Anemia and acute coronary syndrome: current perspectives.
TL;DR: Estimated prevalence of anemia on admission in the setting of an acute coronary syndrome (ACS) is between 10% and 43% of the patients depending upon the specific population under investigation, and up to 57% of ACS patients may develop hospital-acquired anemia (HAA), even if different mechanisms contribute to their prognostic impact.
Abstract: Reference hemoglobin (Hb) values for the definition of anemia are still largely based on the 1968 WHO Scientific Group report, which established a cutoff value of <13 g/dL for adult men and <12 g/dL for adult nonpregnant women. Subsequent studies identified different normal values according to race and age. Estimated prevalence of anemia on admission in the setting of an acute coronary syndrome (ACS) is between 10% and 43% of the patients depending upon the specific population under investigation. Furthermore, up to 57% of ACS patients may develop hospital-acquired anemia (HAA). Both anemia on admission and HAA are associated with worse short- and long-term mortality, even if different mechanisms contribute to their prognostic impact. Baseline anemia can usually be traced back to preexisting disease that should be specifically investigated and corrected whenever possible. HAA is associated with clinical characteristics, medical therapy and interventional procedures, all eliciting cardiovascular adaptive response that can potentially worsen myocardial ischemia. The intrinsic fragility of anemic patients may limit aggressive medical and interventional therapy due to an increased risk of bleeding, and could independently contribute to worse outcome. However, primary angioplasty for ST elevation ACS should not be delayed because of preexisting (and often not diagnosed) anemia; delaying revascularization to allow fast-track anemia diagnosis is usually feasible and justified in non-ST-elevation ACS. Besides identification and treatment of the underlying causes of anemia, the only readily available means to reverse anemia is red blood cell transfusion. The adequate transfusion threshold is still being debated, although solid evidence suggests reserving red blood cell transfusions for patients with Hb level <8 g/dL and considering it in selected cases with Hb levels of between 8 and 10 g/dL. No evidence supports the use of iron supplements and erythropoiesis-stimulating agents in the setting of ACS.
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01 Jul 2020
TL;DR: Using raw ECG data, a deep learning algorithm (DLA) that enables non-invasive anaemia screening from electrocardiograms (ECGs) might improve the detection of anaemia.
Abstract: Summary Background Anaemia is an important health-care burden globally, and screening for anaemia is crucial to prevent multi-organ injury, irreversible complications, and life-threatening adverse events. We aimed to establish whether a deep learning algorithm (DLA) that enables non-invasive anaemia screening from electrocardiograms (ECGs) might improve the detection of anaemia. Methods We did a retrospective, multicentre, diagnostic study in which a DLA was developed using ECGs and then internally and externally validated. We used data from two hospitals, Sejong General Hospital (hospital A) and Mediplex Sejong Hospital (hospital B), in South Korea. Data from hospital A was for DLA development and internal validation, and data from hospital B was for external validation. We included individuals who had at least one ECG with a haemoglobin measurement within 1 h of the index ECG and excluded individuals with missing demographic, electrocardiographic, or haemoglobin information. Three types of DLA were developed with 12-lead, 6-lead (limb lead), and single-lead (lead I) ECGs to detect haemoglobin concentrations of 10 g/dL or less. The DLA was built by a convolutional neural network and used 500-Hz raw ECG, age, and sex as input data. Findings The study period ran from Oct 1, 2016, to Sept 30, 2019, in hospital A and March 1, 2017, to Sept 30, 2019, in hospital B. 40 513 patients at hospital A and 4737 patients at hospital B were eligible for inclusion. We excluded 281 patients at hospital A and 72 patients at hospital B because of missing values for clinical information and ECG data. The development dataset comprised 57 435 ECGs from 31 898 patients, and the algorithm was internally validated with 7974 ECGs from 7974 patients. The external validation dataset included 4665 ECGs from 4665 patients. 586 (internal) and 194 (external) patients within the combined dataset were found to be anaemic. During internal and external validation, the area under the receiver operating characteristics curve (AUROC) of the DLA using a 12-lead ECG for detecting anaemia was 0·923 for internal validation and 0·901 for external validation. Using a 90% sensitivity operating point for the development data, the sensitivity, specificity, negative predictive value, and positive predictive value of internal validation were 89·8%, 81·5%, 99·4%, and 20·0%, respectively, and those of external validation were 86·1%, 76·2%, 99·2%, and 13·5%, respectively. The DLA focused on the QRS complex for deciding the presence of anaemia in a sensitivity map. The AUROCs of DLAs using 6 leads and a single lead were in the range of 0·841–0·890. Interpretation In this study, using raw ECG data, a DLA accurately detected anaemia. The application of artificial intelligence to ECGs could enable screening for anaemia. Funding None.
51 citations
TL;DR: In this paper, admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage, and the primary outcome was 3-month post-intervention post-traumatic hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6).
Abstract: OBJECTIVES To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage. DESIGN Individual patient data meta-analysis of three studies of intracerebral hemorrhage. SETTING Two randomized clinical trials and one multiethnic observational study. PATIENTS Patients with spontaneous, nontraumatic intracerebral hemorrhage. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion. CONCLUSIONS Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.
21 citations
TL;DR: In this paper , a cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumabi (RAV), and found that patients on ECU (88.6%) and RAV (74.7%) reported fatigue symptoms.
Abstract: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening disease with symptoms of hemolysis and thrombosis. Current therapies for this complement-mediated disease rely predominantly on inhibition of the C5 complement protein. However, data on treatment responses and quality of life in C5-inhibitor (C5i)-treated PNH patients are scarce. The objective of this study was to determine C5i treatment effects on clinical parameters, PNH symptoms, quality of life, and resource use for PNH patients. This cross-sectional study surveyed 122 individuals in the USA receiving treatment for PNH with C5-targeted monoclonal antibodies, eculizumab (ECU) or ravulizumab (RAV). Despite most patients receiving C5i therapy for ≥ 3 months (ECU 100%, n = 35; RAV 95.4%, n = 83), many patients remained anemic with hemoglobin levels ≤ 12 g/dL in 87.5% (n = 28/32) and 82.9% (n = 68/82) of ECU and RAV recipients, respectively. A majority of patients on ECU (88.6%; n = 31/35) and RAV (74.7%; n = 65/87) reported fatigue symptoms. Among PNH patients receiving C5i therapy for ≥ 12 months, some still reported thrombotic events (ECU, 10.0%, n = 1/10; RAV, 23.5%, n = 4/17) and required transfusions within the past year (ECU, 52.2%, n = 12/23; RAV, 22.6%, n = 7/31). Other patient-reported PNH symptoms included breakthrough hemolysis, shortness of breath, and headaches. Patients reported scores below the average population norms on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scales. Overall, this study found that PNH patients receiving ECU or RAV therapy demonstrated a significant burden of illness, highlighting the need for improved PNH therapies.
11 citations
TL;DR: A commonly used and accurate definition in the context of patients undergoing percutaneous coronary intervention and stent implantation for ACS is still lacking, and therapeutic options to address anemia remain limited.
Abstract: Introduction: Anemia is one of the most frequent comorbidities in acute coronary syndrome (ACS) patients and is associated with a significant impact on clinical outcomes. This review summarizes the...
9 citations
References
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TL;DR: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.
Abstract: BACKGROUND To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.
4,529 citations
TL;DR: Advances in knowledge of the causes and management of the anemia of chronic disease are discussed.
Abstract: New therapeutic strategies have emerged along with our understanding that disturbances of iron homeostasis, impaired proliferation of erythroid progenitor cells, and blunted erythropoietin response occur in anemia of chronic disease. This review discusses advances in our knowledge of the causes and management of the condition.
2,922 citations
Autonomous University of Barcelona1, National and Kapodistrian University of Athens2, Lund University3, University of Bergen4, Hannover Medical School5, University of Zurich6, Russian National Research Medical University7, SOCAR8, University of London9, Imperial College London10, Wrocław Medical University11
TL;DR: Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable.
Abstract: BACKGROUND Iron deficiency may impair aerobic performance. This study aimed to determine whether treatment with intravenous iron (ferric carboxymaltose) would improve symptoms in patients who had heart failure, reduced left ventricular ejection fraction, and iron deficiency, either with or without anemia. METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association (NYHA) functional class II or III, a left ventricular ejection fraction of 40% or less (for patients with NYHA class II) or 45% or less (for NYHA class III), iron deficiency (ferritin level <100 μg per liter or between 100 and 299 μg per liter, if the transferrin saturation was <20%), and a hemoglobin level of 95 to 135 g per liter. Patients were randomly assigned, in a 2:1 ratio, to receive 200 mg of intravenous iron (ferric carboxymaltose) or saline (placebo). The primary end points were the self-reported Patient Global Assessment and NYHA functional class, both at week 24. Secondary end points included the distance walked in 6 minutes and the health-related quality of life. RESULTS Among the patients receiving ferric carboxymaltose, 50% reported being much or moderately improved, as compared with 28% of patients receiving placebo, according to the Patient Global Assessment (odds ratio for improvement, 2.51; 95% confidence interval [CI], 1.75 to 3.61). Among the patients assigned to ferric carboxymaltose, 47% had an NYHA functional class I or II at week 24, as compared with 30% of patients assigned to placebo (odds ratio for improvement by one class, 2.40; 95% CI, 1.55 to 3.71). Results were similar in patients with anemia and those without anemia. Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality-of-life assessments. The rates of death, adverse events, and serious adverse events were similar in the two study groups. CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency, with or without anemia, improves symptoms, functional capacity, and quality of life; the side-effect profile is acceptable. (ClinicalTrials.gov number, NCT00520780.)
1,616 citations
TL;DR: Blood transfusion in the setting of acute coronary syndromes is associated with higher mortality, and this relationship persists after adjustment for other predictive factors and timing of events.
Abstract: ContextIt is unclear if blood transfusion in anemic patients with acute coronary
syndromes is associated with improved survival.ObjectiveTo determine the association between blood transfusion and mortality
among patients with acute coronary syndromes who develop bleeding, anemia,
or both during their hospital course.Design, Setting, and PatientsWe analyzed 24 112 enrollees in 3 large international trials of
patients with acute coronary syndromes (the GUSTO IIb, PURSUIT, and PARAGON
B trials). Patients were grouped according to whether they received a blood
transfusion during the hospitalization. The association between transfusion
and outcome was assessed using Cox proportional hazards modeling that incorporated
transfusion as a time-dependent covariate and the propensity to receive blood,
and a landmark analysis.Main Outcome MeasureThirty-day mortality.ResultsOf the patients included, 2401 (10.0%) underwent at least 1 blood transfusion
during their hospitalization. Patients who underwent transfusion were older
and had more comorbid illness at presentation and also had a significantly
higher unadjusted rate of 30-day death (8.00% vs 3.08%; P<.001), myocardial infarction (MI) (25.16% vs 8.16%; P<.001), and death/MI (29.24% vs 10.02%; P<.001)
compared with patients who did not undergo transfusion. Using Cox proportional
hazards modeling that incorporated transfusion as a time-dependent covariate,
transfusion was associated with an increased hazard for 30-day death (adjusted
hazard ratio [HR], 3.94; 95% confidence interval [CI], 3.26-4.75) and 30-day
death/MI (HR, 2.92; 95% CI, 2.55-3.35). In the landmark analysis that included
procedures and bleeding events, transfusion was associated with a trend toward
increased mortality. The predicted probability of 30-day death was higher
with transfusion at nadir hematocrit values above 25%.ConclusionsBlood transfusion in the setting of acute coronary syndromes is associated
with higher mortality, and this relationship persists after adjustment for
other predictive factors and timing of events. Given the limitations of post
hoc analysis of clinical trials data, a randomized trial of transfusion strategies
is warranted to resolve the disparity in results between our study and other
observational studies. We suggest caution regarding the routine use of blood
transfusion to maintain arbitrary hematocrit levels in stable patients with
ischemic heart disease.
979 citations
"Anemia and acute coronary syndrome:..." refers result in this paper
...et al: among 24,112 subjects affected by ACS enrolled in 3 international trials, 10% of patients underwent at least 1 blood transfusion during the hospitalization, and RBC transfusion was associated with an increased hazard for 30-day death and 30-day death/MI compared with patients who did not receive transfusions.(46) Different results were obtained by Alexander et al who analyzed RBC transfusion policies and outcomes across 4 distinct nadir Hct groups (Hct ≤24% vs....
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TL;DR: The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease, however, most of the data on clinical outcomes were generated by a single trial.
Abstract: Background
There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients.
Objectives
The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL).
Search methods
We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials.
Selection criteria
We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered.
Data collection and analysis
We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'.
Main results
A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.
Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia).
Authors' conclusions
Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.
948 citations