dependent,higher risk myelodysplastic syndromes: a retrospective,multicentre study

Iron chelation is controversial in higher risk myelodysplastic syndromes (HR‐MDS), outside the allogeneic transplant setting. We conducted a retrospective, multicentre study in 51 patients with transfusion‐dependent, intermediate‐to‐very high risk MDS, according to the revised international prognostic scoring system, treated with the oral iron chelating agent deferasirox (DFX). Thirty‐six patients (71%) received azacitidine concomitantly. DFX was given at a median dose of 1000 mg/day (range 375–2500 mg) for a median of 11 months (range 0·4–75). Eight patients (16%) showed grade 2–3 toxicities (renal or gastrointestinal), 4 of whom (8%) required drug interruption. Median ferritin levels decreased from 1709 μg/l at baseline to 1100 μg/l after 12 months of treatment (P = 0·02). Seventeen patients showed abnormal transaminase levels at baseline, which improved or normalized under DFX treatment in eight cases. One patient showed a remarkable haematological improvement. At a median follow up of 35·3 months, median overall survival was 37·5 months. The results of this first survey of DFX in HR‐MDS are comparable, in terms of safety and efficacy, with those observed in lower‐risk MDS. Though larger, prospective studies are required to demonstrate real clinical benefits, our data suggest that DFX is feasible and might be considered in a selected cohort of HR‐MDS patients.     

Intravenous immunoglobulin in the management of severe early onset red blood cell alloimmunisation

Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case–control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti-D or anti-K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti-D in 17 women and anti-K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8–53.2, p = 0.0013) and improved perinatal survival (eight of eight vs. none of six, p = 0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early-onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.     

Impact of red blood cell transfusion strategies in haemato‐oncological patients: a systematic review and meta‐analysis

Haemato‐oncological patients receive many red blood cell (RBC) transfusions, however evidence‐based guidelines are lacking. Our aim is to quantify the effect of restrictive and liberal RBC transfusion strategies on clinical outcomes and blood use in haemato‐oncological patients. A literature search, last updated on 11 August 2016, was performed in PubMed, EMBASE (Excerpta Medica Database), Web of Science, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and Academic Search Premier without restrictions on language and year of publication. Randomized controlled trials and observational studies that compared different RBC transfusion strategies in haemato‐oncological patients were eligible for inclusion. Risk of bias assessment according to the Cochrane collaboration's tool and Newcastle‐Ottawa scale was performed. After removing duplicates, 1142 publications were identified. Eventually, 15 studies were included, reporting on 2636 patients. The pooled relative risk for mortality was 0·68 [95% confidence interval (CI) 0·46–1·01] in favour of the restrictive strategy. The mean RBC use was reduced with 1·40 units (95% CI 0·70–2·09) per transfused patient per therapy cycle in the restrictive strategy group. There were no differences in safety outcomes. All currently available evidence suggests that restrictive strategies do not have a negative impact regarding clinical outcomes in haemato‐oncological patients, while it reduces RBC use and associated costs.     

Comparison of restrictive and liberal transfusion strategy on postoperative delirium in aged patients following total hip replacement: A preliminary study

Few studies have examined the association between perioperative blood transfusion and postoperative delirium (POD) in aged patients undergoing total hip replacement surgery. In this prospective study, 186 patients older than 65 years undergoing elective unilateral total hip replacement surgery were enrolled. Of those, 94 patients were randomly assigned to the restrictive strategy transfusion strategy group, in which red blood cells were transfused in order to maintain 10.0 g/dL > hemoglobin ≧ 8.0 g/dL. Ninety-two patients were randomly assigned to the liberal transfusion strategy group, in which red blood cells were transfused in order to maintain hemoglobin ≧ 10.0 g/dL. POD was diagnosed by confusion assessment method. The baseline characteristics of patients, the length of hospital stay, the incidence of POD, myocardial infarction, stroke, wound infection, pulmonary embolism, and the transfusion volume were recorded. No difference was observed in the baseline characteristics, the length of hospital stay, and the incidence of POD, myocardial infarction, stroke, wound infection, and pulmonary embolism between the two groups (P > 0.05). The proportion of patients transfused with red blood cell and frozen plasma was decreased in the restrictive transfusion group compared with the liberal transfusion group (P < 0.05). In conclusion, restrictive transfusion does not influence the incidence of POD but reduces blood transfusion. Thus, restrictive transfusion may serve as an effective and safe strategy for aged patients following total hip replacement.     

Transfusion practice and complications after laparotomy--an observational analysis of a randomized clinical trial

Background Transfusion of allogeneic red blood cells (RBC) may be associated with side effects. This study aimed to assess whether an association could be detected between transfusion practice and the occurrence of complications after laparotomy. Study design and methods This study is an observational analysis of data from a randomized trial in 1400 patients who underwent laparotomy. A subgroup of 224 transfused patients with an intraoperative blood loss ≥200 ml were included in the analysis. Logistic regression analysis was used to investigate risk factors for postoperative complications. The ratio of intraoperative RBC transfusion to blood loss was computed, and patients grouped by the median into a liberal transfusion practice (ratio equal to or above the median) and a restrictive transfusion practice group (ratio below the median). Results Surgical site infection occurred in 27% of patients in the liberal group vs. 20% of patients in the restrictive group with an OR of 1·5 [95% CI: 0·8–2·9] (P = 0·18) and an OR of 1·2 [95% CI: 0·5–2·9] (P = 0·73) when adjusting for known confounding variables. Pneumonia occurred in 14% vs. 8% in the liberal and restrictive group, respectively (adjusted P = 0·07), and admission to the intensive care unit was 15% vs. 7%, respectively (adjusted P = 0·02), but no other significant differences were found. Conclusion A liberal transfusion practice was not significantly associated with postoperative complications, but pneumonia tended to be more common in the liberal group, which was more often admitted to the intensive care unit.     

Conservative versus liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study)

Red blood cell transfusion is common in patients with acute myocardial infarction (AMI). However, observational data suggest that this practice may be associated with worse clinical outcomes and data from clinical trials are lacking in this population. We conducted a prospective multicenter randomized pilot trial in which 45 patients with AMI and a hematocrit level ≤30% were randomized to a liberal (transfuse when hematocrit <30% to maintain 30% to 33%) or a conservative (transfuse when hematocrit <24% to maintain 24% to 27%) transfusion strategy. Baseline hematocrit was similar in those in the liberal and conservative arms (26.9% vs 27.5%, p = 0.4). Average daily hematocrits were 30.6% in the liberal arm and 27.9% in the conservative arm, a difference of 2.7% (p <0.001). More patients in the liberal arm than in the conservative arm were transfused (100% vs 54%, p <0.001) and the average number of units transfused per patient tended to be higher in the liberal arm than in the conservative arm (2.5 vs 1.6, p = 0.07). The primary clinical safety measurement of in-hospital death, recurrent MI, or new or worsening congestive heart failure occurred in 8 patients in the liberal arm and 3 in the conservative arm (38% vs 13%, p = 0.046). In conclusion, compared to a conservative transfusion strategy, treating anemic patients with AMI according to a liberal transfusion strategy results in more patients receiving transfusions and higher hematocrit levels. However, this may be associated with worse clinical outcomes. A large-scale definitive trial addressing this issue is urgently required.     

A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes

To evaluate the effect of recombinant human erythropoietin (rHuEpo) on the haemoglobin level and transfusion requirement in low-risk myelodysplastic syndromes (MDS), 87 patients were enrolled in a randomized double-blind placebo-controlled study. 44 patients were assigned to epoetin α (150 U/kg/d s.c. for 8 weeks) and 43 to placebo arms. MDS types were homogenous in both groups: refractory anaemia (RA) 47.7–48.8%, refractory anaemia with ringed sideroblasts (RAS) 20.5–25.6%, refractory anaemia with excess of blasts (RAEB) (blasts < 10%) 31.8–25.6%. 14/38 evaluable patients responded to epoetin α versus 4/37 to placebo (P = 0.007). 50% of RA responded to epoetin α versus 5.9% to placebo (P = 0.0072), RAS 37.5% v 18.2% (P = 0.6) and RAEB 16.7% v 11.1% (P = 1.00). 60% of non-pretransfused patients responded to epoetin α (Hb 8.35 ± 0.73 to 10.07 ± 1.87 g/dl), whereas a slight decrease was observed in the placebo group (8.4 ± 0.66 to 8.19 ± 0.92 g/dl) (P = 0.0004). Percentage of transfused patients was similar in both arms. Basal erythropoietin (Epo) serum levels > 200 mU/l predicted for a non-response. At week 4 sTfR levels were increased > 50% in responders (P = 0.013), whereas an increase < 18% predicted for non-response (P = 0.006). Leucocyte and platelet counts were not influenced by epoetin α treatment. Adverse events occurred in 31.8% of the rHuEpo-treated versus 42.9% of the placebo-treated patients (P = 0.2), and seven patients did not complete the course. In conclusion, rHuEpo was effective in the treatment of low-risk MDS. RA subtype, no transfusions prior to rHuEpo therapy, and low basal Epo levels were associated with higher probability of response. Soluble transferrin receptor level at the fourth week was an early predictor of response.     

Transfusion thresholds in common elective surgical procedures in Finland

Background and Objectives: Transfusion practices and thresholds in common elective surgical procedures were investigated in a nationwide multicenter survey in Finland. Materials and Methods: The records of 764 total hip replacement (THR), 397 total knee replacement (TKR) and 343 transurethral resection of the prostate (TURP) patients were reviewed by four anesthesiologists. Results: The allogeneic red cell (RBC) transfusion rates in THR, TKR and TURP operations were 92, 84 and 18%, respectively. In THR and TKR, 74% of patients who lost 20% or less of their blood volume during hospitalization were transfused with RBCs. Postoperatively, the median pretransfusion hemoglobin values were 9.6 g/dl in orthopedic operations and 10.7 g/dl in TURP. In some hospitals, the median transfusion threshold in TURP patients was as high as 11.2 g/dl. Conclusion: The transfusion thresholds in all operations were liberal compared to recent international recommendations. Inappropriate thresholds were reflected in the high transfusion rates. This study accentuates the need for continuous discussion and educational measures to find optimal indications for transfusion in surgery, and to rationalize the transfusion policy in Finland.     

Prevalence,severity and correlates of fatigue in newly diagnosed patients with myelodysplastic syndromes

The primary objective of this study was to investigate factors associated with fatigue severity in newly diagnosed patients with higher‐risk myelodysplastic syndromes (MDS). The secondary objectives were to assess symptom prevalence and to examine the relationships between fatigue, quality of life (QoL) and overall symptom burden in these patients. The analyses were conducted in 280 higher‐risk MDS patients. Pre‐treatment patient‐reported fatigue was evaluated with the Functional Assessment of Chronic Illness Therapy (FACIT)‐Fatigue scale and QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30). Female gender (P = 0·018), poor performance status (i.e., ECOG of 2–4) (P < 0·001) and lower levels of haemoglobin (Hb) (P = 0·026) were independently associated with higher fatigue severity. The three most prevalent symptoms were as follows: fatigue (92%), dyspnoea (63%) and pain (55%). Patients with higher levels of fatigue also had greater overall symptom burdens. The mean global QoL scores of patients with the highest versus those with the lowest levels of fatigue were 29·2 [standard deviation (SD), 18·3] and 69·0 (SD, 18·8), respectively and this difference was four times the magnitude of a clinically meaningful difference. Patient‐reported fatigue severity revealed the effects of disease burden on overall QoL more accurately than did degree of anaemia. Special attention should be given to the female patients in the management of fatigue.