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1.  Patient blood management in orthopaedic surgery: a four-year follow-up of transfusion requirements and blood loss from 2008 to 2011 at the Balgrist University Hospital in Zurich, Switzerland 
Blood Transfusion  2014;12(2):195-203.
Background
The aim of this study was to investigate the impact of the introduction of a Patient Blood Management (PBM) programme in elective orthopaedic surgery on immediate pre-operative anaemia, red blood cell (RBC) mass loss, and transfusion.
Materials and methods
Orthopaedic operations (hip, n=3,062; knee, n=2,953; and spine, n=2,856) performed between 2008 and 2011 were analysed. Period 1 (2008), was before the introduction of the PBM programme and period 2 (2009 to 2011) the time after its introduction. Immediate pre-operative anaemia, RBC mass loss, and transfusion rates in the two periods were compared.
Results
In hip surgery, the percentage of patients with immediate pre-operative anaemia decreased from 17.6% to 12.9% (p<0.001) and RBC mass loss was unchanged, being 626±434 vs 635±450 mL (p=0.974). Transfusion rate was significantly reduced from 21.8% to 15.7% (p<0.001). The number of RBC units transfused remained unchanged (p=0.761). In knee surgery the prevalence of immediate pre-operative anaemia decreased from 15.5% to 7.8% (p<0.001) and RBC mass loss reduced from 573±355 to 476±365 mL (p<0.001). The transfusion rate dropped from 19.3% to 4.9% (p<0.001). RBC transfusions decreased from 0.53±1.27 to 0.16±0.90 units (p<0.001). In spine surgery the prevalence of immediate pre-operative anaemia remained unchanged (p=0.113), RBC mass loss dropped from 551±421 to 404±337 mL (p<0.001), the transfusion rate was reduced from 18.6 to 8.6% (p<0.001) and RBC transfusions decreased from 0.66±1.80 to 0.22±0.89 units (p=0.008).
Discussion
Detection and treatment of pre-operative anaemia, meticulous surgical technique, optimal surgical blood-saving techniques, and standardised transfusion triggers in the context of PBM programme resulted in a lower incidence of immediate pre-operative anaemia, reduction in RBC mass loss, and a lower transfusion rate.
doi:10.2450/2014.0306-13
PMCID: PMC4039701  PMID: 24931841
anaesthesia audit; pre-anaesthetic assessment; blood transfusion; orthopaedic surgery
2.  Improvements in patient blood management for pediatric craniosynostosis surgery using a ROTEM®-assisted strategy – feasibility and costs 
Paediatric Anaesthesia  2014;24(7):774-780.
Background
Moderate to severe intraoperative bleeding and the presence of acquired coagulopathy remain serious problems in the management of major pediatric craniosynostosis surgery. After implementation of a ROTEM®-assisted patient blood management (PBM) strategy, using primarily purified coagulation factor concentrates, feasibility and costs of this new regimen were analyzed.
Methods
Retrospective analysis of all consecutive children who underwent primary elective major craniofacial surgery for craniosynostosis repair was carried out at the Children's University Hospital, Zurich, between 2007 and 2013. Laboratory workup and transfusion requirements were compared.
Results
A total of 47 children (36 in the historic group and 11 after implementation of PBM) were analyzed. Although all patients in this study needed transfusion of red blood cell concentrates, there was a total avoidance of perioperative transfusion of fresh frozen plasma and a reduction in transfused platelets (one of nine children vs nine of 36 children in the historic group) after implementation of the PBM strategy. Based on a predefined ROTEM® threshold in the PBM group (FibTEM MCF <8 mm), administration of fibrinogen concentrate was necessary in all of these children. The mean total costs per patient consisting of transfused allogeneic blood products and coagulation factor concentrates were reduced by 17.1% after implementation of PBM (1071.82 EUR per patient before vs 888.93 EUR after implementation).
Conclusions
The implementation of a ROTEM®-assisted PBM is feasible and is associated with a considerable reduction in intraoperative transfusion requirements and thereby a decrease in transfusion-related direct costs.
doi:10.1111/pan.12341
PMCID: PMC4207194  PMID: 24417649
blood transfusion; blood coagulation disorders; blood coagulation factors; blood coagulation tests; thromboelastometry; hemorrhage
3.  Patient Blood Management: A Patient-Orientated Approach to Blood Replacement with the Goal of Reducing Anemia, Blood Loss and the Need for Blood Transfusion in Elective Surgery 
Patient Blood Management (PBM) describes an evidence-based, multidisciplinary therapeutic approach. Its focus is on the treatment of the individual patient and as such comprises transfusion therapy and pharmacotherapy. Furthermore, the applicability of PBM is not limited to the perioperative setting but is applicable also to other therapeutic measures and disciplines where significant blood loss is known to occur and where transfusion of blood products is part of the established treatment. PBM is fundamentally based on 3 pillars: (1) optimization of the (preoperative) erythrocyte volume, (2) reduction of diagnostic, therapeutic, or intraoperative blood loss, and (3) increasing individual tolerance towards anemia and accurate blood transfusion triggers. PBM primarily identifies patients at risk of transfusion and provides a management plan aimed at reducing or eliminating the risk of anemia and the need for allogeneic transfusion, thus reducing the inherent risks, inventory pressures, and the escalating costs associated with transfusion.
doi:10.1159/000337183
PMCID: PMC3364034  PMID: 22670124
Patient blood management; Anemia; Transfusion; Blood loss
4.  “Transfusion indication RBC (PBM-02)”: gap analysis of a Joint Commission Patient Blood Management Performance Measure at a community hospital 
Blood Transfusion  2014;12(Suppl 1):s187-s190.
Background
The Joint Commission accredits health care organisations in the USA as a prerequisite for licensure. In 2011, TJC published seven Patient Blood Management Performance Measures to improve the safety and quality of care. These Measures will provide hospital-specific information about clinical performance.
Materials and methods
Of the seven TJC PBM Performance Measures, we decided to evaluate PBM-02, “Transfusion indication RBC”, at our hospital. Blood transfusion orders were collected from May 2 to August 2, 2011 and the data analysed.
Results
Of the 724 consecutive red blood cell transfusion orders, 694 (96%) documented both clinical indication and pre-transfusion haemoglobin/haematocrit results. The leading transfusion indication (47% of total) was “high risk patients with pre-transfusion Hb of <9 g/dL”. The majority (72%) of non-actively bleeding patients received a single unit of blood as recommended by our transfusion guidelines. However, 70% of these patients went on to receive additional units and 21% of the initial orders were placed for two or more units. Patients with active bleeding and special circumstances accounted for 17% and 4% of the transfusions, respectively. Our blood utilisation did not change by introducing the single-unit transfusion policy.
Discussion
The majority (96%) of the transfusion orders met The Joint Commission criteria by providing both transfusion indication and pre-transfusion Hb and/or Hct values. Our transfusion guidelines recommend single-unit red blood cell transfusions with reassessment of the patient after each transfusion for need to receive more blood. Although most (72%) initial orders followed our transfusion guidelines, 70% of patients who received a single unit initially went on to receive more blood (some in excess of 10 units). Our objective data may be helpful in evaluating blood ordering practices at our hospital and in identifying specific clinical services for review.
doi:10.2450/2012.0088-12
PMCID: PMC3934221  PMID: 23149139
blood utilisation; The Joint Commission; Performance Measures; transfusion indications; single-unit policy
5.  Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines 
Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.
doi:10.1093/bja/aeq361
PMCID: PMC3000629  PMID: 21148637
anaemia; blood transfusion; orthopaedic surgery; preoperative assessment; preoperative preparation
6.  Safety and effectiveness of a Patient Blood Management (PBM) program in surgical patients - the study design for a multi-centre prospective epidemiologic non-inferiority trial 
Background
Preoperative and hospital-acquired anaemia is common among surgical patients. It is associated with an increased risk of morbidity and mortality and a strong risk factor for allogeneic blood transfusions with their own inherent risks. Patient Blood Management (PBM) concepts aim to increase and preserve autologous erythrocyte volume and to optimise haemotherapy. They thus have great potential to benefit patients.
Methods/Design
This prospective, multi-centre clinical trial tests the hypothesis that PBM programs are safe and effective in the care of adult surgical patients. Primary outcome is a composite endpoint of adverse events and in-hospital mortality.
Discussion
This trial will determine whether the implementation of a PBM program is safe and effective in terms of clinical outcome compared to a pre-implementation cohort. This trial is registered at www.clinicaltrials.gov (NCT01820949).
doi:10.1186/s12913-014-0576-3
PMCID: PMC4261241
Patient Blood Management; Red Blood Cell Transfusion Practice, Patient Safety; Anaemia; Clinical Outcome; Perioperative Care
7.  Perioperative blood management 
Indian Journal of Anaesthesia  2014;58(5):573-580.
Perioperative anaemia and allogenic blood transfusion (ABT) are known to increase the risk of adverse clinical outcomes. The quality, cost and availability of blood components are also major limitations with regard to ABT. Perioperative patient blood management (PBM) strategies should be aimed at minimizing and improving utilization of blood components. The goals of PBM are adequate preoperative evaluation and optimization of haemoglobin and bleeding parameters, techniques to minimize blood loss, blood conservation technologies and use of transfusion guidelines with targeted therapy. Attention to these details can help in cost reduction and improved patient outcome.
doi:10.4103/0019-5049.144658
PMCID: PMC4260303  PMID: 25535419
Anaemia; blood conservation; cell salvage; patient blood management; perioperative
8.  Well being of obstetric patients on minimal blood transfusions (WOMB trial) 
Background
Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands.
Methods/Design
The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs.
The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%).
Discussion
This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs.
Trial registration
ClinicalTrials.gov NCT00335023, Nederlands Trial Register NTR335
doi:10.1186/1471-2393-10-83
PMCID: PMC3022737  PMID: 21162725
9.  Predictive Performance of Serum Procalcitonin for the Diagnosis of Bacterial Meningitis after Neurosurgery 
Infection & Chemotherapy  2013;45(3):308-314.
Background
Postoperative bacterial meningitis (PBM) is a serious potential complication after neurosurgery. Early diagnosis and introduction of antimicrobial therapy are necessary to reduce the rate of fatal outcomes from PBM. However, PBM is not easily differentiated from postoperative aseptic meningitis (PAM), which usually has favorable clinical outcomes. Serum procalcitonin (S-PCT) has been found to be a useful marker for distinguishing community-acquired bacterial from viral meningitis. We investigated the predictive performance of S-PCT for PBM in patients who underwent neurosurgery.
Materials and Methods
Between September 2009 and August 2010, we prospectively collected data from patients who underwent neurosurgery and had cerebrospinal fluid (CSF) pleocytosis within 14 days of surgery. Based on the CSF culture results, patients were categorized as either PBM or PAM cases. We compared the laboratory test results including S-PCT levels between PBM and PAM cases, and investigated the predictive performance of S-PCT for PBM.
Results
During the study period, PBM and PAM occurred in 14 and 64 patients, respectively. There was no significant difference in CSF profiles between PBM and PAM cases. S-PCT level ≥ 0.15 ng/mL (50.0% vs. 20.0%, P = 0.07) and C-reactive protein (CRP) level ≥ 2.5 mg/dL (75.0% vs. 46.5%, P = 0.16) tended to be more frequent in PBM than in PAM cases. A blood white blood cell (B-WBC) count ≥ 9,500/mm3 was more frequently found in PBM cases (85.7% vs. 50.8%, P = 0.02) than in PAM cases. For the diagnosis of PBM, an S-PCT level ≥ 0.15 ng/mL had a specificity of 80.0%. The combined criteria of a CRP level ≥ 2.5 mg/dL, B-WBC count ≥ 9,500/mm3, and an S-PCT level ≥ 0.15 ng/mL had the highest specificity (92.6%) of all the criteria. An S-PCT level ≥0.15 ng/mL had low sensitivity (50.0%), and the combined criteria of CRP level ≥ 2.5 mg/dL, B-WBC count ≥ 9,500/mm3, and S-PCT level ≥ 0.15 ng/mL had an improved sensitivity of 85.7%. However, the sensitivity did not significantly differ from that of a B-WBC count ≥ 9,500/mm3 (85.7%).
Conclusions
S-PCT showed limited performance for the diagnosis of postoperative meningitis. However, it could be a useful adjunct for the improvement of diagnostic sensitivity when used in combination with other inflammatory markers.
doi:10.3947/ic.2013.45.3.308
PMCID: PMC3848519  PMID: 24396632
Meningitis; Procalcitonin; Adenosine deaminase; Neurosurgery
10.  Emerging Trends in Cancer Care: Health Plans’ and Pharmacy Benefit Managers’ Perspectives on Changing Care Models 
American Health & Drug Benefits  2012;5(4):242-253.
Background
Cancer care in the United States is being transformed by a number of medical and economic trends, including rising drug costs, increasing availability of targeted therapies and oral oncolytic agents, healthcare reform legislation, changing reimbursement practices, a growing emphasis on comparative effectiveness research (CER), the emerging role of accountable care organizations (ACOs), and the increased role of personalization of cancer care.
Objective
To examine the attitudes of health plan payers and pharmacy benefit managers (PBMs) toward recent changes in cancer care, current cost-management strategies, and anticipated changes in oncology practice during the next 5 years.
Methods
An online survey with approximately 200 questions was conducted by Reimbursement Intelligence in 2011. The survey was completed by 24 medical directors and 31 pharmacy directors from US national and regional health plans and 8 PBMs. All respondents are part of a proprietary panel of managed care decision makers and are members of the Pharmacy and Therapeutics Committees of their respective plans, which together manage more than 150 million lives. Survey respondents received an honorarium for completing the survey. The survey included quantitative and qualitative questions about recent developments in oncology management, such as the impact on their plans or PBMs of healthcare reform, quality improvement initiatives, changes in reimbursement and financial incentives, use of targeted and oral oncolytics, and personalized medicine. Respondents were treated as 1 group, because there were no evident differences in responses between medical and pharmacy directors or PBMs.
Results
Overall, survey respondents expressed interest in monitoring and controlling the costs of cancer therapy, and they anticipated increased use of specialty pharmacy for oncology drugs. When clinical outcomes are similar for oral oncolytics and injectable treatments, 93% prefer the oral agents, which are covered under the specialty tier by 59% of the plans. The use of the National Comprehensive Cancer Network practice guidelines for coverage and reimbursement of oncologic agents is reported as “very frequent” by 10% of survey respondents, “frequent” by 21%, and “moderately frequent” by 7%. Most (66%) respondents believe that it is probable and 3% believe it is highly probable that healthcare reform will help to control oncology treatment costs, although 59% also predict an increase in utilization restrictions and 48% predict more stringent comparative effectiveness evidence requirements. The survey reveals a considerable uncertainty among health plans and PBMs about the eventual impact of ACOs on oncology care. Although 82% of those surveyed believe that measures such as increasing adherence to evidence-based treatments will achieve cost-savings, nearly half (48%) had no plans to use such measures.
Conclusions
Recent trends in healthcare legislation, rising drug costs, and changing reimbursement practices are poised to significantly alter conventional models of cancer care delivery and payment. The results of this survey indicate that health plans and PBMs anticipate greater use of evidence-based management strategies, including CER, quality initiatives, and biomarker testing for appropriate cancer therapy selection. In addition, they anticipate greater focus on cost control, with a greater role for utilization management and increased patient cost-sharing. Finally, there is a high level of uncertainty among plans and PBMs about the eventual impact of ACOs and other aspects of healthcare reform on oncology practice.
PMCID: PMC4046474  PMID: 24991323
11.  The use of partial exchange blood transfusion and anaesthesia in the management of sickle cell disease in a perioperative setting: two case reports 
Introduction
Homozygous sickle cell carriers have an increased perioperative mortality. Some indications may justify an exchange blood transfusion to reduce the proportion of haemoglobin S. The advantages of general blood transfusion in a perioperative setting have not been proven and thus remain controversial. It is not clear whether reducing the proportion of haemoglobin S minimizes perioperative complications or whether patients with sickle cell disease in a stable clinical condition benefit from an exchange blood transfusion in a perioperative setting.
Case presentation
We report the case of two Angolan children aged 10 and 11 respectively, of African origin with sickle cell anaemia who underwent surgery to treat chronic necrosis, fistula of the bones and bone destruction. This presentation describes the perioperative course, including general anaesthesia. A partial exchange blood transfusion decreased S-haemoglobin levels from 81% to 21% and simultaneously treated the anaemia.
Conclusion
There is a consensus that imbalances in homoeostasis, including operative procedures, can cause a critical exacerbation of sickle cell disease. The case presented here illustrates a strategy for successfully managing sickle cell disease in the perioperative period to minimize its complications. It is important for the anaesthesiologist to carefully manage pulmonary gas exchange and to ensure sufficient tissue perfusion, balanced fluid resuscitation and normothermia, while keeping in mind the level of organ impairment in order to prevent an acute exacerbation of sickle cell disease.
We performed a partial exchange blood transfusion due to the following factors: high haemoglobin S-fraction, anaemia, operating procedure at several sites, and difficult management of body temperature. Esmarch ischemia is an established tool for preventing uncontrolled blood loss. There is no known contraindication for this, but attention must be paid to prevent uncontrolled tissue ischemia and acidosis. The use of regional anaesthesia should be considered for postoperative pain management.
doi:10.1186/1752-1947-4-82
PMCID: PMC2838918  PMID: 20205732
12.  National Comparative Audit of Blood Use in Elective Primary Unilateral Total Hip Replacement Surgery in the UK 
INTRODUCTION
Blood is a scarce and expensive product. Although it may be life-saving, in recent years there has been an increased emphasis on the potential hazards of transfusion as well as evidence supporting the use of lower transfusion thresholds. Orthopaedic surgery accounts for some 10% of transfused red blood cells and evidence suggests that there is considerable variation in transfusion practice.
PATIENTS AND METHODS
NHS Blood and Transplant, in collaboration with the Royal College of Physicians, undertook a national audit on transfusion practice. Each hospital was asked to provide information relating to 40 consecutive patients undergoing elective, primary unilateral total hip replacement surgery. The results were compared to indicators and standards.
RESULTS
Information was analysed relating to 7465 operations performed in 223 hospitals. Almost all hospitals had a system for referring abnormal pre-operative blood results to a doctor and 73% performed a group-and-save rather than a cross-match before surgery. Of hospitals, 47% had a transfusion policy. In 73%, the policy recommended a transfusion threshold at a haemoglobin concentration of 8 g/dl or less. There was a wide variation in transfusion rate among hospitals. Of patients, 15% had a haemoglobin concentration less than 12 g/dl recorded in the 28 days before surgery and 57% of these patients were transfused compared to 20% with higher pre-operative values. Of those who were transfused, 7% were given a single unit and 67% two units. Of patients transfused two or more units during days 1–14 after surgery, 65% had a post transfusion haemoglobin concentration of 10 g/dl or more.
CONCLUSIONS
Pre-operative anaemia, lack of availability of transfusion protocols and use of different thresholds for transfusion may have contributed to the wide variation in transfusion rate. Effective measures to identify and correct pre-operative anaemia may decrease the need for transfusion. A consistent, evidence-based, transfusion threshold should be used and transfusion of more than one unit should only be given if essential to maintain haemoglobin concentrations above this threshold.
doi:10.1308/003588409X432464
PMCID: PMC2966170  PMID: 19686612
Orthopaedic surgery; Blood transfusion; Total hip replacement
13.  Red Blood Cell Transfusion and Mortality in Trauma Patients: Risk-Stratified Analysis of an Observational Study 
PLoS Medicine  2014;11(6):e1001664.
Using a large multicentre cohort, Pablo Perel and colleagues evaluate the association of red blood cell transfusion with mortality according to the predicted risk of death for trauma patients.
Please see later in the article for the Editors' Summary
Background
Haemorrhage is a common cause of death in trauma patients. Although transfusions are extensively used in the care of bleeding trauma patients, there is uncertainty about the balance of risks and benefits and how this balance depends on the baseline risk of death. Our objective was to evaluate the association of red blood cell (RBC) transfusion with mortality according to the predicted risk of death.
Methods and Findings
A secondary analysis of the CRASH-2 trial (which originally evaluated the effect of tranexamic acid on mortality in trauma patients) was conducted. The trial included 20,127 trauma patients with significant bleeding from 274 hospitals in 40 countries. We evaluated the association of RBC transfusion with mortality in four strata of predicted risk of death: <6%, 6%–20%, 21%–50%, and >50%. For this analysis the exposure considered was RBC transfusion, and the main outcome was death from all causes at 28 days. A total of 10,227 patients (50.8%) received at least one transfusion. We found strong evidence that the association of transfusion with all-cause mortality varied according to the predicted risk of death (p-value for interaction <0.0001). Transfusion was associated with an increase in all-cause mortality among patients with <6% and 6%–20% predicted risk of death (odds ratio [OR] 5.40, 95% CI 4.08–7.13, p<0.0001, and OR 2.31, 95% CI 1.96–2.73, p<0.0001, respectively), but with a decrease in all-cause mortality in patients with >50% predicted risk of death (OR 0.59, 95% CI 0.47–0.74, p<0.0001). Transfusion was associated with an increase in fatal and non-fatal vascular events (OR 2.58, 95% CI 2.05–3.24, p<0.0001). The risk associated with RBC transfusion was significantly increased for all the predicted risk of death categories, but the relative increase was higher for those with the lowest (<6%) predicted risk of death (p-value for interaction <0.0001). As this was an observational study, the results could have been affected by different types of confounding. In addition, we could not consider haemoglobin in our analysis. In sensitivity analyses, excluding patients who died early; conducting propensity score analysis adjusting by use of platelets, fresh frozen plasma, and cryoprecipitate; and adjusting for country produced results that were similar.
Conclusions
The association of transfusion with all-cause mortality appears to vary according to the predicted risk of death. Transfusion may reduce mortality in patients at high risk of death but increase mortality in those at low risk. The effect of transfusion in low-risk patients should be further tested in a randomised trial.
Trial registration
www.ClinicalTrials.gov NCT01746953
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Trauma—a serious injury to the body caused by violence or an accident—is a major global health problem. Every year, injuries caused by traffic collisions, falls, blows, and other traumatic events kill more than 5 million people (9% of annual global deaths). Indeed, for people between the ages of 5 and 44 years, injuries are among the top three causes of death in many countries. Trauma sometimes kills people through physical damage to the brain and other internal organs, but hemorrhage (serious uncontrolled bleeding) is responsible for 30%–40% of trauma-related deaths. Consequently, early trauma care focuses on minimizing hemorrhage (for example, by using compression to stop bleeding) and on restoring blood circulation after blood loss (health-care professionals refer to this as resuscitation). Red blood cell (RBC) transfusion is often used for the management of patients with trauma who are bleeding; other resuscitation products include isotonic saline and solutions of human blood proteins.
Why Was This Study Done?
Although RBC transfusion can save the lives of patients with trauma who are bleeding, there is considerable uncertainty regarding the balance of risks and benefits associated with this procedure. RBC transfusion, which is an expensive intervention, is associated with several potential adverse effects, including allergic reactions and infections. Moreover, blood supplies are limited, and the risks from transfusion are high in low- and middle-income countries, where most trauma-related deaths occur. In this study, which is a secondary analysis of data from a trial (CRASH-2) that evaluated the effect of tranexamic acid (which stops excessive bleeding) in patients with trauma, the researchers test the hypothesis that RBC transfusion may have a beneficial effect among patients at high risk of death following trauma but a harmful effect among those at low risk of death.
What Did the Researchers Do and Find?
The CRASH-2 trail included 20,127 patients with trauma and major bleeding treated in 274 hospitals in 40 countries. In their risk-stratified analysis, the researchers investigated the effect of RBC transfusion on CRASH-2 participants with a predicted risk of death (estimated using a validated model that included clinical variables such as heart rate and blood pressure) on admission to hospital of less than 6%, 6%–20%, 21%–50%, or more than 50%. That is, the researchers compared death rates among patients in each stratum of predicted risk of death who received a RBC transfusion with death rates among patients who did not receive a transfusion. Half the patients received at least one transfusion. Transfusion was associated with an increase in all-cause mortality at 28 days after trauma among patients with a predicted risk of death of less than 6% or of 6%–20%, but with a decrease in all-cause mortality among patients with a predicted risk of death of more than 50%. In absolute figures, compared to no transfusion, RBC transfusion was associated with 5.1 more deaths per 100 patients in the patient group with the lowest predicted risk of death but with 11.9 fewer deaths per 100 patients in the group with the highest predicted risk of death.
What Do These Findings Mean?
These findings show that RBC transfusion is associated with an increase in all-cause deaths among patients with trauma and major bleeding with a low predicted risk of death, but with a reduction in all-cause deaths among patients with a high predicted risk of death. In other words, these findings suggest that the effect of RBC transfusion on all-cause mortality may vary according to whether a patient with trauma has a high or low predicted risk of death. However, because the participants in the CRASH-2 trial were not randomly assigned to receive a RBC transfusion, it is not possible to conclude that receiving a RBC transfusion actually increased the death rate among patients with a low predicted risk of death. It might be that the patients with this level of predicted risk of death who received a transfusion shared other unknown characteristics (confounders) that were actually responsible for their increased death rate. Thus, to provide better guidance for clinicians caring for patients with trauma and hemorrhage, the hypothesis that RBC transfusion could be harmful among patients with trauma with a low predicted risk of death should be prospectively evaluated in a randomised controlled trial.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001664.
This study is further discussed in a PLOS Medicine Perspective by Druin Burch
The World Health Organization provides information on injuries and on violence and injury prevention (in several languages)
The US Centers for Disease Control and Prevention has information on injury and violence prevention and control
The National Trauma Institute, a US-based non-profit organization, provides information about hemorrhage after trauma and personal stories about surviving trauma
The UK National Health Service Choices website provides information about blood transfusion, including a personal story about transfusion after a serious road accident
The US National Heart, Lung, and Blood Institute also provides detailed information about blood transfusions
MedlinePlus provides links to further resources on injuries, bleeding, and blood transfusion (in English and Spanish)
More information in available about CRASH-2 (in several languages)
doi:10.1371/journal.pmed.1001664
PMCID: PMC4060995  PMID: 24937305
14.  A European patient record study on diagnosis and treatment of chemotherapy-induced anaemia 
Supportive Care in Cancer  2014;22(8):2197-2206.
Purpose
Patients with cancer frequently experience chemotherapy-induced anaemia (CIA) and iron deficiency. Erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions are available therapies. This study evaluated routine practice in CIA management.
Methods
Medical oncologists and/or haematologists from nine European countries (n = 375) were surveyed on their last five cancer patients treated for CIA (n = 1,730). Information was collected on tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT), as well as applied anaemia therapies.
Results
Diagnostic tests and therapies for CIA varied across Europe. Anaemia and iron status were mainly assessed by Hb (94 %) and ferritin (48 %) measurements. TSAT was only tested in 14 %. At anaemia diagnosis, 74 % of patients had Hb ≤10 g/dL, including 15 % with severe anaemia (Hb <8 g/dL). Low-iron levels (ferritin ≤100 ng/mL) were detected in 42 % of evaluated patients. ESA was used in 63 % of patients, blood transfusions in 52 % and iron supplementation in 31 % (74 % oral, 26 % intravenous iron). Only 30 % of ESA-treated patients received a combination of ESA and iron supplementation. Blood transfusions formed part of a regular anaemia treatment regimen in 76 % of transfused patients. Management practices were similar in 2009 and 2011.
Conclusion
Management of anaemia and iron status in patients treated for CIA varies substantially across Europe. Iron status is only assessed in half of the patients. In contrast to clinical evidence, iron treatment is underutilised and mainly based on oral iron supplementation. Implementation of guidelines needs to be increased to minimize the use of blood transfusions.
doi:10.1007/s00520-014-2189-0
PMCID: PMC4082648  PMID: 24659244
Anaemia; Chemotherapy-induced anaemia; Intravenous iron; Iron deficiency; Diagnosis; Erythropoiesis-stimulating agents
15.  Importance of early diagnosis of pancreaticobiliary maljunction without biliary dilatation 
AIM: To clarify the strategy for early diagnosis of pancreaticobiliary maljunction (PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.
METHODS: The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography (ERCP). Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM. Of these, patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation. The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated. Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted.
RESULTS: Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain (n = 16) or jaundice (n = 12). Radical surgery for gallbladder cancer was only possible in 11 patients (31%) and only 4 patients (11%) survived for 5 years. Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography (MRCP). The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer. All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred. Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls, and hyperplastic changes, hypertrophic muscular layer, subserosal fibrosis, and adenomyomatosis were detected in 7 (88%), 5 (63%), 7 (88%) and 5 (63%) patients, respectively. Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients.
CONCLUSION: To detect PBM without biliary dilatation before onset of gallbladder cancer, we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.
doi:10.3748/wjg.v18.i26.3409
PMCID: PMC3396193  PMID: 22807610
Pancreaticobiliary maljunction; Pancreatobiliary reflux; Ultrasound; Gallbladder cancer; Endoscopic ultrasonography
16.  Anemia and blood transfusion in the critically ill patient: role of erythropoietin 
Critical Care  2004;8(Suppl 2):S42-S44.
Critically ill patients receive an extraordinarily large number of blood transfusions. Between 40% and 50% of all patients admitted to intensive care units receive at least 1 red blood cell (RBC) unit during their stay, and the average is close to 5 RBC units. RBC transfusion is not risk free. There is little evidence that 'routine' transfusion of stored allogeneic RBCs is beneficial to critically ill patients. The efficacy of perioperative recombinant human erythropoietin (rHuEPO) has been demonstrated in a variety of elective surgical settings. Similarly, in critically ill patients with multiple organ failure, rHuEPO therapy will also stimulate erythropoiesis. In a randomized, placebo-controlled trial, therapy with rHuEPO resulted in a significant reduction in RBC transfusions. Despite receiving fewer RBC transfusions, patients in the rHuEPO group had a significantly greater increase in hematocrit. Strategies to increase the production of RBCs are complementary to other approaches to reduce blood loss in the intensive care unit, and they decrease the transfusion threshold in the management of all critically ill patients.
doi:10.1186/cc2411
PMCID: PMC3226146  PMID: 15196323
anemia; blood transfusion; critical illness; erythropoietin
17.  Risk Factors of Red Blood Cell Transfusion in Isolate off Pump Coronary Artery Bypass Surgery 
Background
Perioperative transfusion of red blood cell (RBC) may cause adverse effects. Bloodless-cardiac surgery has been spotlighted to avoid those problems. Off pump coronary artery bypass (OPCAB) surgery can decrease the transfusion. However, the risk factors of transfusions in OPCAB have not been investigated properly.
Materials and Methods
One hundred and thirteen patients (male:female=35:78, mean age=66.7±9.9 years) who received isolated OPCAB were retrospectively analyzed from March 2006 to September 2007. The threshold of RBC transfusion was 28.0% of hematocrit. Bilateral internal thoracic arteries graft were used for 99 patients (87.6%). One hundred and three (91.1%) and 35 patients (31.5%) took aspirin and clopidogrel just before surgery.
Results
Sixty-five patients (47.5%) received the RBC transfusion (mean 2.2±3.2 units). Mortality and major complications were not different between transfusion and no-transfusion group. But, ventilator support time, intensive care unit stay and hospitalization period had been reduced in no-transfusion group (p<0.05). In multivariate analysis, patients risk factors for RBC transfusion were preoperative low hematocrit (<37.5%) and clopidogrel medication. Surgical risk factors were longer graft harvesting time (>75 minutes) and total operation time (>5.5 hours, p<0.05).
Conclusion
We performed the transfusion according to transfusion guideline; over 40% cases could conduct the OPCAB without transfusion. There were no differences in major clinical results between transfusion and non-transfusion group. In addition, when used together with accurate understanding of transfusion risk factors, it is expected to increase the proportion of patients that do not undergo transfusions.
doi:10.5090/kjtcs.2012.45.5.301
PMCID: PMC3487013  PMID: 23130303
Blood transfusion; Coronary artery bypass; Cardiopulmonary bypass
18.  Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases 
Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient’s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a “one-by-one” administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better prospects for blood conservation in selected IBD patients undergoing elective surgery.
doi:10.3748/wjg.15.4686
PMCID: PMC2754517  PMID: 19787832
Anaemia; Blood transfusion; Autologous blood transfusion; Inflammatory bowel diseases; Risk assessment
19.  Risk analysis of blood transfusion requirements in emergency and elective spinal surgery 
European Spine Journal  2010;20(5):753-758.
Spinal surgery has long been considered to have an elevated risk of perioperative blood loss with significant associated blood transfusion requirements. However, a great variability exists in the blood loss and transfusion requirements of differing patients and differing procedures in the area of spinal surgery. We performed a retrospective study of all patients undergoing spinal surgery who required a transfusion ≥1 U of red blood cells (RBC) at the National Spinal Injuries Unit (NSIU) at the Mater Misericordiae University Hospital over a 10-year period. The purpose of this study was to identify risk factors associated with significant perioperative transfusion allowing the early recognition of patients at greatest risk, and to improve existing transfusion practices allowing safer, more appropriate blood product allocation. 1,596 surgical procedures were performed at the NSIU over a 10-year period. 25.9% (414/1,596) of these cases required a blood transfusion (n = 414). Surgical groups with a significant risk of requiring a transfusion >2 U RBC included deformity surgery (RR = 3.351, 95% CI 1.123–10.006, p = 0.03), tumor surgery (RR = 3.298, 95% CI 1.078–10.089, p = 0.036), and trauma surgery (RR = 2.444, 95% CI 1.183–5.050, p = 0.036). Multivariable logistic regression analysis identified multilevel surgery (>3 levels) as a significant risk of requiring a transfusion >2 U RBC (RR = 4.682, 95% CI 2.654–8.261, p < 0.0001). Several risk factors in the spinal surgery patient were identified as corresponding to significant transfusion requirements. A greater awareness of the risk factors associated with transfusion is required in order to optimize patient management.
doi:10.1007/s00586-010-1500-0
PMCID: PMC3082666  PMID: 20582708
Blood loss; Transfusion requirement; Spinal surgery
20.  Health Care–Associated Infection After Red Blood Cell Transfusion 
JAMA  2014;311(13):1317-1326.
IMPORTANCE
The association between red blood cell (RBC) transfusion strategies and health care–associated infection is not fully understood.
OBJECTIVE
To evaluate whether RBC transfusion thresholds are associated with the risk of infection and whether risk is independent of leukocyte reduction.
DATA SOURCES
MEDLINE, EMBASE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, Cochrane Database of Sytematic Reviews, ClinicalTrials.gov, International Clinical Trials Registry, and the International Standard Randomized Controlled Trial Number register were searched through January 22, 2014.
STUDY SELECTION
Randomized clinical trials with restrictive vs liberal RBC transfusion strategies.
DATA EXTRACTION AND SYNTHESIS
Twenty randomized trials with 8598 patients met eligibility criteria, of which 17 trials (n = 7456 patients) contained sufficient information for meta-analyses. DerSimonian and Laird random-effects models were used to report pooled risk ratios. Absolute risks of infection were calculated using the profile likelihood random-effects method.
MAIN OUTCOMES AND MEASURES
Incidence of health care–associated infection such as pneumonia, mediastinitis, wound infection, and sepsis.
RESULTS
The pooled risk of all serious infections was 10.6% (95% CI, 5.6%-15.9%) in the restrictive group and 12.7% (95% CI, 7.0%-18.7%) in the liberal group. The risk ratio (RR) for the association between transfusion strategies and infection (serious infections and selected infections, combined) was 0.92 (95% CI, 0.82-1.04) with little heterogeneity (I2 = 6.3%; τ2 = .0041). The RR for the association between transfusion strategies and serious infection was 0.84 (95% CI, 0.73-0.96; I2 = 0%, τ2 <.0001). The number needed to treat (NNT) with restrictive strategies to prevent serious infection was 48 (95% CI, 36-71). The risk of infection remained reduced with a restrictive strategy, even with leukocyte reduction (RR, 0.83 [95% CI, 0.69-0.99]). For trials with a restrictive hemoglobin threshold of <7.0 g/dL, the RR was 0.86 (95% CI, 0.72-1.02). With stratification by patient type, the RR for serious infection was 0.72 (95% CI, 0.53-0.97) in patients undergoing orthopedic surgery and 0.51 (95% CI, 0.28-0.95) in patients presenting with sepsis. There were no significant differences in the incidence of infection by RBC threshold for patients with cardiac disease, the critically ill, those with acute upper gastrointestinal bleeding, or for infants with low birth weight.
CONCLUSIONS AND RELEVANCE
Among hospitalized patients, a restrictive RBC transfusion strategy compared with a liberal transfusion strategy was not associated with a reduced risk of health care–associated infection overall, although it was associated with a reduced risk of serious infection. Implementing restrictive strategies may have the potential to lower the incidence of serious health care–associated infection.
doi:10.1001/jama.2014.2726
PMCID: PMC4289152  PMID: 24691607
21.  A randomised controlled trial on the Four Pillars Approach in managing pregnant women with anaemia in Yogyakarta–Indonesia: a study protocol 
Background
Anaemia is a common health problem among pregnant women and a contributing factor with a major influence on maternal mortality in Indonesia. The Four Pillars Approach is a new approach to anaemia in pregnancy, combining four strategies to improve antenatal and delivery care. The primary objective of this study is to measure the effectiveness of the Four Pillars Approach. The barriers, the facilitators, and the patients’ as well as the midwives’ satisfaction with the Four Pillars Approach will also be measured.
Methods/Design
This study will use a cluster randomised controlled trial. This intervention study will be conducted in the Public Health Centres with basic emergency obstetric care in Yogyakarta Special Province and in Central Java Province. We will involve all the Public Health Centres (24) with emergency obstetric care in Yogyakarta Special Province. Another 24 Public Health Centres with emergency obstetric care in Central Java Province which have similarities in their demographic, population characteristics, and facilities will also be involved. Each Public Health Centre will be asked to choose two or three nurse-midwives to participate in this study. For the intervention group, the Public Health Centres in Yogyakarta Special Province, training on the Four Pillars Approach will be held prior to the model’s implementation. Consecutively, we will recruit 360 pregnant women with anaemia to take part in part in the study to measure the effectiveness of the intervention. The outcome measurements are the differences in haemoglobin levels between the intervention and control groups in the third trimester of pregnancy, the frequency of antenatal care attendance, and the presence of a nurse-midwife during labour. Qualitative data will be used to investigate the barriers and facilitating factors, as to nurse-midwives’ satisfaction with the implementation of the Four Pillars Approach.
Discussion
If the Four Pillars Approach is effective in improving the outcome for pregnant women with anaemia, this approach could be implemented nationwide and be taken into consideration to improve the outcome for other conditions in pregnancy, after further research.
Trial registration
Current Controlled Trials ISRCTN35822126.
doi:10.1186/1471-2393-14-163
PMCID: PMC4018617  PMID: 24884497
Four Pillars Approach; Healthy life style; Social support; Nurse-midwives’ competencies; Professional behaviour; Pregnant women; Anaemia; Antenatal care
22.  Massive Bleeding and Massive Transfusion 
Massive bleeding in trauma patients is a serious challenge for all clinicians, and an interdisciplinary diagnostic and therapeutic approach is warranted within a limited time frame. Massive transfusion usually is defined as the transfusion of more than 10 units of packed red blood cells (RBCs) within 24 h or a corresponding blood loss of more than 1- to 1.5-fold of the body's entire blood volume. Especially male trauma patients experience this life-threatening condition within their productive years of life. An important parameter for clinical outcome is to succeed in stopping the bleeding preferentially within the first 12 h of hospital admission. Additional coagulopathy in the initial phase is induced by trauma itself and aggravated by consumption and dilution of clotting factors. Although different aspects have to be taken into consideration when viewing at bleedings induced by trauma compared to those caused by major surgery, the basic strategy is similar. Here, we will focus on trauma-induced massive hemorrhage. Currently there are no definite, worldwide accepted algorithms for blood transfusion and strategies for optimal coagulation management. There is increasing evidence that a higher ratio of plasma and RBCs (e.g. 1:1) endorsed by platelet transfusion might result in a superior survival of patients at risk for trauma-induced coagulopathy. Several strategies have been evolved in the military environment, although not all strategies should be transferred unproven to civilian practice, e.g. the transfusion of whole blood. Several agents have been proposed to support the restoration of coagulation. Some have been used for years without any doubt on their benefit-to-risk profile, whereas great enthusiasm of other products has been discouraged by inefficacy in terms of blood transfusion requirements and mortality or significant severe side effects. This review surveys current literature on fluid resuscitation, blood transfusion, and hemostatic agents currently used during massive hemorrhage in order to optimize patients’ blood and coagulation management in emergency medical aid.
doi:10.1159/000337250
PMCID: PMC3364037  PMID: 22670125
Bleeding complication; Coagulation factors; Colloids; Erythrocyte transfusion; Fresh frozen plasma; Massive transfusion; Thrombocytes; Volume replacement
23.  Balanced massive transfusion ratios in multiple injury patients with traumatic brain injury 
Critical Care  2011;15(1):R68.
Introduction
Retrospective studies have demonstrated a potential survival benefit from transfusion strategies using an early and more balanced ratio between fresh frozen plasma (FFP) concentration and packed red blood cell (pRBC) transfusions in patients with acute traumatic coagulopathy requiring massive transfusions. These results have mostly been derived from non-head-injured patients. The aim of the present study was to analyze whether a regime using a high FFP:pRBC transfusion ratio (FFP:pRBC ratio >1:2) would be associated with a similar survival benefit in severely injured patients with traumatic brain injury (TBI) (Abbreviated Injury Scale (AIS) score, head ≥3) as demonstrated for patients without TBI requiring massive transfusion (≥10 U of pRBCs).
Methods
A retrospective analysis of severely injured patients from the Trauma Registry of the Deutsche Gesellschaft für Unfallchirurgie (TR-DGU) was conducted. Inclusion criteria were primary admission, age ≥16 years, severe injury (Injury Severity Score (ISS) ≥16) and massive transfusion (≥10 U of pRBCs) from emergency room to intensive care unit (ICU). Patients were subdivided into patients with TBI (AIS score, head ≥3) and patients without TBI (AIS score, head <3), as well as according to the transfusion ratio they had received: high FFP:pRBC ratio (FFP:pRBC ratio >1:2) and low FFP:pRBC ratio (FFP:pRBC ratio ≤1:2). In addition, morbidity and mortality between the two groups were compared.
Results
A total of 1,250 data sets of severely injured patients from the TR-DGU between 2002 and 2008 were analyzed. The mean patient age was 42 years, the majority of patients were male (72.3%), the mean ISS was 41.7 points (±15.4 SD) and the principal mechanism of injury was blunt force trauma (90%). Mortality was statistically lower in the high FFP:pRBC ratio groups versus the low FFP:pRBC ratio groups, regardless of the presence or absence of TBI and across all time points studied (P < 0.001). The frequency of sepsis and multiple organ failure did not differ among groups, except for sepsis in patients with TBI who received a high FFP:pRBC ratio transfusion. Other secondary end points such as ventilator-free days, length of stay in the ICU and overall in-hospital length of stay differed significantly between the two study groups, but not when only data for survivors were analyzed.
Conclusions
These results add more detailed knowledge to the concept of a high FFP:pRBC ratio during early aggressive resuscitation, including massive transfusion, to decrease mortality in severely injured patients both with and without accompanying TBI. Future research should be conducted with a larger number of patients to prove these results in a prospective study.
doi:10.1186/cc10048
PMCID: PMC3222001  PMID: 21342499
24.  Carcinoma of the papilla of Vater following treatment of pancreaticobiliary maljunction 
Pancreaticobiliary maljunction (PBM) is frequently associated with biliary cancer due to reflux of pancreatic enzymes into the choledochus, and even after surgery to correct the PBM such patients still have a risk of residual bile duct cancer. Here, we report the case of a 59-year-old female with carcinoma of the papilla of Vater which developed 2.5 years after choledochoduodenostomy for PBM. During the postoperative follow-up period, computed tomography obtained 2 years after the first operation demonstrated a tumor in the distal end of the choledochus, although she did not have jaundice and laboratory tests showed no abnormalities caused by the previous operation. As a result, carcinoma of the papilla of Vater was diagnosed at an early stage, followed by surgical cure. For early detection of periampullary cancer in patients undergoing surgery for PBM, careful long-term follow-up is needed.
doi:10.3748/wjg.15.6126
PMCID: PMC2797673  PMID: 20027689
Pancreaticobiliary maljunction; Biliary cancer; Carcinoma of the papilla of Vater
25.  Reduction of Fresh Frozen Plasma Requirements by Perioperative Point-of-Care Coagulation Management with Early Calculated Goal-Directed Therapy 
Background
Massive bleeding and transfusion of packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets are associated with increased morbidity, mortality and costs.
Patients and Methods
We analysed the transfusion requirements after implementation of point-of-care (POC) coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in different perioperative settings (trauma surgery, visceral and transplant surgery (VTS), cardiovascular surgery (CVS) and general and surgical intensive care medicine) at 3 different hospitals (AUVA Trauma Centre Salzburg, University Hospital Innsbruck and University Hospital Essen) in 2 different countries (Austria and Germany).
Results
In all institutions, the implementation of POC coagulation management algorithms was associated with a reduction in the transfusion requirements for FFP by about 90% (Salzburg 94%, Innsbruck 88% and Essen 93%). Furthermore, PRBC transfusion was reduced by 8.4–62%. The incidence of intraoperative massive transfusion (≥10 U PRBC) could be more than halved in VTS and CVS (2.56 vs. 0.88%; p < 0.0001 and 2.50 vs. 1.06%; p = 0.0007, respectively). Platelet transfusion could be reduced by 21–72%, except in CVS where it increased by 115% due to a 5-fold increase in patients with dual antiplatelet therapy (2.7 vs. 13.7%; p < 0.0001).
Conclusions
The implementation of perioperative POC coagulation management algorithms based on early, calculated, goal-directed therapy with fibrinogen concentrate and PCC is associated with a reduction in the transfusion requirements for FFP, PRBC and platelets as well as with a reduced incidence of massive transfusion. Thus, the limited blood resources can be used more efficiently.
doi:10.1159/000337186
PMCID: PMC3364099  PMID: 22670128
Thromboelastometry; Transfusion algorithms; Fibrinogen concentrate; Prothrombin complex concentrate; Transfusion-associated adverse events; Pharmacoeconomics

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