The impact of anemia and blood transfusion on mortality after open abdominal surgery in the elderly.

BACKGROUND: Major abdominal surgery is associated with considerable mortality in the elderly. Anemia has been linked to increased mortality in other types of surgery, such as hip and cardiac surgery. This study aimed to assess the impact of preoperative anemia on mortality in the elderly undergoing major abdominal surgery, and how allogeneic red cell blood transfusion influences mortality in these patients. MATERIALS AND METHODS: We conducted a single-center, register-based retrospective study on patients, who were aged beyond 60 years and underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1, 2000, to May 31, 2013, were consecutively identified in the Danish National Patient Registry. Plasma hemoglobin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. Information about patient transfusions from the hospital blood bank was available from 1998 to 2010. RESULTS: A total of 3199 patients were included of whom 85% underwent emergency surgery. The total mortality after 30 days was 20%. The median preoperative hemoglobin value of survivors was 7.7 mmol/L vs 6.9 mmol/L in those who died. The difference in hemoglobin values, between those who survived or died, decreased from the pre- to the post-operative phase. The 30-day postoperative mortality was 28%, 20%, and 12% in patients with a preoperative hemoglobin level in the lower, median, and upper quartile respectively. Transfusion therapy was associated with higher postoperative mortality, except in patients with very low hemoglobin values. CONCLUSION: Preoperative anemia has a clear association with surgically related mortality. The distribution of hemoglobin values in patients with a fatal outcome differs significantly from that of survivors. Red cell transfusion is associated with increased mortality, except in patients with very low hemoglobin values which supports recent guidelines suggesting a restrictive transfusion strategy.

Transfusion-associated circulatory overload in adult, medical emergency patients with perspectives on early warning practice: a single-centre, clinical study.

BACKGROUND: Transfusion-associated circulatory overload is characterised by acute respiratory distress, tachycardia, increased blood pressure, acute pulmonary oedema and/or evidence of positive fluid balance occurring within 6 hours after transfusion. Transfusion-associated circulatory overload is a serious, underreported reaction, which makes this iatrogenic condition difficult to prevent. We present an audit of patients admitted to a medical emergency unit, aiming to investigate: (i) the incidence of transfusion-associated circulatory overload; and (ii) whether cases were reported to the haemovigilance system. The clinical implications are discussed within the frame of the Early Warning Score. METHODS: We conducted a retrospective audit of electronic hospital medical records of patients receiving blood transfusion in a single medical emergency unit. Patients were admitted during a 6-month period and data on symptoms and vital signs were extracted from the records. RESULTS: Of 4,353 consecutively admitted patients, 156 patients were transfused with a total of 411 blood components. The audit identified five cases of transfusion-associated circulatory overload (incidence 3.2%) and four cases of transfusion-associated dyspnoea. Vital signs and changes in dyspnoea and blood pressure were registered within the frame of the Early Warning Score, and one case was documented as being transfusion-related in the medical record. No cases were reported to the haemovigilance system. DISCUSSION: The incidence of transfusion-associated circulatory overload in acute emergency patients was similar to that in other clinical studies. Lack of recognition and reporting was marked, even though changes in vital signs were monitored in the context of the Early Warning Score. This study points to a missing link in the transfusion chain, namely recognising the vital signs of circulatory overload during or shortly after transfusion as being a serious adverse transfusion reaction.

Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial.

AIM: We compared the iron concentration in breast milk after a single high dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. METHODS: In this randomised controlled trial, the women were allocated a single dose of intravenous 1200 mg iron isomaltoside or oral iron at a mean daily dose of 70.5 mg. We included 65 women with sufficient breast milk three days after inclusion - 30 from the intravenous iron group and 35 from the oral iron group - and collected breast milk and maternal blood samples three days and one week after allocation. RESULTS: The mean (±SD) iron concentration in breast milk in the intravenous and oral groups was 0.72 ± 0.27 and 0.40 ± 0.18 mg/L at three days (p < 0.001) and 0.47 ± 0.17 and 0.44 ± 0.25 mg/L after one week (p = 0.64). Baseline samples were not available that soon after birth. CONCLUSION: A single high dose of intravenous iron isomaltoside for postpartum haemorrhage led to a transient increase in the iron concentration in breast milk three days after treatment compared with oral iron. The difference disappeared one week after treatment, and mean iron concentrations were within the normal range in all samples.

Treatment for women with postpartum iron deficiency anaemia.

BACKGROUND: Postpartum iron deficiency anaemia is caused by bleeding or inadequate dietary iron intake/uptake. This condition is defined by iron deficiency accompanied by a lower than normal blood haemoglobin concentration, although this can be affected by factors other than anaemia and must be interpreted in the light of any concurrent symptoms. Symptoms include fatigue, breathlessness, and dizziness. Treatment options include oral or intravenous iron, erythropoietin which stimulates red blood cell production, and substitution by red blood cell transfusion. OBJECTIVES: To assess the efficacy and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. SEARCH METHODS: The Cochrane Pregnancy and Childbirth Group's Trials Register (9 April 2015); the WHO International Clinical Trials Registry Portal (ICTRP), and the Latin-American and Caribbean Health Sciences Literature database (LILACS) (8 April 2015) and reference lists of retrieved studies. SELECTION CRITERIA: We included published, unpublished and ongoing randomised controlled trials that compared a treatment for postpartum iron deficiency anaemia with placebo, no treatment, or another treatment for postpartum iron deficiency anaemia, including trials described in abstracts only. Cluster-randomised trials were eligible for inclusion. We included both open-label trials and blinded trials, regardless of who was blinded. The participants were women with a postpartum haemoglobin of 120 g per litre (g/L) or less, for which treatment was initiated within six weeks after childbirth.Non-randomised trials, quasi-randomised trials and trials using a cross-over design were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, quality, and extracted data. We contacted study authors and pharmaceutical companies for additional information. MAIN RESULTS: We included 22 randomised controlled trials (2858 women), most of which had high risk of bias in several domains. We performed 13 comparisons. Many comparisons are based on a small number of studies with small sample sizes. No analysis of our primary outcomes contained more than two studies.Intravenous iron was compared to oral iron in 10 studies (1553 women). Fatigue was reported in two studies and improved significantly favouring the intravenously treated group in one of the studies. Other anaemia symptoms were not reported. One woman died from cardiomyopathy (risk ratio (RR) 2.95; 95% confidence interval (CI) 0.12 to 71.96; two studies; one event; 374 women; low quality evidence). One woman developed arrhythmia. Both cardiac complications occurred in the intravenously treated group. Allergic reactions occurred in three women treated with intravenous iron, not statistically significant (average RR 2.78; 95% CI 0.31 to 24.92; eight studies; 1454 women; I² = 0%; low quality evidence). Gastrointestinal events were less frequent in the intravenously treated group (average RR 0.31; 95% CI 0.20 to 0.47; eight studies; 169 events; 1307 women; I² = 0%; very low quality evidence).One study evaluated red blood cell transfusion versus non-intervention. General fatigue improved significantly more in the transfusion group at three days (MD -0.80; 95% CI -1.53 to -0.07; women 388; low quality evidence), but no difference between groups was seen at six weeks. Maternal mortality was not reported.The remaining comparisons evaluated oral iron (with or without other food substances) versus placebo (three studies), intravenous iron with oral iron versus oral iron (two studies) and erythropoietin (alone or combined with iron) versus placebo or iron (seven studies). These studies did not investigate fatigue. Maternal mortality was rarely reported. AUTHORS' CONCLUSIONS: The body of evidence did not allow us to reach a clear conclusion regarding the efficacy of the interventions on postpartum iron deficiency anaemia. The quality of evidence was low.Clinical outcomes were rarely reported. Laboratory values may not be reliable indicators for efficacy, as they do not always correlate with clinical treatment effects. It remains unclear which treatment modality is most effective in alleviating symptoms of postpartum anaemia.Intravenous iron was superior regarding gastrointestinal harms, however anaphylaxis and cardiac events occurred and more data are needed to establish whether this was caused by intravenous iron.The clinical significance of some temporarily improved fatigue scores in women treated with blood transfusion is uncertain and this modest effect should be balanced against known risks, e.g. maternal mortality (not reported) and maternal immunological sensitisation, which can potentially harm future pregnancies.When comparing oral iron to placebo it remains unknown whether efficacy (relief of anaemia symptoms) outweighs the documented gastrointestinal harms.We could not draw conclusions regarding erythropoietin treatment due to lack of evidence.Further research should evaluate treatment effect through clinical outcomes, i.e. presence and severity of anaemia symptoms balanced against harms, i.e. survival and severe morbidity.

Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage: study protocol for a randomised controlled trial.

BACKGROUND: Postpartum haemorrhage can lead to iron deficiency with and without anaemia, the clinical consequences of which include physical fatigue. Although oral iron is the standard treatment, it is often associated with gastrointestinal side effects and poor compliance. To date, no published randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside 1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard medical care. Healthy parturients with a singleton pregnancy will be included within 48 hours after delivery.Participants will complete structured questionnaires that focus on several dimensions of fatigue and mental health (Multidimensional Fatigue Inventory, Edinburgh Postnatal Depression Scale and the Postpartum Questionnaire), at inclusion and at follow-up visits after three days, one week, three weeks, eight weeks, and 12 weeks postpartum. The primary endpoint is the aggregated change in physical fatigue score within 12 weeks postpartum, as measured by a subscale of the Multidimensional Fatigue Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant difference between the mean scores at 1.8, and the assumed standard deviation at 4.2. Hence, 87 participants per treatment group are needed in order to demonstrate superiority; to provide an extra margin for missing data and dropouts, 200 women will be included. DISCUSSION: The study will provide evidence on relevant clinical outcomes beyond biochemical parameters for intravenous iron isomaltoside 1000 compared to standard medical care in women after postpartum haemorrhage. TRIAL REGISTRATION: This trial is registered with Clinicaltrials.gov (identifier: NCT01895218) on 26 June 2013.

[Adverse effects to transfusion with red donor blood cells are frequent].

Adverse effects to transfusion with red donor blood cells are potentially life-threatening. Due to screening, transmission of infectious diseases has decreased; however, the risk is still present. Various immune reactions are common including simple allergic reactions as well as devastating conditions such as transfusion-related acute lung injury and circulatory overload in patients with heart disease. Knowledge of the clinical signs of transfusion-related complications is important for clinicians in order to provide the best possible treatment.

[Liberal red blood cell transfusion may increase mortality].

In addition to the known adverse effects of red blood cell transfusion, evidence suggests that transfusion with allogeneic red blood cells in itself may increase mortality, risk of infection and even cancer recurrence rates. Among possible mechanisms to explain this effect are transfusion-related immune modulation and storage lesions. However, anaemia may also increase mortality and the risk of anaemia should be balanced against the risks of transfusion. Further properly designed and powered studies are needed to clarify the beneficial and harmful effects of red blood cell transfusion in well-defined patient categories.

Monitoring compliance with transfusion guidelines in hospital departments by electronic data capture.

BACKGROUND: The practice of transfusing red blood cells is still liberal in some centres suggesting a lack of compliance with guidelines recommending transfusion of red blood cells at haemoglobin levels of 6-8 g/dL in the non-bleeding patient. Few databases provide ongoing feedback of data on pre-transfusion haemoglobin levels at the departmental level. In a tertiary care hospital, no such data were produced before this study. Our aim was to establish a Patient Blood Management database based on electronic data capture in order to monitor compliance with transfusion guidelines at departmental and hospital levels. MATERIALS AND METHODS: Hospital data on admissions, diagnoses and surgical procedures were used to define the populations of patients. Data on haemoglobin measurements and red blood cell transfusions were used to calculate pre-transfusion haemoglobin, percentage of transfused patients and transfusion volumes. RESULTS: The model dataset include 33,587 admissions, of which 10% had received at least one unit of red blood cells. Haemoglobin measurements preceded 96.7% of the units transfused. The median pre-transfusion haemoglobin was 8.9 g/dL (interquartile range 8.2-9.7) at the hospital level. In only 6.5% of the cases, transfusion was initiated at 7.3 g/dL or lower as recommended by the Danish national transfusion guideline. In 27% of the cases, transfusion was initiated when the haemoglobin level was 9.3 g/dL or higher, which is not recommended. A median of two units was transfused per transfusion episode and per hospital admission. Transfusion practice was more liberal in surgical and intensive care units than in medical departments. DISCUSSION: We described pre-transfusion haemoglobin levels, transfusion rates and volumes at hospital and departmental levels, and in surgical subpopulations. Initial data revealed an extensive liberal practice and low compliance with national transfusion guidelines, and identified wards in need of intervention.

Preoperative factors associated with red blood cell transfusion in hip fracture patients.

INTRODUCTION: Red blood cell (RBC) transfusion is a frequently used treatment in patients admitted with a fractured hip, but the use remains an area of much debate. The aim of this study was to determine preoperative factors associated with the risk of receiving a red blood cell transfusion in hip fracture patients. METHOD: The study included 986 consecutive hip fracture patients (aged 60 years or above). The patients were identified from a database of all hip fracture patients admitted to Bispebjerg University Hospital. Data for the database are collected via chart review and data extraction from the hospitals laboratory system, public registries and from the Capital Region Blood Bank Database. RESULTS: Overall transfusion rate was 58.7 %. The univariate analyses showed that transfusion rate was higher among women (p = 0.004), older patients (p < 0.0001), patients with high ASA scores (p < 0.0001), patients with more severe fractures (p < 0.0001), patients with lower admission haemoglobin levels (p < 0.0001), patients not admitted from own home (p = 0.02) and patients taking aspirin (p = 0.007) or other platelet inhibitors (p = 0.01) on admission. In the multivariate analysis, increasing age, ASA ≥3, being admitted from own home, extracapsular fractures, decreasing admission haemoglobin and use of platelet inhibitors were all significantly associated with the risk of receiving a RBC transfusion. CONCLUSION: Several readily available preoperative factors in the form of age, residence, ASA, admission haemoglobin, medication and type of fracture were independently associated with the likelihood of receiving a red blood cell transfusion in patients admitted with a fractured hip.

Evaluation of multi-professional obstetric skills training for postpartum hemorrhage.

OBJECTIVE: To evaluate the effect of multi-professional obstetric skills training on the incidence of postpartum hemorrhage (PPH) indicated by red blood cell (RBC) transfusion and time delay in surgical interventions before, during, and after implementation of the training. DESIGN: A database audit. SETTING: University hospital, Rigshospitalet, Copenhagen, Denmark. POPULATION: Women receiving red blood cell (RBC) transfusion up to seven days postpartum before (2003), during (2005), and after (2007) the introduction of training. METHODS: Linkage of the Danish Medical Birth Registry and the local transfusion database, followed by audit of medical records. We identified 148 women with RBC transfusion for PPH in 10 461 deliveries and assessed the cause of PPH, surgical interventions and transfusion data. MAIN OUTCOME MEASURES: RBC transfusion. Delay to surgical intervention. RESULTS: RBC transfusion rates for PPH were 1.5% (2003), 1.6% (2005), and 1.2% (2007) (not statistically significant). The transfusion rates did not change after vaginal delivery but decreased after cesarean section [2.4, 2.1 and 0.7% (p<0.01)]. Transfusion requirements and pre-transfusion hemoglobin values did not change. The median time from delivery to manual removal of the placenta increased non-significantly (64, 70 and 75 minutes). The median time from decision to manual removal of the placenta remained unchanged (30 minutes). CONCLUSION: There was no effect of multi-professional obstetric skills training on the rate of RBC transfusion for PPH. The unchanged long delay in handling a retained placenta indicates a need for multi-disciplinary training in collaboration with staff from anesthesiology and the operation theater.

Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts.

INTRODUCTION: Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between FoxP3 expression and acute rejection is still being debated. Some studies have been performed on blood samples from lung-transplanted patients, while others have investigated the local immune response in the lungs by analysing broncho-alveolar-lavage (BAL) fluids or biopsies. Biopsies are considered the gold standard in diagnosis of acute rejection. AIM: The aim was to measure the expression of both Treg (FoxP3, CD25 and CTLA-4) and cytotoxic (granzyme B, granulysin, and perforin) markers in BAL and blood samples from lung-transplanted patients to investigate the possible relation of expression and acute rejection incidents in order to develop a non-invasive diagnostic method for acute rejection. MATERIALS AND METHODS: 24 lung-transplanted patients were included in this 6-month cross-section study. BAL and blood samples were analysed for FoxP3, CD25, CTLA-4, granzyme B, granulysin, perforin, CD4 and CD8 mRNA by QRT-PCR with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as primary reference. RESULTS: We demonstrate that the mRNA levels in BAL relative to GAPDH of nearly all markers are elevated during acute rejection; CTLA-4, FoxP3, and granzyme B significantly, while a strong tendency is seen among the others. No significant differences were detected in blood. CONCLUSION: CTLA-4, FoxP3 and Granzyme B mRNA levels are elevated during acute rejection in BAL, but not in blood, following lung transplantation, indicating that evaluation of Treg and cytotoxic marker expression in BAL can be used in the assessment of allograft rejection state.