Increasing rates of screening and treatment of iron deficiency in ambulatory patients with heart failure with reduced ejection fraction: a quality improvement cohort study.

INTRODUCTION: Iron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of life, and decreases symptoms among patients with HF with reduced ejection fraction (HFrEF) and iron deficiency. Despite this, many patients are not screened or treated for IDA. We aimed to increase rates of screening and treatment of IDA among HF patients through the introduction of curated materials to aid HF clinicians with appropriate screening and treatment. METHODS: We conducted a retrospective chart review to identify the baseline number of HFrEF patients screened and treated for IDA at two ambulatory cardiology clinics in Toronto, Ontario. A quality improvement initiative was then introduced, which consisted of education and curated materials to aid clinicians in the screening and treatment of IDA among HFrEF patients. The proportion of patients screened and treated for IDA preintervention and postintervention were compared using χ2 tests of Independence. RESULTS: In the preintervention cohort, 36.3% (n=45) of patients with anaemia were screened for IDA. Among those screened, 64.4% (n=29) had IDA. Only 17.2% (n=5) of these were treated with IV iron. After implementation of the quality improvement initiative, 90.9% (n=60) of patients with anaemia were screened for IDA (p<0.001) and 90.3% (n=28) of those with IDA were treated with IV iron (p<0.001). CONCLUSION: The introduction of curated materials to aid clinicians was associated with increased rates of screening and treatment of IDA among ambulatory HFrEF patients. Further work is required to identify barriers and implement strategies to increase screening and treatment rates of IDA among HFrEF patients.

Red Blood Cell Transfusion: 2023 AABB International Guidelines.

Importance: Red blood cell transfusion is a common medical intervention with benefits and harms. Objective: To provide recommendations for use of red blood cell transfusion in adults and children. Evidence Review: Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed. Findings: For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence). Conclusions and Relevance: It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.

Survey of iron prescribing practices for post-partum anaemia.

OBJECTIVE: Treatment for postpartum anaemia frequently entails iron supplementation, but questions remain regarding its optimal dosing, frequency, and efficacy. Our objective was to learn about the current prescribing practices of obstetrical providers at multiple hospitals, including indications and regimens used; further, we sought to understand how these practices are learned. METHODS: A 10-question web-based survey was developed via expert consensus. The survey was distributed via email to obstetrical providers (including trainees) practising at seven hospitals affiliated with the University of Toronto, including from Obstetrics & Gynaecology (OBGYN), Family Practice (FP-OB) and midwifery. RESULTS: The survey was directly sent to 469 participants and 140 responses were collected from the direct email recruitment pool (response rate 30%). Half of respondents were OBGYN physicians. The most common indication was a post-partum haemoglobin threshold of 90 g/L. Both intravenous and oral formulations were used; the most common oral formulation was ferrous fumarate (77%). Prescribing practices were most commonly shaped using passed-down knowledge. CONCLUSION: Through this survey, we have learned about the most common post-partum iron supplementation indications, formulations and regimens used in both academic and community hospitals in the greater Toronto area. This insight will help inform future studies investigating the efficacy of oral iron supplementation in the treatment of post-partum anaemia.

Daily versus every other day oral iron supplementation in patients with iron deficiency anemia (DEODO): study protocol for a phase 3 multicentered, pragmatic, open-label, pilot randomized controlled trial.

BACKGROUND: Iron deficiency anemia (IDA) accounts for the majority of anemia cases across the globe and can lead to impairments in both physical and cognitive functioning. Oral iron supplementation is the first line of treatment to improve the hemoglobin level for IDA patients. However, gaps still exist in understanding the appropriate dosing regimen of oral iron. The current trial proposes to evaluate the feasibility of performing this study to examine the effectiveness and side-effect profile of oral iron once daily versus every other day. METHODS: In this open-label, pilot, feasibility, randomized controlled trial, 52 outpatients over 16 years of age with IDA (defined as hemoglobin < 12.0 g/dL in females and < 13.0 g/dL in males and ferritin < 30 mcg/L) will be enrolled across two large academic hospitals. Participants are randomized in a 1:1 ratio to receive 300 mg oral ferrous sulfate (60 mg of elemental iron) either every day or every other day for 12 weeks. Participants are excluded if they are as follows: (1) pregnant and/or currently breastfeeding, (2) have a disease history that would impair response to oral iron (e.g., thalassemia, celiac disease), (3) intolerant and/or have an allergy to oral iron or vitamin C, (4) on new anticoagulants in the past 6 months, (5) received IV iron therapy in the past 12 weeks, (6) have surgery, chemotherapy, or blood donation planned in upcoming 12 weeks, (7) a creatinine clearance < 30 mL/min, or (8) hemoglobin less than 8.0 g/dL with active bleeding. The primary outcome is feasibility to enroll 52 participants in this trial over a 2-year period to determine the effectiveness of daily versus every other day oral iron supplementation on hemoglobin at 12 weeks post-initiation and side-effect profile. DISCUSSION: The results of this trial will provide additional evidence for an appropriate dosing schedule for treating patients with IDA with oral iron supplementation. Additional knowledge will be gained on how the dosing regimen of oral iron impacts quality of life and hemoglobin repletion in IDA patients. If this trial is deemed feasible, it will inform the development and implementation of a larger multicenter definitive trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03725384 . Registered 31 October 2018.

Examining prescribing practices with respect to oral iron supplementation for post-partum anemia: a retrospective review.

PURPOSE: Treatment for post-partum anemia frequently entails oral iron supplementation, but questions remain regarding optimal dosing, frequency, and efficacy. The objective of this study was to describe oral iron prescribing practices in post-partum women delivered via Cesarean section, and identify factors associated with iron supplementation. METHODS: A retrospective review of Cesarean section deliveries at a single tertiary center between May 2019 and April 2020 was undertaken. Patient demographics, hematological indices, indication for Cesarean section and discharge prescriptions were collected. Univariate and multivariable analyses were performed to identify factors associated with oral iron prescription at discharge. RESULTS: During the study period, 1470 women were eligible for inclusion. The mean age at delivery was 34.4 ± 4.9 years and mean gestational age was 37.2 ± 3.6 weeks. Most pregnancies (92%) were singleton. Ninety-six total patients (6.5%) received intravenous iron post-partum. Fourteen percent of women (210/1470) received prescriptions for oral iron at discharge, most commonly ferrous fumarate (61.9%, 130/210). The most common dose provided was 300 mg (145/210). Ante-partum ferritin was available for most patients (64.3%, 945/1470), but only for 17 post-partum patients (1.2%). Factors significantly associated with oral iron prescription were earlier gestational age at birth (aOR 0.93, 95% CI 0.89-0.97), history of complications during pregnancy or labor (aOR 1.92, 95% CI 1.26-2.98), higher blood loss (aOR 2.66, 95% CI 1.36-5.44), post-partum anemia (aOR 6.28, 95%-CI 4.41-8.96), blood transfusion (aOR 5.43, 95%-CI 1.81-18.19) and antenatal iron supplementation (aOR 5.70, 95%-CI 4.02-8.17). CONCLUSIONS: In summary, a relatively small proportion of women following Cesarean section were prescribed oral iron at discharge. We identified several factors associated with post-partum iron supplementation. This information will inform future prospective studies investigating the efficacy of iron supplementation in the treatment of post-partum anemia.

Red blood cell transfusion: 2023 AABB international guidelines

Red blood cell transfusion is a common medical intervention with benefits and harms. To provide recommendations for use of red blood cell transfusion in adults and children. Standards for trustworthy guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed. For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence). It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.

Impact of red blood cell alloimmunization on fetal and neonatal outcomes: A single center cohort study.

BACKGROUND: Alloimmunization can impact both the fetus and neonate. STUDY OBJECTIVES: (a) calculate the incidence of clinically significant RBC isoimmunization during pregnancy, (b) review maternal management and neonatal outcomes, (c) assess the value of prenatal and postnatal serological testing in predicting neonatal outcomes. STUDY DESIGN AND METHODS: A retrospective audit of consecutive alloimmunized pregnancies was conducted. Data collected included demographics, clinical outcomes, and laboratory results. Outcomes included: incidence of alloimmunization; outcomes for neonates with and without the cognate antigen; and sensitivity and specificity of antibody titration testing in predicting hemolytic disease of the fetus and newborn (HDFN). RESULTS: Over 6 years, 128 pregnant women (0.4%) were alloimmunized with 162 alloantibodies; anti-E was the most common alloantibody (51/162; 31%). Intrauterine transfusions (IUTs) were employed in 2 (3%) of 71 mothers of cognate antigen positive (CoAg+) neonates. Of 74 CoAg+ neonates, 58% required observation alone, 23% intensive phototherapy, 9% top up transfusion, and 3% exchange transfusion; no fetal or neonatal deaths occurred. HDFN was diagnosed in 28% (21/74) of neonates; anti-D was the most common cause. The sensitivity and specificity of the critical gel titer >32 in predicting HDFN were 76% and 75%, respectively (negative predictive value 95%; positive predictive value 36%). The sensitivity and specificity of a positive direct antiglobulin test (DAT) in predicting HDFN were 90% and 58%, respectively (NPV 97%; PPV 29%). CONCLUSION: Morbidity and mortality related to HDFN was low; most alloimmunized pregnancies needed minimal intervention. Titers of >32 by gel warrant additional monitoring during pregnancy.

Preoperative anemia-screening clinics.

Preoperative anemia is associated with increased postoperative morbidity and mortality and with increased risk of perioperative transfusion. It is an important and modifiable risk factor for surgical patients. For high-blood-loss surgery, preoperative anemia is defined as hemoglobin <13 g/dL for both male and female patients. Preoperative anemia is common, ranging from 25% to 40% in large observational studies. The most common treatable cause of preoperative anemia is iron-deficiency anemia; the initial laboratory tests should focus on making this diagnosis. Management of iron-deficiency anemia includes iron supplementation with IV iron therapy when oral iron is ineffective or not tolerated, there is severe anemia, and there is insufficient time to surgery (<4 weeks). In other situations, erythropoiesis-stimulating agents may be considered, particularly for those patients with multiple alloantibodies or religious objections to transfusion. To facilitate the diagnosis and management of preoperative anemia, establishment of preoperative anemia-screening clinics is essential. The goals of management of preoperative anemia are to treat anemia, reduce the need for transfusion, and improve patient outcomes.

Patient blood management for liver resection: consensus statements using Delphi methodology.

BACKGROUND: Blood loss and transfusion remain a significant concern in liver resection (LR). Patient blood management (PBM) programs reduce use of transfusions and improve outcomes and costs, but are not standardized for LR. This study sought to create an expert consensus statement on PBM for LR using modified Delphi methodology. METHODS: An expert panel representing hepato-biliary surgery, anesthesiology, and transfusion medicine was invited to participate. 28 statements addressing the 3 pillars of PBM were created. Panelists were asked to rate statements on a 7-point Likert scale. Three-rounds of iterative rating and feedback were completed anonymously, followed by an in-person meeting. Consensus was reached with at least 70% agreement. RESULTS: The 35 experts panel recommended routine pre-operative transfusion risk assessment, and investigation and management of anemia with iron supplementation. Intra-operatively, restrictive fluid administration without routine central line insertion was recommended, along with intermittent hepatic pedicle occlusion and surgical techniques considerations. Specific criteria for restrictive intra-operative and post-operative transfusion strategy were recommended. CONCLUSIONS: PBM for LR included medical and technical interventions throughout the perioperative continuum, addressing specificities of LR. Diffusion and adoption of these recommendations can standardize PBM for LR to improve patient outcomes and resource utilization.

Complications of a severe autoimmune hemolytic anemia crisis: transfusional iron overload and gangrenous cholecystitis.

BACKGROUND: Evans syndrome is a rare autoimmune disorder that is defined by the simultaneous or sequential presence of two or more cytopenias without an obvious underlying precipitating cause. Evans syndrome usually follows a chronic relapsing and remitting course and is quite rare, making it difficult to evaluate in clinical studies. CASE REPORT: A 66-year-old male patient with a 17-year history of Evans syndrome presented with fulminant autoimmune hemolytic anemia (AIHA). He presented with a markedly elevated C-reactive protein (CRP; 46 mg/L [normal, 0-5 mg/L]) before onset of a decrease in hemoglobin. He required the transfusion of 20 units of red blood cells while awaiting response to aggressive immunosuppressive therapy including high-dose corticosteroids, intravenous immunoglobin therapy, and rituximab. He achieved a complete hematologic response. RESULTS: His postdischarge course was complicated by acute cholecystitis requiring laparoscopic cholecystectomy. In addition, his transfusional iron overload requiring 16 phlebotomies to reduce his ferritin level from 4933 µg/L to 326 µg/L, with phlebotomies ongoing every 2 weeks to achieve a ferritin level of less than 100 µg/L. CONCLUSION: Neither transfusional iron overload nor acute cholecystitis are well-recognized complications of a severe episode of AIHA. An elevated CRP has been recently recognized as an important prognostic marker in patients with immune thrombocytopenic purpura and this case suggests a need to evaluate its utility in AIHA.

Prothrombin Complex Concentrate for Major Bleeding on Factor Xa Inhibitors: A Prospective Cohort Study.

Oral factor Xa inhibitors are increasingly used for anticoagulation, but there is no approved reversal agent. Prothrombin complex concentrate (PCC) for the management of Xa-inhibitor-associated bleeding has been described in small case series and one cohort study. Patients on apixaban or rivaroxaban, suffering a major bleed, were treated at nine Canadian hospitals as per existing hospital protocol with a fixed dose of PCC 2,000 units and subsequently recruited for a 30-day follow-up. The treating physician evaluated the haemostatic effectiveness as observed during the first day as good, moderate or poor/none, using an assessment guide. Safety outcomes were thromboembolism or death. We recruited 66 patients with major bleeding who were treated with PCC and who were receiving rivaroxaban (56%) or apixaban (44%). The effectiveness was assessed as good in 65% (95% confidence interval [CI], 53-77), moderate in 20% (95% CI, 10-30) and poor/none in 15% (95% CI, 6-24). For the 36 patients with intracranial haemorrhage, the corresponding ratings were 67, 17 and 17%, and for 16 patients with gastrointestinal bleeding they were 69, 12 and 19%, respectively. There were nine deaths (14%) by 30 days, and five (8%) major thromboembolic events. In a post hoc analysis, according to International Society on Thrombosis and Haemostasis criteria, reversal was effective in 68% and ineffective in 32%. For major bleeding associated with oral Xa inhibitors, PCC may have a beneficial effect. The risk of thromboembolism after reversal of anticoagulation in patients with a prothrombotic background has to be taken into account.

Iron deficiency anemia in the emergency department: over-utilization of red blood cell transfusion and infrequent use of iron supplementation.

OBJECTIVES: Three are no clinical practice guidelines that specifically address the management of patients with iron deficiency anemia (IDA) in the emergency department (ED). The goal of this study was to describe the characteristics of IDA patients who present to the ED, documentation of IDA by emergency physicians, utilization of iron supplementation, and the appropriateness of red blood cell (RBC) transfusions ordered in the ED. METHODS: A retrospective medical chart review was performed of IDA patients who visited the ED of a large tertiary center over a three-month period. Appropriateness of RBC transfusion was determined using a novel algorithm developed by our institution. RESULTS: Over the study period, there was a 0.3% (49/14,394) prevalence of IDA in the ED. In thirty (30/49; 61%) patients, IDA was documented by an emergency physician. RBC transfusions were administered to 19 patients; 10 transfusions (53%) were appropriate, 3 (16%) were appropriate for indication, but more than the required number of units were ordered, and 6 (32%) were inappropriate. Of the patients discharged, one (1/25; 4%) patient received intravenous iron in the ED and 6 of the 11 patients (55%) that were not already taking oral iron received a prescription at discharge from the ED. CONCLUSIONS: This assessment demonstrated that management of IDA patients presenting to the ED may represent an important knowledge-to-practice gap. It revealed that RBC transfusion may be over-utilized and could be replaced by safer, lower-cost alternatives such as intravenous and oral iron. Guidelines for management of IDA in the ED may be necessary to achieve consistent IDA management and avoid inappropriate use of RBC transfusion.

Understanding Perioperative Transfusion Practices in Gastrointestinal Surgery-a Practice Survey of General Surgeons.

BACKGROUND: Despite guidelines recommending restrictive red blood cell transfusion (RBCT) strategies, perioperative transfusion practices still vary significantly. To understand the underlying mechanisms that lead to gaps in practice, we sought to assess the attitudes of surgeons regarding the perioperative management of anemia and use of RBCT in patients having gastrointestinal surgery. METHODS: We conducted a self-administered Web-based survey of general surgery staff and residents, in a network of eight academic institutions at the University of Toronto. We developed a questionnaire using a systematic approach of items generation and reduction. We tested face and content validity and test-retest reliability. We administered the survey via emails, with planned reminders. RESULTS: Total response rate was 48.1 % (62/125). Half (51.0 %) of respondents stated that they were unlikely to conduct a preoperative anemia work-up. About 54.0 % reported ordering preoperative oral iron supplementation for anemia. Most respondents indicated using a 70 g/L hemoglobin trigger (92.0 %) for transfusion. Factors increasing thresholds above 70 g/L included cardiac comorbidity (58.0 %), acute cardiac disease (94.0 %), symptomatic anemia (68.0 %), and suspected bleeding (58.0 %). With those factors, the transfusion threshold often increased above 90 g/L. Respondents perceived RBCTs to increase the postoperative morbidity (62 %), but not to impact the mortality (48 %) and cancer recurrence (52 %). Institutional protocols (68.0 %), blood conservation clinics (44.0 %), and clinical practice guidelines (84.0 %) were believed to encourage restrictive use of RBCTs. CONCLUSION: Self-reported perioperative transfusion practices for GI surgery are heterogeneous. Few respondents investigated preoperative anemia. Stated use of RBCT indications varied from recommendations in published guidelines for patients with symptomatic anemia. Establishing team consensus and implementing local blood management guidelines appear necessary to improve uptake of evidence-based recommendations.

Hemolytic disease of the newborn caused by anti-Wright (anti-Wra): case report and review of literature.

Antibodies to red cell antigens that are found at low frequency in the general population are rare causes of hemolytic disease of the newborn. To understand how to detect these cases, we provide a basic review of routine antenatal maternal antibody testing and report a case of a neonate with severe HDN caused by anti-Wright (anti-Wra), successfully managed with transfusion, phototherapy, and high-dose intravenous immunoglobulin. When hemolysis in a newborn is suspected in the absence of major blood group incompatibility or commonly detected maternal red cell antibodies, a direct antiglobulin test should be performed. A positive DAT should alert the clinician to the presence of maternal antibodies against low-incidence antigens. Antibodies to the Wra antigen are one such rare cause of HDN.