Red blood cell transfusion in clinical practice

doi:10.1016/S0140-6736(07)61197-0

The Lancet

Volume 370, Issue 9585, 4–10 August 2007, Pages 415-426

https://doi.org/10.1016/S0140-6736(07)61197-0 Get rights and content

Summary

Every year, about 75 million units of blood are collected worldwide. Red blood cell (RBC) transfusion is one of the few treatments that adequately restore tissue oxygenation when oxygen demand exceeds supply. Although the respiratory function of blood has been studied intensively, the trigger for RBC transfusion remains controversial, and doctors rely primarily on clinical experience. Laboratory assays that indicate failing tissue oxygenation would be ideal to guide the need for transfusion, but none has proved easy, reproducible, and sensitive to regional tissue hypoxia. The clinical importance of the RBCs storage lesion (ie, the time-dependent metabolic, biochemical, and molecular changes that stored blood cells undergo) is poorly understood. RBCs can be filtered, washed, frozen, or irradiated for specific indications. Donor screening and testing have dramatically reduced infectious risks in the developed world, but infection remains a major hazard in developing countries, where 13 million units of blood are not tested for HIV or hepatitis viruses. Pathogen inactivation techniques are in clinical trials for RBCs, but none is available for use. Despite serious immunological and non-immunological complications, RBC transfusion holds a therapeutic index that exceeds that of many common medications.

Introduction

After the first successful human blood transfusions in the 17th century, James Blundell, the English obstetrician who undertook some of the early procedures, cautioned that blood transfusion should be reserved for emergencies.¹ Half of Blundell's first ten transfusion recipients died. One can only wonder how many of his patients might have been saved by appropriate transfusion, how many benefited from the small increments in oxygen-carrying capacity they received, and how many succumbed to transfusion-related complications.

Modern transfusion began with the identification of the major blood groups in 1901 and subsequent use of the agglutination technique for compatibility testing in 1907.² The development of anticoagulant-preservative solutions led to the establishment of World War I blood depots in British Casualty Clearing Stations.³ The quality of these early red blood cell (RBC) components was not well documented, but by all accounts, war-time transfusions saved lives.⁴ Clinicians now have an array of RBC components, and the physiology of oxygen delivery has been researched extensively. However, the decision to begin blood transfusion remains controversial.

Section snippets

Whole blood and RBCs

Whole blood (450–500 mL per unit) is collected for refrigerated storage into plastic packs with pre-measured anticoagulant-preservative.⁵ The volume, preservative, haemoglobin content (usually >50 g), and storage interval or “shelf life” differ according to national criteria.6, 7 Plasma proteins and other cells in RBCs preserve differently—for example, platelets and granulocytes in refrigerated blood lose biological function within 48 h. In practice, whole blood is rarely available and used

Fresh or stored cells: the storage lesion

Erythrocytes age more rapidly during refrigeration than they do in the body.¹³ The gold standard for red cell viability is the survival of 75% of injected radiolabelled cells at 24 h—an arbitrary standard that permits a quarter of transfused erythrocytes to be non-viable. Time-dependent changes in RBC quality and quantity are commonly referred to as the storage lesion. In storage, adenosine triphosphate (ATP) declines with time, resulting in changes in red-cell shape, and decline in membrane

RBC compatibility, and modifications to RBCs

Compatibility testing is designed to ensure that the patient receives the intended units of RBCs and that transfusion will be effective with minimum risk of an adverse reaction.⁵ The process includes ABO and Rh typing of donor and recipient, testing recipient serum for clinically important alloantibodies, and crossmatching donor red cells with recipient serum by a technique that detects serological incompatibility. Many laboratories now use computer software instead of the serological

Respiratory function of RBCs

Few clinical signs or symptoms reliably predict early tissue hypoxia, and not many physicians will wait for hypotension, oliguria, or impaired consciousness before starting treatment. Assays that indicate failing tissue oxygenation during acute blood loss or chronic anaemia should guide transfusion need. In practice, however, none has proved easy, reproducible, or sensitive to regional tissue hypoxia. Oxygen delivery from the lungs to the tissues takes place in a complex system in which the

Principles of oxygen transport

Acute loss of about 20% of blood volume elicits compensatory increases in heart rate and cardiac output, as well as a rise in vasoactive hormones, redistribution of blood flow, and influx of extravascular fluid to the intravascular compartment.36, 37, 38, 39 Acute blood loss is managed initially by restoring volume to avoid haemorrhagic shock. Infusions and fluid shifts result in an abrupt decrease in haemoglobin. As haemoglobin falls, compensatory mechanisms reach their limits in the different

Physiological adaptation to progressive normovolaemic anaemia

Progressive anaemia results in reduction of blood viscosity, which favours venous return to the heart and facilitates ejection of stroke volume.41, 47 In addition, normovolaemic anaemia increases sympathetic stimulation of the heart, which contributes to the increase of cardiac output during anaemia.⁴⁸ In anaesthetised patients, the increase in cardiac output results almost exclusively from an increase in stroke volume,49, 50, 51 while in conscious individuals, heart rate increases as well.41,

The limits of compensation

One approach to deciding when to transfuse RBCs compares oxygen delivery with oxygen consumption and defines a “critical haemoglobin concentration”—the point at which compensatory mechanisms for anaemia have been maximised and further reduction in haemoglobin would result in compromised cellular metabolism.⁵⁴

As haematocrit falls, oxygen consumption remains unchanged until a critical DO₂ (CO×CaO₂) is reached where cardiac output and extraction compensation can increase no further and oxygen

Indications for RBC transfusion

Despite extensive physiological data, indications for RBCs transfusion are controversial. Before the 1980s, most perioperative transfusion protocols used the “10/30 rule,” which held that haemoglobin must exceed 10 g/dL and haematocrit should be higher than 30% before operation.⁶⁷ This recommendation, intended for high-risk anaesthesia patients, was later applied to all transfusion settings, acute or chronic, and became synonymous with the single haemoglobin value 10 g/dL at which transfusion

Transfusion during intensive care

The Transfusion Requirement in Critical Care (TRICC) is the largest and most widely cited clinical trial evaluating RBC transfusion thresholds.⁷⁹ The TRICC investigators randomly allocated 838 adults with haemoglobin lower than 9 g/dL to two transfusion groups.⁷⁹ The “liberal” transfusion group received enough blood to maintain haemoglobin at 10–12 g/dL. The “restrictive” group received blood when the haemoglobin fell below 7 g/dL to maintain the haemoglobin at 7–9 g/dL. The primary outcome was

Perioperative RBC transfusion

Careful preoperative preparation for elective surgery and use of other blood management techniques reduce the need for allogeneic blood transfusion. Undiagnosed anaemia might be detected first during preadmission testing and is common in the elderly.82, 83 The lower the preoperative haemoglobin concentration, the more likely that a patient will be transfused in the preoperative period. Unsuspected anaemia before elective surgery should prompt a diagnostic evaluation and, if possible, correction

Autologous transfusion

With preoperative autologous RBC donation, patients donate up to several units of blood before surgery and then receive their own stored blood during or after operation. The underlying assumption is that transfusing a patient's own blood carries a reduced risk of infectious and immunological complications, and that the patient regenerates some of the blood stored, resulting in less allogeneic transfusion. Meta-analysis of clinical trials confirms a 40% reduction of allogeneic blood transfusion.

Allogeneic transfusion

Clinical trials evaluating allogeneic transfusions in surgical patients provide little guidance for transfusion practice because most are small94, 95, 96, 97, 98, 99 or include healthy patients with low frequency of adverse outcomes.¹⁰⁰ Two large observational studies of RBC transfusion in surgical patients reached opposing conclusions. A study in 8787 hip-fracture patients that investigated the association between postoperative transfusion, and mortality and morbidity found neither harm nor

Patients with cardiovascular disease

In healthy patients, coronary blood flow increases greatly during acute anaemia to compensate for the decrease in CaO₂. Cardiovascular disease could increase the risk from anaemia because of restricted oxygen delivery to the myocardium.103, 104, 105, 106, 107 This concern is supported by results from a study⁷⁶ in surgical patients who refuse blood transfusion for religious reasons—irrespective of haemoglobin concentration, patients with cardiovascular disease had a greater risk of dying than

Chronic anaemia

In chronic anaemia, increased cardiac output, an increase in red cell DPG, and redistribution of blood flow compensate for the reduced capacity of the blood to carry oxygen.104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115 Cardiac output is inversely related to haemoglobin. The symptoms of anaemia include fatigue, weakness, dizziness, and reduced exercise tolerance. Transfusion is not usually indicated for these symptoms unless the haemoglobin is so low that the patient cannot function

Adverse events associated with RBC transfusion

Transfusion safety involves both the quality of the RBC component and the integrity of the transfusion process from donor collection through administration of the blood. Although the safety of RBC transfusion has improved dramatically during the past 50 years, major risks remain (table 3). Some adverse events such as acute haemolysis occur after only a few millilitres of blood are transfused, while others, such as transfusional haemosiderosis and variant Creutzfeldt-Jakob disease (vCJD) may not

Immune-mediated reactions

The frequency of acute haemolytic reactions has changed little in the past quarter of a century and is calculated at 1 in 18 000 with mortality between 1 in 600 000 and 1 in 1 800 000 per unit transfused.126, 127 Accidental transfusion of ABO-incompatible RBCs remains a leading cause of fatal transfusion reactions.¹²⁸ The rate of mislabelled and miscollected samples for the transfusion service has been measured at 1000–10 000 times more frequent than the risk of viral infection from blood.¹²⁹

Non-immune reactions

Transfusion-associated circulatory overload is neither acknowledged nor reported often enough. Over 7 years, 1 in 3168 patients transfused with RBCs at the Mayo Clinic reportedly had circulatory overload. After a bedside consultation service was introduced, the frequency of reports rose to 1 in 708 patients, the increase undoubtedly related to improved awareness.¹⁶² A separate retrospective analysis in 385 elderly patients who had had orthopaedic surgery detected a volume overload rate of about

Future directions

Several developments promise to revolutionise RBC transfusion. The genes encoding the major blood group antigens have been cloned, and differences in DNA sequence have been associated with erythrocyte surface antigen expression. Molecular technology has already been used to determine fetal Rh blood group in the maternal circulation. Using a microarray chip format, rapid screening for single-nucleotide polymorphisms (SNPs) in blood group coding sequences has been accomplished and suggests that a

Conclusion

The physiology of oxygen delivery and clinical data indicate little need to transfuse patients with a haemoglobin of 10 g/dL or higher. Between 8 g/dL and 10 g/dL, the risk of hypoxic organ damage is low for most patients. Patients with a haemoglobin below 6 g/dL are usually at substantial risk, particularly if postoperative or gastrointestinal bleeding is a possibility. The decision to transfuse red cells should be made in conjunction with analysis of volume, pulmonary, cardiovascular, and

Search strategy and selection criteria

We identified reports by searching Medline (1960–2006) with the following MeSH subject headings: “erythrocyte transfusion”, “blood component transfusion”, “blood transfusion”, and “erythrocytes/transplantation”. The terms were combined using the Boolean operator “OR” since the MeSH term “erythrocyte transfusion” was previously indexed in Medline as “blood component transfusion” (1992–93), “blood transfusion” (1969–92), and “erythrocytes/transplantation” (1968–92). Search results were

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Cited by (351)

Peripheral perfusion index stratifies risk in patients with intraoperative anemia: A multicentre cohort study
2024, Journal of Clinical Anesthesia
Evidence for red blood cell (RBC) transfusion thresholds in the intraoperative setting is limited, and current perioperative recommendations may not correspond with individual intraoperative physiological demands. Hemodynamics relevant for the decision to transfuse may include peripheral perfusion index (PPI). The objective of this prospective study was to assess the associations of PPI and hemoglobin levels with the risk of postoperative morbidity and mortality.
Multicenter cohort study.
Bispebjerg and Hvidovre University Hospitals, Copenhagen, Denmark.
We included 741 patients who underwent acute high risk abdominal surgery or hip fracture surgery.
No interventions were carried out.
Principal values collected included measurements of peripheral perfusion index and hemoglobin values.
The study was conducted using prospectively obtained data on adults who underwent emergency high-risk surgery. Subjects were categorized into high vs. low subgroups stratified by pre-defined PPI levels (PPI: > 1.5 vs. < 1.5) and Hb levels (Hb: > 9.7 g/dL vs. < 9.7 g/dL). The study assessed mortality and severe postoperative complications within 90 days.
We included 741 patients. 90-day mortality was 21% (n = 154), frequency of severe postoperative complications was 31% (n = 231).
Patients with both low PPI and low Hb had the highest adjusted odds ratio for both 90-day severe postoperative complications (2.95, [1.62–5.45]) and 90-day mortality (3.13, [1.45–7.11]).
A comparison of patients with low PPI and low Hb to those with high PPI and low Hb detected significantly higher 90-day mortality risk in the low PPI and low Hb group (OR 8.6, [1.57–162.10]).
High PPI in acute surgical patients who also presents with anemia was associated with a significantly better outcome when compared with patients with both low PPI and anemia. PPI should therefore be further investigated as a potential parameter to guide intraoperative RBC transfusion therapy.
Efficacy of early intrauterine balloon tamponade for immediate postpartum hemorrhage after vaginal delivery: a randomized clinical trial
2023, American Journal of Obstetrics and Gynecology
Many questions remain about the appropriate use of intrauterine balloon devices in postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. Available data suggest that early use of intrauterine balloon tamponade might be beneficial.
This study aimed to compare the effect of intrauterine balloon tamponade used in combination with second-line uterotonics vs intrauterine balloon tamponade used after the failure of second-line uterotonic treatment on the rate of severe postpartum hemorrhage in women with postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics.
This multicenter, randomized, controlled, parallel-group, nonblinded trial was conducted at 18 hospitals and enrolled 403 women who had just given birth vaginally at 35 to 42 weeks of gestation. The inclusion criteria were a postpartum hemorrhage refractory to first-line uterotonics (oxytocin) and requiring a second-line uterotonic treatment with sulprostone (E1 prostaglandin). In the study group, the sulprostone infusion was combined with intrauterine tamponade by an ebb balloon performed within 15 minutes of randomization. In the control group, the sulprostone infusion was started alone within 15 minutes of randomization, and if bleeding persisted 30 minutes after the start of sulprostone infusion, intrauterine tamponade using the ebb balloon was performed. In both groups, if the bleeding persisted 30 minutes after the insertion of the balloon, an emergency radiological or surgical invasive procedure was performed. The primary outcome was the proportion of women who either received ≥3 units of packed red blood cells or had a calculated peripartum blood loss of >1000 mL. The prespecified secondary outcomes were the proportions of women who had a calculated blood loss of ≥1500 mL, any transfusion, an invasive procedure and women who were transferred to the intensive care unit. The analysis of the primary outcome with the triangular test was performed sequentially throughout the trial period.
At the eighth interim analysis, the independent data monitoring committee concluded that the incidence of the primary outcome did not differ between the 2 groups and stopped inclusions. After 11 women were excluded because they met an exclusion criterion or withdrew their consent, 199 and 193 women remained in the study and control groups, respectively, for the intention-to-treat analysis. The women’s baseline characteristics were similar in both groups. Peripartum hematocrit level change, which was needed for the calculation of the primary outcome, was missing for 4 women in the study group and 2 women in the control group. The primary outcome occurred in 131 of 195 women (67.2%) in the study group and 142 of 191 women (74.3%) in the control group (risk ratio, 0.90; 95% confidence interval, 0.79–1.03). The groups did not differ substantially for rates of calculated peripartum blood loss pf ≥1500 mL, any transfusion, invasive procedure, and admission to an intensive care unit. Endometritis occurred in 5 women (2.7%) in the study group and none in the control group (P=.06).
The early use of intrauterine balloon tamponade did not reduce the incidence of severe postpartum hemorrhage compared with its use after the failure of second-line uterotonic treatment and before recourse to invasive procedures.
Comparison of quantitative and calculated postpartum blood loss after vaginal delivery
2023, American Journal of Obstetrics and Gynecology MFM
Because there is no consensus on the method of assessing postpartum blood loss, the comparability and relevance of the postpartum hemorrhage–related literature are questionable. Quantitative blood loss assessment using a volumetric technique with a graduated collector bag has been proposed to overcome limitations of intervention-based outcomes but remains partly subjective and potentially biased by amniotic fluid or missed out-of-bag losses. Calculated blood loss based on laboratory parameters has been studied and used as an objective method expected to reflect total blood loss. However, few studies have compared quantitative with calculated blood loss.
This study aimed to compare the distribution of postpartum blood loss after vaginal delivery assessed by 2 methods—quantitative and calculated blood loss—and the incidence of abnormal blood loss with each method.
Data were obtained from the merged database of 3 multicenter, randomized controlled trials, all testing different interventions to prevent postpartum blood loss in individuals with a singleton live fetus at ≥35 weeks of gestation, born vaginally. All 3 trials measured blood loss volume by using a graduated collector bag. Hematocrit was measured in the eighth or ninth month of gestation and on day 2 postpartum. The 2 primary outcomes were: quantitative blood loss, defined by the total volume of blood loss measured in a graduated collector bag, and calculated blood loss, mathematically defined from the peripartum hematocrit change (estimated blood volume × [(antepartum hematocrit–postpartum hematocrit)/antepartum hematocrit], where estimated blood volume [mL]=booking weight [kg] × 85). We modeled the association between positive quantitative blood loss and positive calculated blood loss with polynomial regression and calculated the Spearman correlation coefficient.
Among the 8341 individuals included in this analysis, the median quantitative blood loss (100 mL; interquartile range, 50–275) was significantly lower than the median calculated blood loss (260 mL; interquartile range, 0–630) (P<.05). The incidence of abnormal blood loss was lower with quantitative blood loss than calculated blood loss for all 3 thresholds: for ≥500 mL, it was 9.6% (799/8341) and 32.3% (2691/8341), respectively; for ≥1000 mL, 2.1% (176/8341) and 11.5% (959/8341); and for ≥2000 mL, 0.1% (10/8341) and 1.4% (117/8341) (P<.05). Quantitative blood loss and calculated blood loss were significantly but moderately correlated (Spearman coefficient=0.44; P<.05). The association between them was not linear, and their difference tended to increase with blood loss. Negative calculated blood loss values occurred in 23% (1958/8341) of individuals; among them, >99% (1939/1958) had quantitative blood loss ≤500 mL.
Quantitative and calculated blood loss were significantly but moderately correlated after vaginal delivery. However, clinicians should be aware that quantitative blood loss is lower than calculated blood loss, with a difference that tended to rise as blood loss increased.
2021: Perioperative and critical care year in review for the cardiothoracic surgery team
2022, Journal of Thoracic and Cardiovascular Surgery
For yet another year, our lives have been dominated by a pandemic. This year in review, we feature an expert panel opinion regarding extracorporeal support in the context of COVID-19, challenging previously held standards. We also feature survey results assessing the impact of the pandemic on cardiac surgical volume. Furthermore, we focus on a single center experience that evaluated the use of pulmonary artery catheters and the comparison of transfusion strategies in the Restrictive and Liberal Transfusion Strategies in Patients With Acute Myocardial Infarction (REALITY) trial. Additionally, we address the impact of acute kidney injury on cardiac surgery and highlight the controversy regarding the choice of fluid resuscitation. We close with an evaluation of dysphagia in cardiac surgery and the impact of prehabilitation to optimize surgical outcomes.
Reduction in perioperative blood loss using ultrasound-activated scissors during tumour surgery
2022, International Journal of Oral and Maxillofacial Surgery
The aim of this study was to compare the effectiveness of Harmonic Focus+ scissors with the conventional surgical method regarding surgical blood loss and transfusion of blood products in the surgical treatment of head and neck tumours. In a retrospective study, the intraoperative blood loss, number of units of transfusion products given, operating time, and inpatient length of stay of 74 patients with squamous cell carcinoma were compared. Patients who underwent classic tumour surgery were compared with a group treated with Harmonic Focus+ scissors. A significantly lower intraoperative blood loss (496.15⬰ml vs 1096.0⬰ml, respectively; P⬰=⬰0.002) and shorter operation time (436.89 minutes vs 493.13 minutes, respectively; P⬰=⬰0.030) were achieved using the Harmonic Focus+ scissors when compared to the classic tumour surgery. Additionally, fewer units of blood products needed to be transfused (administration of red cell concentrates, P⬰<⬰0.001) and the length of stay in the intensive care unit was shorter for patients treated with the Harmonic Focus+ scissors (P⬰=⬰0.009). The study results indicate that the use of Harmonic Focus+ scissors during surgery for cancer of the oral cavity and pharynx is a safe and cost-effective method. This is of paramount importance during a pandemic when medical resources are scarce, including access to blood reserves.
Core–Shell Microfiber Encapsulation Enables Glycerol-Free Cryopreservation of RBCs with High Hematocrit
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SeriesRed blood cell transfusion in clinical practice

Summary

Introduction

Section snippets

Whole blood and RBCs

Fresh or stored cells: the storage lesion

RBC compatibility, and modifications to RBCs

Respiratory function of RBCs

Principles of oxygen transport

Physiological adaptation to progressive normovolaemic anaemia

The limits of compensation

Indications for RBC transfusion

Transfusion during intensive care

Perioperative RBC transfusion

Autologous transfusion

Allogeneic transfusion

Patients with cardiovascular disease

Chronic anaemia

Adverse events associated with RBC transfusion

Immune-mediated reactions

Non-immune reactions

Future directions

Conclusion

Search strategy and selection criteria

J Pediatr

Clin Lab Med

Arch Biochem Biophys

Lancet

Lancet

Respir Physiol

J Cardiothorac Vasc Anesth

Crit Care Clin

Br J Anaesth

Chest

Lancet

Br J Anaesth

Lancet

Lancet

Chest

Blood

J Thorac Cardiovasc Surg

Am J Surg

Journal of Arthroplasty

Some account of a case of obstinate vomiting in which an attempt was made to prolong life by the injection of blood into the veins

Med Chir Trans

Uber Agglutinationserscheinungen normalen menschlichen Blutes

Klin Wschr

Transfusion with preserved red blood cells

Brit Med J

The first blood banker: Oswald Hope Robertson

Transfusion

Technical Manual (15 edn)

Standards for blood banks and transfusion services

Guidelines for the Blood Transfusion Services in the United Kingdom

Mollison's Blood transfusion in Clinical Medicine

Splenectomy in leukemia and myelofibrosis—changes in the erythrocyte values

Am J Clin Pathol

A new formula for blood transfusion volume in the critically ill

Arch Dis Child

Erythrocyte preservation I: the relation of the storage lesion to in vivo erythrocyte senescence

J Clin Invest

Studies on the preservation of human blood. II. The relationship of erythrocyte adenosine triphosphate levels and other in vitro measures to red cell storageability

J Lab Clin Med

Erythrocyte membrane vesiculation and changes in membrane composition during storage in citrate-phosphate-dextrose-adenine-1

Vox Sang

Recovery of membrane micro-vesicles from human erythrocytes stored for transfusion: a mechanism for the erythrocyte discocyte-to-spherocyte shape transformation

Biochem Soc Trans

Chemical and hematologic changes in stored CPDA-1 blood

Transfusion

Volume control of erythrocytes during storage. The role of mannitol

Transfusion

Studies in red blood cell preservation 2—comparison of vesicle formation, morphology, and membrane lipids during storage in AS-1 and CPDA-1

Vox Sang

Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase

J Lab Clin Med

Depletion and regeneration of 2,3-diphosphoglyceric acid in stored red blood cells

Transfusion

Restoration in vivo of erythrocyte adenosine triphosphate, 2,3-diphosphoglycerate, potassium ion, and sodium ion concentrations following the transfusion of acid-citrate-dextrose-stored human red blood cells

J Lab Clin Med

Association of mortality with age of blood transfused in septic ICU patients

Series
Red blood cell transfusion in clinical practice