Blood transfusion thresholds: a narrative review of the literature and recent guidelines

Introduction

While the decision to transfuse blood products should be guided by the complete clinical picture of the patient, including clinical signs and symptoms, comorbidities, and diagnostic findings, transfusion thresholds utilizing laboratory testing provide valuable points of reference when assessing the hematologic status of patients. Over the years, an emphasis on patient blood management and the growing evidence in this area have driven a change in practice toward more restrictive thresholds whereby blood products are transfused at lower hemoglobin levels and in more coagulopathic states. Overall, this change in practice has resulted in less blood product utilization, which in turn reduces the risks of transfusion-associated adverse events, promotes blood stewardship, and assists in curtailing healthcare costs—all while being largely demonstrated to either improve patient outcomes or show non-inferiority to more liberal transfusion strategies (1-3).

Research on the optimal transfusion parameters, as well as recommendations from professional societies, however, have been inconsistent. As such, transfusion practices amongst institutions have been shown to vary widely (4). Moreover, large, randomized controlled trials (RCTs) evaluating transfusion thresholds have mostly focused on red blood cells (RBCs), while data on platelet, plasma, and cryoprecipitate transfusions has been lacking (5-7). Accordingly, much of the current practice has been guided by expert consensus, and recommendations may not always be rooted in strong evidence.

This narrative review will explore recent literature on transfusion thresholds, with a focus on the more common indications for transfusion. Both research studies and clinical practice guidelines will be reviewed, and the strengths, gaps, and conflicting findings of the currently available evidence will be highlighted. As the urgency of massive transfusion often precludes the use of laboratory testing to guide transfusions, massive transfusion protocols will not be extensively discussed here except where clinical practice guidelines have recommended notable target thresholds in this setting. With the production of a number of RCTs and guidelines on transfusion thresholds observed in the last few years, this review will provide a timely summary of this critical topic. We present this article in accordance with the Narrative Review reporting checklist (available at https://aob.amegroups.com/article/view/10.21037/aob-2026-1-0007/rc).

Methods

We conducted a literature search on selected topics, including RBC, platelet, plasma and cryoprecipitate transfusion, as well as transfusion in neonatal and pediatric groups. Details of the literature search are provided in Table 1, and a search strategy example can be found online at https://cdn.amegroups.cn/static/public/aob-2026-1-0007-1.docx.

RBC transfusion thresholds

Clinical guidelines for the transfusion of RBCs have evolved dramatically over time, favoring restrictive rather than liberal thresholds. Early practices favoring a threshold of at least 10 g/dL began to be challenged in the 1980s, along with growing concerns over transfusion-transmitted infections (8). One of the first and largest studies evaluating transfusion thresholds for RBCs was the Transfusion Requirements in Critical Care (TRICC) trial (9). The TRICC trial demonstrated that a restrictive transfusion strategy (transfusing at a hemoglobin level below 7 g/dL in stable patients) is as effective as a liberal strategy (transfusing at a hemoglobin level below 10 g/dL) in critically ill patients, with no discernible difference in mortality rates. Moreover, patients in the restrictive group received fewer transfusions without an increase in adverse outcomes compared to the liberal group. Subgroup analyses of the TRICC trial subsequently examined outcomes by patient characteristics, including age, illness severity, and the presence of cardiovascular disease. These analyses found consistent results across subgroups, supporting the safety and efficacy of a restrictive transfusion strategy in various patient populations (10).

These seminal findings were followed by RCTs in various other populations, including cardiac surgery, major orthopedic surgery, critical care, acute brain injury, and others (11) (Table 2). Notably, study designs have varied in their definitions of restrictive versus liberal thresholds, with hemoglobin levels ranging from <7–8 g/dL for restrictive thresholds and <8–10 g/dL for liberal ones, rendering direct comparisons difficult. Nevertheless, while many recent studies have generally supported restrictive transfusion strategies, several well-powered trials have also challenged this paradigm. These conflicting findings validate concerns over reducing the decision to transfuse to a single laboratory parameter (22). Instead, caution should be exercised: transfusion guidelines must be interpreted in the context of the individual patient, taking into account the patient’s clinical status, signs and symptoms, and comorbidities. The etiology of anemia is likewise critical to consider, as anemia may be due to various causes, such as acute blood loss, nutritional deficiency, anemia of chronic disease, congenital disorders, hemolysis, and malignancy, and may thus present at varying levels of acuity or be best managed without transfusion support. Still, when considered within the patient’s overall clinical context, transfusion thresholds for RBCs can serve as valuable benchmarks for determining the need for transfusion.

RBC transfusion in critically ill patients

Following the findings of the TRICC trial demonstrating the noninferiority of restrictive transfusion practices for critically ill patients (9), a shift in practice patterns towards adopting these strategies has been observed across intensive care units (ICUs) worldwide (23,24). Recent studies have also continued to evaluate this population with largely consistent results. Lilly et al. performed an observational study of 375,478 episodes of ICU care over 5 years and observed that hemodynamically stable patients transfused above 9 g/dL were significantly less likely to survive their ICU stay than those not transfused (25). While limited in the number of completed trials to evaluate, meta-analyses of RCTs evaluating transfusion thresholds in critically ill populations have also found no significant differences in short-term mortality (26) and potentially reduced in-hospital mortality for patients transfused at lower versus higher thresholds (27).

Subpopulations of critically ill patients have also been studied and have similarly demonstrated either noninferiority or improved outcomes in support of restrictive transfusion practices. For mechanically ventilated critically ill patients older than 54 years, a randomized pilot trial conducted across six ICUs in the United Kingdom found no significant differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications between restrictive (hemoglobin <7 g/dL) versus liberal (hemoglobin <9 g/dL) groups, though mortality at 180 days did trend towards lower mortality with restrictive transfusion practices (28). In a multicenter, parallel-group trial of patients in the ICU with septic shock, Holst et al. showed that patients randomized to receive transfusion at lower transfusion thresholds (hemoglobin <7 g/dL) had similar rates of ischemic events, use of life support, and mortality at 90 days compared to patients randomized to higher thresholds (hemoglobin <9 g/dL) (14). As many prior studies of critically ill patients excluded patients with gastrointestinal bleeding, Villanueva et al. performed an RCT specifically enrolling patients with severe acute upper gastrointestinal bleeding and likewise identified improved outcomes, including survival at 6 weeks and rates of further bleeding, for patients assigned to receive transfusion at lower versus higher thresholds (13).

Nevertheless, not all trials have supported restrictive transfusion practices for critically ill patients. In a single-center, RCT of critically ill oncologic patients with septic shock, mortality rates in the liberal group (hemoglobin <9 g/dL) 90 days after randomization were lower than in the restrictive group (hemoglobin <7 g/dL), countering the prevailing hypothesis (29). For cancer patients requiring intensive care after major abdominal surgery, de Almeida et al. also observed fewer postoperative complications associated with a liberal transfusion strategy compared to a restrictive one in an RCT that included 198 patients (15). These conflicting findings become even more apparent in subpopulations of critically ill patients with cardiac disease, as discussed separately below.

RBC transfusion in cardiac disease

While numerous large clinical trials have demonstrated comparability between restrictive and liberal transfusion strategies, the use of lower thresholds in cardiac disease remains a contentious area. Studies have been performed in the settings of both cardiac surgery and acute coronary syndrome to determine whether higher hemoglobin levels may improve oxygen delivery or unnecessarily provoke unintended consequences such as fluid overload in these susceptible populations. The Transfusion Requirements in Cardiac Surgery (TRICS) III trial, one of the largest randomized trials evaluating transfusion thresholds for cardiac surgery, enrolled over 5,000 patients undergoing cardiac surgery to either restrictive transfusion (hemoglobin <7.5 g/dL) or liberal transfusion (hemoglobin <9.5 g/dL), and found the former to be non-inferior to the latter with respect to mortality from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis (16). These findings may be viewed somewhat in contrast to those of the Transfusion Indication Threshold Reduction (TITRe2) trial, a multicenter, parallel-group trial conducted over 17 centers in the United Kingdom, which similarly randomized 2,007 patients to restrictive (hemoglobin <7.5 g/dL) and liberal (hemoglobin <9 g/dL) groups (1). While the TITRe2 study found a restrictive transfusion threshold to be not superior to a liberal transfusion threshold in reducing postoperative morbidity and health care costs, liberal transfusion did appear to have an advantage in specific secondary outcome measures, including mortality and serious non-infectious, non-ischemic postoperative complications, creating uncertainty about recommending restrictive transfusion (30). Several smaller RCTs have nonetheless demonstrated no significant differences between restrictive and liberal transfusion strategies by various measures, including all-cause mortality, severe post-operative morbidity, bleeding, and coagulation parameters (12,31,32).

For cases of acute coronary syndrome, transfusion threshold studies have likewise demonstrated conflicting findings. An earlier pilot trial of 110 patients with symptomatic coronary artery disease randomized patients to either liberal (hemoglobin <10 g/dL) or restrictive (hemoglobin <8 g/dL) groups and found liberal transfusions to be associated with fewer major cardiac events and death than the restrictive group (33). The Restrictive and Liberal Transfusion Strategies in Patients with Acute Myocardial Infarction (REALITY) randomized trial subsequently performed a similar comparison in 668 patients with myocardial infarction and anemia, finding that a restrictive strategy was non-inferior to a liberal strategy in preventing major adverse cardiovascular events at 30 days (17). Most recently, however, the results of the multicenter Myocardial Ischemia and Transfusion (MINT) trial have again raised concern that patients with acute myocardial infarction may be more optimally treated by using higher transfusion thresholds. In this study, a total of 3,504 patients with myocardial infarction and hemoglobin levels less than 10 g/dL were randomized to either a restrictive (hemoglobin 7–8 g/dL) or liberal (hemoglobin <10 g/dL) transfusion strategy. While a liberal transfusion strategy did not significantly reduce the risk of myocardial infarction or death at 30 days, the lower rates of both observed in the liberal strategy group has prompted concerns over the potential harms of restrictive transfusion in this patient population (18). Given these contradictory observations, the validity of these findings has been called into question, underscoring the need for careful consideration before adopting any practice changes in promoting patient blood management based solely on these studies (34).

RBC transfusion for acute brain injury

Transfusion thresholds for acute brain injury are highlighted here, given the recent surge in large trials published on this topic. This patient population has been specifically evaluated as the optimal hemoglobin levels to prevent brain tissue hypoxia while reducing the risk of complications from blood transfusion are unknown. An earlier randomized clinical trial of 200 patients with closed head injury compared the effects of erythropoietin and two transfusion thresholds (hemoglobin of 7 and 10 g/dL) and found a higher incidence of thromboembolic events in the liberal threshold group, without any improvement in neurologic outcome at 6 months (35). More recently, three large trials evaluating transfusion thresholds in the setting of acute brain injury have been published with somewhat conflicting results. The Hemoglobin Transfusion Threshold in Traumatic Brain Injury Optimization (HEMOTION) trial randomized 742 patients with severe traumatic brain injury and anemia to receive transfusion using a liberal strategy (hemoglobin <10 g/dL) or restrictive strategy (hemoglobin <7 g/dL), and subsequently assessed for unfavorable neurologic outcomes at 6 months using the Glasgow Outcome Scale-Extended in addition to secondary outcomes including mortality, functional independence, quality of life, and depression (19). While the liberal strategy was associated with higher scores on some scales, trial design precluded assessing for noninferiority of restrictive transfusions. Instead, it could only support the conclusion that a liberal strategy did not reduce the risk of an unfavorable neurologic outcome. The Transfusion Strategies in Acute Brain Injured Patients (TRAIN) trial similarly evaluated liberal (hemoglobin <9 g/dL) versus restrictive (hemoglobin <7 g/dL) strategies in 820 patients with acute brain injury, to include traumatic brain injury, aneurysmal subarachnoid hemorrhage, and intracerebral hemorrhage (20). Primary outcome was also measured by the Glasgow Outcome Scale Extended; however, in this study, patients in the liberal transfusion arm were found to be significantly less likely to have an unfavorable neurological outcome as well as a cerebral ischemic event. These findings were further in contrast with those of the Subarachnoid Hemorrhage Red Cell Transfusion Strategies and Outcome (SAHARA) trial, which enrolled 742 patients with aneurysmal subarachnoid hemorrhage and found that a liberal strategy (hemoglobin <10 g/dL) versus a restrictive one (hemoglobin <8 g/dL) did not reduce the risk of an unfavorable neurologic outcome at 12 months as measured by the Rankin scale (21). Between these studies on acute brain injury, the heterogeneity of the subgroups evaluated and the differences in inclusions/exclusion criteria likely contributed to the conflicting conclusions observed as well as those of the meta-analyses that have evaluated them (36-38). Together, these studies demonstrate how the nuances of trial design render it challenging to generalize findings when prescribing RBC transfusion strictly based on laboratory values.

Clinical guidelines overview

Several professional associations have published consensus guidelines on red cell transfusion thresholds. As with the studies on which these recommendations are based, the criteria for restrictive and liberal thresholds vary between guidelines with hemoglobin levels ranging from 7–8 g/dL for restrictive strategies and 9–10 g/dL for liberal ones. Most recommendations continue to favor restrictive strategies, with exceptions in specific clinical situations, and are supported by a grading scale for the quality of evidence. For example, the recently issued American College of Chest Physicians (CHEST) guidelines strongly recommended restrictive RBC transfusions for critically ill patients, including those with acute gastrointestinal bleeding; however, they recommended against restrictive RBC transfusions for critically ill patients with acute coronary syndrome as a conditional recommendation (39). The Association for the Advancement of Blood and Biotherapies (AABB) also provided updated international guidelines in 2023 and included recommendations for both adult and pediatric populations (40). In the AABB guidelines, a restrictive strategy was also favored; however, hemoglobin targets were stratified by clinical condition: 7 g/dL for hospitalized, hemodynamically stable patients, 7.5 g/dL for patients undergoing cardiac surgery, and 8 g/dL for patients undergoing orthopedic surgery or those with preexisting cardiovascular disease. A selection of additional clinical practice guidelines is summarized in Table 3.

Platelet transfusion thresholds

The recently published 2025 AABB guidelines, developed in collaboration with the International Collaboration for Transfusion Medicine Guidelines (ICTMG), represent a major update in platelet transfusion practice (6). They are based on a comprehensive review of randomized trials and observational studies and provide evidence-based recommendations across adult and pediatric populations. The guidelines support a restrictive transfusion strategy, demonstrating that lower platelet thresholds do not increase mortality or bleeding compared to liberal approaches.

Prophylactic platelet transfusion

Prophylactic platelet transfusions are a critical component in the care of patients on chemotherapy, following hematopoietic stem cell transplantation, or before surgeries and invasive procedures (Table 4). Platelet transfusion is strongly recommended for hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia to reduce the risk of spontaneous bleeding when the platelet count is ≤10,000/µL (6). This threshold is increased to 15,000–20,000/µL for patients with additional risk factors for bleeding or for clinically unstable patients (50,51).

There is variability in platelet threshold recommendations for invasive procedures and surgeries due to the lack of strong evidence, which leads to inconsistency of platelet transfusion guidelines (Table 4). Most guidelines agree on a platelet threshold of 10,000–20,000/µL for central venous catheter placement (6,48,49,52). It is worth mentioning that the PACER trial demonstrated that withholding prophylactic platelet transfusions prior to central venous catheter placement in severe thrombocytopenia (10,000–50,000/µL) was non-inferior to prophylactic transfusion regarding bleeding outcomes (52). For patients undergoing major non-neuraxial surgery, most guidelines support a platelet transfusion threshold of 50,000/µL (6,48,49). A platelet count of 100,000/µL has been suggested before neurosurgery or ophthalmic surgery, although evidence is limited and of low quality (49,53). Platelet transfusion is advocated for a platelet count of 20,000–40,000/µL and 80,000/µL for elective diagnostic lumbar puncture and spinal/epidural anesthesia, respectively (49).

Therapeutic platelet transfusion

Minor bleeding

While definitions of major and minor bleeding vary across studies, referencing the World Health Organization (WHO) definitions can be useful to interpreting transfusion thresholds. Minor bleeding (or Grade 1 bleeding) is defined by the WHO as (I) petechiae/purpura that is localized to 1 or 2 dependent sites, or is sparse/non-confluent, or (II) oropharyngeal bleeding or epistaxis of <30-minutes duration. Many minor bleeding episodes resolve spontaneously without sequelae. The British Committee for Standards in Haematology (BCSH) recommends that patients with WHO Grade 1 bleeding and no additional risk factors should be transfused if the platelet count is below 10,000/µL (49). Platelet transfusion may be considered for Grade 2 bleeding (or moderate bleeding defined as clinically evident bleeding that requires medical attention, but is not immediately life-threatening) if the platelet count is below 30,000/µL (49).

Trauma

Low platelet counts on admission and during trauma management have been strongly associated with mortality (54). A meta-analysis of five RCTs (n=1,757 patients) showed improved mortality with a high platelet:RBC ratio as compared to a low platelet:RBC ratio in traumatic bleeding (55). However, evidence is lacking on specific thresholds for platelet transfusion in trauma patients. The BCSH recommends plasma and RBCs in a ratio of 1:1 in major bleeding; platelet transfusion is recommended when the platelet count is below 50,000/µL (56).

Intracerebral hemorrhage

The recommendation to maintain a platelet count above 100,000/µL in patients with central nervous system bleeding is a common practice in clinical settings, although data is limited on the impact of platelet transfusion on overall survival. The high-quality research on platelet transfusion in the context of intracerebral hemorrhage has focused on patients who are on antiplatelet therapy. The randomized controlled PATCH trial on antiplatelet therapy-associated intracranial hemorrhage showed that platelet transfusion was inferior to standard care; platelet transfusion at counts of >100,000/µL was associated with increased 3-month mortality and serious adverse events (57). In addition, a recent meta-analysis involving 577 patients concluded that platelet transfusion did not enhance the prognosis of patients with antiplatelet therapy-associated intracranial hemorrhage (58).

Disseminated intravascular coagulation (DIC)

The mainstay of DIC management is addressing the underlying cause. Platelet transfusion in DIC patients should be considered for patients actively bleeding or at risk for bleeding when the platelet count is below 50,000/µL (59). Prophylactic platelet transfusion is not recommended unless in the setting of high-risk bleeding patients (60). It has been suggested to keep the platelet count above 20,000/µL in DIC patients with acute promyelocytic leukemia, severe sepsis, and pregnancy (59).

Platelet transfusion in specific settings

Immune thrombocytopenia (ITP)

Primary ITP is characterized by a low platelet count due to presence of platelet-specific antibodies (61). Prophylactic platelet transfusion is not recommended in ITP, knowing that the effect of transfusion is limited due to rapid clearance of platelets by circulating antibodies. However, platelet transfusion can be considered prior to high-risk bleeding procedures or surgeries. In bleeding patients, studies have shown that intravenous immunoglobulin, glucocorticoids, and platelet transfusion are effective in increasing the platelet count rapidly when used in combination (62).

Cardiothoracic surgery

Cardiothoracic surgery is a high-risk procedure for blood loss, especially the procedures requiring cardiopulmonary bypass. These procedures can lead to both quantitative and qualitative platelet defects due to factors such as hemodilution, platelet activation, exposure to extracorporeal circulation, and antiplatelet medications. The literature on platelet transfusion in the context of cardiovascular surgery is limited, with most data coming from observational studies. A pooled meta-analysis of nine observational studies involving 101,511 patients concluded that platelet transfusion after cardiac surgery did not significantly affect operative mortality or perioperative complications, including stroke, myocardial infarction, reoperation for bleeding, or infection (63). An RCT involving 28 patients evaluated prophylactic platelet transfusion in individuals undergoing their first cardiopulmonary bypass operation. The results indicated that prophylactic platelet transfusion did not impact clinical outcomes or transfusion requirements. Additionally, thrombocytopenia and transient platelet dysfunction after bypass surgery did not necessitate platelet administration or prophylactic platelet transfusion (64). According to the latest guidelines from the AABB and the ICTMG there are conditional recommendations (with very low certainty evidence) for no platelet transfusion in non-thrombocytopenic patients undergoing cardiovascular surgery in the absence of hemorrhage, including those undergoing cardiopulmonary bypass (6).

Obstetrics

Platelet transfusions in pregnancy and the postpartum period are performed in thrombocytopenic patients experiencing bleeding or undergoing a surgical procedure such as cesarean section. Generally, it is recommended to achieve a platelet count of 50,000 or greater (65). As per British Society of Haematology guidelines, prophylactic platelet transfusion threshold is >50,000/µL prior to major surgical procedure in the general population, and therapeutic platelet transfusion is indicated to maintain platelet count >50,000/µL in the setting of major bleeding (49). However, there is no such specific recommendation for the obstetric population.

Plasma transfusion thresholds

Plasma transfusion has historically been driven by perceived coagulopathy based on abnormalities in laboratory tests such as the prothrombin time (PT), the international normalized ratio (INR), and the partial thromboplastin time (PTT), particularly when multiple coagulation factor deficiencies are present. As plasma is the liquid portion of whole blood, it is also generally advised that when massive hemorrhage is occurring, a balanced ratio of RBC units to plasma units is transfused to replace the whole blood volume being lost. Plasma transfusions are also indicated for patients with certain coagulation factor deficiencies when a recombinant product is not available, as well as the replacement fluid for plasma exchange procedures treating thrombotic thrombocytopenic purpura (66). Plasma transfusion has been used to reverse the effects of vitamin K antagonists in bleeding patients. Current practice advises the use of prothrombin complex concentrates to reverse warfarin effects, as it is considered more expedient than transfusion of plasma and carries less risk for complications (67,68).

While many studies have evaluated the use of plasma transfusion in the setting of massive hemorrhage (69-71), data from large RCTs examining optimal plasma transfusion thresholds continue to be lacking. Accordingly, much of plasma transfusion practice remains focused on correcting an elevated INR, even in the absence of bleeding (72). Basing plasma transfusion on INR levels has been suggested to have created three main assumptions that are widely prevalent: (I) that an elevated PT/INR predicts bleeding tendency during a procedure; (II) that transfusion of plasma will correct a prolonged clotting time test result by raising plasma coagulation factor levels; and (III) that prophylactic transfusion of plasma results in fewer bleeding complications (73). However, there continues to be insufficient evidence to support these assumptions and, in turn, to support the utilization of PT/INR to guide plasma transfusions. In fact, clinical practice guidelines have recommended against prophylactic plasma transfusion for non-bleeding critically ill patients with coagulopathy given the known risks and lack of clear benefit (74-76).

Still, some institutions have adopted INR as a measure to guide plasma transfusions, used alongside clinical assessments (77). However, it is estimated that nearly half of all plasma transfusions occur outside of guidelines (78). Accepted practice generally favors restrictive strategies, and advocates for transfusion of plasma only when clotting tests are abnormally high, and not only minimally elevated, such as an INR >2.0 (79). Patients with an INR <1.7 should only be transfused with plasma when actively bleeding (78,80,81). Attempts to correct an elevated INR before an impending procedure account for one third of all plasma transfusions (82). Unfortunately, using the INR to assess coagulopathy and bleeding risk is not standardized and has been shown to vary widely in practice, especially when attempting to correct a minimally elevated INR (73,78,80,83,84). Donated plasma itself has been shown to have INR values ranging from 0.9 to 1.3, which helps explain why it will only affect a patient’s INR when there is a significant elevation, and why the effect of plasma transfusion on each patient’s INR value reduction can vary (78,85,86).

Typical dosing of plasma to correct coagulopathy has been suggested to be 15 mL/kg, which equates to about 4 units for an adult. Many studies have shown that patients transfused prophylactically to correct an elevated INR are being given 1–2 units of plasma, meaning that they are being exposed to plasma units needlessly by being underdosed (87,88). Since many transfusions are potentially not clinically warranted, advocating for transfusing more plasma units to patients may be more harmful than beneficial, especially for patients with minimal coagulopathy. In fact, when prophylactic plasma is transfused, it has been shown that patients tend to require more RBC transfusions, have a longer hospital length of stay, higher morbidity, increased incidence of multiorgan failure, and an increased incidence of acute respiratory distress syndrome (79,89,90).

Viscoelastic testing (VET) is also being increasingly used to guide plasma transfusion, particularly in the perioperative setting. Several types of VET analyzers are currently available, including the ROTEM sigma, TEG6s, and the Quantra Hemostasis System. These tests evaluate coagulopathy by testing whole blood samples, providing an overall picture of clot formation and stability. In turn, deficiencies in coagulation factors and platelets may be identified to inform transfusion decisions. Studies have evaluated the use of VET in various clinical settings, particularly where high-volume transfusion is frequently needed, such as in liver disease and trauma (83,91-93). Chow et al. found that lower R-time thresholds on TEG analyzers, such as an R-time >4.45 minutes, should be used to guide plasma transfusion in hemorrhaging multi-trauma patients (93). The use of VET to guide prophylactic plasma transfusion in non-bleeding patients, however, has not been well established and requires further study.

Cryoprecipitate transfusion thresholds

Cryoprecipitate is a source of fibrinogen, factors VIII and XIII, and von Willebrand factor, and is now most commonly used for hemostasis management in the setting of a fibrinogen deficiency (66). Cryoprecipitate can also be used as a second-line therapy when recombinant factor preparations are unavailable. Fibrinogen measurement is the standard laboratory parameter used to determine the need for cryoprecipitate transfusion. Fibrinogen is critical to clot formation and strength due to its combined effects with platelet glycoproteins and other coagulation factors to create the fibrin monomer net that is the backbone of an effective clot. Since fibrinogen circulates at the highest concentration of coagulation factors in normal plasma, fibrinogen replacement is an essential component after major injury or bleeding. Hemodilution from volume replacement and consumption due to clot formation are the most common causes of hypofibrinogenemia. In the United States, a single unit of cryoprecipitate is required to contain a minimum of 150 mg of fibrinogen. It should be expected to raise plasma fibrinogen levels by about 50–75 mg, as only 50–60% of the transfused fibrinogen is recovered (66). Pathogen-reduced products and fibrinogen concentrate preparations, which carry a lower risk of infectious disease, are also available and may be used for fibrinogen replacement.

Determining what threshold to start fibrinogen replacement has historically been difficult, as earlier studies were based on patients with congenital fibrinogen deficiency and defined a hemostatic threshold of 100 mg/dL (94,95). However, concerns have been raised that this transfusion threshold does not adequately address hypofibrinogenemia due to consumption as is seen with bleeding and in DIC (96). One in vitro study utilizing a model of dilutional coagulopathy compared clot characteristics using VET to predict that a fibrinogen concentration of 200 mg/dL was necessary to optimize clot formation (97). In another observational study of patients who underwent cardiac surgery with cardiopulmonary bypass, Karkouti et al. found that the probability of requiring large-volume red cell transfusion increased when fibrinogen levels fell below 200 mg/dL (98). Similarly, Ranucci et al. reported an association between severe postoperative bleeding and fibrinogen levels lower than 220 mg/dL in patients undergoing cardiac surgery (99). While these findings support a higher threshold for fibrinogen replacement, the lack of trials evaluating this practice has led some to question whether the associated transfusion risks and added costs can be justified (100).

Recent RCTs have assessed fibrinogen replacement in various settings of anticipated or active bleeding, however, largely either with fibrinogen concentrate only or as a comparison to cryoprecipitate. Studies have been performed in the setting of postpartum hemorrhage (101), liver transplantation (102), cardiac surgery (103-105), trauma (106,107), and urologic procedures (108), however, many of these studies were designed to evaluate a set empiric dose of fibrinogen concentrate, rather than goal-directed administration to achieve a target level. Other studies have used a pre-specified fibrinogen threshold to administer cryoprecipitate or fibrinogen concentrate; however, they compared this to a cohort that did not receive any fibrinogen replacement (102,105), thus limiting the conclusions that can be made on what the optimal levels should be. A recent prospective, single-center, observational study evaluating patients undergoing plasma exchange compared fibrinogen thresholds of 80 and 100 mg/dL and found no increased risk of bleeding unless patients were on anticoagulant therapy (109). Some studies have used VET-specific thresholds to guide replacement (110). For example, Collins et al. enrolled 55 women with postpartum hemorrhage who received fibrinogen concentrate or placebo if Fibtem measurements on ROTEM analyzers were below 15 mm (corresponding to fibrinogen approximately 300 mg/dL) and found no difference in the number of allogeneic blood products transfused (111).

While there continues to be a lack of RCTs evaluating optimal thresholds for fibrinogen replacement, many professional guidelines have gradually moved towards recommending higher thresholds over time, particularly for bleeding patients (112). Though largely based on consensus and expert opinions, these recommendations can provide interim guidance until these thresholds can be further studied. Recommendations vary across organizations and should be applied while accounting for the patient’s clinical condition and other coagulation parameters. For example, guidelines from the European Society of Intensive Care Medicine suggested a fibrinogen level of 150 mg/dL should be maintained for critically ill patients with non-massive bleeding after cardiac surgery; however, they made no recommendations for all other critically ill patients with non-massive bleeding, both statements being based on low-quality evidence (45). For patients with a significant bleeding risk prior to a procedure, the British Society of Haematology guidelines note that a starting dose of two five-donor pools of cryoprecipitate can be considered if fibrinogen is less than 100 mg/dL (113). Additional clinical practice guidelines are summarized in Table 5.

Neonatal and pediatric transfusion thresholds

RBCs

Transfusion thresholds for neonatal patients are primarily based on studies of very low birth weight and preterm neonates (116-121). These neonates often develop anemia of prematurity, leading to impaired oxygen supply and potential brain injury (117). “Top-up” transfusions are commonly used to maintain hemoglobin levels or address other signs of anemia. According to the BCSH Guidelines, hemoglobin thresholds for preterm neonates vary with postnatal age and whether the patient is ventilated or receiving supplemental oxygen (122).

Studies have examined the effects of restrictive versus liberal hemoglobin thresholds in premature neonates. The Effects of Liberal vs. Restrictive Transfusion Thresholds on Survival and Neurocognitive Outcomes (ETTNO) trial evaluated extremely low-birth-weight infants. It found that liberal RBC transfusion thresholds did not significantly reduce the composite risk of death or neurodevelopmental disability at 24 months of corrected age compared to restricted thresholds. Specifically, there were no statistically significant differences between liberal and restrictive groups regarding cognitive deficits, cerebral palsy, or severe visual and hearing impairment (117). In the Premature Infants in Need of Transfusion (PINT) study, patients were randomized to low or high hemoglobin thresholds, with primary outcomes of death before discharge or survival with severe retinopathy, bronchopulmonary dysplasia, or brain injury (119). The Transfusion of Prematures (TOP) study randomized patients to similar thresholds, assessing death or survival with cognitive delay, cerebral palsy, or hearing/vision loss (118). Both studies found no benefit of higher hemoglobin thresholds compared with restrictive thresholds. The Iowa study also compared low-birth-weight infants using restrictive and liberal thresholds, finding no significant differences in survival or clinical outcomes. However, infants in the restrictive group had more frequent apnea, potentially affecting neurodevelopment (120). Overall, the findings from these studies suggest that lower hemoglobin thresholds do not adversely affect long-term brain development in premature neonates (117-120).

For pediatric patients, studies on hemoglobin thresholds have been conducted in critically ill, cardiac, hematological, oncological, and surgical populations, as these groups receive the most transfusions (123-132). The suggested thresholds for these conditions are listed in Table 6.

The Transfusion Requirements in Pediatric Intensive Care Units (TRIPICU) study, a large RCT, evaluated hemoglobin thresholds in pediatric ICU patients, comparing restrictive and liberal transfusion thresholds. The study found that the restrictive threshold significantly reduced RBC transfusions without increasing adverse outcomes, such as organ dysfunction (123). Subgroup analyses showed no significant differences in organ dysfunction for post-cardiac surgery patients and septic patients, and a reduced length of stay for general surgery patients with the restrictive threshold (124-126).

Platelets

In neonates, platelet transfusions are used for thrombocytopenia with active bleeding. For preterm neonates, transfusions are recommended for severe thrombocytopenia (<25,000/µL) (136). The PlaNeT-1 study found that 91% of neonates with a platelet count of <20,000/µL did not develop major hemorrhage (137). A retrospective study of 1,569 neonates found no significant association between thrombocytopenia severity and intraventricular hemorrhage or mortality, suggesting that other factors contribute to hemorrhage risk (138). Additional neonatal platelet thresholds include <50,000/µL for neonates with bleeding or coagulopathy, or before surgery, and <100,000/µL for neonates with significant bleeding or requiring major surgery (122).

Studies comparing restrictive and liberal platelet transfusion thresholds in preterm infants have shown that restrictive thresholds result in fewer transfusions without increasing intraventricular hemorrhage or death rates (139). The PlaNeT-2 study found that infants assigned to higher thresholds had higher rates of death and major bleeding (140). A follow-up trial (PlaNeT-2/MATISSE) showed that higher thresholds led to increased death or significant neurodevelopmental impairment at two years. In this study, 50% of infants in the higher threshold group met this composite primary outcome compared to 30% in the restrictive group. The higher rates of impairment were primarily driven by global developmental delay (22% vs. 14%) and cerebral palsy (13% vs. 10%) (141). Additionally, the Preterm Erythropoietin Neuroprotection (PENUT) trial suggested that platelet transfusions in extremely premature infants might be linked to increased risks of death or severe neurodevelopmental impairment at 2 years (142). These findings strongly support the safety and benefit of lower prophylactic thresholds to avoid the long-term developmental harm associated with liberal transfusion thresholds.

For pediatric populations, several studies have evaluated platelet transfusions in critically ill, hematological, oncological, and cardiac surgery settings (122,129,130,143,144). The BCSH Guidelines have also issued suggested transfusion thresholds, to include <10,000/µL for stable patients, <20,000/µL for patients with sepsis and other risk factors for bleeding, <40,000/µL before lumbar puncture, <50,000/µL for moderate bleeding, and <75–100,000/µL for major hemorrhage or surgery at critical sites (122).

Plasma and cryoprecipitate

Because of uncertainties regarding the use of plasma and cryoprecipitate in neonates, there are no established transfusion thresholds, and products are administered according to clinical need to address bleeding or the risk of bleeding. Plasma may be administered for purpura fulminans secondary to severe hereditary deficiency of protein C or S, when concentrates are unavailable (122).

In pediatric patients, plasma and cryoprecipitate are used prophylactically or therapeutically for bleeding. Cryoprecipitate is commonly given for DIC with bleeding, post-cardiac surgery bleeding, and major hemorrhage. Cryoprecipitate thresholds are likewise not well established; however, fibrinogen thresholds of 100 mg/dL are recommended for inherited hypofibrinogenemia and for surgeries at risk of bleeding. Plasma may be beneficial for DIC, with specific lab values indicating significant bleeding. However, plasma use for minor PT/INR corrections before surgery is inappropriate (122). In liver disease patients, a clinical judgment approach has been suggested for plasma and cryoprecipitate transfusions, reducing plasma use without affecting outcomes (145).

Conclusions

While clinical guidelines have supported the use of transfusion thresholds in different clinical settings, the levels of evidence to support these recommendations have varied in strength. While thresholds will vary according to the patient population being considered, studies of similar populations have yielded differing conclusions due to variable trial design, methodological differences, and potential biases. RBC transfusion thresholds have been most widely studied, yet the optimal thresholds remain debated, as recent RCTs have yielded conflicting results. In general, however, the primary outcomes have continued to demonstrate restrictive thresholds to be non-inferior to liberal ones. Overall, data on thresholds for platelet, plasma, and cryoprecipitate transfusions continue to be limited and provide opportunities for future research. Still, transfusion thresholds should be cautiously used in conjunction with a thorough assessment of patients’ clinical status and comorbidities, rather than in isolation as a ‘number’ to be treated.

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-2026-1-0007/rc

Peer Review File: Available at https://aob.amegroups.com/article/view/10.21037/aob-2026-1-0007/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-2026-1-0007/coif). The series “Patient Blood Management’s Role in Current Healthcare Environment” was commissioned by the editorial office without any funding or sponsorship. R.R.G. served as the unpaid Guest Editor of the series. G.K.G. reports a MSK Cancer Center Support Grant/Core Grant (P30 CA008748), unrelated to this submitted work. 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.

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