A randomized comparison of transfusion triggers in elective orthopaedic surgery using leucocyte-depleted red blood cells

Objective  In elective orthopaedic hip- and knee replacement surgery patients, we studied the effect of implementation of a uniform transfusion policy on RBC usage.
Study Design and Methods  A randomized, controlled study. A new uniform, restrictive transfusion policy was compared with standard care, which varied among the three participating hospitals. Only prestorage leucocyte-depleted RBC(s) were used. Primary end-point was RBC usage, related to length of hospital stay. Secondary end-points were Hb levels, mobilization delay and postoperative complications.
Results  Six hundred and three patients were evaluated. Adherence to the protocol was over 95%. Overall mean RBC usage was 0·78 U/patient in the new policy group and 0·86 U/patient in the standard care policy group (mean difference 0·08;95% CI [−0·3; 0·2]; P  = 0·53). In two hospitals, the new transfusion policy resulted in a RBC reduction of 30% (0·58U RBC/patient) ( P  = 0·17) and 41% (0·29 U RBC/patient) ( P  = 0·05) respectively. In the third hospital, however, RBC usage increased by 39% (0·31 U RBC/patient) ( P  = 0·02) with the new policy, due to a more restrictive standard care policy in that hospital. Length of hospital stay was not influenced by either policy.
Conclusions  Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible, but does not always lead to a RBC reduction. Length of hospital stay was not affected.     

Role of tranexamic acid in blood loss control and blood transfusion management of patients undergoing multilevel spine surgery: A meta-analysis

Background:This study aimed to explore the role of tranexamic acid (TXA) in blood loss control and blood transfusion management of patients undergoing multilevel spine surgery.Methods:In this meta-analysis, a comprehensive search of literatures was performed from PubMed, Embase, Cochrane Library, and Web of Science from inception to June 23rd, 2020. Weighed mean difference (WMD) was used as the effect size for measurement data, and risk ratio for enumeration data. Publication bias was assessed by Begg test.Results:Totally 23 studies (11 randomized controlled trials and 12 cohort studies) involving 1621 participants were enrolled in this meta-analysis. The results showed that the administration of TXA can significantly decrease the intraoperative [WMD: –215.655, 95%CI: (–307.462, –123.847), P < .001], postoperative [WMD: –69.213, 95%CI: (–104.443, –33.983), P = .001] and total [WMD: –284.388, 95%CI: (–437.66, –131.116), P < .001] volumes of blood loss of patients undergoing multilevel spine surgery. It can also significantly reduce the intraoperative [WMD: –333.775, 95%CI: (–540.45, –127.099), P = .002] and postoperative [WMD: –114.661, 95%CI: (–219.58, –9.742), P = .032] volumes of transfusion. In addition, TXA was found to significantly increase the preoperative [WMD: 0.213, 95%CI: (0.037, 0.389), P = .018] and postoperative [WMD: 0.433, 95%CI: (0.244, 0.622), P < .001] hemoglobin levels as well as the preoperative platelet count [WMD: 14.069, 95%CI: (0.122, 28.015), P = .048].Conclusion:The administration of TXA can effectively reduce blood loss and transfusion, and improve hemoglobin levels and preoperative platelet count in patients undergoing multilevel spine surgery.     

Red cell transfusion in orthopaedic surgery: a benchmark study performed combining data from different data sources

Background

Previous studies have shown the usefulness of combining information from different data sources to identify and analyse variations in transfusion practices. Good knowledge of the conditions leading to blood use is a fundamental requirement for the assessment of the appropriateness of blood transfusion.

Materials and methods

In this study we combined blood transfusion data obtained from the Blood Bank information system with patients’ data from the Hospital Discharge Database, based on the ICD9 classification system, from 1,827 surgical procedures performed in seven different orthopaedic divisions in the Ravenna area between January and December 2009. Hip and knee replacement surgery (primary or revision) and operations following femoral fractures (partial hip replacement and reduction with internal fixation) were considered. For a subgroup of patients clinical and transfusion data were also combined with haemoglobin values obtained from the laboratory information system.

Results

Of the 1,827 surgical procedures, 1,038 (56.8%) were followed by transfusion of red cells. The likelihood of receiving a transfusion varied depending on the patient’s sex (49% for males, 60% for females), age, and on the surgical procedure, being higher for interventions following femoral fractures and for revisions of hip replacement: about 70% of patients undergoing these interventions required transfusion. A large variability in transfusion rates was observed between the seven divisions, which was only partially explained by the different types of surgery (post-traumatic or elective) performed by any of them: relevant variations were also observed for the same type of intervention.

Discussion

Combining information from different data sources could be a time-sparing way to gain useful information about transfusion practices, so contributing to optimising blood usage.     

Rationalizing blood transfusion in cardiac surgery: preliminary findings with a red cell volume-based model

BACKGROUND AND OBJECTIVES: Cardiac surgery, utilizing extracorporeal circulation, is associated with a heavy fluid load that may significantly depress haemoglobin concentration. Thus, considering haemoglobin alone may be an inaccurate method of replacing red cell volume loss. This study was designed to examine the impact on red cell transfusion of a red cell volume-based guideline. MATERIALS AND METHODS: Patients were randomized to receive red cells as dictated by the red cell volume-based guideline or a haemoglobin-based protocol. End-points considered were red cell transfusion and clinical outcome. RESULTS: Patients transfused as per the red cell volume-based guideline received significantly less red cells with no associated difference in clinical outcome. CONCLUSION: Considering haemoglobin concentration alone may significantly overestimate the requirement for red cell transfusion in elective cardiac surgery patients.     

Practical management of anticoagulation, bleeding and blood product support for cardiac surgery. Part two: transfusion issues

We summarise recent advances in transfusion medicine applicable to cardiac surgery and cardiac transplantation. It is important that clinicians know the risks of blood transfusion in Australia. They should also be aware of the different types of transfusion reaction so that there is early recognition and investigation. Blood conservation strategies including acceptance of normovolaemic anaemia in clinically stable patients are important in reducing the requirement for red cell transfusion. Cytomegalovirus (CMV) seronegative blood products are recommended for heart transplant recipients with no evidence of prior CMV infection. Leucodepletion of units of unknown CMV status reduces the risk of CMV infection and are an acceptable alternative when seronegative units are unavailable. Leucodepletion of cellular blood products has been shown to reduce infection rates postoperatively in a large trial involving cardiac surgical patients. Further studies are needed to confirm this promising finding. Irradiation of blood products eliminates the risk of transfusion-associated graft versus host disease. Routine preoperative screening for cold agglutinins is no longer recommended.     

Oxygenating the microcirculation: the perspective from blood transfusion and blood storage

Tissue oxygen delivery depends on red blood cell (RBC) content and RBC flow regulation in the microcirculation. The important role of the RBC in tissue oxygenation is clear from anaemia and the use of RBC transfusion which has saved many lives. Whether RBC transfusion actually restores tissue oxygenation is difficult to determine due to the lack of appropriate clinical monitoring techniques. Some patients with restored haemoglobin levels and stable haemodynamics still develop tissue hypoxia, emphasizing that, in addition to global parameters, local microcirculatory control mechanisms are also important in the restoration of tissue oxygenation. Both clinical and animal experimental studies have indicated that storage of RBC diminishes their ability to oxygenate the tissue. Several intrinsic RBC parameters that change during storage and might influence tissue oxygenation will be mentioned. The release of vasodilators from RBC that will alter blood flow during hypoxia, mediated by haemoglobin in the RBC that functions as an oxygen sensor, could be impaired during storage. A better understanding of hypoxia-induced vasodilator release from RBC might become a potential target for drug development and improve tissue oxygenation after transfusion.     

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

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

Significant reduction of red blood cell transfusion requirements by changing from a double-unit to a single-unit transfusion policy in patients receiving intensive chemotherapy or stem cell transplantation

Background

Traditionally, single-unit red blood cell transfusions were believed to be insufficient to treat anemia, but recent data suggest that they may lead to a safe reduction of transfusion requirements. We tested this hypothesis by changing from a double- to a single-unit red blood cell transfusion policy.

Design and Methods

We performed a retrospective cohort study in patients with hematologic malignancies receiving intensive chemotherapy or hematopoietic stem cell transplantation. The major end-points were the reduction in the total number of red blood cell units per therapy cycle and per day of aplasia. The study comprised 139 patients who received 272 therapy cycles. Overall 2212 red blood cell units were administered in 1548 transfusions.

Results

During the periods of the double- and single-unit policies, one red blood cell unit was transfused in 25% and 84% of the cases and the median number of red blood cell units per transfusion was two and one, respectively. Single-unit transfusion led to a 25% reduction of red blood cell usage per therapy cycle and 24% per aplasia day, but was not associated with a higher out-patient transfusion frequency. In multivariate analysis, single-unit transfusion resulted in a reduction of 2.7 red blood cell units per treatment cycle (P=0.001). The pre-transfusion hemoglobin levels were lower during the single-unit period (median 61 g/L versus 64 g/L) and more transfusions were administered to patients with hemoglobin values of 60 gl/L or less (47% versus 26%). There was no evidence of more severe bleeding or more platelet transfusions during the single-unit period and the overall survival was similar in both cohorts.

Conclusions

Implementing a single-unit transfusion policy saves 25% of red blood cell units and, thereby, reduces the risks associated with allogeneic blood transfusions.     

General thoracic surgery in Finland,a perspective from the Helsinki University Hospital

The field of thoracic surgery is a rapidly developing field due to exciting developments in technology and oncologic treatments as well as continuous innovation in surgical technique. Although the population of Finland is relatively small, general thoracic surgery is represented at a high level in five centralized university centers, Helsinki University Hospital, Tampere University Hospital, Turku University Hospital, Kuopio University Hospital and Oulu University Hospital. Thus, high case volume and good results are achieved in these centers. Here, we describe a short history, current state and future prospects of the field of cardiothoracic surgery in Finland, with a focus on general thoracic surgery and the perspective of Helsinki University Hospital. From the field’s birth in Finland, marked by the first lobectomy, in the late 1930’s, it has grown and adapted more and more modern techniques such as totally minimally invasive esophagectomy and robotic lung cancer surgery. Nowadays, most of general thoracic surgery in Helsinki University Hospital is either minimally invasive or robotic and open surgery is the exception to the norm. Helsinki University Hospital has a strong presence in the European general thoracic surgery community and aims to do so in the future by investing on training & education, research and surgical innovation.     

Humoral immune response to autologous blood transfusion in hip surgery: whole blood versus packed red cells and plasma.

BACKGROUND AND OBJECTIVES: The immune response to the transfused autologous buffy coat content in whole blood has, to date, not been studied in detail. SUBJECTS AND METHODS: Patients undergoing hip arthroplasty were studied according to whether they received autologous whole blood (WB) (n = 30), autologous fresh-frozen plasma and buffy coat-poor red cells (RC) (n = 40), or no transfusion (NT) (n = 27). Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and complement SC5b-9 were analysed by enzyme-linked immunosorbent assay (ELISA) 7 days after surgery. RESULTS: There were no significant between-group differences regarding the time course of TNF-alpha, IL-6 and complement SC5b-9 plasma level changes, the infection rate, or the length of hospital stay. CONCLUSION: In comparison to the impact of surgery on cytokine and complement levels, the transfusion of autologous buffy coat is not relevant.     

Pathogen reduction and blood transfusion safety in Africa: strengths,limitations and challenges of implementation in low‐resource settings

Transfusion‐transmitted infection risk remains an enduring challenge to blood safety in Africa. A high background incidence and prevalence of the major transfusion‐transmitted infections (TTIs), dependence on high‐risk donors to meet demand, suboptimal testing and quality assurance collectively contribute to the increased risk. With few exceptions, donor testing is confined to serological evaluation of human immunodeficiency virus (HIV), hepatitis B and C (HBV and HCV) and syphilis. Barriers to implementation of broader molecular methods include cost, limited infrastructure and lack of technical expertise. Pathogen reduction (PR), a term used to describe a variety of methods (e.g. solvent detergent treatment or photochemical activation) that may be applied to blood following collection, offers the means to diminish the infectious potential of multiple pathogens simultaneously. This is effective against different classes of pathogen, including the major TTIs where laboratory screening is already implemented (e.g. HIV, HBV and HCV) as well pathogens that are widely endemic yet remain unaddressed (e.g. malaria, bacterial contamination). We sought to review the available and emerging PR techniques and their potential application to resource‐constrained parts of Africa, focusing on the advantages and disadvantages of such technologies. PR has been slow to be adopted even in high‐income countries, primarily given the high costs of use. Logistical considerations, particularly in low‐resourced parts of Africa, also raise concerns about practicality. Nonetheless, PR offers a rational, innovative strategy to contend with TTIs; technologies in development may well present a viable complement or even alternative to targeted screening in the future.     

Orthopaedic surgery in haemophilia patients with inhibitors: a practical guide to haemostatic, surgical and rehabilitative care

Summary.  All but essential surgery is generally avoided in haemophilia patients with inhibitor antibodies, because of concern about the reliability with which haemostasis can be achieved and maintained in such patients. Orthopaedic surgical procedures which are not required to preserve life fall under this category. As a result, patients with inhibitors may be denied operations, which could greatly enhance their quality of life, and which are routinely offered to other haemophilia patients. While caution is appropriate in recommending surgery in any circumstance, we believe that the threshold for offering validated surgical procedures to patients with inhibitors should be re-evaluated in the light of current surgical and rehabilitative techniques, and the long experience with safe and effective factor VIII inhibitor bypassing agents, namely activated prothrombin complex concentrates and recombinant activated factor FVII. In this article, we review the haematological, surgical and rehabilitative considerations relevant to orthopaedic surgery in haemophilia patients with inhibitors, and provide recommendations for carrying out such procedures.     

Effects of perioperative erythropoietin administration on acute kidney injury and red blood cell transfusion in patients undergoing cardiac surgery: A systematic review and meta-analysis

Background:The renoprotective effects of erythropoietin (EPO) are well-known; however, the optimal timing of EPO administration remains controversial. Red blood cell (RBC) transfusion is an independent risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). We aimed to evaluate the efficacy of EPO on CSA-AKI and RBC transfusion according to the timing of administration.Methods:We searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials. The primary outcome was the incidence of CSA-AKI following perioperative EPO administration, and the secondary outcomes were changes in serum creatinine, S-cystatin C, S-neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, length of hospital and intensive care unit (ICU) stay, volume of RBC transfusion, and mortality. The subgroup analysis was stratified according to the timing of EPO administration in relation to surgery.Results:Eight randomized controlled trials with 610 patients were included in the study. EPO administration significantly decreased the incidence of CSA-AKI (odds ratio: 0.60, 95% confidence interval [CI]: 0.43–0.85, P = .004; I ² = 52%; P for heterogeneity = .04), intra-operative RBC transfusion (standardized mean difference: −0.30, 95% CI: −0.55 to −0.05, P = .02; I ² = 15%, P for heterogeneity = .31), and hospital length of stay (mean difference: −1.54 days, 95% CI: −2.70 to −0.39, P = .009; I ² = 75%, P for heterogeneity = .001) compared with control groups. Subgroup analyses revealed that pre-operative EPO treatment significantly reduced the incidence of CSA-AKI, intra-operative RBC transfusion, serum creatinine, and length of hospital and ICU stay.Conclusion:Pre-operative administration of EPO may reduce the incidence of CSA-AKI and RBC transfusion, but not in patients administered EPO during the intra-operative or postoperative period. Therefore, pre-operative EPO treatment can be considered to improve postoperative outcomes by decreasing the length of hospital and ICU stay in patients undergoing cardiac surgery.     

Management of haemophilic patients with inhibitors in major orthopaedic surgery by immunadsorption, substitution of factor VIII and recombinant factor VIIa (NovoSeven®): a single centre experience

Inhibitors of factor VIII or FIX in haemophilic patients are a common and serious complication associated with an increased risk of life-threatening bleeding during elective surgery. Substitution therapy fails to be effective, therefore an alternative treatment is needed. We have performed six major elective orthopaedic interventions in four patients with haemophilia A and inhibitors. A preoperative immunadsorbant therapy with Therasorb to eliminate inhibitors was successful in four cases, but during FVIII substitution inhibitors increased on day 4 to day 6 after surgery, leading to decreasing FVIII levels. Therefore, therapy was changed to recombinant FVIIa (rFVIIa; NovoSeven). Two interventions had to be covered with sole rFVIIa therapy as immunadsorbant therapy failed to be effective in one case and the need for acute intervention did not allow pretreatment in the other. We did not see increased bleeding during or after surgery when compared to our experience with non-inhibitor haemophilic patients. In conclusion, a preoperative decrease of inhibitors from immunadsorbant therapy, perioperative substitution of FVIII and changing treatment to rFVIIa when inhibitors are increased, is a safe and economic therapy for guaranteeing haemostasis in major elective orthopaedic surgery. On the contrary, sole therapy with rFVIIa allows immediate surgical intervention without a long hospital stay prior to surgery and a need for laboratory monitoring of inhibitor titres and FVIII levels. Our findings support data previously published.     

Multidisciplinary management of patients with haemophilia with inhibitors undergoing surgery in the United States: perspectives and best practices derived from experienced treatment centres

Since the 1980s, major surgical interventions in patients with congenital haemophilia with inhibitors have been performed utilizing bypassing agents for haemostatic coverage. While reports have focused on perioperative management and haemostasis, the US currently lacks consensus guidelines for the management of patients with inhibitors during the surgical procedure, and pre‐ and postoperatively. Many haemophilia treatment centres (HTCs) have experience with surgery in haemophilia patients, including those with inhibitors, with approximately 50% of these HTCs having performed orthopaedic procedures. The aim of this study was to present currently considered best practices for multidisciplinary care of inhibitor patients undergoing surgery in US HTCs. Comprehensive haemophilia care in the US is provided by ~130 federally designated HTCs staffed by multidisciplinary teams of healthcare professionals. Best practices were derived from a meeting of experts from leading HTCs examining the full care spectrum for inhibitor patients ranging from identification of the need for surgery through postoperative rehabilitation. HTCs face challenges in the care of inhibitor patients requiring surgery due to the limited number of surgeons willing to operate on this complex population. US centres of excellence have developed their own best practices around an extended comprehensive care model that includes preoperative planning, perioperative haemostasis and postoperative rehabilitation. Best practices will benefit patients with inhibitors and allow improvement in the overall care of these patients when undergoing surgical procedures. In addition, opportunities for further education and outcomes assessment in the care of this patient population have been identified.     

Autologous blood collection in abdominal vascular surgery. Assessment of a low pressure blood salvage system with particular reference to the preservation of cellular elements,triglyceride, complement and bacterial content in the collected blood

Summary. A simple, low pressure, blood scavenging system has been assessed in major abdominal vascular operations. The aim of this study was to assess the quality of blood obtained with this device and its suitability for reinfusion. Three areas of special interest, which have not been reported so far, are the fate of plasma complement, the load of fat aspirated after tissue dissection and the degree of bacterial contamination in the scavenged blood. The development of autologous blood scavenging systems is reviewed. The features which most affect the quality of scavenged blood are identified and their importance discussed by comparison with our experience. Key features of our system were: simplicity of the apparatus, controlled low-pressure aspiration, the use of systemic heparin and the avoidance of mechanical pumps. The blood obtained was of excellent quality with good preservation of cellular elements, platelets and fibrinogen. Plasma total haemolytic complement, C₃, and C₄, fractions were preserved in normal, though slightly reduced, quantities. Lipid (triglyceride) content was minimally increased after filtration. Bacterial contamination was present in all cases, but at a very low level provided that aspiration was limited to the peritoneal cavity. This low-level of contamination is not thought to be of great significance; its origin and importance are discussed     

The role of the direct antiglobulin test in pre-transfusion investigations and the approach to selecting blood for transfusion in autoimmune haemolytic anaemia: results of a regional survey

Introduction

The aim of this study was to conduct a Regional survey to determine the policies and ways of performing the direct antiglobulin test in pre-transfusion screening, the approach used in cases giving positive results with this test and the technical and operative modalities for choosing blood for transfusion in cases of autoimmune haemolytic anaemia.

Materials and methods

A questionnaire, containing ten multiple-choice questions, was sent to all the transfusion centres in the Region of Tuscany.

Results

The data from all 40 regional centres were analysed. Direct antiglobulin tests and autocontrols were not regularly used in pre-transfusion screening. The direct antiglobulin test was predominantly reserved for suspected cases of autoimmune haemolytic anaemia. Sixty percent of the laboratories characterised the specificity of samples that were positive for IgG and complement by the direct antiglobulin test, 45% that were positive for IgM, 35% also for IgA, and 13% also for subclasses of IgG. Elution studies were reserved (in 18% of laboratories) for those cases in which it was expected that transfusion therapy would be used. In cases of autoimmune haemolytic anaemia, autologous/allogeneic adsorption was carried out in 27% of the structures (the use of proteolytic enzymes is predominant, followed by the “ZZAP” reagent – a mixture of dithiothreitol and an enzyme) and the dilution method in 20%; transfusion of red blood cells with a phenotype extensively compatible (c, C, D, E, e, K, Jk^a, Jk^b, Fy^a, Fy^b, S, s) with that of the recipient is practised in 17% of the centres, while transfusion of units of “least incompatible” red blood cells was reported by 95% of the centres, but in 88% this is preceded by at least one of the above mentioned immunohaematological investigations.

Conclusions

The organisation of a network of Services of Immunohaematology and Transfusion Medicine can be exploited to overcome some technical and operative limitations of peripheral, dependent Transfusion Sections. The results of this study reveal which immunohaematology laboratory is endowed with the greatest potential and which could, therefore, become the regional reference centre. This investigation could lay the basis for defining behavioural algorithms and recommendations on the issues considered.