AimsTo evaluate the safety and efficacy of tranexamic acid (TXA) in total knee arthroplasty (TKA) and total hip arthroplasty (THA). The specific endpoints assessed in this meta-analysis include the total blood loss, the incidence rate of deep vein thrombosis (DVT) and pulmonary embolisms (PE), the number of patients requiring at least 1U of red blood cell following surgery. BackgroundThe prevalence of THA and TKA is increasing and both are usually accompanied by considerable blood loss. TXA has been reported to reduce total blood loss in many orthopaedic surgeries. TXA administration continues to be a controversial topic in the literature about joint arthroplasty, and many studies have reported substantial doubt with respect to its benefits and safety. Methods/materialsWe conducted a meta-analysis that combined all data from available randomised controlled trials, regardless the methods of TXA administration, which included administrated intravenously, intra-articularly, topically or orally. Finally, available data from the 39 included trials were pooled for analysis. Then, mean differences with 95% confidence intervals (CIs) was calculated for continuous outcomes and relative risks with 95% CIs for dichotomous outcomes. ResultsThis meta-analysis suggests that the administration of TXA significantly reduced blood loss and the need for allogeneic blood transfusion, without apparent increased risk of DVT or PE thromboembolic complications. ConclusionTo our knowledge, this meta-analysis is more powerful and persuasive than any other published before. It suggests that the use of TXA reduced the risk of blood loss and the need for allogeneic blood transfusion significantly, without apparent increased risk of DVT or PE complications.
Aim: In this study, we performed weekly assessment of morphology‐related parameters through monitoring of CPD‐SAGM leuco‐filtered erythrocyte concentrates from blood withdrawal until the 42nd day of storage. Background: Liquid storage of red blood cells (RBCs) delivers a blood‐derived therapeutic, which is safe, available, effective and affordable for most patients who need transfusion therapy in developed countries. However, a growing body of accumulating controversial evidences, from either biochemical or retrospective clinical studies, prompted safety concerns about longer stored RBCs. Methods: Statistical image analysis through scanning electron microscope was coupled to osmotic fragility and erythrocyte sedimentation rate. Results: We could observe that by day 21 more than 50% of RBCs displayed non‐discocyte phenotypes. This observation was related to an increase in osmotic fragility, which was totally overlapped in day 0 controls and day 7 RBCs while only slightly augmented in day 14 samples. Cation dysregulation (pH internal/external alteration and potassium) might both reflect and trigger a negative feedback loop with metabolic fluxes and membrane cation pumps. Conclusion: Morphology parameters suggest that significant alterations to RBC morphology over storage duration occur soon after the 14th day of storage, as to become significant enough within the 21st day.
Background/Objectives: The safety of administering uncross-matched, groupO, cold-stored, whole blood (cWB) during civilian trauma resuscitation was evaluated. Methods/Materials: Male trauma patients with haemorrhage-induced hypotension who received leuko-reduced uncross-matched group O+, low titre (<50) anti-A and -B, platelet-replete cWB during initial resuscitation were included. The biochemical markers of haemolysis (lactate dehydrogenase, total bilirubin, haptoglobin, creatinine, serum potassium) were measured on the day of cWB receipt (day 0), and over the next 2 days, reports of transfusion reactions and total blood product administration in first 24 h of admission were recorded. Results: There were 27 non-group O and 17 group O cWB recipients. The median number of cWB units transfused was 1 [interquartile range (IQR): 1-2] in both groups. Themedian day 0 post-transfusion serum total bilirubin concentration, although still in the normal range, was higher in the non-group O versus group O recipients (1.4 versus 0.5 mg/dL, P < 0.01). There were no significant differences in any of the other biochemical parameters at any other time point. Non-group O recipients received a median of 3 times more red blood cell (RBC) units compared with group O recipients (P = 0.01 RBCs), likely explaining the bilirubin difference on day 0. Themedian volume of ABO-incompatible plasma transfused to non-group O recipients was 600 mL (IQR: 300-1140 mL). There were no reports of adverse events related to the cWB transfusion in either group. Conclusions: Administration of <= 2 units of cWB in civilian trauma resuscitation was not associated with clinically significant changes in laboratory haemolysis markers. Efficacy will be determined when larger quantities are transfused.
Erythrocyte transfusion is essential in conditions of large blood loss, of inadequate bone marrow production and of increased erythrocyte breakdown. The structural and biochemical changes that erythrocytes go through during storage, probably associated with the disappearance of up to 30% of the erythrocytes within 24 h after transfusion, are likely to contribute to the transfusion side effects: iron overload, erythrocyte adhesion to the endothelial surface with proinflammatory consequences, autoantibody formation, endothelial damage by released erythrocyte constituents, a hampered microcirculation and oxygen delivery. In vivo, senescent erythrocytes are marked for removal by binding of autologous immunoglobulin G to ageing antigens, which arise by changes in the conformation of the membrane domain of band 3. Also, vesicle formation has been described as an integral part of the erythrocyte ageing process. Comparable changes occur during erythrocyte storage. This review describes the current state of knowledge of the mechanism of erythrocyte ageing in vivo, ageing-related changes occurring during erythrocyte storage in blood bank conditions and their possible relation with the transfusion side effects. In view of the key position of band 3 in the maintenance of erythrocyte structure and function, elucidation of the pathways that control posttranslational modification of band 3 during storage may lead to new approaches towards maintaining ATP concentration and cellular integrity. This review concludes with the challenge to further explore the underlying processes of erythrocyte ageing in order to provide physiologically relevant tools for assessing and predicting erythrocyte homeostasis in vitro and in vivo and thereby to contribute to the development of rational transfusion protocols for various patient categories.
The hepatitis E virus ( HEV ) is a major cause of acute hepatitis globally. Genotypes 1 and 2 ( G1 and G2 ) are obligate human pathogens transmitted faeco‐orally, leading to epidemics in developing countries. In contrast, genotypes 3 and 4 ( G3 and G4 ) have a wider host range, including humans, but are primarily porcine viruses and are transmitted from animals to humans as a food‐borne zoonosis when meat from an infected animal is consumed. HEV is increasingly recognised as a problem in developed countries, including countries in Europe. G3 HEV is now the most common cause of acute viral hepatitis in the UK and cases continue to rise. The majority of these infections are acquired within the UK and thought to be from insufficiently cooked meat, predominantly processed pork meat. Previously thought to only cause self‐limiting disease, HEV infection can persist in immunosuppressed patients, which may lead to chronic hepatitis and the rapid development of cirrhosis. Of particular interest to the transfusion community has been the possibility of transfusion‐transmitted HEV , which has been reported from countries classically considered HEV ‐endemic but also non‐endemic countries in Europe and Japan. This has prompted some countries to introduce screening for HEV in blood donations.
Objectives To describe the Resuscitation with Pre-HospItaL bLood products' trial (RePHILL)-a multi-centre randomised controlled trial of pre-hospital blood product (PHBP) administration vs standard care for traumatic haemorrhage. BackgroundMethodsPHBP are increasingly used for pre-hospital trauma resuscitation despite a lack of robust evidence demonstrating superiority over crystalloids. Provision of PHBP carries additional logistical and regulatory implications, and requires a sustainable supply of universal blood components. RePHILL is a multi-centre, two-arm, parallel group, open-label, phase III randomised controlled trial currently underway in the UK. Patients attended by a pre-hospital emergency medical team, with traumatic injury and hypotension (systolic blood pressure<90mmHg or absent radial pulse) believed to be due to traumatic haemorrhage are eligible. Exclusion criteria include age<16years, blood product receipt on scene prior to randomisation, Advanced Medical Directive forbidding blood product administration, pregnancy, isolated head injury and prisoners. A total of 490 patients will be recruited in a 1:1 ratio to receive either the intervention (up to two units of red blood cells and two units of lyophilised plasma) or the control (up to four boluses of 250mL 0.9% saline). The primary outcome measure is a composite of failure to achieve lactate clearance of 20%/h over the first 2hours after randomisation and all-cause mortality between recruitment and discharge from the primary receiving facility to non-acute care. Secondary outcomes include pre-hospital time, coagulation indices, in-hospital transfusion requirements and morbidity. ResultsConclusionsPilot study recruitment began in December 2016. Approval to proceed to the main trial was received in June 2017. Recruitment is expected to continue until 2020. RePHILL will provide high-quality evidence regarding the efficacy and safety of PHBP resuscitation for trauma.
Patient blood management (PBM) is the timely application of evidence-informed medical and surgical concepts designed to maintain haemoglobin concentration, optimise haemostasis and minimise blood loss in an effort to improve patient outcomes. The aim of this consensus statement is to provide recommendations on the management of anaemia and haematinic deficiencies in pregnancy and in the post-partum period as part of PBM in obstetrics. A multidisciplinary panel of physicians with expertise in obstetrics, anaesthesia, haematology, policymaking and epidemiology was convened by the Network for the Advancement of Patient Blood Management, Haemostasis and Thrombosis (NATA) in collaboration with the International Federation of Gynaecology and Obstetrics (FIGO) and the European Board and College of Obstetrics and Gynaecology (EBCOG). Members of the task force assessed the quantity, quality and consistency of the published evidence and formulated recommendations using the system developed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group. The recommendations in this consensus statement are intended for use by clinical practitioners managing the perinatal care of women in all settings and by policymakers in charge of decision making for the update of clinical practice in health-care establishments. They need to be tailored for application in individual patients or any population after consideration of the values and preferences of both health-care providers and patients, as well as equity issues; explicit assessment of harms and benefits of each recommendation; feasibility including resources, capacity and equipment; and implementability.
This narrative review examines current research on risk factors, prevention methods and management strategies for vasovagal reactions (VVRs) that occur during or as a result of blood donation. VVRs are important to blood collection agencies (BCAs) as they negatively impact the number of completed collections, perceptions of the safety of blood donation and rates of donor return. There has been significant progress in understanding and preventing VVRs in blood donation in recent years, with a multitude of risk factors identified. This has resulted in many BCAs implementing evidence‐based strategies, such as donor age and weight restrictions. However, the profile of our most vulnerable donors and features of the donation setting that may protect these donors from experiencing a VVR have not been identified. Furthermore, an increased number of trials of physiological and psychological prevention interventions to reduce both immediate and delayed VVRs have been reported. However, a lack of methodological consistency in operationalising interventions to reduce or prevent VVRs means that the identification of effective VVR prevention strategies remains a challenge for practitioners. Furthermore, research is still required to determine how to successfully implement prevention and management strategies into standard operating procedures within collection centres. Finally, research in the management and mitigation of the effect of VVRs is currently only suggestive of what should be done to care for the donor who reacts and how to empower those donors to return. Collectively, research into these aspects of VVRs will provide support to donors and BCAs and improve the safety of blood donation.
Platelet additive solutions (PASs) are becoming increasingly popular for storage of platelets, and PAS is steadily replacing plasma as the storage medium of platelets. PASs are electrolyte solutions intended for storage of platelets, and they are used to modulate the quality of the platelets by adding specific ingredients. All currently available PASs contain acetate. Acetate reduces the amount of glucose that is oxidised into lactic acid and thereby prevents the lowering of pH, which decreases platelet quality. Furthermore, the oxidation of acetate leads to the production of bicarbonate, which serves as buffer. The presence of potassium and magnesium in PAS prevents the lowering of pH and reduces the degree of spontaneous activation of the platelets during storage. In the hospital, platelets stored in PAS result in about half of the number of allergic transfusion reactions as compared with platelets in plasma. Recovery and survival after transfusion, as well as corrected count increments, are at least as good for platelets in PAS as for plasma, and recent data suggest they may even be better. Therefore, with the current generation of PASs, PAS should be preferred over the use of plasma for the storage of platelet concentrates.
Background Fibrinogen replacement is critical in major obstetric haemorrhage (MOH). Purified, pasteurised fibrinogen concentrate appears to have benefit over cryoprecipitate in ease of administration and safety but is unlicensed in pregnancy. In July 2009, the Irish Blood Transfusion Service replaced cryoprecipitate with fibrinogen. Objectives To examine the impact of this externally imposed change on blood product use and clinical outcomes in MOH. Methods Women with MOH requiring fibrinogen between 1 January 2009 and 30 June 2011 were identified from an MOH database. Aetiology of MOH, medical treatments, blood product use and clinical outcomes were compared between the cryoprecipitate and fibrinogen groups. Results Of 21 614 deliveries, 77 cases of MOH were identified. Of the 77 cases, 34 (44%) received cryoprecipitate (n?=?14) or fibrinogen concentrate (n?=?20). The mean (+/- SEM) dose utilised was 2.21 +/- 0.35 pools of cryoprecipitate and 4 +/- 0.8 g of fibrinogen. There was a stronger correlation between the increase in fibrinogen level and dose of fibrinogen (Pearson co-efficient 0.5; P?=?0.03) than dose of cryoprecipitate (Pearson co-efficient 0.32; P?=?0.3). Mean (+/- SEM) estimated blood loss (EBL), red cell concentrate (RCC) and Octaplas transfused were greater (but not significantly) in the cryoprecipitate group compared with the fibrinogen group; EBL?=?5.2 +/- 1.1 vs 3.3 +/- 0.5 L (P?=?0.1); RCC?=?7.2 +/- 1.2 vs 5.9 +/- 1.0 U (P?=?0.4); Octaplas?=?4.1 +/- 0.7 vs 3.2 +/- 0.7 U (P?=?0.36), respectively. Haemostasis was secured, and there were no adverse reactions or thrombotic complications. Conclusion Purified virally inactivated fibrinogen concentrate is as efficacious as cryoprecipitate in correcting hypofibrinogenaemia in MOH.
With the development of several ‘vein‐to‐vein’ databases, which capture data on the entire donor–recipient continuum and link this data to health outcomes, there has been an increasing number of studies investigating the health effects of all aspects of the practice of transfusion medicine. The Scandinavian Donations and Transfusions (SCANDAT) database is one of several such databases, which includes all electronically available data on blood donors, donations and transfusions since the late 1960s in Sweden and the early 1980s in Denmark. The SCANDAT database has been used to characterise disease occurrence among blood donors and transfused patients, as well as to investigate possible health effects of blood donations, aspects of transfusion care and possible transfusion transmission of disease. Recent publications include studies on recipient mortality associated with the storage lesion, studies on the effects of donor demographics on patient mortality and health effects of frequent blood donation. Although this research approach is clearly very powerful, the appropriate analysis of such real‐world data is complex and requires close methodological attention. The purpose of this review is to present some of the research conducted within the SCANDAT collaboration. We hope more international collaboration may help improve our understanding of the important remaining questions about donor and recipient health.
Aims This study aimed at quantifying the healthy donor effect by comparing self-perceived mental and physical health between blood donors and non-donors. Background In theory, the selection process known as the healthy donor effect should result in better self-perceived, health-related quality of life in donors than in non-donors. Methods The Short Form-12 data from the Danish Twin Registry (DTR) was compared with the data from the Danish Blood Donor Study (DBDS). Data on age, sex and smoking status were included in the analyses. The multivariable linear regression analysis was stratified by sex and age group intervals. Outcome variables were the mental component score (MCS) and the physical component score (PCS). Results A total of 28 982 and 36 913 participants from the DTR and the DBDS, respectively, were included in this study. Younger donors had higher MCS than non-donors, whereas MCS was only marginally high in older donors compared with non-donors. In contrast, PCS was almost similar for both young donors and non-donors. With the increase in age, non-donors had lower PCS than donors. Conclusions Two selection patterns were revealed. Among young individuals, better self-perceived mental health was associated with a blood donor. With the increase in age, better self-perceived physical health was associated with blood donation.
Objectives The aim of this study was to characterise a novel mutation in the gene encoding RhAG in order to elucidate a molecular mechanism for Rh antigen expression and spherocytosis. Background Rhesus-associated glycoprotein (RhAG) is critical for maintaining the structure and stability of erythrocytes. Single missense mutations in the gene encoding RhAG are sufficient to induce spherocytosis and deficiencies in Rh complex formation. We report a novel missense mutation that incompletely disrupts Rh antigen expression and selectively knocks out RhD antigen expression. Methods Blood samples were taken from a 38-year-old male, his brother, his wife and his daughter in Xi'an, China. To detect the proband's RhAG and D antigen expression, the RBC were stained with anti-D and anti-RhAG and analysed by flow cytometry. Red blood cell morphology was detected with atomic force microscopy (AFM). Genomic DNA was isolated from whole blood samples, and the RHD, RHCE and RHAG alleles were sequenced and analysed. The mutation was mapped onto a predicted crystal structure of RhAG by the I-TASSER server and visualised using PyMOL. Results Morphological testing by AFM found clear evidence of spherocytosis in the proband's erythrocytes. RHAG gene sequencing identified the mutation at sequence 236G > A, resulting in a serine to asparagine substitution at residue 79 (S79N). Family survey indicated that inheriting this allele is necessary and sufficient to cause the condition. Mapping the mutation onto a predicted crystal structure of RhAG revealed the proximity of the mutation to the critical structural elements of the protein. Conclusions A novel RHAG mutation significantly lowers RhAG antigen expression and antigen-mediated agglutination intensity.
Objectives The aim of this research was to test a model integrating self-determination theory (SDT) and the theory of planned behaviour (TPB) to predict intention to donate blood. Background Social science research suggests that motivational orientations outlined by SDT can be usefully integrated with constructs from the TPB to collectively predict intention and behaviour. Such analysis has not yet been undertaken in the context of blood donation. Methods A total of 458 currently eligible donors completed measures of blood donor motivations, attitudes, subjective norms, perceived behavioural control (PBC) and intention. Path analyses modelled the direct and indirect effects (via TPB constructs) of motivational orientations on intention. Results SDT motivational orientations explained an additional 14% of the variance in blood donation intention, compared to a TPB-only model. Amotivation had a negative direct effect on intention; external regulation had no overall effect on intention; introjected regulation had positive direct and indirect effects on intention; and autonomous motivation predicted intention both directly as well as via attitudes, subjective norms and PBC. Conclusion This research provides the first evidence that integrating SDT and the TPB is a useful approach in donor research, particularly for specifying plausible pathways through which motivational orientations impact intention to donate blood.
Blood components collected from blood donors are an invaluable part of modern‐day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood donors is not reflected in a reduced self‐perceived mental and physical health. In general, the high proportion of iron‐deficient donors can be alleviated either by extending the inter‐donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark, is that routine ferritin measurements and iron supplementation are feasible and effective ways of reducing the proportion of donors with low haemoglobin levels.
summary . Indigenous hepatitis E is increasingly recognized in developed countries, where it may be a zoonosis. We describe the first case of transfusion‐transmitted hepatitis E in the UK from a blood donor who had no history of recent travel abroad. Follow‐up of the donor and recipients of the blood products was carried out using serological and molecular techniques. Acute hepatitis E was transmitted to one of two recipients. The infected patient would have received a larger volume of the donor's plasma. HEV subgenomic sequences carried by the donor and recipient were identical. This is the first case of post‐transfusion hepatitis E in the UK. Secondary transmission of hepatitis E indigenous to a nonhyperendemic country may occur by blood transfusion. It is important that blood donors inform the transfusion service of all post‐donation illnesses so that appropriate interventions can take place.