Susana Gómez-Ramírez

Very‐short‐term perioperative intravenous iron administration and postoperative outcome in major orthopedic surgery: a pooled analysis of observational data from 2547 patients

Postoperative nosocomial infection (PNI) is a severe complication in surgical patients. Known risk factors of PNI such as allogeneic blood transfusions (ABTs), anemia, and iron deficiency are manageable with perioperative intravenous (IV) iron therapy. To address potential concerns about IV iron and the risk of PNI, we studied a large series of orthopedic surgical patients for possible relations between IV iron, ABT, and PNI.

Perioperative anemia management in colorectal cancer patients: A pragmatic approach

Anemia, usually due to iron deficiency, is highly prevalent among patients with colorectal cancer. Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization. Preoperative anemia predicts for decreased survival. Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes, increased post-operative nosocomial infections, longer hospital stays, increased rates of cancer recurrence and perioperative venous thromboembolism. Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management, minimizes or eliminates allogeneic blood transfusion. This includes restrictive transfusion policy, thromboprophylaxis and anemia management to improve outcomes. Normalization of preoperative hemoglobin levels is a World Health Organization recommendation. Iron repletion should be routinely ordered when indicated. Oral iron is poorly tolerated with low adherence based on published evidence. Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions. Serious adverse events with intravenous iron are extremely rare. Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care. Erythropoiesis stimulating agents may improve response rates. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes.

Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study.

BACKGROUND Requirements for allogeneic red cell transfusion after total lower limb arthroplasty are still high (20-50%), and post-operative intravenous iron has been shown to reduce transfusion requirements for this surgery. We performed a cost analysis to ascertain whether this alternative is also likely to be cost-effective. MATERIALS AND METHODS Data from 182 matched-pairs of total lower limb arthroplasty patients, managed with a restrictive transfusion protocol and without (control group) or with post-operative intravenous iron (iron group), were retrospectively reviewed. Acquisition and administration costs of iron (iron sucrose or ferric carboxymaltose) and allogeneic red cell concentrates, haemoglobin measurements, and prolonged stay in hospital were used for blood management cost analysis. RESULTS Patients in the iron group received 600 mg intravenous iron, without clinically relevant incidents, and had a lower allogeneic transfusion rate (11.5% vs 26.4% for the iron and control groups, respectively; p=0.001). The reduction in transfusion rate was more pronounced in anaemic patients (17% vs 40%; p=0.015) than in non-anaemic ones (9.6% vs 21.2%; p=0.011). There were no differences with respect to post-operative infection rate. Patients receiving allogeneic transfusion stayed in hospital longer (+1.9 days [95% CI: 1.2-2.6]). As intravenous iron reduces the allogeneic transfusion rate, both iron formulations were cost-neutral in the different cost scenarios (-25.5 to 62.1 €/patient for iron sucrose, and -51.1 to 64.4 €/patient for ferric carboxymaltose). DISCUSSION In patients presenting with or without pre-operative anaemia, post-operative intravenous iron after total lower limb arthroplasty seems to be safe and is associated with reduced transfusion rates, without incremental costs. For anaemic patients, its efficacy could be increased by associating some other blood-saving method.

Pre-operative anaemia: prevalence, consequences and approaches to management

Prevalence of pre-operative anaemia A recent study, using public data from 187 countries worldwide and World Health Organization (WHO) definitions of anaemia (Table I), found a significant decrement in the global prevalence of anaemia, which decreased from 40.2% in 1990 to 32.9% in 2010, though the prevalence varied widely across regions1. However, a lower prevalence of mild and moderate anaemia accounted for most of the reduction, while the prevalence of severe anaemia remained largely unchanged1. Previously, the third US National Health and Nutrition Examination Survey (NHANES III, Phases 1&2, 19881994; 26,372 individuals), showed an average prevalence of anaemia of 7% in the 1to 64-year old age group, with the prevalence being slightly higher among females2. In people 65 years old or more, the prevalence of anaemia increased progressively with age (13% in subjects aged 75-84, 23% in those over 85 years) and the condition was more common among males2. However, analysing the distribution of haemoglobin (Hb) levels in men and women aged 65 years and older showed that 32.4% of women and 23.3% of men had Hb levels lower than 13 g/dL, indicating that the higher overall prevalence of anaemia among older men just results from the genderspecific WHO definitions of anaemia2. This progressive increase of anaemia prevalence with age was also noted in a meta-analysis of 34 studies (85,409 elderly individuals); the overall prevalence was 17%, but fell to 6% when considering cases with a Hb of ≤11 g/dL, which indicates that anaemia was mild in the majority of cases3. Do these figures of anaemia prevalence in individuals living in the community apply to hospitalised patients? In a cohort investigation of adult patients (n=232,440) hospitalised for surgical or medical pathologies between January 2009 and August 2011, 19% presented with anaemia upon admission, whereas 60% of those who were not anaemic upon presentation developed hospital-acquired anaemia4. Another retrospective study of patients of any age (n=2,234) hospitalised in the departments of digestive diseases, internal medicine, cardiology or respiratory diseases between September and October 2010 found an anaemia prevalence of 50%5. In cancer patients, the European cancer anaemia survey found a prevalence of anaemia (Hb cut-off 12 g/dL) at recruitment which varied between 25% in patients with head and neck cancer and 53% in those with a haematological cancer5. In addition, among patients receiving treatment, the mean anaemia prevalence was 53%, ranging from 29% for those being treated with radiotherapy to 75% for those given cis-platinum based chemotherapy6. In 18 large observational studies encompassing over 650,000 surgical patients, the mean prevalence of pre-operative anaemia was around 35%, varying between 10.5% and 47.9%7-24. There were

A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia

BACKGROUND Clinically significant anaemia, requiring red blood cell transfusions, is frequently observed in Emergency Departments (ED). To optimise blood product use, we developed a clinical protocol for the management of iron-deficiency anaemia in a fast-track anaemia clinic within the ED. MATERIALS AND METHODS From November 2010 to January 2014, patients presenting with sub-acute, moderate-to-severe anaemia (haemoglobin [Hb] <11 g/dL) and confirmed or suspected iron deficiency were referred to the fast-track anaemia clinic. Those with absolute or functional iron deficiency were given intravenous (IV) ferric carboxymaltose 500-1,000 mg/week and were reassessed 4 weeks after receiving the total iron dose. The primary study outcome was the haematological response (Hb≥12 g/dL and/or Hb increment ≥2 g/dL). Changes in blood and iron parameters, transfusion rates and IV iron-related adverse drug effects were secondary outcomes. RESULTS Two hundred and two anaemic patients with iron deficiency (150 women/52 men; mean age, 64 years) were managed in the fast-track anaemia clinic, and received a median IV iron dose of 1,500 mg (1,000-2,000 mg). Gastro-intestinal (44%) or gynaecological (26%) bleeding was the most frequent cause of the anaemia. At follow-up (183 patients), the mean Hb increment was 3.9±2.2 g/dL; 84% of patients were classified as responders and blood and iron parameters normalised in 90%. During follow-up, 35 (17%) patients needed transfusions (2 [range: 1-3] units per patient) because they had low Hb levels, symptoms of anaemia and/or were at risk. Eight mild and one moderate, self-limited adverse drug effects were witnessed. DISCUSSION Our data support the feasibility of a clinical protocol for management of sub-acute anaemia with IV iron in the ED. IV iron was efficacious, safe and well tolerated. Early management of anaemia will improve the use of blood products in the ED.

A fast-track anaemia clinic in the Emergency Department: cost-analysis of intravenous iron administration for treating iron-deficiency anaemia.

BACKGROUND A fast-track anaemia clinic (FTAC) for the management of moderate-to-severe iron-deficiency anaemia (IDA) was established in our Emergency Department in 2010. In this FTAC, the replacement of packed red cell transfusion by ferric carboxymaltose administration was proven to be safe and effective. The aim of this study was a cost-analysis of IDA management in the FTAC, comparing this management with the previous standard care pathway consisting of packed red cell transfusion, if needed, and referral to outpatient specialised care. MATERIALS AND METHODS A cost study was performed for patients with IDA who were at risk of requiring transfusion (haemoglobin <9 g/dL) but did not require hospitalisation. Total IDA treatment costs in the FTAC were compared to those theoretically incurred if these patients had been managed using the standard care pathway. In addition, a sensitivity analysis considering variations of up to ±30% in ferric carboxymaltose and packed red cell acquisition costs was performed (49 possible scenarios). RESULTS Between 2012 and 2015, 238 IDA patients were treated in the FTAC. The average treatment cost was € 594±337/patient in the FTAC group and € 672±301/patient in the standard care pathway group, with a saving of € 78±28/patient (95% CI, 22-133; p<0.001). The sensitivity analysis showed that IDA treatment costs in the FTAC (€ 480-722/patient), compared with those of the standard care pathway (€ 550-794/patient), resulted in significant cost-savings for all studied scenarios (€ 51-104/patient; p<0.005). DISCUSSION The administration of ferric carboxymaltose for IDA management in a FTAC may be cost-saving compared with the standard care pathway.

Stimulating erythropoiesis before hip fracture repair for reducing blood transfusion: should we change the hemoglobin cutoff level for defining anemia in females?

H ip fractures (HFs) are a common cause of morbidity and mortality among the elderly population. The incidence of HF is increasing as the mean age of populations rises in western countries. It has been estimated that the number of HFs worldwide will increase from 1.7 million in 1990 to 6.3 million in 2050. Blood loss at the fracture site and during surgical repair, iatrogenic hemodilution, and inhibition of erythropoiesis due to trauma and surgery-induced inflammation may lead to acute perioperative anemia requiring allogeneic blood transfusion (ABT). In addition, on admission to hospital, up to 40% to 50% may present with low preoperative hemoglobin (Hb), which is one of the risk factors for ABT. As a result, 30% to 70% are transfused perioperatively to rapidly and effectively, but transiently, restore Hb levels, although it is a suboptimal means of treating anemia. Evidence of clinical and economic disadvantages of ABT for perioperative anemia has prompted a growing interest in multidisciplinary, multimodal, individualized strategies, collectively termed “patient blood management” (PBM), aimed to minimize ABT and improve patient outcomes. PBM relies on the perioperative implementation of three pillars of care: stimulation of erythropoiesis, reduction of blood loss, and tolerance of normovolemic anemia (restrictive transfusion threshold). This new standard is now being implemented in many countries, especially for elective cardiac and orthopedic surgery. The integration of PBM strategies into routine care for patients undergoing nonelective surgery, such as HF repair, may present challenging limitations. After HF, the preponderance of published evidence supports the use of restrictive transfusion thresholds using lower Hb concentrations or symptoms of anemia in deference to liberal transfusion thresholds based on a 100 g/L Hb trigger. Although a restrictive transfusion protocol should be the cornerstone of any PBM program, other strategies to reduce both the frequency and the volume of ABT should be implemented. Reduction of perioperative blood loss with administration of tranexamic acid is being evaluated in a number of ongoing trials (NCT02664909, NCT02580227, NCT02736073, NCT01714336, NCT0155781, NCT10940536). At present, data are inconclusive, especially in terms of safety. One option, low vacuum drains, has only been reported in observational studies on subcapital HF. In contrast, very short-term stimulation of erythropoiesis with intravenous (IV) iron, with or without recombinant human erythropoietin (EPO), has been shown to reduce ABT requirements in two randomized trials and a large observational study. In this issue of TRANSFUSION, Bernabeu-Wittel and colleagues reported on the results of a multicenter, randomized, double-blinded, clinical trial, assessing efficacy of ferric carboxymaltose (FCM) with or without EPO in reducing ABT perioperatively after HF repair. A total of 306 patients with anemia (Hb 90-120 g/L) with pertrochanteric or subcapital HF who received preoperative IV FCM (FE group), IV FCM plus EPO (EPOFE group), or placebo were evaluated. The observed ABT rate was approximately 50% with no significant differences in the number of ABTs per patient, survival, health-related quality of life (HRQoL), and adverse events among treatment groups, although early postoperative complications (hypotension, major bleeding, other anesthetic or surgical complications) were decreased in EPOFE (23%) and FE (30%), compared to placebo (41%). A significant increase in Hb levels was achieved at discharge and 60 days after discharge in EPOFE compared to the placebo arm. There was a higher rate of anemia recovery in EPOFE compared with placebo 60 days after discharge. The authors concluded that preoperative treatment with FCM alone or in combination with EPO did not reduce ABT in patients with HF. There are issues of concern regarding this study. We believe that there are two major problems with the inclusion criteria. First, virtually all HF patients with preoperative Hb level of less than 100 g/L will be transfused perioperatively due to a further Hb decrease induced by perioperative blood loss. Therefore, they should not have been included in a trial evaluating the effect of IV iron with or without EPO on transfusion rate as the primary outcome. Second, observational and randomized studies in HF repair showed a benefit of IV doi:10.1111/trf.13750

The safety of available treatment options for iron-deficiency anemia

ABSTRACT Introduction: Iron deficiency (ID), with or without anemia, is highly prevalent worldwide and has clinical consequences. The prevention and treatment of ID is a major public health goal. Accurate diagnosis, selection of the appropriate iron replacement therapy and addressing the underlying cause, remain as the main challenges in ID management. Areas covered: This review aims to provide a narrative review of current available evidence on iron supplementation options regularly used to treat ID, including oral and intravenous (IV) iron formulations, with emphasis on safety issues. Analyzed safety concerns include gastrointestinal side effects (oral iron) and risks of hypotension, anaphylaxis, infection, hypophosphatemia, oxidative stress and mortality (IV iron). Expert opinion: Low-to-moderate doses of oral iron supplementation remains as first line therapy for uncomplicated ID, but it has been scarcely discussed in the setting of inflammation. Confirmatory studies on the efficacy of newer oral iron formulations in this setting are needed. Compared with oral iron, short-term IV iron administration is more efficacious in ID correction, without significant safety concerns. However, long-term safety of IV iron maintenance therapy, head to head comparisons of IV iron preparations, pharmacological modulation of hepcidin and HIF, and extra-erythropoietic effects of iron are among the important areas of research.

Preoperative management of colorectal cancer–induced iron deficiency anemia in clinical practice: data from a large observational cohort

Preoperative anemia prevalence among colorectal cancer (CRC) patients is high and may adversely influence postoperative outcome. This study assesses the efficacy of a preoperative anemia managing protocol in CRC.

Implementing Patient Blood Management in major orthopaedic procedures: orthodoxy or pragmatism?

Pre-operative anaemia is present in 20–40% of patients scheduled for major elective orthopaedic procedures1–3. Pre-operative anaemia has been linked to post-operative infections, poorer physical functioning and recovery, decreased quality of life, and increased length of hospital stay and mortality1–6. It is not, however, clear whether anaemia is a modifiable risk factor of poorer outcomes and not simply a marker of other conditions that confer increased risk3.