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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.  Patient blood management in Europe 
Summary
Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed ‘patient blood management’ (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PBM.
doi:10.1093/bja/aes139
PMCID: PMC3374574  PMID: 22628393
anaemia; outcome; patient blood management; transfusion
3.  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
4.  Iron Supplementation for Postoperative Anaemia Following Major Paediatric Orthopaedic Surgery 
INTRODUCTION
There is increasing evidence that the anaemia of surgery is not iron deficient and is, therefore, unresponsive to iron supplementation. Oral iron is best avoided postoperatively, particularly in children, due to its dose-dependent side effects. We undertook a national survey of major paediatric orthopaedic surgical units in the UK to investigate the current management of postoperative anaemia with particular reference to iron supplementation.
MATERIALS AND METHODS
Middle-grade doctors and charge nurses at 23 major paediatric orthopaedic units in the UK were contacted by telephone and a structured questionnaire was used to determine the management of postoperative anaemia in major hip, pelvic and spinal surgery.
RESULTS
Only one (4.3%) of the units surveyed had a formally established protocol for the management of postoperative anaemia. Only 10 out of 23 units (43.5%) did not routinely prescribe iron postoperatively. Of the remaining units, 11 commenced iron based on the postoperative haemoglobin level while only 2 used iron supplementation after investigation of serum haematinics for iron deficiency. One unit used erythropoietin in the treatment of postoperative anaemia.
CONCLUSIONS
Iron supplementation continues to be used in major paediatric orthopaedic surgery in the treatment of postoperative anaemia in the absence of iron deficiency. Given the current available evidence, we call for an end to the practice of routine iron supplementation for postoperative anaemia following major paediatric orthopaedic surgery in the UK.
doi:10.1308/003588407X160837
PMCID: PMC1963521  PMID: 17316521
Postoperative anaemia; Iron supplementation; Survey
5.  Recognising anaemia and malnutrition in vascular patients with critical limb ischaemia 
INTRODUCTION
Anaemia is a common problem in surgical patients. Patients with critical limb ischaemia (CLI) suffer chronic inflammation, repeated infection, require intervention, and can have a protracted hospital stay. The aims of this study were to assess anaemia and nutritional status in patients presenting with CLI.
PATIENTS AND METHODS
Two observational studies were undertaken, initially a retrospective series of 27 patients with CLI. Patient demographics, clinical details, transfusion status and in-patient laboratory haemoglobin values (Hb) were recorded. In a prospective series of 32 patients, laboratory markers to identify the cause for anaemia were assessed. Further nutritional status was assessed by records of height, weight, body mass index and a validated scoring system.
RESULTS
In the retrospective series, 15 patients (56%) were anaemic. Ten (37%) were transfused a median of 2 units (range, 2–13), a total of 35 units. Patients who were transfused had lower Hb on admission (P = 0.0019), most were anaemic on admission (90%). At discharge, most patients were anaemic (n = 23; 83%). In the prospective series of 32 patients, 20 (63%) were anaemic. Nutritional assessment was performed on 18, only seven patients were scored undernourished. This was increased to 23 by an independent assessor. Anaemia was associated with malnutrition (n = 17; P = 0.049) and an increased hospital stay (mean 25 days [SD 16] vs mean 12 days [SD 8], P = 0.0125; total 513 vs 144 bed days).
CONCLUSIONS
Anaemia and poor nutrition are common and not recognised in vascular patients presenting with critical limb ischaemia. Anaemia is associated with and increased length of hospital stay.
doi:10.1308/003588410X12664192075738
PMCID: PMC3182792  PMID: 20513273
Critical limb ischaemia; Anaemia; Malnutrition
6.  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
7.  Combination treatment with an erythropoiesis-stimulating agent and intravenous iron alleviates anaemia in patients with hereditary haemorrhagic telangiectasia 
Upsala Journal of Medical Sciences  2014;119(4):350-353.
Background
Patients with hereditary haemorrhagic telangiectasia (HHT) suffer from recurrent epistaxis and bleeding from gastrointestinal telangiectasias that occur despite otherwise normal haemostasis and result in iron deficiency anaemia with increasing severity. In advanced disease, anaemia may be severe, be irresponsive to iron supplementation, and may lead to red blood cell transfusion dependency.
Methods
We conducted a retrospective study at our Centre for Osler’s Disease to evaluate the effectiveness of adding an erythropoiesis-stimulating agent (ESA) to intravenous iron supplementation in the management of anaemic HHT patients. Blood values and treatment parameters were collected for nine months before combination therapy (iron supplementation only) and 12 months during combination therapy (iron supplementation plus ESA).
Results
Four patients received intravenous iron and an ESA with mean weekly doses of 126 mg and 17,300 units (U), respectively. Mean haemoglobin improved significantly during combination therapy, from 106 g/L to 119 g/L (p < 0.001).
Conclusion
Conclusion. Anaemia can be alleviated in patients with HHT who are irresponsive to intravenous iron supplementation, by addition of an ESA. The proposed mechanism behind the iron irresponsiveness is that the anaemia is caused by a combination of recurrent haemorrhage and anaemia of chronic disease.
doi:10.3109/03009734.2014.955619
PMCID: PMC4248076  PMID: 25188751
Anaemia; erythropoiesis-stimulating agents; hereditary haemorrhagic telangiectasia; iron
8.  Course and characteristics of anaemia in patients with rheumatoid arthritis of recent onset. 
Annals of the Rheumatic Diseases  1996;55(3):162-168.
OBJECTIVE: To describe the incidence, cause, and course of anaemia in rheumatoid arthritis (RA). METHODS: Medical records of 225 patients who received a diagnosis of RA between 1990 and 1992 were reviewed longitudinally for mention of anaemia. Anaemia was classified as anaemia of chronic disease if ferritin concentrations reflected adequate body iron stores. Among iron depleted anaemic patients, iron deficiency anaemia was identified using the response to iron supplementation. RESULTS: Anaemia developed in 64% of the patients, mostly within 18 months of follow up, but disappeared again in 54% of those patients. The prevalence of anaemia varied from 39% to 53% throughout follow up. Iron depletion was found in 38% of anaemic patients; 40% of them did not recover from their anaemia after iron supplementation and were classified as having anaemia of chronic disease. Anaemia of chronic disease thus caused 77% and iron deficiency anaemia 23% of observed anaemia. Recovery from anaemia occurred in 42% of the patients with anaemia of chronic disease and in 72% of iron depleted patients after iron supplementation. Anaemic patients, particularly those with anaemia of chronic disease, had a significantly greater number of the American College of Rheumatism criteria for RA, significantly more erosive joint damage, and significantly increased concentrations of serum rheumatoid factor than patients without anaemia. CONCLUSION: Anaemia appeared as a frequent and dynamic manifestation. Recovery and recurrence of anaemia was observed throughout follow up, leading to a longstanding and relatively high prevalence of the condition. Iron deficiency was diagnosed frequently and follow up revealed a considerable overlap with anaemia of chronic disease, making this the most important cause of anaemia in RA. Recovery from anaemia occurred more frequently in iron depleted anaemic patients than in those with anaemia of chronic disease. Anaemic patients, particularly those with anaemia of chronic disease, seemed to have a more serious course of their RA compared with non-anaemic patients.
PMCID: PMC1010122  PMID: 8712878
9.  Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery 
Annals of the Rheumatic Diseases  2001;60(3):214-217.
OBJECTIVES—To determine whether continued methotrexate treatment increases the risk of postoperative infections or of surgical complications in patients with rheumatoid arthritis (RA) within one year of elective orthopaedic surgery.
DESIGN—A prospective randomised study of postoperative infection or surgical complications occurring within one year of surgery in patients with RA who underwent elective orthopaedic surgery.
SUBJECTS—388 patients with RA who were to undergo elective orthopaedic surgery. Patients who were receiving methotrexate were randomly allocated to groups who either continued methotrexate (group A) or who discontinued methotrexate from two weeks before surgery until two weeks after surgery (group B). Their complication rates were compared with complications occurring in 228 patients with RA (group C) who were not receiving methotrexate and who also underwent elective orthopaedic surgery.
MAIN OUTCOME MEASURES—Signs of postoperative infection were recorded, including rubor, discharge, systemic infection, and frequency of wound dehiscence as well as the incidence of any surgical complication requiring a secondary revision procedure that occurred within one year of surgery. The frequencies of flare up activity of RA at six weeks and six months after surgery were also recorded. A flare of rheumatoid disease was defined as an increase in joint pain in two or more joints notified by the patient as well as by an increase in articular index of at least 25% after surgery.
RESULTS—Signs of infection or surgical complications occurred in two of 88 procedures in group A (2%), 11 of 72 procedures in group B (15%), and 24 of 228 (10.5%) procedures in group C. The surgical complication or infection frequency in group A was less than that in either group B (p<0.003) or group C (p=0.026). At six weeks after surgery there were no flares in group A, six flares in group B (8%), and six flares in group C (2.6%). Logistic regression analysis of the overall surgical complication rate in all the patients with RA studied showed that methotrexate, whether continued or discontinued before surgery, did not increase the early complication rate in the patients with RA who underwent elective orthopaedic surgery. Other drugs—penicillamine, indometacin, cyclosporin, hydroxychloroquine, chloroquine, and prednisolone—all did significantly increase the risk of infection or surgical complication after elective orthopaedic surgery. The risk of surgery was also increased in the presence of intercurrent chronic diseases—diabetes, hypertension, bronchiectasis, psoriasis, asthma, and ischaemic heart disease.
CONCLUSION—Continuation of methotrexate treatment does not increase the risk of either infections or of surgical complications occurring in patients with RA within one year of elective orthopaedic surgery. Thus methotrexate treatment should not be stopped in patients whose disease is controlled by the drug before elective orthopaedic surgery.


doi:10.1136/ard.60.3.214
PMCID: PMC1753573  PMID: 11171680
10.  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
11.  Reviewing the blood ordering schedule for elective orthopedic surgeries at a level one trauma care center 
Background:
Patients undergoing elective orthopedic surgeries often incur excess blood loss necessitating transfusion. The preoperative placement of blood requests frequently overshoots the actual need resulting in unnecessary crossmatching.
Aims:
Our primary goal was to audit the blood utilization in elective orthopedic surgeries in our hospital over a 1-year period and recommend a blood ordering schedule.
Materials and Methods:
A retrospective analysis of patients who underwent elective orthopedic surgeries over a period of 1 year was done. The data collected include patients’ age, sex, type of surgical procedure, pre- and postoperative hemoglobin (Hb) levels, number of units crossmatched, returned, transfused, crossmatch to transfusion ratio (C:T), transfusion indices, estimated blood loss for each surgical procedure, and the actual and predicted fall in Hb. We propose a blood ordering schedule based on surgical blood ordering equation.
Results and Conclusions:
A total of 487 patients with a median age of 37±17 years (mean ± standard deviation) were evaluated. One thousand three hundred and seventy-seven units of blood were crossmatched and only 564 units were transfused to 260 patients. Fifty-nine percent of the units crossmatched were not transfused. Six of the 12 elective procedures had a C:T ratio higher than 2.5. Ten of the 12 procedures (83.3%) had a low transfusion index (TI < 0.5). The calculated red blood cell units were less than 0.5 in 5 of the 12 elective procedures, and hence we recommend a group and save policy for these procedures. Blood ordering schedule based on patient and surgical variables would provide an efficient way of blood utilization and management of resources.
doi:10.4103/0974-2700.66521
PMCID: PMC2938486  PMID: 20930965
Audit; blood ordering schedule; elective orthopedic surgeries; surgical blood ordering equation; transfusion
12.  Iron Deficiency and Bariatric Surgery 
Nutrients  2013;5(5):1595-1608.
It is estimated that the prevalence of anaemia in patients scheduled for bariatric surgery is higher than in the general population and the prevalence of iron deficiencies (with or without anaemia) may be higher as well. After surgery, iron deficiencies and anaemia may occur in a higher percentage of patients, mainly as a consequence of nutrient deficiencies. In addition, perioperative anaemia has been related with increased postoperative morbidity and mortality and poorer quality of life after bariatric surgery. The treatment of perioperative anaemia and nutrient deficiencies has been shown to improve patients’ outcomes and quality of life. All patients should undergo an appropriate nutritional evaluation, including selective micronutrient measurements (e.g., iron), before any bariatric surgical procedure. In comparison with purely restrictive procedures, more extensive perioperative nutritional evaluations are required for malabsorptive procedures due to their nutritional consequences. The aim of this study was to review the current knowledge of nutritional deficits in obese patients and those that commonly appear after bariatric surgery, specifically iron deficiencies and their consequences. As a result, some recommendations for screening and supplementation are presented.
doi:10.3390/nu5051595
PMCID: PMC3708339  PMID: 23676549
obesity; bariatric surgery; iron deficiency; iron deficiency anaemia; nutritional assessment; nutritional supplementation
13.  The Problem of Anaemia in Patients with Colorectal Cancer 
ISRN Hematology  2014;2014:547914.
Background. Surgical patients are often anaemic preoperatively subsequently requiring blood transfusion. The aim of this study was to assess the problem of anaemia and transfusion rates in patients undergoing surgery for colorectal cancer. Methods. Haemoglobin levels and transfusion requirements were assessed retrospectively in 199 sequential patients operated on for colorectal cancer. This was followed by prospective analysis of 147 patients to correlate preoperative anaemia, stage of bowel cancer, and operation performed with rates of blood transfusion and length of hospital stay. Results. Preoperatively 44% patients were anaemic retrospectively and 60% prospectively. Anaemia increased the risk of transfusion in both studies (69% anaemic versus 31% nonanaemic, P = 0.002 in retrospective series, and 83.7% versus 16.3%, P < 0.0001 in prospective series). Anaemia was proportionally higher in patients with Dukes B (65.2%) and Dukes C (66.6%) than in patients with Dukes A (28.5%). Length of stay was prolonged in transfused patients excluding those requiring major blood transfusion (median 13 versus 7 days, P < 0.0001). Transfusion was also associated with higher mortality (P = 0.05). Conclusion. Anaemia is common in patients with colorectal cancer. Anaemic patients were at high risk of receiving blood transfusion, which in turn increased length of stay and mortality.
doi:10.1155/2014/547914
PMCID: PMC3947861  PMID: 24696785
14.  Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding – a European perspective 
Critical Care  2006;10(4):R120.
Introduction
Our aim was to develop consensus guidelines for use of recombinant activated factor VII (rFVIIa) in massive hemorrhage.
Methods
A guidelines committee derived the recommendations using clinical trial and case series data identified through searches of available databases. Guidelines were graded on a scale of A to E (with A being the highest) according to the strength of evidence available. Consensus was sought among the committee members for each recommendation.
Results
A recommendation for the use of rFVIIa in blunt trauma was made (grade B). rFVIIa might also be beneficial in post-partum hemorrhage (grade E), uncontrolled bleeding in surgical patients (grade E), and bleeding after cardiac surgery (grade D). rFVIIa could not be recommended for use in the following: in penetrating trauma (grade B); prophylactically in elective surgery (grade A) or liver surgery (grade B); or in bleeding episodes in patients with Child–Pugh A cirrhosis (grade B). Efficacy of rFVIIa was considered uncertain in bleeding episodes in patients with Child–Pugh B and C cirrhosis (grade C). Monitoring of rFVIIa efficacy should be performed visually and by assessment of transfusion requirements (grade E), while thromboembolic adverse events are a cause for concern. rFVIIa should not be administered to patients considered unsalvageable by the treating medical team.
Conclusion
There is a rationale for using rFVIIa to treat massive bleeding in certain indications, but only adjunctively to the surgical control of bleeding once conventional therapies have failed. Lack of data from randomized, controlled clinical trials, and possible publication bias of the case series data, limits the strength of the recommendations that can be made.
doi:10.1186/cc5026
PMCID: PMC1750973  PMID: 16919168
15.  Identification and key management of non-transfusion-dependent thalassaemia patients: not a rare but potentially under-recognised condition 
Patients with non-transfusion-dependent thalassaemia (NTDT) have a genetic defect or combination of defects that affect haemoglobin synthesis, but which is not severe enough to require regular blood transfusions. The carrier frequency of NTDT is high (up to 80% in some parts of the world) but the prevalence of symptomatic patients varies with geography and is estimated to be from 1 in 100,000 to 1 in 100. NTDT has a variable presentation that may include mild to severe anaemia, enlarged spleen and/or liver, skeletal deformities, growth retardation, elevated serum ferritin and iron overload. The contributing factors to disease progression are ineffective erythropoiesis and increased haemolysis, which lead to chronic anaemia. The body’s attempts to correct the anaemia result in constantly activated erythropoiesis, leading to marrow expansion and extramedullary haematopoiesis. Diagnosis of NTDT is largely clinical but can be confirmed by genetic sequencing. NTDT must be differentiated from other anaemias including sideroblastic anaemia, paroxysmal nocturnal haemoglobinuria, congenital dyserythropoietic anaemia, myelodysplastic syndromes and iron-deficiency anaemia. Management of NTDT is based on managing symptoms, and includes blood transfusions, hydroxyurea treatment, iron chelation and sometimes splenectomy. Prognosis for well managed patients is good, with most patients living a normal life. Since NTDT is mainly prevalent in sub-tropical regions, patients who present in other parts of the world, in particular the Northern hemisphere, might not been correctly recognised and it can be considered a ‘rare’ condition. It is particularly important to identify and diagnose patients early, thereby preventing complications.
doi:10.1186/s13023-014-0131-7
PMCID: PMC4193991  PMID: 25265971
Non-transfusion-dependent thalassaemia; Thalassaemia intermedia; HbE disease; HbH disease; Iron chelation; RBC transfusion; Hydroxyurea
16.  A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group Study 
British Journal of Cancer  2007;96(4):551-558.
The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m−2) administered on days 1–5 and 29–33 followed by low dose LV (20 mg m−2) and 5FU (350 mg m−2 over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three- or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6–10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26–75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m−2 when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m−2 dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 (24%) and 12 out of 57 (21%) overall. A histologically confirmed clear circumferential resection margin (CRM) was achieved in 39 out of 49 (80%) of those resected, and 39 out of 57 (68%) overall. In conclusion, MTD with this scheduled regimen of irinotecan is 20 mg m−2 (days 1–5 and 29–33). The acceptable toxicity and compliance at 18 mg m−2 recommend testing this dose in future phase III studies. The tumour downstaging and complete resection rates (negative CRM) are encouragingly high for this very locally advanced group.
doi:10.1038/sj.bjc.6603570
PMCID: PMC2360056  PMID: 17262086
5-fluorouracil; irinotecan; locally advanced rectal cancer; preoperative chemoradiation
17.  The appropriateness of blood transfusion following primary total hip replacement 
INTRODUCTION
A significant proportion of all red cell transfusions are given to patients undergoing elective orthopaedic surgery. Concern over transfusion safety and cost, coupled with evidence showing that restrictive transfusion policies benefit patients, prompted us to audit our blood prescribing practice at Gloucestershire Hospitals NHS Foundation Trust in order to assess the appropriateness of every transfusion episode following elective primary total hip replacement.
METHODS
All patients undergoing a primary total hip replacement in our department over a six-month period were included in the study. Data were collected retrospectively using case note examination and transfusion service data. Standards were dictated by the British Orthopaedic Association guidelines on blood conservation in elective orthopaedic surgery.
RESULTS
Twenty-seven per cent of patients (39/143) were transfused. Forty-six per cent of these (18/39) were transfused inappropriately and twenty-three per cent (9/39) appropriately. Thirteen per cent (5/39) had a valid indication for transfusion but were over-transfused and in eighteen per cent (7/39) the quality of documentation did not allow an assessment to be made. Fifty-two per cent of patients who had surgical drains (29/56) were transfused. Reaudit following staff education and amendments to the local transfusion policy did not demonstrate a reduction in transfusion rates.
CONCLUSIONS
This audit showed that significant potential exists for reducing transfusion rates based on optimising prescribing practice alone. It also demonstrated that changing local practice based on audit data can be challenging.
doi:10.1308/003588412X13171221501384
PMCID: PMC3705237  PMID: 22507728
Arthroplasty; Hip; Anaemia; Blood transfusion
18.  Audit of open tibial diaphyseal fracture management at a district accident centre. 
Preston Acute Hospital is a designated district accident centre with a 24 h flying squad and on-site plastic and orthopaedic units. We performed a retrospective 5-year survey of open tibial shaft fracture management at our unit and compared our treatment to the guidelines of the British Orthopaedic Association (BOA) and British Association of Plastic Surgeons (BAPS). Deficiencies were highlighted and changes in practice made. We then re-audited our figures over an 18-month period to see if clinical improvements had been made. The audit demonstrated an incidence of open tibial shaft fractures of 15 per 50,000 new patients per year in accident and emergency. Gustilo grading, and thus full appreciation of soft tissues injury, was being underestimated, with 8% of the injuries undergraded at the time of surgery: 17% of Gustilo IIIA and 85% Gustilo IIIB required flap cover. Seventy-four percent of patients received their first orthopaedic procedure within the recommended 6 h of admission, but despite the on-site plastics unit, only 50% of cases in the initial survey had their soft tissue defect covered by the recommended 5 days. After changes to practice, 80% patients received their first orthopaedic procedure within the recommended 6 h of admission, and all had their soft tissue defect covered within 5 days; 5% of cases required fasciotomy to relieve compartment syndrome. We highlight features to alert the high energy (Gustilo III) status and recommend immediate involvement of plastic surgical colleagues with these injuries. We also highlight a high incidence of compartment syndrome in the young male patient with the lower energy Gustilo I injury.
PMCID: PMC2503484  PMID: 11103167
19.  Identification and Treatment of Anaemia in Patients Awaiting Hip Replacement 
INTRODUCTION
The correction of anaemia prior to total hip arthroplasty reduces surgical risk, hospital stay and cost. This study considers the benefits of implementing a protocol of identifying and treating pre-operative anaemia whilst the patient is on the waiting list for surgery.
PATIENTS AND METHODS
From a prospective series of 322 patients undergoing elective total hip arthroplasty (THA), patients identified as anaemic (haemoglobin (Hb) < 12 g/dl) when initially placed upon the waiting list were appropriately investigated and treated. Pre- and postoperative Hb levels, need for transfusion, and length of hospital stay were collated for the entire patient cohort.
RESULTS
Of the cohort, 8.8% of patients were anaemic when initially placed upon the waiting list for THA and had a higher transfusion rate (23% versus 3%; P < 0.05) and longer hospital stay (7.5 days versus 6.6 days; P < 0.05). Over 40% of these patients responded to investigation and treatment whilst on the waiting list, showing a significant improvement in Hb level (10.1 g/dl to 12.7 g/dl) and improved transfusion rate.
CONCLUSIONS
Quantifying the haemoglobin level of patients when initially placed on the waiting list helps highlight those at risk of requiring a postoperative blood transfusion. Further, the early identification of anaemia allows for the utilisation of the waiting-list time to investigate and treat these patients. For patients who respond to treatment, there is a significant reduction in the need for blood transfusion with its inherent hazards.
doi:10.1308/003588408X301163
PMCID: PMC2647246  PMID: 18765030
Total hip arthroplasty; Anaemia
20.  Blood Transfusion Policies in Elective General Surgery: How to Optimise Cross-Match-to-Transfusion Ratios 
Objective
Preoperative over-ordering of blood is common and leads to the wastage of blood bank resources. The preoperative blood ordering and transfusion practices for common elective general surgical procedures were evaluated in our university hospital to formulate a maximum surgical blood order schedule (MSBOS) for those procedures where a cross-match appears necessary.
Methods
We evaluated blood ordering practices retrospectively in all elective general surgical procedures in our institution over a 6-month period. Cross-match-to-transfusion ratios (C:T) were calculated and compared to current trust and the British Society of Haematology (BSH) guidelines. The adjusted C:T ratio was also calculated and was defined as the C:T ratio when only cross-matched blood used intraoperatively was included in the calculation.
Results
541 patients were identified during the 6-month period. There were 314 minor and 227 major surgeries carried out. 99.6% (n = 226) of the patients who underwent major surgery and 95.5% (n = 300) of the patients having minor surgery had at least a group and save (G and S) test preoperatively. A total of 507 units of blood were cross-matched and 238 units were used. The overall C:T ratio was therefore 2.1:1, which corresponds to a 46.9% red cell usage. There was considerable variation in the C:T ratio, depending on the type of surgery performed. The adjusted C:T ratio varied between 3.75 and 37.
Conclusions
Compliance with transfusion policies is poor and over-ordering of blood products commonplace. Implementation of the updated recommended MSBOS and introduction of G and S for eligible surgical procedures is a safe, effective and cost-effective method to prevent preoperative over-ordering of blood in elective general surgery. Savings of GBP 8,596.00 per annum are achievable with the incorporation of updated evidence-based guidelines in our university hospital.
doi:10.1159/000345660
PMCID: PMC3635964  PMID: 23637646
Cross-match/transfusion ratio; Transfusion; Surgery; Maximum surgical blood ordering schedule; MSBOS
21.  Challenges in the Diagnosis of Iron Deficiency in Children Exposed to High Prevalence of Infections 
PLoS ONE  2012;7(11):e50584.
Background
While WHO guidelines recommend iron supplements to only iron-deficient children in high infection pressure areas, these are rarely implemented. One of the reasons for this is the commonly held view that iron supplementation increases the susceptibility to some infectious diseases including malaria. Secondly, currently used markers to diagnose iron deficiency are also modified by infections. With the objective of improving iron deficiency diagnosis and thus, its management, we evaluated the performance of iron markers in children exposed to high infection pressure.
Methodology/Principal Findings
Iron markers were compared to bone marrow findings in 180 anaemic children attending a rural hospital in southern Mozambique. Eighty percent (144/180) of the children had iron deficiency by bone marrow examination, 88% (155/176) had an inflammatory process, 66% (119/180) had moderate anaemia, 25% (45/180) severe anaemia and 9% (16/180) very severe anaemia. Mean cell haemoglobin concentration had a sensitivity of 51% and specificity of 71% for detecting iron deficiency. Soluble transferrin receptor (sTfR) and soluble transferrin receptor/log ferritin (TfR-F) index (adjusted by C reactive protein) showed the highest areas under the ROC curve (AUCROC) (0.75 and 0.76, respectively), and were the most sensitive markers in detecting iron deficiency (83% and 75%, respectively), but with moderate specificities (50% and 56%, respectively).
Conclusions/Significance
Iron deficiency by bone marrow examination was extremely frequent in these children exposed to high prevalence of infections. However, even the best markers of bone marrow iron deficiency did not identify around a quarter of iron-deficient children. Tough not directly extrapolated to the community, these findings urge for more reliable, affordable and easy to measure iron indicators to reduce the burden of iron deficiency anaemia in resource-poor settings where it is most prevalent.
doi:10.1371/journal.pone.0050584
PMCID: PMC3507793  PMID: 23209786
22.  Prevalence of Anaemia and Evaluation of Transferrin Receptor (sTfR) in the Diagnosis of Iron Deficiency in the Hospitalized Elderly Patients: Anaemia Clinical Studies in Chile 
Anemia  2012;2012:646201.
Iron constitutes the most prevalent nutritional deficiency worldwide. In Chile, anaemia epidemiological data is scarce, evaluating mainly children and women. Our objective was to determine prevalence of anaemia in an inpatient elderly population (≥60 years) and assess the usefulness of sTfR levels analyzed by other authors as a good predictor in the differential diagnosis of iron deficiency anaemia and anaemia of chronic disease. Method. We studied medical patients admitted at Hospital of Valdivia (HV), Chile, in a 2month period. World Health Organization criteria were used for anaemia. Results. 391 patients were hospitalized, average age 62.5 years, 247 elderly and 99 of which had anaemia. Anaemia was normocytic in 88.8%, and we observed: low serum iron in 46.3%, low ferritin 10.1%, high TIBC 2%, low % transferrin saturation (Tsat) 40%, and high sTfR 25%. Conclusions. As a first figure known in Chile, the prevalence of anaemia in the elderly inpatient was 40.1%. Our findings encourage us to promote the implementation of sTfR determination in the clinical setting to analyze the state of erythropoiesis in patients with chronic diseases wich commonly occurs in elderly.
doi:10.1155/2012/646201
PMCID: PMC3352183  PMID: 22611486
23.  Prevalence and management of anaemia in patients with non-myeloid cancer undergoing systemic therapy: a Spanish survey 
Clinical & Translational Oncology  2012;15(6):477-483.
Background
The present study aimed to provide updated data on anaemia prevalence and management in cancer patients undergoing systemic therapy in Spain.
Methods
This was a multicenter, observational, cross-sectional study performed in 2008. Eligible patients were ≥18 years, with non-myeloid malignancies treated with systemic therapy [chemotherapy (CT), hormonal therapy or immunotherapy]. Anaemia was defined according to WHO as haemoglobin (Hb) < 12 g/dL.
Results
The study included 214 patients with a median age of 63 years (range 20–91), 58 % women, 73 % with solid tumours, and 79 % with advanced disease. CT was used in 91 % of patients (26 % with platinum compounds), hormonal therapy in 8.5 %, and immunotherapy in 8.5 %. In our study, 48.1 % of patients [95 % confidence interval (CI) 45.2–58.6] showed anaemia (31 % symptomatic): 42.0 % mild (10 ≤ Hb ≤ 11.9 g/dL), 5.6 % moderate (8 ≤ Hb ≤ 9.9 g/dL), and 0.5 % severe (Hb <  8 g/dL). A higher prevalence was observed in patients treated with CT (51 vs. 20 %, p = 0.01), platinum-based CT (70 vs. 47 %, p = 0.01) or palliative CT (61 vs. 39 %, p = 0.003). Anaemia was also more frequent in patients with more than three lines of CT (83 %) and in the fourth or subsequent CT cycle (58 %). Management in the previous 4 weeks in patients with anaemia was: 62 % did not receive treatment (92 % mild), 24 % received erythropoiesis-stimulating agents (ESAs), 14 % received iron and 8.7 % received transfusion.
Conclusions
In Spanish hospitals, about half of patients with non-myeloid malignancies undergoing systemic therapy fulfilled anaemia criteria (87 % mild). Approximately two-third of patients with anaemia do not receive specific treatment and ESA use is below current guidelines.
doi:10.1007/s12094-012-0953-5
PMCID: PMC3663988  PMID: 23263906
Anaemia; Darbepoetin alfa; Chemotherapy; Solid tumours; Haematological malignancies; Transfusion
24.  Influence of changing trends in anaesthetic practice on morbidity and mortality in elderly patients undergoing lower limb surgery 
Indian Journal of Anaesthesia  2014;58(2):132-137.
Background and Aims:
Several changes in the management protocols of anaesthesia for geriatric patients were introduced into clinical practice to improve the outcome. Very few studies have evaluated the impact of these management protocols. The aim of our study was to evaluate impact of some of the changes in the peri-operative management protocols of geriatric patients undergoing elective orthopaedic lower limb surgeries on the outcomes.
Methods:
A retrospective chart review of thirty-eight surgical patients from 1999 (Group 1999) before the introduction of changes and 107 patients from 2007 (Group 2007) after establishing changes was performed and data of peri-operative variables were collected and analysed. The primary outcome measured was in-hospital mortality. The secondary outcomes were occurrence of intra-operative and post-operative complications. Comparison of continuous variables between the two groups was performed using independent sample T test and categorical variables using Chi-square test. Multivariate logistic regression was done to identify independent predictors of mortality.
Results:
The use of beta blockers, deep vein thrombosis prophylaxis with low molecular weight heparin and epidural technique for post-operative analgesia was higher in group 2007. Despite higher prevalence of patients with electrocardiographic changes and anaemia, the incidence of intra-operative or post-operative complications was lower in 2007, though the mortality rate in both the groups was comparable. The independent risk factors for mortality in these geriatric patients were intra-operative hypotension (Odds Ratio (OR) =11.33) and post-operative myocardial ischaemia (OR = 34.5), pulmonary embolism (OR = 17.1) and neurologic changes (OR = 17.1).
Conclusions:
Implementation of new management practices had significantly reduced the incidence of intra- and post-operative complications.
doi:10.4103/0019-5049.130807
PMCID: PMC4050927  PMID: 24963175
Anaesthesia; beta-2 adrenergic blocking agents; deep vein thrombosis; epidural; geriatrics; in hospital mortality; lower extremity; peri-operative complications
25.  Preoperative testing in elective surgery: Is it really cost effective? 
Introduction:
During preoperative preparation, patients undergo investigations to detect asymptomatic diseases. The probability of finding significant abnormalities on such routine investigations is small, and these investigations unnecessarily increase costs of perioperative care. We evaluated current practices, compliance with national guidelines and costs of preoperative investigations at the National Hospital of Sri Lanka (NHSL).
Materials and Methods:
Patients undergoing elective surgery at the general surgical units of the NHSL from June to August 2010 were included in this study. The National Guidelines on Preoperative Investigations were the standard of assessment. Data on preoperative investigations were collected using an expert-validated pretested interviewer-administered questionnaire.
Results:
Sample size was 2,061 patients. Mean age of the patients was 46.7±15.8 years; males constituted 54.2% of the study population. Majority of the patients were ASA-I (68.5%) and surgical grade II (62.0%). Request for chest X-ray and prothrombin time / international normalized ratio least conformed to the guidelines. Only fasting blood sugar / random blood sugar demonstrated ‘good’ compliance (>70%) to the guidelines. An ‘acceptable’ compliance (50%-70%) was seen for electrocardiogram, blood grouping and full blood count. All other investigations demonstrated ‘poor’ compliance (<50%) with the guidelines. The total excess cost incurred due to non-recommended investigations during the study period of 3 months was Sri Lankan Rupees (LKR.) 1,324,860 to 2,044,210 (per patient LKR. 642.82-991.85). Intern house officers (IHOs) were involved in the planning of preoperative investigations in 2,001 patients (97.1%), followed by medical officeranesthesia / registrar-anesthesia (n=1,625; 78.8%), surgical registrars (n=190; 9.2%), consultant (n=70; 3.4%), senior registrar (n=46; 2.2%) and senior house officers (n=22; 1.1%). Non-recommended investigations were requested mostly by the IHOs and medical officer–anesthesia / registrar-anesthesia.
Conclusions:
Unnecessary preoperative investigations are common at our institution, leading to substantially excessive costs. There is ample opportunity to rationalize practices and reduce expenditure.
doi:10.4103/0259-1162.84177
PMCID: PMC4173361
Elective surgery; National Hospital of Sri Lanka (NHSL); preoperative assessment; Sri Lanka

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