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.

Prevalence of anaemia before major joint arthroplasty and the potential impact of preoperative investigation and correction on perioperative blood transfusions.

BACKGROUND: Preoperative investigation and treatment of anaemia is recommended before orthopaedic surgery. We measured the prevalence of anaemia among admissions presenting for elective major joint arthroplasty (MJA), assessed their transfusion requirements, and investigated factors associated with perioperative blood transfusion. METHODS: All admissions to a dedicated elective orthopaedic hospital during 2000-2001 were studied. The patients' database was merged with the haematology and transfusion databases. Population estimates for different types of anaemia and their blood transfusion requirements were generated using local reference ranges (males <130 g litre(-1); females <115 g litre(-1)). RESULTS: One thousand three hundred and twenty-two admissions were included; haematology data were complete for 1142 (544 primary hip, 490 primary knee, 77 revision hip, 31 revision knee). About 19.6% were anaemic [7.1% haemoglobin (Hb) <110 g litre(-1); 1.6% Hb<100 g litre(-1)]. Overall, 21.3% of admissions were transfused (mean 0.58 units per case: 95% CI 0.50-0.61). For anaemic admissions, 42.0% were transfused (mean 1.11 units per case: 95% CI 0.90-1.32). Mean red cell use for admissions with normocytic normochromic anaemia (12.7% of admissions) and hypochromic anaemia (4.6%) was 1.04 (95% CI 0.78-1.31) and 1.14 (95% CI 0.71-1.57) units per admission, respectively. Factors strongly associated independently with transfusion were preoperative haemoglobin

The EU optimal blood use project.

The EU optimal blood use project (EUOBUP) is co-funded by the European Commission and led by the Scottish National Blood Transfusion Service (SNBTS). Its purpose is to develop, evaluate and disseminate a manual that provides practical guidance and support for those seeking to improve the safety of the clinical transfusion process and the effectiveness of the prescribing of blood components. We define the optimal use of blood components as the safe, clinically effective and efficient use of the scarce resource of donated human blood. The project will build on the experience of a pilot project in optimal use of blood in the national health service in Scotland. This pilot developed training resources in the safe and effective use of blood and delivered training to a large number of practitioners. It has also developed systems to provide hospitals with comparative information on their use of blood components for specific clinical groups of patients to assist them in reviewing practice against that of their peers.

Appraisal of the evidence for the clinical use of FFP and plasma fractions.

Randomised, controlled trials of good quality are a recognised means to robustly assess the efficacy of interventions in clinical practice. A systematic identification and appraisal of all randomised trials involving fresh frozen plasma (FFP) indicates that most clinical indications for FFP, as currently recommended by practice guidelines, are not supported by evidence from randomised trials. This chapter will largely consider the implications of some of the findings from this systematic review. Many published trials on the use of FFP have enrolled small numbers of patients, and provided inadequate information on the ability of the trial to detect meaningful differences in outcomes between the two patient groups. Other concerns about the design of the trials include the dose of FFP used, and the potential for bias; no studies had taken adequate account of the extent to which adverse effects might negate the clinical benefits of treatment with FFP. In addition, there is little evidence for the effectiveness of the prophylactic use of FFP. There is a pressing need to consider how best to develop new trials to determine the effectiveness of FFP. How this can be achieved can be illustrated by reference to studies of albumin in critical care. A recent, large and well-designed randomised trial (Saline versus Albumin Fluid Evaluation study; SAFE) in critical care found no evidence of an increase in mortality with the use of albumin compared to saline, which had been hypothesised in an earlier systematic review. How the study findings will actually now influence the clinical use of albumin remains to be seen. Although the SAFE trial showed no increase in mortality with albumin compared with saline, it is difficult to justify its use in critical care given its considerably greater cost.

Anaemia and red blood cell transfusion in the critically ill patient.

Anaemia is a common finding in critically ill patients. There are often multiple causes. Obvious causes include surgical bleeding and gastrointestinal haemorrhage but many patients have no overt bleeding episodes. Phlebotomy can be a significant source of blood loss. In addition, critically ill patients have impaired erythropoiesis as a consequence of blunted erythropoietin production and direct inhibitory effects of inflammatory cytokines. The ability of a patient to tolerate anaemia depends on their clinical condition and the presence of any significant co-morbidity; maintenance of circulating volume is of paramount importance. There is no universal transfusion trigger. Current guidelines for critically ill and perioperative patients advise that at Hb values <70 g/L red blood cell transfusion is strongly indicated and at Hb values >100 g/L transfusion is unjustified. For patients with Hb values in the range 70 to 100 g/L the transfusion trigger should be based on clinical indicators. Most stable critically ill patients can probably be managed with a Hb concentration between 70 and 90 g/L. Uncertainties exist concerning the most appropriate Hb concentration for patients with significant cardio-respiratory disease.

Humoral defence factors in the breast milk of Ethiopian women with leprosy and healthy controls.

Secretory IgA, lactoferrin, albumin, and total protein were quantitated in colostrum and milk samples obtained from 215 Ethiopian nursing mothers over a period ranging from 1 day to 2 yr postparturition. IgG, IgM, C3, and C4 complement components were quantitated in 11 day 1 samples. The subjects were classified into three groups: lepromatous leprosy, borderline lepromatous leprosy, and a nonlepromatous group consisting of women with tuberculoid leprosy and healthy controls. Results obtained from the above groups were also compared with a group from Edinburgh. No major variation in levels of secretory IgA, lactoferrin, albumin, and total protein was found between the three groups of Ethiopian women. Results from the Edinburgh group were significantly higher, mainly in the level of total protein. When the individual proteins were expressed as a percentage of the total protein, there was no difference between the milk samples from the Ethiopian and Edinburgh mothers.

Measurement of human and mouse anti-tetanus antibodies and isotype analysis by ELISA.

A rapid and sensitive enzyme immunoassay (ELISA) was developed for the quantitation of anti-tetanus antibodies. This technique was used to measure antibody levels in the plasma of immunized donors, in human anti-tetanus IgG preparations and in human and mouse hybridomas producing monoclonal antibodies to tetanus toxoid. The assay was capable of detecting antibody levels as low as 5 X 10(-4) IU/ml. By inclusion of an extra step involving antibodies to mouse Ig isotypes, a sandwich enzyme immunoassay (SEI) was developed which permitted determination of the Ig isotype of mouse anti-tetanus antibodies including tetanus-specific mouse monoclonal antibodies. SEI confirmed Protein A-Sepharose fractionation of mouse ascites fluid containing anti-tetanus antibody. The tetanus toxoid-coated plates have a shelf life of at least 1 year.

Enhancement of factor VIII-von Willebrand factor ristocetin cofactor activity by monoclonal antibodies.

Five monoclonal antibodies to human von Willebrand factor were selected for characterization from 18 produced in murine hybridomas. All showed a high and specific affinity for human von Willebrand factor (vWf) but exhibited little if any cross-reaction with sera from other species. The antibodies defined four epitopes on vWf, none of which were involved in platelet binding. Binding of two distinct antibodies at one of these epitopes was associated with enhancement of the rate of vWf-dependent platelet agglutination in the presence of ristocetin. This effect was more noticeable when cryosupernatant plasma was used in place of normal plasma as the source of vWf, and was not explicable simply in terms of antibody-induced cross-linking of vWf.

Milk protein concentrations in galactorrhoeic mammary secretions.

Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA) or single radial immunodiffusion (IgG, lactoferrin, lysozyme and albumin) in the mammayr secretions of one nulliparous and three parous female patients with galactorrhoea due to hyperprolactinaemia. Concentrations of all the proteins studied were found to be similar to the concentrations observed in post-partum colostrum. In particular, secretory IgA was the only form of IgA detected in galactorrhoeic secretions. It is suggested that hyperprolactinaemia alone can result in increased mammary synthesis of the milk proteins since the steroid changes associated with a full-term pregnancy and delivery of the placenta did not immediately precede the galactorrhoea in three of the four patients studied.

Milk protein concentrations in the mammary secretions of non-lactating women.

Milk protein concentrations were determined either by double antibody radioimmunoassay (IgA and IgG) or single radial immunodiffusion (lactoferrin) in the mammary secretions of seven healthy non-lactating subjects and eight patients with breast disease. IgA and IgG were detected in all samples of breast secretion (whether from normal or diseased breasts) and the concentrations observed were very similar to those in post-partum colostrum and milk. However, because the volume of secretion obtained was very small compared with colostrum and milk, total IgA synthesis by the non-lactating breast is very much less than in the lactating breast. The IgA detected in the mammary secretions was demonstrated to be secretory IgA by gel filtration and it is therefore suggested that the secretory immune system is functional in the non-lactating breast.

Characterisation of mouse monoclonal antibodies produced by immunisation with a single serotype component of a polyvalent Pseudomonas aeruginosa vaccine.

Mouse monoclonal antibodies raised by immunisation with a protective antigen extract from Pseudomonas aeruginosa serotype 1 varied in immunoglobulin isotype, in passive protective properties against infection by homologous P. aeruginosa serotype 1, and in cross-reactions in ELISA against antigen preparations from 15 other P. aeruginosa serotypes. All monoclonal antibodies with specificity in ELISA for the immunising antigen gave some degree of protection to mice against lethal infection by the homologous P. aeruginosa serotype. The IgG antibodies were more protective than the IgM antibodies.

An evaluation of the safety of three intravenous immunoglobulin preparations in patients with primary hypogammaglobulinaemia.

In an open study, three different immunoglobulin preparations for intravenous use (IV IgG), namely pH4 and pepsin treated immunoglobulin ('Sandoglobulin'); reduced and alkylated immunoglobulin ('Gamimune') as well as ultrafiltered, pH4 and pepsin treated immunoglobulin manufactured by the Scottish National Blood Transfusion Service ('SNBTS IV IgG'), were compared with intramuscular immunoglobulin (IM IgG) in five patients with primary hypogammaglobulinaemia, by treating each patient consecutively with each immunoglobulin preparation for 3 months. Few adverse reactions were noted with any of the intravenous immunoglobulin preparations and these mainly consisted of mild fever (less than 38 degrees C). Concentrations of serum IgG were higher with all intravenous immunoglobulin preparations compared with IM IgG. Furthermore, all the patients preferred IV to IM IgG therapy. As higher doses of immunoglobulin are associated with a reduction in infections in hypogammaglobulinaemic patients, we conclude that intravenous immunoglobulin therapy should be considered for the prophylaxis of infection in patients with primary hypogammaglobulinaemia.

Double-blind comparative trial of standard (commercial) and antibody-affinity-purified tetanus toxoid vaccines.

Tetanus toxoid purified by antibody-affinity chromatography, was compared with conventionally purified material in a double-blind trial in 205 healthy blood donors. There was neither any difference in immunogenicity as assessed by enzyme-linked immunoassay nor in side-reactions between the two vaccines. This study confirms that side-reactions to tetanus toxoid are not eliminated by purifying it.

Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.

BACKGROUND: Most clinical practice guidelines recommend restrictive red cell transfusion practices with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers). OBJECTIVES: To examine the evidence on the effect of transfusion thresholds, on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: Trials were identified by: computer searches of OVID Medline (1966 to December 2000), Current Contents (1993 to Week 48 2000), and the Cochrane Controlled Trials Register (2000 Issue 4). References in identified trials and review articles were checked and authors contacted to identify any additional studies. SELECTION CRITERIA: Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where the intervention groups were assigned on the basis of a clear transfusion "trigger", described as a haemoglobin (Hb) or haematocrit (Hct) level below which a RBC transfusion was to be administered. DATA COLLECTION AND ANALYSIS: Trial quality was assessed using criteria proposed by Schulz et al. (1995). Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials using a random effects model. MAIN RESULTS: Ten trials were identified that reported outcomes for a total of 1780 patients. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 42% (RR=0.58: 95%CI=0.47,0.71). This equates to an average absolute risk reduction (ARR) of 40% (95%CI=24% to 56%). The volume of RBCs transfused was reduced on average by 0.93 units (95%CI=0.36,1.5 units). However, heterogeneity between these trials was statistically significant (p<0.00001) for these outcomes. Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. Trials were of poor methodological quality. REVIEWER'S CONCLUSIONS: The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

Clinicians' satisfaction with a hospital blood transfusion service: a marketing analysis of a monopoly supplier.

One of the objectives of the NHS reforms is to improve customer focus within the health service. In a study to assess the quality of customer service provided by the Edinburgh and South East Scotland Blood Transfusion Service a 19 item questionnaire survey of the main clinical users of the service was performed to ascertain their satisfaction, measured on a 5 point anchored scale, with important aspects of the service, including medical consultation, diagnostic services, blood and blood components or products and their delivery, and general satisfaction with the service. Of 122 clinicians in medical and surgical disciplines in five hospitals in Edinburgh, 72 (59%) replied. Fourteen (22%) indicated dissatisfaction with any aspect of the medical consultation service, owing to inadequate follow up of clinical contacts and unsatisfactory routing of incoming calls. Diagnostic services were criticised for the presentation, communication, and interpretation of results. The restricted availability of whole blood, the necessity to order platelets and plasma through the duty blood transfusion service doctor, and the use of a group and screen policy, attracted criticism from a small number of clinicians. Ten of 68 respondents expressed dissatisfaction with delivery of blood and components to the wards and theatres. The findings indicate that the clinicians served by this blood transfusion service are largely satisfied with the service. Changes are being implemented to improve reporting of laboratory results and measures taken to improve liaison with clinicians.

Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports.

OBJECTIVE: To receive and collate reports of death or major complications of transfusion of blood or components. DESIGN: Haematologists were invited confidentially to report deaths and major complications after blood transfusion during October 1996 to September 1998. SETTING: Hospitals in United Kingdom and Ireland. SUBJECTS: Patients who died or experienced serious complications, as defined below, associated with transfusion of red cells, platelets, fresh frozen plasma, or cryoprecipitate. MAIN OUTCOME MEASURES: Death, "wrong" blood transfused to patient, acute and delayed transfusion reactions, transfusion related acute lung injury, transfusion associated graft versus host disease, post-transfusion purpura, and infection transmitted by transfusion. Circumstances relating to these cases and relative frequency of complications. RESULTS: Over 24 months, 366 cases were reported, of which 191 (52%) were "wrong blood to patient" episodes. Analysis of these revealed multiple errors of identification, often beginning when blood was collected from the blood bank. There were 22 deaths from all causes, including three from ABO incompatibility. There were 12 infections: four bacterial (one fatal), seven viral, and one fatal case of malaria. During the second 12 months, 164/424 hospitals (39%) submitted a "nil to report" return. CONCLUSIONS: Transfusion is now extremely safe, but vigilance is needed to ensure correct identification of blood and patient. Staff education should include awareness of ABO incompatibility and bacterial contamination as causes of life threatening reactions to blood.

Tolerance of Scottish National Blood Transfusion Service intravenous immunoglobulin in patients with primary hypogammaglobulinaemia: report of 1235 infusions.

A total of 1235 immunoglobulin infusions were carried out as replacement therapy in 37 patients suffering from primary hypogammaglobulinaemia from 1983 to 1987, using Scottish National Blood Transfusion Service (SNBTS) IV IgG, manufactured by cold ethanol fractionation of plasma, ultrafiltration and mild pepsin proteolysis at pH4. Ten patients experienced adverse reactions during 34 infusions (2.8% of all infusions) and all but five were mild; 21 (62%) of the adverse reactions were encountered in the patients' first five infusions. A maximum immunoglobulin infusion rate of 5 mg/kg/min was tolerated without adverse reaction.