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BACKGROUND Bone marrow biopsy (BMB) is an accepted investigation in fever of unknown origin (FUO) to uncover haematological malignancies, such as lymphoma, and sometimes infections. With the advance in imaging modalities, such as 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to identify the focus of lymphoma, BMB may not contribute to the diagnosis when there are no other clinical features to suggest an underlying haematological disease. AIM To investigate the utility of BMB in determining the cause of FUO, when there are no other indications for BMB. METHODS Medical records of adult patients who had BMB performed for FUO or febrile illness from 1 January 2005 to 31 December 2014 in four metropolitan tertiary hospitals in Melbourne, Australia were reviewed. Patients with other concurrent indications for BMB, known human immunodeficiency virus infection and previously diagnosed connective tissue diseases were excluded. RESULTS Seventy-three patients were included in the study. Fifty-one patients had a final diagnosis for fever (systemic inflammatory diseases, infective, malignancy or other) while 22 patients had no diagnoses. In only 10 patients (13.7%) did BMB contribute to the diagnosis, finding either malignancy or granulomata. However, all these diagnoses could have been made without BMB. Two patients with diffuse large B-cell lymphoma had normal BMB. FDG-PET was helpful in making a diagnosis in eight (25%) out of 32 patients. CONCLUSION Performing BMB in patients with FUO and no other haematological abnormalities is of very limited value, and other investigations, such as FDG-PET, may be more likely to help establish a definitive diagnosis.

Acquired aplastic anaemia is a rare, serious, immunologically mediated bone marrow failure syndrome, characterised by marrow hypoplasia of varying severity and significant pancytopenia. Careful attention and investigation, including molecular testing, is required to confirm the diagnosis and exclude other mimicking conditions, such as inherited bone marrow failure syndromes. In a proportion of patients, the disease evolves to myelodysplasia or acute myeloid leukaemia and in some there is an association with paroxysmal nocturnal haemoglobinuria. The disease has a major impact on patient quality of life. Haemopoietic stem/progenitor cell transplantation for eligible patients with an available donor is the only current curative therapy. Other patients may receive immunosuppression, most commonly with anti-thymocyte globulin and cyclosporin. An initial response to immunosuppression is often encouraging, but relapse is common. Supportive care, including management of transfusion requirements and infections, is central to management. Promising new diagnostic tools and emerging therapies will likely transform approaches to this important, chronic and life-threatening condition.

Background:Treatment of hematological malignancies with conventional DNA-damaging drugs, such as chlorambucil (CLB), commonly results in p53-dependent chemo-resistance. Chromatin modifying agents, such as histone deacetylase inhibitors (HDACIs), sodium butyrate (NaBu) and trichostatin A (TSA), may reverse chemo-resistance by modulating the activity of chromatin remodeling enzymes and/or genes that control cell proliferation, differentiation and survival.Objective:This study examined the potential use of HDACIs and CLB combination therapies in an in vitro chemo-resistant leukemia model.Methods:The p53-null promyelocytic leukemia cell line, HL60, was used as an in vitro model of chemo-resistant leukemia. Drug cytotoxicity was determined by tetrazolium salt-based colorimetric assays and Annexin V/propidium iodide staining (flow cytometry). The level of mRNA expression of the chromatin modifying genes was measured by quantitative real-time PCR.Results:Micromolar concentrations of CLB combined with either NaBu or TSA triggered synergistic cytotoxic effects in HL-60 cells (p < 0.001). The effects of the combination treatments resulted in upregulated p21 gene expression (up to 59-fold; pConclusion:The combination treatment of p53-null HL-60 cells with DNA-damaging agent CLB and HDACIs NaBu and TSA triggered additive to synergistic effects on apoptosis and upregulated BCL6 and p21 expression. These findings reveal BCL6 and p21 as potential targets of chemo-resistance for the development of anti-leukemic drugs.

BACKGROUND: Transfusion of platelets is common in cardiac surgery, and while there are guidelines for their use, there are concerns about potential risks. We aimed to assess the impact of platelet transfusion on mortality, thrombosis, and infection in this patient group. STUDY DESIGN AND METHODS: A retrospective cohort study of all patients at St Vincent's Hospital Melbourne who underwent a first cardiac surgery procedure from June 2001 to June 2014 was conducted. A propensity-weighted analysis was performed to examine the association between intraoperative platelet transfusion and outcomes. RESULTS: A total of 5233 patients met inclusion criteria, and 531 (10.15%) received intraoperative platelet transfusion (median two platelet doses, interquartile range, 1-17). Patients receiving platelets were older, had higher body mass index, lower rates of diabetes and dyslipidemia, higher rates of infective endocarditis, recent myocardial infarction and unstable angina, and exposure to aspirin or clopidogrel. On univariable analysis, platelet transfusion was associated with increased 30-day mortality (2.4% vs. 10.55%, p

In recent years, the anti-CD38 monoclonal antibody daratumumab (Darzalex; Janssen-Cilag Pty Ltd) has been shown to be highly efficacious in relapsed and refractory multiple myeloma, with the final results of treatment in newly diagnosed patients awaited. Despite awareness of the potential interference of daratumumab in pre-transfusion immunohaematology testing during phase I and II clinical studies, there was a degree of unpreparedness in the community upon the introduction of this drug into the clinics, particularly the impact that it has on the operational processes in hospital transfusion laboratories and timely issue of red blood cells (RBCs). Anti-CD38 interference in pre-transfusion immunohaematology tests is a particular problem in patients being treated with daratumumab for multiple myeloma as many will require RBC transfusions during their disease treatment. Panagglutination caused by anti-CD38 monoclonal antibody during the indirect antiglobulin test may mask the presence of a clinically significant RBC alloantibody in the patient's plasma during the antibody screen and identification process, which may be overlooked, particularly in urgent situations, subsequently resulting in a delayed or acute haemolytic transfusion reaction. Here, we summarise daratumumab's effects on pre-transfusion immunohaematology testing and its impact on clinical practice and make practical recommendations based on a consensus from medical and scientific transfusion experts and myeloma specialists on behalf of the Australian and New Zealand Society of Blood Transfusion and Myeloma Scientific Advisory Group to Myeloma Australia, respectively.

Objective The aim of the study is to describe the epidemiology of major bleeding fatalities. Methods A case series analysis of Australia's National Coronial Information System was conducted. Keywords were used to search for closed cases of major haemorrhage in the state of Victoria for the period 1 January 2009 to 31 December 2011. Coroners' findings, autopsy reports and police reports of cases were reviewed. Demographic data were extracted, and cases were assigned to a clinical bleeding context. Results A total of 427 cases of major bleeding causing death were identified. The cohort was predominately men (69%), with a median age of 63 years (interquartile range 45-77 years). Trauma accounted for 38%, gastrointestinal haemorrhage 28%, surgical/procedural bleeding 14%, ruptured/leaking aneurysms 12% and other 8%. Most events began in homes (46%), hospitals (22%) and at the roadside (17%). Of those whose haemorrhage began in the community, 69% did not survive to hospital. Conclusions Major bleeding fatalities occurred across a diverse range of contexts, with trauma and gastrointestinal bleeding accounting for most deaths. The majority of patients did not survive to reach hospital. Major haemorrhage occurring entirely outside hospital may be underrecognised from analyses of datasets based primarily on traumatic or in-hospital bleeding. These findings have implications for management of pre-hospital resuscitation and development of clinical practice guidelines for identification and management of major bleeding in the community.

In patients with anemia, transfusion of red blood cells (RBCs) can save lives and improve quality of life. The choice to transfuse should be cautiously made owing to risks of transfusion, economic costs, and limitations on the blood supply. Until the 1980s, the decision for RBC transfusion was guided by Hb threshold, with the aim of maintaining the patient's blood Hb level over 100 grams per liter. Since then, multiple randomized controlled trials and key systematic reviews have provided evidence-based guidelines as to appropriate transfusion thresholds in a number of clinical settings. Here, we aimed to address the outcome of defining different anemia criteria in specific clinical populations exclusively on the basis of the need for RBC transfusion based on Hb concentration. We focused on the patient populations, where there were the most available data on differing transfusion thresholds, which looked at transfusing to a higher or liberal transfusion threshold in comparison with a lower or restrictive transfusion threshold. These included patients in intensive care with or without septic shock, hip fracture surgery, cardiovascular surgery, and upper gastrointestinal bleeding, the pediatric population, and also those with malaria, by reviewing key randomized controlled trials and systematic reviews. Twenty-four randomized controlled studies and 12 systematic reviews have been included, and these are discussed below.

SUMMARYObjectives To evaluate the use of routinely collected data to determine the cause(s) of critical bleeding in patients who receive massive transfusion (MT). Background Routinely collected data are increasingly being used to describe and evaluate transfusion practice. Materials/methods Chart reviews were undertaken on 10 randomly selected MT patients at 48 hospitals across Australia and New Zealand to determine the cause(s) of critical bleeding. Diagnosis-related group (DRG) and International Classification of Diseases (ICD) codes were extracted separately and used to assign each patient a cause of critical bleeding. These were compared against chart review using percentage agreement and kappa statistics. Results A total of 427 MT patients were included with complete ICD and DRG data for 427 (100%) and 396 (93%), respectively. Good overall agreement was found between chart review and ICD codes (78·3%; κ = 0·74, 95% CI 0·70–0·79) and only fair overall agreement with DRG (51%; κ = 0·45, 95% CI 0·40–0·50). Both ICD and DRG were sensitive and accurate for classifying obstetric haemorrhage patients (98% sensitivity and κ > 0·94). However, compared with the ICD algorithm, DRGs were less sensitive and accurate in classifying bleeding as a result of gastrointestinal haemorrhage (74% vs 8%; κ = 0·75 vs 0·1), trauma (92% vs 62%; κ = 0·78 vs 0·67), cardiac (80% vs 57%; κ = 0·79 vs 0·60) and vascular surgery (64% vs 56%; κ = 0·69 vs 0·65). Conclusion Algorithms using ICD codes can determine the cause of critical bleeding in patients requiring MT with good to excellent agreement with clinical history. DRG are less suitable to determine critical bleeding causes.

Background There continues to be uncertainty about the optimal approach to documenting bleeding data in platelet transfusion trials, with a desire to apply a common assessment tool across all trials. With this in mind, a consensus bleeding assessment tool (BAT) has been developed by the Biomedical Excellence for Safer Transfusion (BEST) collaborative, based on review of data collection forms used in published randomized trials and following content validation with a range of healthcare professionals at seven haematology centres through BEST members. This study aimed to evaluate reliability and reproducibility of the consensus BAT. Methods Replicated clinical assessments of bleeding were undertaken by participants with haematological malignancies recruited at four haematology centres in an international, multicentred, observational study. Concordance of repeat assessments was calculated for agreement in site and grade of bleeding observed. Results Forty patients consented to participate, and 13 trained bleeding assessors collected these data. Bleeding assessments were carried out on 113 separate days. Of all 225 bleeding assessments, 204 were compared for grade concordance, and 160 were compared for site concordance. There was very good grade concordance (83%, 95% confidence interval 74–93%) and good bleeding site concordance (69%, 95% confidence interval 57–79%) in observations of bleeding. Discordance was primarily in relation to assessing skin bleeding. Conclusions Alongside a structured training programme, levels of concordance for a consensus BAT were high. Researchers using assessment tools for bleeding need to balance comprehensive data collection against potential loss of accuracy for some types of bleeding, such as skin findings.

Acquired aplastic anaemia is a rare, serious, immunologically mediated bone marrow failure syndrome, characterised by marrow hypoplasia of varying severity and significant pancytopenia. Careful attention and investigation, including molecular testing, is required to confirm the diagnosis and exclude other mimicking conditions, such as inherited bone marrow failure syndromes. In a proportion of patients, the disease evolves to myelodysplasia or acute myeloid leukaemia and in some there is an association with paroxysmal nocturnal haemoglobinuria. The disease has a major impact on patient quality of life. Haemopoietic stem/progenitor cell transplantation for eligible patients with an available donor is the only current curative therapy. Other patients may receive immunosuppression, most commonly with anti-thymocyte globulin and cyclosporin. An initial response to immunosuppression is often encouraging, but relapse is common. Supportive care, including management of transfusion requirements and infections, is central to management. Promising new diagnostic tools and emerging therapies will likely transform approaches to this important, chronic and life-threatening condition.

Objective To assess whether introduction of universal leukodepletion (ULD) of red blood cells (RBCs) for transfusion was associated with improvements in cardiac surgery patient outcomes. Methods Retrospective study (2005-2010) conducted at 6 institutions. Associations between leukodepletion and outcomes of mortality, infection, and acute kidney injury (AKI) were modeled by logistic regression, and intensive care unit length of stay (LOS) in survivors was explored using linear regression. To examine trends over time, odds ratios (ORs) for outcomes of transfused were compared with nontransfused patients, including a comparison with nontransfused patients who were selected based on propensity score for RBC transfusion. Results We studied 14,980 patients, of whom 8857 (59%) had surgery pre-ULD. Transfusions of RBCs were made in 3799 (43%) pre-ULD, and 2525 (41%) post-ULD. Administration of exclusively leukodepleted, versus exclusively nonleukodepleted, RBCs was associated with lower incidence of AKI (adjusted OR 0.80, 95% confidence interval [CI] 0.65-0.98, P = .035), but no difference in mortality or infection. For post-ULD patients, no difference was found in mortality (OR 0.96, 95% CI 0.76-1.22, P = .76) or infection (OR 0.91, 95% CI 0.79-1.03, P = .161); however, AKI was reduced (OR 0.79 95% CI 0.68-0.92, P = .003). However, ORs for post-ULD outcomes were not significantly different in nontransfused, versus transfused, patients. Furthermore, those who received exclusively nonleukodepleted RBCs were more likely to have surgery post-ULD. Conclusions Universal leukodepletion was not associated with reduced mortality or infection in transfused cardiac surgery patients. An association was found between ULD and reduced AKI; however, this reduction was not significantly different from that seen in nontransfused patients, and other changes in care most likely explain such changes in renal outcomes.

Transfusion of platelets is common in cardiac surgery, and while there are guidelines for their use, there are concerns about potential risks. We aimed to assess the impact of platelet transfusion on mortality, thrombosis, and infection in this patient group.A retrospective cohort study of all patients at St Vincent's Hospital Melbourne who underwent a first cardiac surgery procedure from June 2001 to June 2014 was conducted. A propensity-weighted analysis was performed to examine the association between intraoperative platelet transfusion and outcomes.A total of 5233 patients met inclusion criteria, and 531 (10.15%) received intraoperative platelet transfusion (median two platelet doses, interquartile range, 1-17). Patients receiving platelets were older, had higher body mass index, lower rates of diabetes and dyslipidemia, higher rates of infective endocarditis, recent myocardial infarction and unstable angina, and exposure to aspirin or clopidogrel. On univariable analysis, platelet transfusion was associated with increased 30-day mortality (2.4% vs. 10.55%, p 0.001), return to theatre for bleeding (3.23% vs. 13.37%, p 0.001), and rates of any infection (9.26% vs. 19.17%, p 0.001). After adjusting for confounders, platelet transfusion was not associated with increased risk of 30-day mortality or infective complications. Platelet transfusion was associated with higher rates of return to theatre (relative risk [RR], 2.46; confidence interval [CI], 1.42, 4.04; p = 0.001) and decreased risk of thromboembolic events (RR, 0.28; CI, 0.15, 0.51; p 0.001).Platelet transfusion was not associated with increased mortality or infective complications following first cardiac surgery. Further prospective studies are required to identify patients most likely to benefit from platelet transfusion.

The aim of the study is to describe the epidemiology of major bleeding fatalities.A case series analysis of Australia's National Coronial Information System was conducted. Keywords were used to search for closed cases of major haemorrhage in the state of Victoria for the period 1 January 2009 to 31 December 2011. Coroners' findings, autopsy reports and police reports of cases were reviewed. Demographic data were extracted, and cases were assigned to a clinical bleeding context.A total of 427 cases of major bleeding causing death were identified. The cohort was predominately men (69%), with a median age of 63 years (interquartile range 45-77 years). Trauma accounted for 38%, gastrointestinal haemorrhage 28%, surgical/procedural bleeding 14%, ruptured/leaking aneurysms 12% and other 8%. Most events began in homes (46%), hospitals (22%) and at the roadside (17%). Of those whose haemorrhage began in the community, 69% did not survive to hospital.Major bleeding fatalities occurred across a diverse range of contexts, with trauma and gastrointestinal bleeding accounting for most deaths. The majority of patients did not survive to reach hospital. Major haemorrhage occurring entirely outside hospital may be underrecognised from analyses of datasets based primarily on traumatic or in-hospital bleeding. These findings have implications for management of pre-hospital resuscitation and development of clinical practice guidelines for identification and management of major bleeding in the community.

Background Fatigue is a common symptom in patients with advanced malignancy, and has been associated with both physiological and psychological factors in patients with solid tumours. Aim This study sought to explore the predictors of fatigue in a population with haematological malignancy. Methods Consecutive outpatients and inpatients attending a haematology centre completed the Memorial Symptom Assessment Scale, and clinical, treatment and demographic information were noted. Results Of 180 patients, fatigue was present in 69%, and causing considerable distress in 26%. Univariate analysis revealed fatigue was associated with poor performance status, low haemoglobin, feeling sad, worried, irritable and nervous. Multivariate modeling revealed that those factors predictive of fatigue were poor performance status, having active disease, feeling sad and irritable, while haemoglobin level was not predictive of fatigue. Conclusions Fatigue is a multidimensional symptom in patients with haematological malignancy whose presence must prompt a holistic assessment of potential contributors that goes beyond correction of haemoglobin levels.

Background Few studies have systematically identified factors associated with blood loss in musculoskeletal tumor surgery. We aimed to identify risk factors for requiring large-volume transfusion in musculoskeletal tumor surgery and created an interactive model to predict red blood cell transfusion requirements based on patient characteristics. These data will facilitate planning in hospital blood banks and aid identification of specific groups for future interventions targeted at reducing blood utilization. Only one similar study has been published and there are minimal data surrounding interventions designed to minimize blood loss in musculoskeletal tumor surgery. Study Design and Methods We retrospectively analyzed a database containing 1322 consecutive surgeries, performed at a quaternary referral center in Melbourne, Australia. Using logistic regression analysis and a negative truncated binomial logistic regression model, we developed prediction models for transfusion requirement. Results The following factors were associated with large-volume transfusion: malignant tumors, bone tumors, sacral and pelvic tumors, high American Society of Anesthesiologists (ASA) score, and tumor size of more than 5 cm. High ASA score was also strongly associated with 30-day mortality. Conclusions Preoperative planning in high-risk patients is critical to ensure adequate blood product supply, minimize wastage, and optimize the patient's general health before surgery. These patients would be ideal targets for future randomized studies aimed at reducing blood utilization.

Blood transfusion is not without risk. Although the risks of HIV and hepatitis transmission have diminished, haemovigilance programs highlight that other significant transfusion hazards remain. Sepsis from bacterial contamination is the most common residual infectious hazard in developed countries, and events due to clerical error are problematic. Unnecessary transfusions should be avoided. New national guidelines on patient blood management (PBM) emphasise holistic approaches, including strategies to reduce transfusion requirements. Perioperative PBM should incorporate preoperative haemoglobin and medication optimisation, intraoperative blood conservation, and consideration of restrictive postoperative transfusion and cell-salvage techniques. When massive transfusion is required, hospitals should implement massive transfusion protocols. These protocols reduce mortality, improve communication and facilitate adequate provision of blood products. They should include multidisciplinary team involvement and guidelines for use of blood components and adjunctive agents. Although fresh frozen plasma to red blood cell and platelet to red blood cell ratios of ≥ 1 : 2 appear to reduce mortality in trauma patients who receive massive transfusion, there is insufficient evidence to recommend specific ratios. Systematic reviews have found no significant benefit of recombinant activated factor VII in critical bleeding, and an increase in thromboembolic events; specialist haematology advice is therefore recommended when considering use of this agent. The National Safety and Quality Health Service Standards address use of blood and blood products, and provide important transfusion principles for adoption by all clinicians. Storage of red cells in additive solution results in changes, known as the "storage lesion", and studies to determine the clinical effect of the age of blood at transfusion are ongoing.

S. Panzer, S. Engelbrecht, M. F. Cole-Sinclair, E. M. Wood, S. Wendel, S. Biagini, Z. Zhu, J.-J. Lefrere, G. Andreu, T. Zunino, J.-J. Cabaud, P. Rouger, O. Garraud, K. Janetzko, M. Muller-Steinhardt, P. van der Burg, A. Brand, P. Agarwal, T. Triyono, A. Gharehbaghian, N. Manny, O. Zelig, A. Takeshita, Y. Yonemura, H. Fujihara, K. E. Nollet, H. Ohto, K.-S. Han, V. S. Nadarajan, G. Berlin, S. G. Sandler, R. G. Strauss & H. W. Reesink

BACKGROUND: Critically bleeding trauma patients require coordinated and efficient decision-making processes to ensure optimal management of their massive transfusion (MT) requirements. Human factors (HFs) is a discipline that investigates factors influencing work processes from the organizational, group, and individual levels. Given the complexity of trauma resuscitation, implementing any intervention for decision support in MT is challenging and may benefit from a HFs-assisted approach. STUDY DESIGN AND METHODS: A systematic review was performed to identify reports of the introduction of any type of decision support for the provision of MT in critically bleeding adult trauma patients. Crucial contributions reported to influence design and uptake of the intervention were categorized into four HFs categories (environment, human, machine, and task). Extracted information was supplemented by surveying the contact authors. Evidence of clinical practice changes resulting from the intervention was also considered. RESULTS: We identified nine studies that had reported an intervention implementing new practice guidelines or a MT protocol. All were before-and-after comparative cohort studies and used historical controls as the preintervention cohort. CONCLUSION: Based on the identified reports, this review provides a HFs-assisted approach to aid clinicians and policy makers with the implementation of decision support for MT in the trauma care setting.

Current evidence suggests that patients with hematological malignancies less frequently access palliative care services, and for those who do, this tends to occur later in their illness than their counterparts with solid malignancies. These patients are also more likely to die in hospital following escalating interventions. This approach to care that considers palliative care referral after most treatments are exhausted has implications for the quality of palliative care intervention possible. An episodic approach engaging palliative care according to needs rather than prognosis may be more valuable. The successful integration of palliative care into the care of hemato-oncological patients requires recognition by palliative care physicians of the particular issues encountered in care, namely, the difficulty in individual prognostication; ongoing therapeutic goals of curability or long term survival; the technical nature and complications of treatment; the speed of change to a terminal event; the need for pathology testing and transfusion of blood products as death approaches; the potentially reversible nature of intercurrent events such as infection; and the long relationships that develop between patients and their hematologists. Meanwhile, hematologists should be aware of the benefits of palliative care earlier in an illness trajectory and that palliative care does not equate to terminal care only. This review summarizes current practices and barriers to referral, and suggests recommendations for collaborative care and further research in the palliation of hemato-oncological patients. In doing so, it highlights to palliative care and hematology physicians how successful integration of their disciplines may improve their care of these patients.

Aim Correct patient and specimen identification and labelling are critical to ensuring that the correct results are issued for the right patient, and that medical decisions and treatments given on the basis of these test results are appropriate. This is particularly critical in pre-transfusion testing with the risk of ABO mismatch transfusion and potential fatality a real possibility. Background: Over 11 months, data relating to mislabelled specimens demonstrated a basal rate of 2 ‘wrong-blood-in-tube’(WBIT) incidents per month and 8 of 23 were for pre-transfusion testing. These incidents were detected only where inconsistencies either in clinical information or previous test results were apparent. Intervention Our pathology service developed a set of strict minimum identification criteria for ALL pathology specimens and a policy of rejection of specimens that do not comply. These criteria align with ANZSBT guidelines for pre-transfusion samples. An 8 week education and notification phase followed by strict application of the criteria in February 2004 and a subsequent follow-up phase was conducted. Result Smooth implementation of a major network-wide initiative has occurred over the last 5 months, as evidenced by the low specimen incident rate of 1%. Early indicators of success include an increased awareness of WBIT episodes with three self-reported episodes of WBIT since implementation. Unlabelled specimens have reduced by at least 50% compared to the same period prior to intervention. Conclusion Our experience may be of interest to other institutions considering similar initiatives. A reduction in WBIT events is the most preferred outcome, however it may be many months before this can be appreciated due to low detection levels.

Background and aim Three serious transfusion-related incidents over a 9 month period highlighted the clinical risk in transfusion during 2001–2002. This lead to the development of a strategy to comprehensively review and implement transfusion safety initiatives across the Bayside health network of which the Alfred is a major hospital. Intervention The initiative commenced in January 2003 with the assembly of a multi-disciplinary team that consisted of medical, nursing, scientific as well as hospital executive representation. This was possible with the appointment of a Transfusion Nurse as part of the Victorian Department of Human Services Blood Matters Collaborative and a Transfusion Medicine Registrar, co-appointed by the hospital and Australian Red Cross Blood Service. The activities consisted initially of process mapping blood transfusion practice. Key areas were then selected for targeting process improvement, namely; – Patient and product identification, – Sample labelling, – Blood component administration. Result Initiatives implemented were; – Widespread medical and nursing education on transfusion issues. – Increase transfusion information availability. – Network-wide implementation of strict criteria for specimen labelling (all specimens) in line with ANZSBT pre-transfusion testing guidelines. – Development of a pre-transfusion testing and blood request form. – Development of a blood administration form to reconcile all transfusion related documentation in the medical record. - Policy and guideline development. Conclusion Sustained improvement requires ongoing dedicated personnel to maintain gains, continue to audit practice, analyse incident data both actual adverse incidents as well as near-miss events and to respond to these challenges within an ongoing and operational quality improvement framework.

Anticoagulants have been implicated in up to 10% of all adverse drug events. In 2001, The Alfred established a Medication Safety Committee and identified warfarin therapy as a patient safety priority. Through process mapping and consultation, opportunities for error were identified throughout the warfarin prescribing, dispensing and administration processes. Clinicians considered review of prothrombin international normalised ratio results and routine warfarin dosing at 2000 hours as the most significant risk to patients. This was because warfarin was frequently prescribed by after-hours staff who were not familiar with the patient's history or changes in their clinical condition or medication. Clinicians participated in the development and implementation of a warfarin safety strategy that involved changing the dosing to 1600 hours and alert stickers affixed to drug charts by pharmacists to identify patients prescribed warfarin. This program was effective in improving staff management of inpatients receiving warfarin. It also demonstrated the importance of an effective change management strategy in establishing a sense of urgency in clinicians regarding safety, and engagement in process analysis, risk identification and the development of simple and practical safety strategies.

Summary The ratio of osteoprotegerin [OPG, tumour necrosis factor receptor superfamily, member 11b (TNFRSF11B)] to receptor activator of nuclear factor κB ligand [RANKL, tumour necrosis factor (ligand) superfamily, member 11 (TNFSF11)] in bone is critical for the regulation of bone remodelling. Myeloma cells can home to bone, triggering increased RANKL and decreased OPG expression by stromal cells, leading to osteolysis. Whether myeloma cells contribute directly to the pool of RANKL or OPG in bone has been contentious. Here we provide evidence of RANKL expression by reverse transcription polymerase chain reaction and in situ hybridization, demonstrating transcripts encoding both the membrane-bound and secreted forms of RANKL in five human multiple myeloma cell lines (LP-1, NCI-H929, OPM-2, RPMI8226, U266) and myeloma cells purified from bone marrow aspirates of myeloma patients. We demonstrated that RANKL encoding mRNAs are translated to protein by antibody detection of RANKL. In vitro assays showed that myeloma cells induced bone marrow derived mononuclear cells to differentiate into adherent tartrate-resistant acid phosphatase positive multinucleated cells, indicative of the formation of functional osteoclasts. This differentiation could also be achieved with passaged myeloma media alone, implicating secreted products. Finally, we provide evidence that the differentiation observed is at least in part the result of myeloma cell expression of RANKL. We therefore conclude that myeloma cells can directly contribute to the pool of RANKL in bone.

The BTK (Bruton's tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding. A previous study reported defects in collagen- and adenosine diphosphate (ADP)-dependent platelet responses when ibrutinib was added ex vivo to patient samples. Whereas the collagen defect is expected given the central role of BTK in glycoprotein VI signaling, the ADP defect lacks a mechanistic explanation. In order to determine the real-life consequences of BTK platelet blockade, we performed light transmission aggregometry in 23 patients receiving ibrutinib treatment. All patients had reductions in collagen-mediated platelet aggregation, with a significant association between the degree of inhibition and the occurrence of clinical bleeding or bruising (P=0.044). This collagen defect was reversible on drug cessation. In contrast to the previous ex vivo report, we found no in vivo ADP defects in subjects receiving standard doses of ibrutinib. These results establish platelet light transmission aggregometry as a method for gauging, at least qualitatively, the severity of platelet impairment in patients receiving ibrutinib treatment.

We report here two cases of dyserythropoietic anaemia associated with long-term linezolid use that share striking similarities to chloramphenicol-associated myelotoxicity.

Few studies have systematically identified factors associated with blood loss in musculoskeletal tumor surgery. We aimed to identify risk factors for requiring large-volume transfusion in musculoskeletal tumor surgery and created an interactive model to predict red blood cell transfusion requirements based on patient characteristics. These data will facilitate planning in hospital blood banks and aid identification of specific groups for future interventions targeted at reducing blood utilization. Only one similar study has been published and there are minimal data surrounding interventions designed to minimize blood loss in musculoskeletal tumor surgery.We retrospectively analyzed a database containing 1322 consecutive surgeries, performed at a quaternary referral center in Melbourne, Australia. Using logistic regression analysis and a negative truncated binomial logistic regression model, we developed prediction models for transfusion requirement.The following factors were associated with large-volume transfusion: malignant tumors, bone tumors, sacral and pelvic tumors, high American Society of Anesthesiologists (ASA) score, and tumor size of more than 5 cm. High ASA score was also strongly associated with 30-day mortality.Preoperative planning in high-risk patients is critical to ensure adequate blood product supply, minimize wastage, and optimize the patient's general health before surgery. These patients would be ideal targets for future randomized studies aimed at reducing blood utilization.

Cure can now be achieved in a proportion of patients with ALL. However, relapse and eventual treatment failure occur in many cases receiving identical treatment, presumably as a result of failure to eradicate MRD. While for many years marrow morphology has been the standard by which leukaemic remission has been assessed, more sensitive techniques have been developed for detection of MRD including immunophenotypic analysis, and as discussed in this chapter, methods which detect leukemia-associated clonal genetic changes at the karyotypic and genomic levels. Table 10 lists the applicability and sensitivity of various markers used in MRD analysis in ALL. It is apparent that of the karyotypic and molecular approaches described, only PCR-based strategies for detection of either leukaemia-specific translocations or clonal Ag receptor rearrangements are reliably applicable to a high proportion of both B- and T-ALL at sufficiently high sensitivity. Initial clinical studies of patients undergoing therapy for ALL using a variety of PCR-based methods suggest that in some cases a persistent or increasing level of residual disease may be predictive for clinical relapse, although a number of technical factors and the phenomena of oligo-clonality and clonal evolution may limit the usefulness of this analysis in a few instances. From current available data it appears that in order to define the potential predictive value of PCR detection of MRD a large number of patients will need to be prospectively assessed over several years at multiple time points during and after therapy, preferably using more than one semi-quantitative PCR approach. In addition to reliable prediction of clinical relapse allowing appropriate individual treatment modification, progress in the molecular detection of MRD in ALL is also likely to be of benefit in the assessment of the efficacy of autograft purging and the evaluation of new therapeutic strategies such as the use of biological response modifiers to eliminate a low tumour burden.

Rearrangement of the immunoglobulin heavy chain (IgH) gene can be utilized as a marker of clonality in a number of B-lineage lymphoproliferative disorders including acute lymphoblastic leukaemia (ALL). We have used a PCR technique involving a panel of amplimers for the 6 different Variable (VH) region families and for a consensus sequence of the Joining (JH) segment to detect clonal IgH rearrangements in the peripheral blood (PB) and/or bone marrow (BM) of 28 patients (17 children and 11 adults) with B-lineage ALL at presentation (20 patients) or with overt relapse (8 patients). The age range of the patients was 2-65 years (mean 15.7 years). Follow up remission BM samples were analysed in 22 patients during and after therapy (2-7 samples per patient), 1-50 months after presentation or relapse. In 1 relapsed case, previously stored complete remission (CR) samples were analysed retrospectively. Clonal IgH chain rearrangements were detected by PCR in 90% of patients studied initially. The 2 VH region families most commonly used were the large VH3 family (65%) and the smaller more JH-proximal VH4 family (22%). More than one VH clone was detectable in 25% of the cases. A gene "fingerprinting" modification of a previously described method was applied to the detection of minimal residual disease (MRD) in follow up BM samples with a sensitivity of 10(-3) to 10(-4). In 8 of 14 patients remaining in complete remission (CR) during the time of study, all PCR analyses on BM samples in the first 6 months were negative, in some cases as early as 2 weeks post-induction therapy, and a further patient reverted from being PCR positive in the first month after the commencement of therapy to sustained PCR negativity. One adult remains in CR at 50 months after presentation and has been PCR negative at 2 time points after cessation of maintenance therapy (30 and 50 months). Eight patients relapsed in the study period comprising 6 BM and 2 isolated CNS relapses. In 4 cases of BM relapse occurring within 7 months of the start of therapy, all BM remission samples tested in this period were PCR positive. In 2 other patients BM samples tested 7 and 2 months respectively prior to relapse were PCR negative. In the 2 patients with isolated CNS relapse, PCR of BM samples from 2 and 10 months before the relapse were negative.(ABSTRACT TRUNCATED AT 400 WORDS)

Hospital transfusion laboratories collect information regarding blood transfusion and some registries gather clinical outcomes data without transfusion information, providing an opportunity to integrate these two sources to explore effects of transfusion on clinical outcomes. However, the use of laboratory information system (LIS) data for this purpose has not been validated previously.Validation of LIS data against individual patient records was undertaken at two major centers. Data regarding all transfusion episodes were analyzed over seven 24-hour periods.Data regarding 596 units were captured including 399 red blood cell (RBC), 95 platelet (PLT), 72 plasma, and 30 cryoprecipitate units. They were issued to: inpatient 221 (37.1%), intensive care 109 (18.3%), outpatient 95 (15.9%), operating theater 45 (7.6%), emergency department 27 (4.5%), and unrecorded 99 (16.6%). All products recorded by LIS as issued were documented as transfused to intended patients. Median time from issue to transfusion initiation could be calculated for 535 (89.8%) components: RBCs 16 minutes (95% confidence interval [CI], 15-18 min; interquartile range [IQR], 7-30 min), PLTs 20 minutes (95% CI, 15-22 min; IQR, 10-37 min), fresh-frozen plasma 33 minutes (95% CI, 14-83 min; IQR, 11-134 min), and cryoprecipitate 3 minutes (95% CI, -10 to 42 min; IQR, -15 to 116 min).Across a range of blood component types and destinations comparison of LIS data with clinical records demonstrated concordance. The difference between LIS timing data and patient clinical records reflects expected time to transport, check, and prepare transfusion but does not affect the validity of linkage for most research purposes. Linkage of clinical registries with LIS data can therefore provide robust information regarding individual patient transfusion. This enables analysis of joint data sets to determine the impact of transfusion on clinical outcomes.

Clinical chemoresistance is a frequent complication of alkylating agent treatment of malignant tumours. Chromatin remodelling using histone deacetylase inhibitors (e.g., sodium butyrate, NaBu) may increase target cell chemosensitivity. Apoptotic responses and expression of chromatin modifying enzymes in lymphoid cell lines, LP-1 and NCI-H929, to chlorambucil (CLB) and/or NaBu were examined in this study. NaBu augmented the apoptotic response in CLB-resistant LP-1 cells but antagonised it in CLB-sensitive NCI-H929 cells. CLB increased expression of methyltransferase I and histone acetyltransferase I in both cell lines while NaBu had only small effect. CLB-induced increased gene expression was attenuated by NaBu in CLB-sensitive NCI-H929 cells but not in resistant LP-1 cells. These results suggest that chromatin modifying agents may have differential effects on cells depending on their chemosensitivity.

Current literature suggests that contact with specialist palliative care for patients diagnosed with hematological malignancy is infrequent. As part of an investigation into patterns of care, the symptom profile of this patient group required elucidation.The purpose of this study was to determine the patterns of symptoms and level of distress in patients diagnosed with a hematological malignancy.One hundred eighty patients diagnosed with a hematological malignancy attending a tertiary referral hospital completed the Memorial Symptom Assessment Scale-Short Form. Comparisons were made to published symptom prevalence studies of those with nonhematological malignancies.Patients with hematological malignancy had a considerable physical and psychological symptom burden, with an overall mean of 8.8 (± 5.9) symptoms. The mean number of symptoms was significantly greater in those on treatment (P0.05), those with poorer performance status (P0.001), inpatients (P0.01), and those with a more advanced disease stage (P0.001) than their respective counterparts. Symptom prevalence ranged from 69% for fatigue to 9% for vomiting. Global, physical, and psychological distress scores were high and varied significantly according to disease stage, Eastern Cooperative Oncology Group status, and patient location. The mean number of symptoms and level of distress were comparable to those patients with metastatic nonhematological malignancy.Patients with hematological malignancy are likely to have symptom control needs similar to those with metastatic cancer. Because such symptom burden appears to affect those at all phases of illness, comprehensive symptom assessment is suggested throughout. The introduction of palliative care services during times of increased symptom burden may assist hematologists and other carers in the management of their patients' distress and quality of life.

A 38-year-old man was admitted to hospital with several days of malaise and dyspnoea. He was on no prescribed medications, and had previously been well apart from an episode of gangrenous cholecystitis due to mixed gallstones three years previously. Full blood examination showed haemoglobin 110 g/l, white cell count 12AE9 · 10/l with neutrophil count 9AE2 · 10/l, and platelet count 266 · 10/l. The blood film (left) demonstrated marked polychromasia with features of oxidative haemolysis and hyposplenism. Supravital staining with methyl-violet demonstrated numerous Heinz bodies (top right). Other indicators of haemolysis included a reticulocytosis of 241 · 10/l, lactate dehydrogenase 374 IU/l, bilirubin 54 lmol/l with undetectable haptoglobin and a negative direct antiglobulin test. On further enquiry, the patient denied fava bean ingestion but disclosed heavy recreational use of inhalational amyl nitrite. Avoidance of further nitrite exposure resulted in resolution of haemolysis, and the patient was provided with counselling on drug use. Laboratory testing in the convalescent phase did not detect evidence of glucose-6-phosphate dehydrogenase deficiency or an underlying haemoglobinopathy. Nitrite inhalants, such as amyl nitrite, are highly volatile yellow liquids that cause rapid vasodilation and hence were once used as anti-anginals. Nitrites efficiently oxidize haemoglobin to methaemoglobin and may also increase the proteolytic susceptibility of haemoglobin leading to globin chain denaturation and Heinz body formation. The recreational use of alkyl nitrites, colloquially known as ‘poppers’ (bottom right), should be considered in apparently idiopathic episodes of oxidative haemolysis. Significant complications may occur even in patients with intact red cell reduction pathways.

A 30-year-old man was admitted to hospital following an explosion at the metal foundry where he worked. He had sustained sulphuric acid exposure to 80% of his body, including full thickness skin destruction over 20% of his body surface area. Full blood examination on admission showed haemoglobin 151 g/l, white cell count 24AE3 · 10/l with neutrophil count 20AE4 · 10/l, and platelet count 357 · 10/l. The blood film (illustrated) demonstrated numerous spherocytes and microspherocytes, a number of crenated red cells, occasional red cell fragments and toxic neutrophil granulation. The direct antiglobulin test was negative, and a blood film performed 2 years prior to this presentation had shown no morphological abnormalities. Microspherocytes are a characteristic finding following thermal injury to red cells, such as that resulting from physical burns, but have not to our knowledge been described in association with chemical injury. The mechanism underlying this morphological change is thought to be a decrease in red cell membrane deformability caused by thermal damage to membrane proteins and phospholipids. This may also lead to fragmentation and cell destruction. Microspherocytes and fragments have been implicated in the pathogenesis of renal impairment in the setting of severe burns, through deposition in renal tubules, and may also interfere with automated cell counts. Sulphuric acid (H2SO4), once called oil of vitriol, is a highly corrosive mineral acid. Its destructive properties are enhanced by its exothermic reaction with water, which forms hydronium and sulphate while releasing substantial heat. The chemical injury associated with exposure to sulphuric acid may therefore result in greater damage than that from other acids of similar strength, as local heat and dehydration increase tissue destruction. In this case, it is likely that this secondary thermal damage contributed to the observed morphological changes. This patient was treated with surgical debridement and supportive measures, and made a full recovery. His blood counts and red cell morphology normalized within seven days, with complete resolution of the microspherocytosis.

Objectives Evidence is accumulating of adverse outcomes associated with transfusion of blood components. If there are differences in perioperative transfusion rates in cardiac surgery, and what hospital factors may contribute, requires further investigation. Methods Analysis of 42,743 adult patients who underwent 43,482 procedures from 2005 to 2011 at 25 Australian hospitals, according to the Australian and New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database. Multiple logistic regression examined associations of patient and hospital characteristics with transfusion of ≥1 red blood cell (RBC) unit; platelet (PLT), fresh frozen plasma (FFP), and cryoprecipitate (CRYO) doses; and ≥5 RBC units, from surgery until hospital discharge. Results Procedures included 24,222 (55%) isolated coronary artery bypass grafts, 7299 (17%) isolated valve, 4714 (11%) coronary artery bypass graft and valve, and 7247 (17%) other procedures. After adjustment for various patient and procedure characteristics, transfusion rates varied across hospitals for ≥1 RBC unit from 22% to 67%, ≥5 RBC units from 5% to 25%, ≥1 PLT dose from 11% to 39%, ≥1 FFP dose from 11% to 48% and ≥1 CRYO dose from 1% to 20%. Hospital characteristics, including state or territory, private versus public, and teaching versus nonteaching, were not associated with variation in transfusion rates. Conclusions Variation in transfusion of all components and large volume RBC was identified, even after adjustment for patient and procedural factors known to influence transfusion, and this was not explained by hospital characteristics.

We report two cases of trisomy 4 with double minute chromosomes (dmin): one in a woman with acute myeloid leukemia (AML), French-American-British subtype M2, the other in a man with chronic myelomonocytic leukemia. In the former case, many cells without trisomy 4 but with dmin were present, a finding not observed in previously reported cases. In both cases, fluorescence in situ hybridization studies demonstrated the double minutes to be MYC amplicons. Ten cases of AML with trisomy 4 and dmin have now been described; in the five cases investigated, the dmin have been shown to be amplified MYC gene sequences.

Background and Aim Studies have reported association between red cell (RBC) transfusion (tx) and increased mortality and morbidity in cardiac surgery (CS). Conflicting data exist on whether universal RBC leucodepletion (ULD) reduces mortality and morbidity, particularly infection and intensive care unit (ICU) length of stay (LOS), in CS patients. RBC tx has also been independently associated with renal failure (RF) in CS, however mechanisms for this effect are unclear. An inflammatory basis has been postulated. No large studies have explored the potential benefit of ULD in reducing RF. We investigated whether introduction of ULD in Australia (July 2008) was associated with reduced in-hospital mortality, infection, new RF (NRF) and ICU LOS in a large cohort of CS patients. Methods All consecutive CS patients 18y and older at 6 hospitals between 2005 and 2010 were included. Clinical and outcome data were obtained from the Australian and New Zealand Society for Cardiac and Thoracic Surgeons Cardiac Surgery Database, which prospectively collects data on all CS patients. Laboratory results (pre-operative hemoglobin, platelet, coagulation profile and creatinine) and transfusion data were obtained from hospital laboratory information systems (LIS). Statistical analysis Tx was defined as ≥ 1 RBC within 48h of CS. Patients were categorized as having surgery pre- or post-ULD and as having received either exclusively LD, non-LD or mixed RBC. Logistic regression modeled the association between LD and mortality, infection and NRF. The association with LD was analyzed in two ways: whether surgery occurred pre- or post-ULD, and whether patients received LD or non-LD RBCs. To examine for trends over time, an equal number of non-tx patients were selected as ‘controls’, based on a propensity score for RBC tx. The relationship between LD and ICU LOS among survivors was explored using linear regression. Results 16,253 patients underwent CS in the study period. LIS data were available for 14,980 (92%), and of these, 8857 (59%) had surgery pre-ULD. RBC tx was given in 3799 (43%) pre-ULD, and 2525 (41%) post-ULD. Of the 6324 patients who were tx, 2794 (44%) received LD RBC, 2702 (43%) non-LD RBC and 828 (13%) received mixed LD and non-LD RBCs. In tx patients, there was no significant difference in mortality (136 [5.4%] vs. 240 [6.3%], p=0.125) or infection (310 [11.9%] vs. 510 [13.4%], p=0.080) post-ULD compared with pre-ULD, however there was a significant reduction in NRF (215 [8.5%] vs. 398 [10.5%], p=0.010). After adjusting for hospital, age, sex, co-morbidities, ejection fraction, pre-operative laboratory parameters, surgical history, type and urgency of procedure, pre-operative shock, medications, perfusion time, drain output in first 4 hours and number of RBC, there was no difference in mortality (OR 0.92, 95% CI 0.71-1.20, p=0.534) or infection (OR 0.96, 95% CI 0.81-1.15, p=0.671), however there was a difference in NRF post-ULD compared with pre-ULD (OR 0.77, 95% CI 0.64-0.94, p=0.011). When the analysis was repeated comparing those who received LD vs. non-LD RBC the results were similar, with no difference in mortality or infection, but a reduction in NRF (OR 0.80, 95% CI 0.65-0.98, p=0.035). In the non-tx controls, there was no significant difference in mortality (30 [1.2%] vs. 39 [1.0%], p=0.546), infection (139 [5.5%] vs. 231 [6.1%], p=0.338) or NRF (110 (4.4%] vs. 181 [4.8%], p=0.445) post-ULD compared with pre-ULD. After adjusting as above, there was no significant difference in mortality (OR 1.18, 95% CI 0.72-1.9, p=0.512), infection (OR 0.82, 95% CI 0.66-1.03, p=0.094) or NRF (OR 0.83, 95%CI 0.64-1.07, p=0.148) post-ULD compared with pre-ULD in non-tx pts. In the unadjusted linear regression, post-LD was associated with a small reduction in ICU LOS in transfused (41 vs. 44 h, p=0.034) and with a small increase in non-transfused (29 vs. 31 h, p Conclusions Introduction of ULD was associated with a reduction in NRF but not mortality, infection or ICU LOS in transfused CS pts. These findings support the potential role of inflammation as a contributor to acute RF in tx CS pts. ULD may be worth exploring prospectively as a possible strategy to reduce the incidence of NRF in CS, given its substantial morbidity and mortality. Disclosures: Phillips: CSL Behring: Research Funding. Wood:CSL Behring: Research Funding.

In acute lymphoblastic leukaemia (ALL), investigation of minimal residual disease by conventional morphology and immunology fails to detect levels of residual disease of1 leukaemic in 10-100 normal cells. The use of polymerase chain reaction (PCR) to exploit the diversity of the complementarity determining region (CDR) and immunoglobulin variable heavy chain (VH) family specific usage has greatly improved the sensitivity up to one leukaemic cell in 10(5)-10(6) normal bone marrow cells. Here we report on a prospective study of 14 patients with ALL of B-cell lineage by using a combined PCR approach which estimates levels of disease between 1:10(3) and 1:10(5). The sequential use of allele-specific oligoprimer (ASO) independent tests (using framework 1. FR1 and 3, FR3 primers with a JH consensus primer, sensitivity up to 1:5 x 10(3)) and ASO-dependent PCR (sensitivity up to 1:10(5)) assays were applied to 64 bone marrow (BM) follow-up samples in a sequential array of tests. Results presented in this study indicate high concordance of MRD among different tests for samples with level of residual disease1:5 x 10(3). Consequently, samples positive by the FR1 and FR3 fingerprinting tests were confirmed by the more sensitive ASO-dependent tests, as expected. However, the ASO-dependent assays revealed levels of disease undetected by the FR1 and FR3 test. Although a higher level of sensitivity is provided by the ASO-dependent tests, the FR1 and FR3 fingerprinting tests allow MRD investigation in patients with oligoclonal B cell proliferations, CDR3 region of size15 bp or with ASO primers unsuitable for PCR investigation on technical grounds (i.e. background signal). If a sequential order of investigation from less (e.g. FR1 and FR3 fingerprinting) to more sensitive tests (ASO-dependent) is applied, an indirect estimate of MRD is obtained for patients with level of disease1:10(3).

Abstract 4384 The management of musculoskeletal tumors has evolved markedly over the past 30 years, with improvements in surgical techniques, staging and chemotherapeutic advances delivering improved survival and functional outcomes, both in the setting of primary malignant bone tumors and in the palliation of tumors metastatic to bone. Advances in surgical technique as well as pre-operative chemotherapy has meant that most patients are now able to undergo limb-sparing surgery. Whilst clearly desirable to improve functional outcome, limb-sparing surgery is however more technically challenging and is associated with greater blood loss than amputation. There is a paucity of data concerning blood utilization in the setting of major musculoskeletal tumor surgery. We retrospectively analyzed a database containing 1322 consecutive surgeries in 1222 patients over a 14 year timeframe, performed at a quaternary referral center in Melbourne, Australia. The following factors were significantly associated with high blood utilization: Chordomas, sacral and pelvic tumors, lower starting haemoglobin, tumors >5cm in size and high American Society of Anesthesiologists (ASA) score. The ASA score also clearly correlated with 30 day mortality. Pre-operative planning in these patients is critical to ensure adequate blood supply, minimize wastage and optimize the patient's general health prior to surgery. As such, based on modeling from our data, we propose a maximum surgical blood order schedule based on the presence or absence of the above factors. Allogeneic blood transfusion, while a potentially life-saving intervention, is associated with major complications, including transmission of infectious agents and immunological complications. Longer-term, transfusion has been reported to result in immunomodulation and potentially a higher risk of tumor recurrence. Clearly, minimization of blood loss and avoidance of un-necessary transfusion is desirable. There is also a lack of data surrounding interventions designed to minimize blood loss in musculoskeletal tumor surgery, especially when compared to similar studies performed in major orthopedic surgery for benign conditions. These would be ideal targets for future randomized studies in the high-risk groups we have identified. Disclosures: No relevant conflicts of interest to declare.

Abstract 4385 The multiply alloimmunized patient poses a difficult predicament for clinicians, the hospital blood bank and duty hematologist. Whilst parallels may be drawn between patient blood management strategies used in the setting of blood refusal, others are unique to alloimmunization. There is limited literature guiding the management of the multiply alloimmunized patient requiring transfusion. We describe a 54-year-old lady who presented with symptomatic anaemia due to a delayed haemolytic transfusion reaction from an unidentifiable antibody. She had been transfused 2 units of red cells 13 days earlier in the setting of gastrointestinal bleeding. At this time she was found to have an anti- Fya antibody and was transfused with Rh matched, K negative, Fy(a-) and indirect anti-globulin test (IAT) cross-match compatible red cells. Her history included previous transfusions in the setting of bleeding, but no pregnancies. On admission hemoglobin (Hb) was 69 g/L [115 – 165], reticulocyte count 237× 109/L [20 – 100], bilirubin 33 μmol/L [T, encoding Gln581Leu and a silent 1671C>T, not affecting Ser557. These mutations are 2 out of the 3 mutations describing the LU- 13 genotype1. Our patient lacks the third mutation 1340C>T previously described. The patient's Hb dropped to 42 g/L and her treatment included bed-rest, intravenous iron, intramuscular vitamin B12, oral folate and erythropoietin. Whilst she had no active gastrointestinal bleeding she was given pantoprazole infusions and had a capsule endoscopy. She had a history of menorrhagia so was started on norethisterone and tranexamic acid to suppress menstrual loss. No first degree relatives were available for directed donation. She was transfused with 1 unit of IAT cross match compatible red cells together with 100mg prednisolone orally daily and 1g/kg intravenous immunoglobulin in an attempt to suppress immune haemolysis. She tolerated the transfusion well; however there was no increment in her Hb. Avoidance of unnecessary blood testing and pediatric collection tubes were used to reduce phlebotomy related loss. Over the next 10 days her Hb incremented without further transfusion to 78 g/L and had normalized by 4 weeks. Due to the need for future gastrointestinal surgery, on recovery of her Hb she had 5 autologous units of blood collected and frozen. Patient blood management strategies in the patient where the risk of potentially significant haemolytic reactions to transfusion is high must focus on minimizing blood loss, maximizing tissue oxygenation, promoting erythropoiesis and reducing metabolic needs. Approaches to lessen blood loss include early radiologic or surgical intervention to stop active bleeding, cessation or reversal of anticoagulants or aspirin and avoidance of medications or supplements associated with increased bleeding risk. Reducing phlebotomy-based blood loss includes minimizing the number of blood tests, using pediatric collection tubes and point of care devices. In our patient we investigated for ongoing bleeding sources, utilised proton pump inhibitors and used hormonal control for cessation of menstruation. Erythropoiesis was stimulated by the delivery of iron, folate, vitamin B12 and erythropoietin. Early investigation for associated coagulopathy or thrombocytopenia and early treatment with vitamin K, fresh frozen plasma and cryoprecipitate ensures that red cell volume is optimised. In a patient with multiple alloantibodies, the hospital blood bank should screen their inventory of donated red cells and consult with local and regional blood authorities. The blood typing of family members may allow for identification of potential donors. In the acute setting with an unstable haemorrhaging patient, the decision to transfuse the least incompatible blood may need to be considered. Long-term management plans may include autologous unit collection and identification of alloantibodies at a molecular level. Disclosures: No relevant conflicts of interest to declare.