Background
Many people diagnosed with haematological malignancies experience anaemia, and red blood cell (RBC) transfusion plays an essential supportive role in their management. Different strategies ...have been developed for RBC transfusions. A restrictive transfusion strategy seeks to maintain a lower haemoglobin level (usually between 70 g/L to 90 g/L) with a trigger for transfusion when the haemoglobin drops below 70 g/L), whereas a liberal transfusion strategy aims to maintain a higher haemoglobin (usually between 100 g/L to 120 g/L, with a threshold for transfusion when haemoglobin drops below 100 g/L). In people undergoing surgery or who have been admitted to intensive care a restrictive transfusion strategy has been shown to be safe and in some cases safer than a liberal transfusion strategy. However, it is not known whether it is safe in people with haematological malignancies.
Objectives
To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT).
Search methods
We searched for randomised controlled trials (RCTs) and non‐randomised trials (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 6), and 10 other databases (including four trial registries) to 15 June 2016. We also searched grey literature and contacted experts in transfusion for additional trials. There was no restriction on language, date or publication status.
Selection criteria
We included RCTs and prospective NRS that evaluated a restrictive compared with a liberal RBC transfusion strategy in children or adults with malignant haematological disorders or undergoing HSCT.
Data collection and analysis
We used the standard methodological procedures expected by Cochrane.
Main results
We identified six studies eligible for inclusion in this review; five RCTs and one NRS. Three completed RCTs (156 participants), one completed NRS (84 participants), and two ongoing RCTs. We identified one additional RCT awaiting classification. The completed studies were conducted between 1997 and 2015 and had a mean follow‐up from 31 days to 2 years. One study included children receiving a HSCT (six participants), the other three studies only included adults: 218 participants with acute leukaemia receiving chemotherapy, and 16 with a haematological malignancy receiving a HSCT. The restrictive strategies varied from 70 g/L to 90 g/L. The liberal strategies also varied from 80 g/L to 120 g/L.
Based on the GRADE rating methodology the overall quality of the included studies was very low to low across different outcomes. None of the included studies were free from bias for all 'Risk of bias' domains. One of the three RCTs was discontinued early for safety concerns after recruiting only six children, all three participants in the liberal group developed veno‐occlusive disease (VOD).
Evidence from RCTs
A restrictive RBC transfusion policy may make little or no difference to: the number of participants who died within 100 days (two trials, 95 participants (RR: 0.25, 95% CI 0.02 to 2.69, low‐quality evidence); the number of participants who experienced any bleeding (two studies, 149 participants; RR:0.93, 95% CI 0.73 to 1.18, low‐quality evidence), or clinically significant bleeding (two studies, 149 participants, RR: 1.03, 95% CI 0.75 to 1.43, low‐quality evidence); the number of participants who required RBC transfusions (three trials; 155 participants: RR: 0.97, 95% CI 0.90 to 1.05, low‐quality evidence); or the length of hospital stay (restrictive median 35.5 days (interquartile range (IQR): 31.2 to 43.8); liberal 36 days (IQR: 29.2 to 44), low‐quality evidence).
We are uncertain whether the restrictive RBC transfusion strategy: decreases quality of life (one trial, 89 participants, fatigue score: restrictive median 4.8 (IQR 4 to 5.2); liberal median 4.5 (IQR 3.6 to 5) (very low‐quality evidence); or reduces the risk of developing any serious infection (one study, 89 participants, RR: 1.23, 95% CI 0.74 to 2.04, very low‐quality evidence).
A restrictive RBC transfusion policy may reduce the number of RBC transfusions per participant (two trials; 95 participants; mean difference (MD) ‐3.58, 95% CI ‐5.66 to ‐1.49, low‐quality evidence).
Evidence from NRS
We are uncertain whether the restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low‐quality evidence); decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low‐quality evidence); or decreases the number of RBC transfusions (adjusted for age, sex and acute myeloid leukaemia type geometric mean 1.25; 95% CI 1.07 to 1.47 ‐ data analysis performed by the study authors)
No NRS were found that looked at: quality of life; number of participants with any bleeding; serious infection; or length of hospital stay.
No studies were found that looked at: adverse transfusion reactions; arterial or venous thromboembolic events; length of intensive care admission; or readmission to hospital.
Authors' conclusions
Findings from this review were based on four studies and 240 participants.
There is low‐quality evidence that a restrictive RBC transfusion policy reduces the number of RBC transfusions per participant. There is low‐quality evidence that a restrictive RBC transfusion policy has little or no effect on: mortality at 30 to 100 days, bleeding, or hospital stay. This evidence is mainly based on adults with acute leukaemia who are having chemotherapy. Although, the two ongoing studies (530 participants) are due to be completed by January 2018 and will provide additional information for adults with haematological malignancies, we will not be able to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days we would need 1492 participants to have a 80% chance of detecting, as significant at the 5% level, an increase in all‐cause mortality from 3% to 6%. Further RCTs are required in children.
Thromboelastometric evaluation of coagulation might be useful for prediction and management of bleeding after paediatric cardiac surgery. We tested the hypothesis that the use of a ...thromboelastometry-guided algorithm for blood product management reduces blood loss and transfusion requirements.
We studied 78 patients undergoing paediatric cardiac surgery with cardiopulmonary bypass (CPB) for the initial 12 h after operation. Stepwise multiple linear regression was used to develop an algorithm to guide blood product transfusions. Thereafter, we randomly assigned 100 patients to conventional or algorithm-guided blood product management, and assessed bleeding and red cell transfusion requirements.
CPB time, post-bypass rotational thromboelastometry (ROTEM®) EXTEM amplitude at 10 min (A10), and FIBTEM-A10 were independently associated with chest tube drainage volume during the initial 12 h after operation. Discriminative analysis determined cut-off values of 30 mm for EXTEM-A10 and 5 mm for FIBTEM-A10, and estimated optimal intraoperative fresh-frozen plasma and platelet concentrate transfusion volumes. Thromboelastometry-guided post-bypass blood product management significantly reduced postoperative bleeding (9 vs 16 ml kg−1, P<0.001) and packed red cell transfusion requirement (11 vs 23 ml kg−1, P=0.005) at 12 h after surgery, and duration of critical care stay (60 vs 71 h, P=0.014).
Rotational thromboelastometry-guided early haemostatic intervention by rapid intraoperative correction of EXTEM-A10 and FIBTEM-A10 reduced blood loss and red cell transfusion requirements after CPB, and reduced critical care duration in paediatric cardiac surgical patients.
UMIN Clinical Trials Registry UMIN000006832 (December 4, 2011).
BACKGROUND:Liver transplantation in children is often associated with coagulopathy and significant blood loss. Available data are limited. In this observational retrospective study, we assessed ...transfusion practices in pediatric patients undergoing liver transplantation at a single institution over the course of 9 years.
METHODS:Data were retrospectively collected from patient medical records at the Children’s Hospital of Pittsburgh of University of Pittsburgh Medical Center. All patients who underwent liver transplantation from January 2008 to June 2017 were included. Primary and secondary outcomes were volume of red blood cells (RBCs) transfused and mortality, respectively.
RESULTS:From January 2008 to June 2017, there were 278 liver transplants in 271 patients. The number of primary transplants were 259, second retransplants 15, and third retransplants 4. Average age at transplantation was 6.9 years. Biliary atresia, maple syrup urine disease, urea cycle defect, and liver tumor were the leading indications accounting for 66 (23.7%), 45 (16.2%), 24 (8.6%), and 23 (8.3%) of transplants, respectively. Seventy-six cases (27.3%) did not require RBC transfusions. Among those transfused, 181 (89.6%) of the cases required <1 blood volume (BV). The median BV transfused among all cases was 0.21 (range, 0–9; Q1, 0; Q3, 0.45). There is a trend toward higher volume transfusions among infants (median, 0.46 BV) compared to children >12 months of age (0.12 BV). By diagnosis, the group requiring the highest median volume transfusion was patients with total parenteral nutrition–related liver failure (3.41 BV) followed by patients undergoing repeat transplants (0.6 BV). Comparison of primary versus repeat transplants shows a trend toward higher volume transfusions in third transplants (median, 2.71 BV), compared to second transplants (0.43 BV) and primary transplants (0.18 BV). Four of 271 patients (1.5%) died during admission involving liver transplantation. Nine of 271 patients (3.3%) died subsequently. Total mortality was 4.8%.
CONCLUSIONS:In contrast to historically reported trends, evaluation of current transfusion practices reveals that most patients undergoing liver transplantation receive <1 BV of packed RBCs. More than 1 in 4 transplantations require no transfusion at all. Risk factors for greater transfusion need include younger age, total parenteral nutrition–related liver failure, and repeat transplantation.
Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood.
We performed a noninferiority randomized ...controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin Hb threshold < 70 g/L) or liberal (Hb threshold < 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy.
A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group (
< .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units standard deviation, 4.81 units
5.02 units standard deviation, 6.13 units;
= .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, -2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies.
In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.
BACKGROUND
Although patient blood management (PBM) programs clearly reduce transfusion overuse, the relative impact on red blood cell (RBC), plasma, and platelet (PLT) utilization is unclear.
STUDY ...DESIGN AND METHODS
A retrospective analysis of electronic records was conducted at a medium‐sized academic hospital to assess blood utilization for all inpatients admitted during 1‐year periods before (n = 20,531) and after (n = 19,477) PBM efforts began in September 2014. Transfusion guideline compliance and overall utilization were assessed for RBCs, plasma, and PLTs. The primary PBM efforts included education on evidence‐based transfusion guidelines, decision support in the computerized provider order entry system, and distribution of provider‐specific reports showing comparison to peers for guideline compliance. Cost avoidance was determined by two methods (acquisition cost and activity‐based cost), and clinical outcomes were compared during the two periods.
RESULTS
For RBCs, orders outside hospital guidelines decreased (from 23.9% to 17.1%, p < 0.001), and utilization decreased by 12% (p < 0.035). For plasma and PLTs, both orders outside guidelines and utilization changed minimally. Overall cost avoidance was $181,887/year by acquisition cost (and from $582,039 to $873,058/year by activity‐based cost), 93% of which was attributed to reduction in RBC utilization. Length of stay, morbidity, and mortality were unchanged.
CONCLUSIONS
Our findings demonstrate a greater opportunity for reducing RBC compared to plasma and PLT utilization. A properly implemented PBM program has potential to reduce unnecessary transfusions and their associated risk and costs, without compromising clinical outcomes.
BACKGROUND
There have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) ...study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost‐effectiveness ratio, when estimated using patientsʼ age‐specific life expectancy and cost of care during the 30‐day PROPPR trial period.
STUDY DESIGN AND METHODS
International Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments.
RESULTS
The 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained.
CONCLUSION
The 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost‐effective strategy for increasing hemostasis and decreasing trauma deaths.
BACKGROUND
Relationships between red blood cell (RBC) transfusion, circulating cell‐free heme, and clinical outcomes in critically ill transfusion recipients are incompletely understood. The goal of ...this study was to determine whether total plasma heme increases after RBC transfusion and predicts mortality in critically ill patients.
STUDY DESIGN AND METHODS
This was a prospective cohort study of 111 consecutive medical intensive care patients requiring RBC transfusion. Cell‐free heme was measured in RBC units before transfusion and in the patients' plasma before and after transfusion.
RESULTS
Total plasma heme levels increased in response to transfusion, from a median (interquartile range IQR) of 35 (26–76) μmol/L to 47 (35–73) μmol/L (p < 0.001). Posttransfusion total plasma heme was higher in nonsurvivors (54 35–136 μmol/L) versus survivors (44 31–65 μmol/L, p = 0.03). Posttransfusion total plasma heme predicted hospital mortality (odds ratio 95% confidence interval per quartile increase in posttransfusion plasma heme, 1.76 1.17–2.66; p = 0.007). Posttransfusion total plasma heme was not correlated with RBC unit storage duration and weakly correlated with RBC unit cell‐free heme concentration.
CONCLUSIONS
Total plasma heme concentration increases in critically ill patients after RBC transfusion and is independently associated with mortality. This transfusion‐associated increase in total plasma heme is not fully explained by RBC unit storage age or cell‐free heme content. Additional studies are warranted to define mechanisms of transfusion‐related plasma heme accumulation and test prevention strategies.
Highlights • Restrictive and liberal transfusion strategies in oncology patients were compared • Restrictive transfusion strategy is associated with decreased blood utilization • No differences in ...mortality between the two strategies were identified • No differences in morbidity between the two strategies were identified
Abstract Objective The aim of this study was to compare outcomes in patients undergoing cardiac surgery who are aged 60 years or more or less than 60 years after implementation of a restrictive or a ...liberal transfusion strategy. Methods This is a substudy of the Transfusion Requirements After Cardiac Surgery (TRACS) randomized controlled trial. In this subgroup analysis, we separated patients into those aged 60 years or more (elderly) and those aged less than 60 years randomized to a restrictive or a liberal strategy of red blood cell transfusion. The primary outcome was a composite defined as a combination of 30-day all-cause mortality and severe morbidity. Results Of the 502 patients included in the Transfusion Requirements After Cardiac Surgery study, 260 (51.8%) were aged 60 years or more and 242 (48.2%) were aged less than 60 years and were included in this study. The primary end point occurred in 11.9% of patients in the liberal strategy group and 16.8% of patients in the restrictive strategy group ( P = .254) for those aged 60 years or more and in 6.8% of patients in the liberal strategy group and 5.6% of patients in the restrictive strategy group for those aged less than 60 years ( P = .714). However, in the older patients, cardiogenic shock was more frequent in patients in the restrictive transfusion group (12.8% vs 5.2%, P = .031). Thirty-day mortality, acute respiratory distress syndrome, and acute renal injury were similar in the restrictive and liberal transfusion groups in both age groups. Conclusions Although there was no difference between groups regarding the primary outcome, a restrictive transfusion strategy may result in an increased rate of cardiogenic shock in elderly patients undergoing cardiac surgery compared with a more liberal strategy. Cardiovascular risk of anemia may be more harmful than the risk of blood transfusion in older patients.
BACKGROUND
Chronic transfusion in sickle cell disease (SCD) remains the gold standard therapy for stroke prevention and for patients with severe disease despite adequate hydroxyurea treatment. The ...aim of our study was to assess the safety and efficacy of automated red blood cell exchange (aRBX) in patients with SCD previously treated with manual exchange transfusion (MET). Costs related to transfusion and chelation overtime were evaluated.
STUDY DESIGN AND METHODS
Beginning in January 2012, children with SCD who weighed 30 kg or more on MET could switch to aRBX. Clinical, biological, and procedures' data, including costs, were recorded for the last 6 months on MET and compared to those after the first and the second year on aRBX.
RESULTS
Ten patients switched from MET to aRBX at a median age of 11.8 years. After the switch, median hemoglobin S (HbS) increased significantly (33.5% on MET compared to 45% on aRBX; p < 0.001) but remained in the target values for all patients. Median ferritin decreased significantly (663.3 µg/L on MET compared to 126.8 µg/L on aRBX; p < 0.001) and intervals between procedures were significantly longer. The requirements of red blood cells (RBCs)/kg/year were not different on MET (0.88 unit/kg/year) than during the second year on aRBX (1.07 unit/kg/year; p = NS). MET costs were similar compared to aRBX since chelation was stopped in previously treated patients.
CONCLUSION
Erythrocytapheresis reduces iron overload and allows a longer interval between procedures without a higher RBC requirement from the second year on aRBX. The cost did not increase as estimated in our Belgian Health Care System.
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