Impact of red blood cell transfusion on patient’s quality of life: a comprehensive narrative review

Introduction

Red blood cell (RBC) transfusion is a widely used intervention to manage anemia, aiming to relieve symptoms such as fatigue and dyspnea and ultimately improve patients’ quality of life (QoL) (1). However, the true impact of transfusion on QoL remains controversial. While some studies suggest short-term symptomatic relief, others show minimal or inconsistent benefits, especially in terms of long-term or patient-reported outcomes (2). This variability is compounded by differences in transfusion strategies, patient populations, and the lack of standardized QoL assessment tools.

Given the growing emphasis on patient-centered care and the lack of consensus on when and how transfusion meaningfully improves QoL, a focused synthesis of available evidence is needed. This narrative review aims to bridge that gap by critically examining the impact of RBC transfusion on QoL across diverse patient populations—including those undergoing cardiac or hip surgery, patients with sickle cell disease (SCD) or thalassemia, individuals with hematologic malignancies, gastrointestinal (GI) bleeding, postpartum hemorrhage (PPH), and critically-ill patients—who frequently require transfusion support. Unlike prior reviews, this work highlights both short- and long-term QoL outcomes, identifies methodological limitations in current research, and underscores the need for standardized QoL measurement tools.

This review highlights the critical need for standardized, patient-reported QoL measures and longer-term follow-up in transfusion research. By synthesizing current knowledge and identifying key gaps, it provides a foundation for future studies and supports the refinement of transfusion strategies that align more closely with patient-centered outcomes. Ultimately, this review aims to inform both clinical practice and research agendas by clarifying when and for whom RBC transfusion meaningfully improves QoL. We present this article in accordance with the Narrative Review reporting checklist (available at https://aob.amegroups.com/article/view/10.21037/aob-25-8/rc).

Methods

We conducted a literature search in PubMed covering the years 2000 through 2024, limiting results to articles published in English. Case reports and meeting abstracts were excluded, and no meta-analysis or statistical analysis was planned. Since this research involved only a review of published literature, approval from a human research ethics committee was not required. Details of the literature search are provided in Table 1.

Results

Cardiac surgery

According to the National Blood Collection & Utilization Survey (NBCUS), RBC transfusion rates decreased between 2008 and 2011, stabilizing through 2021 (3). However, RBC transfusions associated with cardiac surgery have continued to increase with 34% of patients undergoing such procedures receiving transfusions (4). This increase came despite the publication of transfusion guidelines in cardiac surgery in 2007 (5). In addition, there is a substantial variation in RBC transfusion rates (7.8–92.8%) across centers in the United States for patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass (6). Cardiac surgeries are high-risk procedures that generate the greatest demand for perioperative blood transfusion. These transfusions are often required to correct anemia, blood loss, coagulopathy, and hemodilution resulting from pump priming (7). However, transfusions have been associated with decrease in QoL, increased morbidity and postoperative complications such as prolonged length of stay (LOS), atrial fibrillation, acute renal failure, pneumonia, and stroke (8).

Table 2 summarizes published clinical trials evaluating the impact of RBC transfusions on patients’ QoL following cardiac surgery.

The Transfusion Requirements After Cardiac Surgery (TRACS) study was a prospective, randomized, controlled trial that showed a restrictive transfusion strategy (hematocrit ≥24%) was as safe as a liberal strategy (hematocrit ≥30%) in patients undergoing elective cardiac surgery (9). A restrictive perioperative transfusion strategy was found to be non-inferior to a more liberal approach in terms of 30-day all-cause mortality and severe morbidity, including cardiogenic shock, acute respiratory distress syndrome (ARDS), and acute kidney injury requiring dialysis or hemofiltration. Additionally, the restrictive strategy appeared more favorable, as each extra RBC unit transfused was independently associated with a higher risk of complications or death at 30 days [hazard ratio (HR) 1.2; 95% confidence interval (CI): 1.1–1.4; P=0.002] (9). In a TRACS substudy, investigators analyzed the relationship between RBC transfusion and hospital LOS (10). RBC transfusion (>3 units) was an independent risk factor for increased LOS (HR 2; 95% CI: 1.44–2.79; P<0.001). This finding highlighted the adequacy and benefit of a restrictive transfusion strategy in cardiac surgery.

The Transfusion Indication Threshold Reduction (TITRe2) trial was a multicenter randomized controlled trial conducted to assess postoperative morbidity and costs of a restrictive threshold [hemoglobin (Hgb) <7.5 g/dL] for RBC transfusion, as compared with a liberal threshold (Hgb <9 g/dL), in adult patients undergoing non-emergency cardiac surgery (11). Patients’ health-related QoL (HRQoL) was assessed at 6 weeks and 3 months after surgery using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire. The EQ-5D consists of a descriptive system comprising 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression (16). EQ-5D scores were similar in the two study arms (11). The restrictive strategy did not reduce postoperative morbidity or healthcare costs compared to the liberal strategy (11).

Koch and colleagues conducted a randomized clinical trial to evaluate whether mortality, morbidity, and resource utilization differed in cardiac patients undergoing coronary artery bypass graft surgery or valve procedures (12). Patients were randomized to either a 24% hematocrit transfusion trigger or 28% hematocrit trigger throughout their operative and postoperative in-hospital course. The investigators used the Short Form (SF)-12 as the QoL measure (17). The SF-12 was administered once between 1 and 3 months postoperatively. The study concluded that hematocrit trigger did not affect SF-12 mental or physical component scores between 1 and 3 months (12).

The Transfusion Requirements in Cardiac Surgery (TRICS) III trial is a multicenter, randomized, controlled, noninferiority study that evaluated restrictive versus liberal perioperative transfusion strategies in adults undergoing cardiac surgery with cardiopulmonary bypass and a moderate-to-high predicted risk of mortality (13). Patients were assigned to either a restrictive transfusion threshold (Hgb <7.5 g/dL) or a liberal threshold [Hgb <9.5 g/dL in the operating room or intensive care unit (ICU), or Hgb <8.5 g/dL in the non-ICU ward]. Trial outcomes were assessed by hospital discharge or by day 28, whichever came first. The median duration of mechanical ventilation was 0.38 days in the restrictive group and 0.36 days in the liberal group [odds ratio (OR) =0.94; 95% CI: 0.89–1.00]. The median LOS in the hospital was 8.0 days in the restrictive group and 8.0 days in the liberal group (OR =0.93; 95% CI: 0.88–0.99), and the median ICU stay was 2.1 and 1.9 days (OR =0.89; 95% CI: 0.84–0.94), respectively (13). At 6-month follow-up of the TRICS III trial, there were no significant differences in long-term outcomes between the restrictive and liberal transfusion strategies, including rates of myocardial infarction, stroke, new-onset renal failure with dialysis, hospital readmission, emergency visit, or coronary revascularization (14).

Improving HRQoL has become one of the main objectives of modern healthcare. In addition to improving survival rates, clinical guidelines emphasize that enhancing HRQoL is a crucial objective of cardiac surgery (18). Improving long-term HRQoL after cardiac surgery is recognized as a key research priority by both patients and healthcare professionals.

Although TRICS III trial demonstrated clinical non-inferiority of a restrictive compared to a liberal RBC transfusion strategy, it was uncertain if these findings would still be applicable to long-term HRQoL for patients who underwent cardiac surgery. In a planned sub-study, patients from the Australian cohort of the TRICS III trial were invited to participate (15). The restrictive transfusion strategy used a Hgb threshold of <7.5 g/dL, while the liberal strategy applied thresholds of <9.5 g/dL during surgery and in the ICU, and <8.5 g/dL on the general ward. The primary and secondary outcomes of this sub-study were to assess the non-inferiority of the restrictive strategy compared to the liberal strategy in terms of HRQoL at 12 and 24 months after surgery, respectively. The SF-36v2 was used to measure HRQOL via telephone at 6 monthly intervals from 12 months after surgery until the conclusion of the study period, with a minimum commitment of 24 months. The study concluded that non-inferiority of the restrictive transfusion strategy at 12 months was not established for HRQoL, with results trending in favor of the liberal transfusion approach. Non-inferiority also could not be established at 18 and 24 months. In certain cases, the upper limit of the two-sided 90% confidence interval fell below 0, suggesting lower HRQoL in patients assigned to the restrictive transfusion threshold (15). However, the confidence intervals were wide, highlighting the need for further research to determine whether a restrictive transfusion strategy is inferior to a liberal approach with regard to longer-term HRQoL outcomes.

This review included seven trials (two are subset analyses of major trials) that assessed QoL in 8,708 patients undergoing cardiac surgery. Although transfusion protocols varied, most defined a liberal strategy threshold at 9–9.5 g/dL and a restrictive strategy threshold at 7–8 g/dL. However, several factors contributed to the differences in QoL outcomes across these studies including choice and timing of QoL tool, and patient population and risk factors. One of these factors is the choice of QoL tool which was not the same across all studies. For example, TITRe2 study used the EQ-5D (11), a brief, generic measure that may lack sensitivity to subtle functional or psychosocial differences, while TRICS III sub-study employed the SF-36v2 (13), which covers broader domains and may better detect small but clinically meaningful differences in both physical and mental health over time. Timing of QoL measurement is another factor contributing to differences: Studies such as TITRe2 and Koch et al. (12) measured QoL relatively early (≤3 months), possibly missing late-emerging functional deficits or persistent symptoms such as fatigue or cognitive impairment that could relate to perioperative anemia or delayed recovery. In contrast, the TRICS III sub-study assessed HRQoL up to 24 months, capturing a more comprehensive picture of recovery and long-term well-being. Another source of difference is patient population and risk factors. TRICS III included patients with moderate-to-high predicted mortality risk, a group potentially more vulnerable to the effects of anemia and under-transfusion. Their QoL may be more sensitive to transfusion thresholds which could explain their finding of statistically significant advantage for the liberal transfusion strategy post-surgery, though the clinical relevance of this finding remains unclear. By contrast, other studies had broader or lower-risk populations, possibly explaining the absence of QoL differences in those cohorts.

Orthopedic/hip surgery

Hip replacement surgery is a common procedure in the elderly and is often accompanied by significant blood loss and anemia, necessitating blood transfusion during the perioperative period (19,20). Patients with hip fracture are frequently anemic, with around 75% exhibiting a postoperative Hgb <10 g/dL (21). Both transfusions and postoperative anemia are associated with increased morbidity, heightened cardiovascular risks, and prolonged hospital stays. Additionally, anemia can contribute to reduced energy levels, impaired rehabilitation, and a diminished QoL for patients undergoing total hip arthroplasty (22). Several studies have evaluated the impact of RBC transfusion on functional outcomes and QoL in patients undergoing orthopedic and hip surgeries.

Table 3 summarizes published clinical trials evaluating the impact of RBC transfusions on patients’ QoL following orthopedic surgery.

Carson et al. conducted the largest randomized trial comparing liberal (Hgb <10 g/dL) and restrictive (symptoms of anemia or Hgb <8 g/dL) transfusion strategies in high-risk patients after hip surgery (23). The study found no significant differences in 60-day mortality or independent walking ability, and no increased risk of myocardial infarction or heart failure with the liberal strategy, suggesting no added functional benefit from liberal transfusion (23).

Furthermore, a randomized controlled trial by Gregersen et al. assessed the impact of different RBC transfusion strategies on overall quality of life (OQoL) and activities of daily living (ADL) in frail elderly patients after hip fracture surgery (24). Patients were randomized to either a restrictive RBC transfusion strategy (Hgb <9.7 g/dL) or a liberal strategy (Hgb <11.3 g/dL) during the first 30 days after surgery. The study found no significant association between OQoL and RBC transfusion strategies at 30 days and 1-year post-surgery. However, ADL recovery was greater in patients following a liberal transfusion strategy compared to a restrictive strategy (24).

Gruber-Baldini et al. conducted a study, part of the randomized clinical trial by Carson et al. (23), to determine whether maintaining a higher transfusion threshold could prevent new or worsening delirium symptoms in hospitalized patients after hip fracture surgery (25). Participants in the liberal transfusion group received one unit of packed RBCs and additional transfusions as needed to maintain Hgb >10 g/dL. In contrast, the restrictive transfusion group received transfusions only if anemia symptoms developed or if Hgb dropped below 8 g/dL. The liberal transfusion group received a median of two blood units, while the restrictive group received none. On the first day after randomization, Hgb levels were 1.4 g/dL higher in the liberal group. However, no significant differences were found between the groups over time in delirium severity (P=0.28) or presence of delirium (P=0.83). These findings suggested that maintaining Hgb concentrations above 10 g/dL through transfusion alone is unlikely to impact delirium severity or incidence in patients with postoperative anemia following hip fracture surgery (25).

Nielsen et al. conducted a randomized trial in hip revision surgery patients comparing restrictive (7.3 g/dL) and liberal (8.9 g/dL) transfusion thresholds. Among 53 patients who completed the Timed Up and Go (TUG) test, the liberal group walked significantly faster (median 30 vs. 36 seconds; P=0.02). However, there were no differences in ambulation milestones or Hgb levels at testing (26).

Gillies et al. conducted a single-center feasibility trial (RESULT-NOF) comparing restrictive (Hgb 7–9 g/dL) and liberal (Hgb 9–11 g/dL) transfusion strategies in patients undergoing surgery for fractured neck of femur, many with cardiovascular disease. Although myocardial injury occurred less often in the liberal group (54% vs. 71%), the difference was not statistically significant. The trial confirmed the feasibility of a larger study focused on cardiac outcomes in this high-risk population (27).

Another prospective study enrolled 186 patients over the age of 65 years undergoing elective unilateral total hip replacement surgery (28). Patients were randomly assigned to a restrictive transfusion group (Hgb levels between 8.0 and 10.0 g/dL) or a liberal transfusion group (Hgb ≥10.0 g/dL). No significant differences were found between the two groups in terms LOS, or incidence of postoperative delirium, myocardial infarction, stroke, pulmonary embolism, and wound infection. The study concluded that a restrictive transfusion strategy may be a safe and effective approach for elderly patients undergoing total hip replacement (28).

Parker and colleagues conducted a study which enrolled 200 patients aged 60 years and older with postoperative Hgb levels between 8.0 and 9.5 g/dL following hip fracture surgery (29). Patients were randomly assigned to either receive a transfusion to raise Hgb to at least 10 g/dL or to forgo transfusion unless clear symptoms of anemia developed. Patients were followed for 1 year, and no statistically significant differences were observed between the two groups in terms of mortality, hospital stay, recovery of mobility, or complications. These findings supported the safety of lowering the transfusion threshold to 8.0 g/dL for this patient population (29).

In a randomized trial of 120 elderly, cognitively intact hip fracture patients, liberal (Hgb ≥10 g/dL) and restrictive (Hgb ≥8 g/dL) transfusion strategies were compared (30). Although the liberal group received more transfusions, there were no significant differences in postoperative mobility or hospital LOS. However, the liberal group experienced fewer cardiovascular complications (2% vs. 10%) and lower mortality (0% vs. 8%), raising concerns about the safety of restrictive thresholds in high-risk elderly patients (30).

The large FOCUS trial by Carson et al. (23) found no differences in mortality, ambulation, or complications between liberal and restrictive strategies, challenging the belief that higher Hgb levels improve recovery or cardiac outcomes. Similarly, the substudy by Gruber-Baldini (25) found no reduction in postoperative delirium with liberal transfusion. In contrast, Gregersen et al. (24) observed better ADL recovery with liberal transfusion in frail elderly patients, despite no change in overall QoL, possibly due to the use of more sensitive functional metrics. Nielsen et al. (26) reported faster TUG test performance with liberal transfusion, but without broader functional or Hgb differences, casting doubt on the clinical significance of the finding. Several factors likely contributed to the heterogeneous outcomes across studies such as patient risk profile, Hgb thresholds and transfusion practices, QoL tools used, and sample size.

Taken together, the evidence suggests that restrictive transfusion strategies (typically with thresholds around 8 g/dL) are safe and appropriate for most elderly patients undergoing orthopedic surgery, including those with cardiovascular comorbidities. Liberal transfusion may offer modest benefits in select high-risk subgroups—particularly those with frailty, limited functional reserve, or high baseline cardiovascular risk—but these benefits are inconsistent and not consistently captured in broad QoL measures. Future research should focus on stratifying patients by functional vulnerability, using standardized QoL measures, and evaluating long-term trajectories in mobility and independence.

Hemoglobinopathies—thalassemia/SCD

Thalassemia and SCD are prevalent hemoglobinopathies, affecting globally around 300,000–400,000 new children annually (31). RBC transfusion therapy is a cornerstone in managing this patient population, significantly impacting their QoL.

Thalassemia is characterized by inadequate alpha and beta Hgb chain synthesis, leading to chronic anemia. Regular RBC transfusions form a pivotal aspect of management, classifying patients into transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) (32). Transfusion therapy significantly influences the QoL among thalassemia patients across multiple domains, encompassing physical, mental, and social well-being (33). TDT patients exhibit heightened levels of moderate to severe impairment, including pain, health alterations, social support issues, and overall QoL, relative to NTDT patients (34). A meta-analysis demonstrated that individuals with TDT exhibited poorer physical, mental, and overall QoL (35). Within the TDT subgroup, those with HgbE beta-thalassemia displayed inferior psychological, emotional, and social QoL compared to beta-thalassemia major patients (36). Additionally, a separate study highlighted that male patients experienced more significant bodily discomfort and physical summary reflected in higher SF-36 scores compared to their female counterparts (34). The impact on QoL begins during pediatric stages and correlates with various factors including parental education, employment status, income level, age, gender, age of blood transfusion initiation, frequency of blood transfusions, pretransfusion Hgb levels, nutritional status, presence of comorbidities and social support level by family and community (37,38).

Although RBC transfusions are essential to manage anemia and prevent complications in TDT, the benefits of transfusion therapy must be weighed against the risks of iron overload and the need for iron chelation therapy, which can further impact QoL. Complications arising from blood transfusions exacerbate the QoL in TDT patients. Iron overload represents a predominant concern, potentially leading to conditions like cirrhosis, cardiac dysfunction, and endocrine disorders (39). A study highlighted that 70% of patients experienced a “moderate” to “extremely high” iron burden due to transfusions, with 81% reporting iron overload and 42% experiencing compromised social lives. Despite temporary improvements in HRQoL post-transfusion, patients continued to face depression, anxiety, and significant economic burdens (40). Furthermore, TDT patients face an elevated risk of transfusion-transmitted infections, including Hepatitis B (0.3–5.7%), Hepatitis C (4.87%), and HIV (1.39%) and RBC alloimmunizations (41,42).

For TDT, the consensus is to maintain a pretransfusion Hgb level of 9–10 g/dL and a post-transfusion level of 13–14 g/dL. This approach suppresses ineffective erythropoiesis, minimizes anemia-related symptoms, and reduces the risk of cardiac complications, while balancing the risk of iron overload. In NTDT, the goal is to avoid chronic severe anemia (Hgb <10 g/dL), but transfusion decisions must also consider the cumulative risk of iron overload (43).

SCD is characterized by the aberrant sickling and decreased pliability of RBCs, culminating in vaso-occlusive crises, hemolytic crises, chronic anemia, and intense pain episodes (44). For SCD patients, RBC transfusions serve as a therapeutic modality to mitigate end-organ damage and avert life-threatening complications such as acute aplastic crises or strokes in pediatric populations (45).

The Silent Cerebral Infarct Transfusion (SIT) trial found that regular blood transfusion therapy significantly reduced the risk of recurrence of cerebral infarcts in children with sickle cell anemia by 58% (46). In addition, the incidence of pain events and acute chest syndrome decreased in children who received transfusion therapy compared to those who did not. Children undergoing transfusion therapy exhibit notably higher self-reported QoL scores in pain-related domains and experience fewer concerns regarding SCD-related complications compared to those not undergoing transfusions (47). Studies have shown that regular blood transfusion therapy aimed at preventing cerebral infarct recurrence yielded improvements in various HRQoL aspects, with parents noting enhanced physical health functioning and overall better health in their children compared to those who did not receive transfusion therapy (48). However, the association of regular transfusion therapy with better HRQL is inconsistent across studies, with some indicating worse HRQL compared to alternative treatments such as hydroxyurea (47,49). Moreover, individuals receiving more than two transfusions may experience diminished QoL, such as anxiety, depression, and activity restriction, among other indicators (50,51). Beyond medical complexities, individuals with SCD grapple with psychosocial challenges such as mental disorders, pain crises, sleep disturbances, interpersonal issues, substance use, stigma, and workplace discrimination (52).

Multiple studies demonstrate that lower Hgb levels in SCD are associated with increased risk of kidney disease, stroke, pulmonary hypertension, and mortality. A meta-analysis found that each 1 g/dL increase in Hgb was associated with a 41–64% reduction in risk for these complications (53). The American Society of Hematology (ASH) guidelines highlight that Hgb levels below approximately 8.5 g/dL are associated with increased risk of acute cerebrovascular events, and that raising Hgb to around 10 g/dL improves oxygen delivery without exceeding the threshold where viscosity impairs perfusion (54).

Chronically transfused pediatric SCD patients demonstrated comparable levels of liver iron deposition but reduced cardiac overload compared to non-SCD patients receiving chronic transfusions (55). However, recipient variability and comorbidities remain influential, as children with SCD who receive transfusions and have underlying liver fibrosis or inflammation exhibit elevated liver iron overload (56).

A higher incidence of alloimmunization is observed in SCD patients compared to other patient cohorts. However, even in chronically and episodically transfused children with SCD, alloimmunization prevalence remains considerable, ranging from 7% to 29% (57). Reported risk factors include patient age, age at first transfusion, recipient inflammatory status during transfusion, and the age of RBC units (58). In ABO/Rh-matched donor-recipient pairs, alloimmunization rates range from 18% to 75% in SCD and 2.8% to 30% in thalassemia (59,60). Delayed hemolytic transfusion reactions (DHTRs) are common in SCD, occurring in 4% to 11% of patients transfused with blood that tested as compatible (61).

Iron chelation therapy is essential in the management of TDT and SCD to prevent iron overload, which can cause irreversible organ damage. The primary goal is to limit iron accumulation and subsequent organ damage, thereby improving QoL, reducing clinical complications, and enhancing overall survival (62). In SCD, iron overload develops more slowly than in thalassemia, but chelation is still indicated after transfusion of 10–20 units or when serum ferritin exceeds 1,000 ng/mL or liver iron is >3.5 mg/g (63). Early initiation and sustained adherence to chelation therapy are associated with improved event-free and overall survival in both thalassemia and SCD (62,64).

Transfusion triggers in SCD and TDT should be used as a guide, but transfusion decisions must be individualized, considering the patient’s clinical status, symptoms, and risk of complications. The benefits of transfusion include symptom relief, prevention of complications (notably stroke and acute chest syndrome), improved QoL, and stabilization of acute conditions (44). On the other hand, transfusion carries significant risks, including iron overload, alloimmunization, acute and DHTRs, cardiopulmonary complications among other side effects (65).

In conclusion, RBC transfusion therapy plays a crucial role in improving QoL outcomes in patients with thalassemia and SCD by ameliorating symptoms of anemia and enhancing overall physical and emotional well-being. However, optimizing QoL outcomes requires a multidisciplinary approach that addresses not only medical management but also psychosocial support and adherence to therapeutic regimens.

Hematological malignancies

The impact of RBC transfusion on QoL has been extensively studied, with varying results depending on the patient population and specific outcomes measured. Accumulated clinical evidence has demonstrated that liberal transfusion strategies (Hgb 9 and 10 g/dL) generally do not improve clinical outcomes. Therefore, restrictive transfusion approaches (Hgb 7 or 8 g/dL) have been adopted to reduce unnecessary transfusion and minimize transfusion-associated risks. Recent international RBC transfusion guidelines also recommend considering a restrictive transfusion strategy when Hgb is <7 g/dL in hemodynamically stable hospitalized patients (66). Most patients with hematological malignancies encounter anemia during their clinical course, requiring RBC transfusion for supportive management (67). There is limited data on the clinical practice of RBC transfusion in patients with hematological malignancies. In a Cochrane analysis comparing restrictive versus liberal RBC transfusion strategy in patients with myelodysplastic syndrome (MDS), aplastic anemia, and congenital bone marrow failure, the authors concluded that there is a lack of evidence to support a specific transfusion strategy (68).

QoL in hematological malignancy patients can be affected by physical symptoms such as fatigue and anemia-related symptoms of decreased oxygen delivery manifesting as dyspnea on minimal exertion. A randomized feasibility trial in patients with MDS assessed QoL outcomes with a restrictive transfusion threshold (8 g/dL, to maintain Hgb 8.5–10 g/dL) versus a liberal transfusion threshold (10.5 g/dL, to maintain Hgb 11–12.5 g/dL) in the outpatient setting showing higher compliance to liberal transfusion threshold arm (99% with 95% CI: 95–100%) vs. restricted arm (86% with 95% CI: 75–94%) and improved QoL domain in the liberal arm on exploratory analysis (69). Another randomized trial investigating liberal (9 g/dL) versus restrictive (7 g/dL) RBC transfusion thresholds in patients undergoing hematopoietic stem cell transplantation (HCT) enrolled 300 patients with different hematologic malignancies. The QoL scores at days 7, 14, 28, and 60 were comparable between the two trial arms. Although QoL scores were higher by day 100 in the restrictive group, investigators determined that the difference was neither clinically nor statistically significant (70).

The RETRO (Red Cells in Outpatients Transfusion Outcomes) study is a prospective observational study that estimated the effect of RBC transfusion on functional status and QoL in patients with ≥50 years with a benign or malignant hematology diagnosis (71). The study enrolled 221 participants and measured six-minute walk test distance along with fatigue- and dyspnea-related QoL scores before and one week after RBC transfusion. Results showed modest but clinically meaningful improvements in walk test performance and fatigue scores, while dyspnea scores showed no significant change. In multiple linear regression analysis, patients with Hgb levels of 8 g/dL or higher one week after transfusion, had not recently undergone cancer treatment, and were not hospitalized during the study exhibited clinically significant improvements in mean walk test distance (71). A study by Bruhn et al. aimed to characterize the fatigue patterns over time after transfusion by including additional fatigue scores from RETRO participants at timepoints three days after transfusion and up to 28 days after transfusion (72). The study demonstrated that RBC transfusion leads to early and sustained improvements in fatigue-related QoL in older outpatients with hematologic disorders. Significant improvements in fatigue were observed in the first few days post-transfusion and were sustained up to 4 weeks (72).

Conversely, a study by Buckstein et al. highlighted the burden of RBC transfusions in patients with lower-risk MDS and ring sideroblasts, associating higher transfusion density with greater mortality, hospitalization, and inferior HRQoL (73).

A feasibility randomized trial in acute leukemia patients with the primary outcome being the feasibility of conducting a larger trial and secondary outcomes were fatigue, bleeding, and a number of RBC and platelets transfused was conducted. The study established the feasibility of a larger trial and showed no significant difference in bleeding events or neutropenic fever between restrictive (trigger 7 g/dL) versus high Hgb trigger (8 g/dL) (74). Recently published Association for the Advancement of Blood & Biotherapies (AABB) international RBC guidelines also provided conditional recommendations with low certainty evidence to transfuse at Hgb <7 g/dL in adult hospitalized patients with hematological malignancies (66). A meta-analysis of randomized control trials evaluating RBC transfusion thresholds involving 489 patients with hematological malignancies showed no evidence that QoL and functional outcomes improve with liberal transfusion strategy (75). However, the authors concluded that many studies have substantial limitations, and further sufficiently powered trials are needed. Overall, there is limited evidence to establish a definitive RBC transfusion threshold in patients with hematological malignancies in the outpatient setting. Therefore, the decision to transfuse RBC should be individualized, taking full clinical context, potential transfusion-related adverse events, and patient perspective into account.

Other indications

Chronic kidney disease (CKD)

Anemia is prevalent in most patients with stage 3–5 CKD and significantly contributes to functional impairment, as well as increased mortality in dialysis patients. Anemia in CKD is an independent risk factor for reduced HRQoL (76). RBC transfusion is a treatment option for anemia in patients with CKD, particularly when erythropoiesis-stimulating agents (ESAs) are ineffective or contraindicated. The impact of RBC transfusion on the QoL in CKD patients is multifaceted and must be considered in the context of both benefits and risks.

The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend avoiding RBC transfusions, when possible, to minimize risks such as alloimmunization, particularly in patients eligible for organ transplantation (77). However, in cases where ESA therapy is ineffective or poses significant risks, the benefits of transfusion may outweigh these risks.

GI bleeding

The impact of blood transfusion on the QoL in patients with GI bleeding is influenced by various factors, including transfusion thresholds, patient characteristics, and the management strategies. The American College of Gastroenterology guidelines recommend a restrictive transfusion strategy for patients with upper GI bleeding, with a Hgb threshold of 7 g/dL, as this approach is associated with improved survival and reduced risk of further bleeding and transfusion reactions (78). This guideline supports using a restrictive transfusion strategy to optimize patient outcomes without compromising QoL. Jairath et al. conducted a feasibility study of a multicenter, cluster-randomized trial to assess transfusion thresholds for acute upper GI bleeding (79). The study compared a restrictive transfusion strategy (transfusion at Hgb <8 g/dL) with a liberal strategy (transfusion at Hgb <10 g/dL). A total of 936 patients were enrolled; no significant differences were found in clinical outcomes defined as further bleeding or 28-day mortality (79).

In summary, the current evidence suggests that a restrictive transfusion strategy, supported by patient blood management programs, is effective in managing GI bleeding without adversely affecting QoL. This approach minimizes the risks associated with transfusions and optimizes patient outcomes.

PPH

PPH is among the top five causes of maternal mortality globally (80). Postpartum Hgb levels largely influence the decision to administer an RBC transfusion. The most significant subacute clinical feature of obstetric hemorrhage is anemia, with severe fatigue being the most prominent symptom (81). The impact of blood transfusion on QoL in PPH has been explored in several studies, focusing on physical fatigue, HRQoL, and economic considerations.

A randomized non-inferiority trial assessed the impact of RBC transfusion on QoL in acutely anemic women after PPH. The study found that women who received RBC transfusions had a slightly lower mean physical fatigue score at three days postpartum compared to those who did not receive transfusions (0.8 points lower, 95% CI: 0.1–1.5, P=0.02) and at one week postpartum (1.06 points lower, 95% CI: 0.3–1.8, P=0.01) (82). None of the above differences were statistically significant. This suggests that restrictive transfusion policies may be clinically justified to minimize transfusion reactions and costs.

The multicenter Well-being of Obstetric patients in Minimal Blood transfusions (WOMB) trial assessed noninferiority in physical fatigue, measured by validated HRQoL questionnaires, of expectant management compared with RBC transfusion. Results have shown that RBC transfusion leads to only a small, clinically irrelevant improvement in physical fatigue, thus justifying a conservative transfusion strategy (83). A cost-effective analysis based on the WOMB trial indicated that RBC transfusion is more costly than non-intervention, with only a marginal gain in HRQoL (84).

In summary, while RBC transfusion can slightly reduce physical fatigue in the short term, the overall impact on HRQoL is minimal, and the economic burden is higher than non-intervention. Therefore, a restrictive transfusion policy may be justified in managing acute anemia after PPH. Furthermore, early identification of postpartum iron deficiency and prompt initiation of iron therapy can significantly accelerate recovery from anemia.

Critically ill patients

The impact of blood transfusion on QoL in critically ill patients has been a research subject. Walsh et al. conducted a randomized pilot trial that compared restrictive vs. liberal transfusion strategies in 100 critically ill, mechanically ventilated patients (≥55 years old) with anemia (Hgb ≤9 g/dL) (85). Patients were assigned to either a restrictive strategy (Hgb trigger 7 g/dL, target 7.1–9 g/dL) or a liberal strategy (Hgb trigger 9 g/dL, target 9.1–11 g/dL) for up to 14 days or until ICU discharge. There were no significant differences in organ dysfunction, ventilation duration, infections, or cardiovascular events. Mortality at 180 days was lower in the restrictive group when compared to the liberal group (37% vs. 55%), but the difference was not statistically significant. The study showed that a larger trial is feasible and suggested a possible survival benefit with a restrictive strategy (85).

Another randomized trial (HEMOTION) studied liberal (Hgb ≤10 g/dL) vs. restrictive (Hgb ≤7 g/dL) transfusion strategies in 742 critically ill traumatic brain injury (TBI) patients with anemia (86). The results showed no significant difference in unfavorable neurologic outcomes at 6 months between liberal and restrictive transfusion strategies. However, a liberal strategy was associated with better scores on some QoL measures among survivors but did not affect mortality or depression. Venous thromboembolism rates were similar (8.4%), but ARDS was more common in the liberal group when compared to the restrictive group (3.3% vs. 0.8%). Investigators concluded that a liberal transfusion strategy did not significantly improve neurologic outcomes compared to a restrictive strategy in TBI patients.

Strengths and limitations

A key strength of this review lies in its comprehensive scope, encompassing a wide range of patient populations with varying transfusion needs—including surgical, hematologic, obstetric, and critically ill patients. This broad inclusion allows for a nuanced synthesis of the literature and provides valuable insights into the differential impact of RBC transfusion on QoL across diverse clinical contexts. Additionally, the review critically appraises both short-term and long-term outcomes, drawing attention to methodological heterogeneity, the limitations of existing QoL tools, and the inconsistent application of transfusion thresholds.

However, several limitations must be acknowledged. As a narrative review, the methodology is inherently non-systematic, which may introduce selection bias and limit reproducibility. The variability in study designs, transfusion protocols, and QoL assessment tools across the included literature further complicates comparisons and precludes meta-analytic synthesis.

Conclusions

RBC transfusion is a key intervention for managing anemia across various patient populations. The impact of transfusion on QoL is complex. This review suggests that RBC transfusion is more frequently associated with improved QoL in patients managed with restrictive transfusion strategies. However, the decision to transfuse should remain individualized, considering the entire clinical context, potential transfusion-related adverse events, and the patient’s perspective. Our review of literature finds that while RBC transfusion may offer modest short-term improvements in fatigue and function in certain groups, long-term QoL benefits remain uncertain. In surgical patients, restrictive transfusion strategies have shown comparable outcomes to liberal approaches. In chronically transfused populations, such as those with thalassemia or SCD, QoL is influenced by disease severity, transfusion complications, and organ damage, making the relationship complex and context-dependent. Across studies, heterogeneity in design and inconsistent use of QoL tools limit the ability to draw firm conclusions. The review highlights the need for standardized QoL measures and longer-term studies to clarify the true benefit of transfusion on patient-centered outcomes. Optimizing QoL outcomes requires a multidisciplinary approach that extends beyond medical management to include psychosocial support and adherence to therapeutic regimens. By integrating these factors, clinicians can ensure a more patient-centered approach to transfusion decision-making, ultimately enhancing clinical outcomes and overall well-being.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Blood for the series “Patient Blood Management’s Role in Current Healthcare Environment”. The article has undergone external peer review.

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aob.amegroups.com/article/view/10.21037/aob-25-8/rc

Peer Review File: Available at https://aob.amegroups.com/article/view/10.21037/aob-25-8/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aob.amegroups.com/article/view/10.21037/aob-25-8/coif). The series “Patient Blood Management’s Role in Current Healthcare Environment” was commissioned by the editorial office without any funding or sponsorship. R.G. served as the unpaid Guest Editor of the series. G.G. reports receiving Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748), but it is not related to this manuscript. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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