HealthDay News – As medical knowledge and patient care concerning anemia continually progresses, clinicians and physicians must remain informed about the field’s most recent advances.
Conscientious medical practitioners, dedicated to enhancing patient welfare, must cultivate their understanding of anemia in particular, as well as its multifaceted nuances. Etiologies, diagnostic headways, and therapeutic interventions are always changing to fit new knowledge.
Anemia, marked by a decrease in red blood cell count or hemoglobin concentration, continues to be a widespread global health issue with complex ramifications. Updates pertaining to various types of anemia include advancements in molecular research, diagnostic methodologies, and tailored therapeutic strategies.
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Anemia in CKD Treatment: Daprodustat Noninferior to ESAs
For chronic kidney disease (CKD) patients who are and are not undergoing hemodialysis, the oral hypoxia-inducible factor prolyl hydroxylase inhibitor daprodustat is noninferior to injectable erythropoiesis-stimulating agent (ESA) for treating anemia, according to two studies published online Nov. 5 in the New England Journal of Medicine.
Anemia: Phase 3 Trial
The research was published to coincide with Kidney Week, the annual meeting of the American Society of Nephrology, held virtually from Nov. 4 to 7.
Ajay K. Singh, M.B., B.S., from Brigham and Women’s Hospital in Boston, and colleagues conducted a phase 3 trial in which 2,964 CKD patients who were undergoing dialysis and had a hemoglobin level of 8.0 to 11.5 g/dL were randomly assigned to receive either daprodustat or ESA.
The researchers found that from baseline to weeks 28 through 52, the mean change in the hemoglobin level was 0.28 ± 0.02 g/dL and 0.10 ± 0.02 g/dL in the daprodustat and ESA groups, respectively (difference, 0.18 g/dL), which met the prespecified noninferiority margin.
A major adverse cardiovascular event occurred in 25.2 and 26.7 percent of patients in the daprodustat and ESA groups, respectively, during a median follow-up of 2.5 years (hazard ratio, 0.93; 95 percent confidence interval, 0.81 to 1.07), which met the prespecified noninferiority margin.
Anemia Treatments Compared
In a second study, Singh and colleagues compared daprodustat with darbepoetin alfa for anemia treatment in 3,872 CKD patients who were not undergoing dialysis. The researchers found that from baseline to weeks 28 through 52, the mean change in the hemoglobin level was 0.74 ± 0.02 and 0.66 ± 0.02 g/dL in the daprodustat and darbepoetin alfa groups, respectively (difference, 0.08 g/dL), which met the prespecified noninferiority margin.
“We found that oral delivery of daprodustat worked just as well as conventional therapy — increasing and maintaining hemoglobin levels among nondialysis patients and maintaining levels among patients on dialysis — and was just as safe,” Singh said in a statement.
Several authors from both studies disclosed financial ties to biopharmaceutical companies, including GlaxoSmithKline, which manufactures daprodustat and funded both studies.
Anemia in Non-Dialysis-Dependent CKD Treated with Roxadustat
For patients with non-dialysis-dependent chronic kidney disease (CKD) and CKD-related anemia, roxadustat increases hemoglobin levels in red blood cells and reduces the need for red blood cell transfusions, according to a study published in the August issue of the Clinical Journal of the American Society of Nephrology.
CKD-Related Anemia: Efficacy of Roxadustat
Robert Provenzano, M.D., from Wayne State University in Detroit, and colleagues examined the efficacy and cardiovascular safety of roxadustat versus placebo using data from three phase 3, double-blind studies in patients with non-dialysis-dependent CKD and CKD-related anemia. Overall, 4,277 patients were randomly assigned as follows: 2,391 to roxadustat and 1,886 to placebo.
The researchers found that regardless of rescue therapy, anemia patients treated with roxadustat versus placebo had a mean change from baseline in hemoglobin of 1.9 versus 0.2 g/dL, averaged over weeks 28 to 52. In the first 52 weeks, roxadustat reduced the need for red blood cell transfusion (6.1 versus 20.4 per 100 patient-exposure years, respectively; hazard ratio, 0.26).
CKD-Related Anemia: No Risk of MACE
In anemia patients treated with roxadustat versus placebo, there were no increased risks for a composite outcome of major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction, and stroke; MACE+ (MACE plus unstable angina and heart failure requiring hospitalization); all-cause mortality; or individual MACE+ components.
“Roxadustat was shown to be effective, with an acceptable safety profile,” Provenzano said in a statement. “As an oral agent, roxadustat addresses the significant unmet need in treating anemia in patients with kidney disease.”
Several authors disclosed financial ties to biopharmaceutical companies, including FibroGen, AstraZeneca, and Astellas, which sponsored the studies.
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Read more: Acute Heart Failure
Transcranial Doppler, Hydroxyurea Use Low for SCA Patients
For children with sickle cell anemia (SCA), transcranial Doppler (TCD) ultrasound screening and hydroxyurea therapy use remains low, according to research published in the Sept. 20 early-release issue of the U.S. Centers for Disease Control and Prevention Morbidity and Mortality Weekly Report.
Transcranial Doppler Screening & Hydroxyurea Use in Children With Sickle Cell Anemia
Laura A. Schieve, Ph.D., from the CDC in Atlanta, and colleagues analyzed data from the IBM MarketScan Multi-State Medicaid Database and examined transcranial Doppler screening and hydroxyurea use for 3,352 children and adolescents with sickle cell anemia aged 2 to 16 years.
The researchers found that transcranial Doppler screening increased 27 percent among children and adolescents aged 10 to 16 years during 2014 to 2019, and hydroxyurea use increased 27 and 23 percent among children aged 2 to 9 and 10 to 16 years, respectively. Only 47 and 38 percent of children aged 2 to 9 and 10 to 16 years, respectively, had received transcranial Doppler screening in 2019, and 38 and 53 percent, respectively, used hydroxyurea.
Usage was highest among children and adolescents with high levels of health care utilization and evidence of previous complications indicative of severe chronic disease, for both prevention strategies.
Untreated Anemia Among Children
“Even among groups with the highest usage rates (younger children with an indication of severe disease for transcranial Doppler screening and older children and adolescents with an indication of severe disease for hydroxyurea) a substantial proportion of children and adolescents for whom these interventions are indicated were not receiving them,” the authors write.
Several authors disclosed financial ties to the biopharmaceutical industry.
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Incident Anemia Increase With Low-Dose Aspirin in Older Adults
For older adults, low-dose aspirin is associated with increased incident anemia and a decrease in ferritin when compared with placebo, according to a study published online June 20 in the Annals of Internal Medicine.
Incident Anemia: Effect of Low-dose Aspirin
Zoe K. McQuilten, M.B.B.S., Ph.D., from Monash University in Melbourne, Australia, and colleagues examined the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations in a post hoc analysis of the Aspirin in Reducing Events in the Elderly trial involving community-dwelling individuals aged 70 years or older. A total of 19,114 individuals were randomly assigned to 100 mg of aspirin daily or placebo.
The researchers found that the incidence of anemia was 51.2 events per 1,000 person-years and 42.9 events per 1,000 person-years in the aspirin and placebo groups, respectively (hazard ratio, 1.20). In the placebo group, hemoglobin concentrations decreased by 3.6 g/L per five years, while a steeper decline of 0.6 g/L per five years was experienced by the aspirin group.
In 7,139 participants with ferritin measures at baseline and year 3, the prevalence of ferritin levels <45 µg/L at year 3 was greater in the aspirin group (13 versus 9.8 percent); the aspirin group also had a greater overall decline in ferritin by 11.5 percent when compared with those receiving placebo. Similar results were seen in a sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding.
Incident Anemia Risk Increased by Daily Aspirin
“Daily low-dose aspirin increased the risk for incident anemia by approximately 20 percent, which, after taking into account risk for clinically significant bleeding, was most likely due to occult blood loss given the observed steeper decline in ferritin in participants allocated to aspirin,” the authors write.
Several authors disclosed financial ties to industry.
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MRI-Based AI Can Distinguish Aplastic Anemia From MDS
A magnetic resonance imaging (MRI)-based machine learning method can distinguish aplastic anemia (AA) from myelodysplastic syndromes (MDS), according to a study published online March 6 in Clinical Radiology.
Bone Marrow Biopsy in Aplastic Anemia or MDS
P. Xiang, from The First Affiliated Hospital of Zhejiang Chinese Medical University in Hangzhou, and colleagues conducted a retrospective study involving patients diagnosed with AA or MDS by pathological bone marrow biopsy who underwent pelvic MRI with the iterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation (IDEAL-IQ).
AA & MDS Identified by Machine Learning Algorithms
Three machine learning algorithms, including linear discriminant analysis, logistic regression, and support vector machine (SVM), were used to identify aplastic anemia and MDS based on values of right ilium fat fraction (FF) and radiomic features extracted from T1-weighted (T1W) and IDEAL-IQ images.
The study included 77 participants (37 men and 40 women), aged 20 to 84 years. Twenty-one patients had MDS and 56 had AA. The researchers found that the ilium FF of AA patients was significantly greater than that of MDS patients (mean ± standard deviation: 79.23 ± 15.04 versus 42.78 ± 30.09 percent).
Highest Predictive Ability
The IDEAL-IQ-based SVM classifier model had the best predictive ability selecting from the machine learning models based on ilium FF, T1W imaging, and IDEAL-IQ.
“IDEAL-IQ-based machine learning of the pelvis can distinguish aplastic anemia from MDS with high accuracy, and its predictive ability was significantly better than ilium FF and T1W-based machine learning,” the authors write. “The combination of machine learning and IDEAL-IQ technology may enable noninvasive differentiation of aplastic anemia from MDS.”
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Anemia & ID Linked to GERD in Children
Gastroesophageal reflux disease (GERD) is associated with the risk of anemia or iron deficiency (ID) among children, according to a study published online Dec. 26 in Diagnostics.
Vasile Valeriu Lupu, Ph.D., from the “Grigore T. Popa” University of Medicine and Pharmacy in Iasi, Romania, and colleagues examined the anemia symptoms and its presence as a result of pediatric GERD in 172 children.
Anemia & GERD Correlation
The researchers found that 23 of the patients with GERD also had anemia, showing a moderate, significant correlation (r = −0.35). Cases with GERD also had significantly lower levels of serum iron (F = 8.46).
GERD May Lead to IDA
“GERD is accompanied by a degree of iron deficiency that opens the way to iron deficiency anemia. Considering the fact that vitamin deficiency anemia can be one of the signs of gastroesophageal reflux disease, especially among pediatric patients, this complication should not be neglected due to its long-term effects in a child’s development and further in adult life,” the authors write.
“When faced with a case of hypochromic hyposideremic anemia in which other causes have been excluded, the clinician should consider it as a result of a gastroesophageal reflux if the patient presents signs and symptoms suggestive for this gastrointestinal pathology, and also if the same anemia occurs and does not respond to oral iron therapy.”
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Iron Deficiency Common Among Teens, Young Women
Iron deficiency (ID) is common among females aged 12 to 21 years and, for most, is not associated with iron deficiency anemia, according to a research letter published in the June 27 issue of the Journal of the American Medical Association.
ID Prevalence
Angela C. Weyand, M.D., from the University of Michigan in Ann Arbor, and colleagues examined ID prevalence among females aged 12 to 21 years using data from 3,490 participants in the National Health and Nutrition Examination Survey (2003 to 2010 and 2015 to March 2020).
The researchers found that the overall prevalence of ID was 38.6 percent (17 percent using a 15-μg/L ferritin cutoff and 77.5 percent using a 50-μg/L cutoff). ID was detected in 27.1 percent of premenarchal individuals using a 25-μg/L ferritin cutoff. For iron-deficiency anemia, the overall prevalence was 6.3 percent (11.0 percent using a 12.5-mg/dL hemoglobin cutoff and 17.2 percent using a 13-mg/dL cutoff).
For the majority of individuals with ID (83.6 percent), ID was not associated with iron-deficiency anemia. ID and iron-deficiency anemia were both associated with non-White race, Hispanic ethnicity, and menstruation.
“The frequency of universal screening for ID and iron-deficiency anemia in menstruating persons and the best ferritin and hemoglobin thresholds should be evaluated,” the authors write.
Several authors disclosed ties to the pharmaceutical industry.
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Suggested Protective Effect of ID Anemia in Acute Bacterial Pneumonia
Mubarak Yusuf, M.D., of Lincoln Medical Center in Bronx, New York, and colleagues identified a possibly protective association between iron deficiency (ID) anemia and outcomes for hospital admission with bacterial pneumonia.
The authors assessed the impact of ID anemia on outcomes for bacterial pneumonia. Patient information was retrieved from a large national inpatient sample within the United States. The clinical outcomes measured included mortality, septic shock, cardiac arrest, and acute respiratory failure. The researchers identified a protective association between bacterial pneumonia and IDA in all of the measured outcomes.
Unique Association Noted by Study
“To the best of our knowledge, this is the first study investigating such an association. We believe further study is needed to validate our study and also answer some unanswered questions,” Yusuf said.
“The impact we think this can have on clinical practice is perhaps that clinicians should consider a delay in treatment of nonsymptomatic ID anemia in admission for bacterial pneumonia.”
Abstract
Many Pregnancies Affected by ID
Less than half of individuals have their ferritin levels checked during pregnancy, and among those who do, half have low iron levels, according to a study published online Aug. 30 in Blood Advances.
Jennifer Teichman, M.D., from the University of Toronto, and colleagues used data from 44,552 pregnant patients with prenatal testing at community laboratories in Ontario, Canada, to determine the prevalence of ferritin testing over five years, as well as the prevalence and severity of iron deficiency (ID), and to identify clinical and demographic variables associated with ID screening.
The researchers found that 59.4 percent of patients had ferritin checked during pregnancy; among these patients, 71.4 percent of ferritin blood tests were ordered in the first trimester when the risk for ID is lowest. Lab results showed that 25.2 percent of patients were iron-insufficient (30 to 44 μg/L), 52.8 percent were iron-deficient (≤29 μg/L) at least once in pregnancy, and 8.3 percent had anemia (hemoglobin <105 g/L).
Subsequent Ferritin Test in Pregnancy With Anemia
Among anemia patients, a subsequent ferritin test in pregnancy was conducted for 22 percent in the lowest anemia severity category to 67 percent in the highest type of anemia severity category. There was a negative association between lower annual household income and odds of a ferritin test. Compared with the highest income quintile, the odds of ferritin testing for anemia patients in the first, second, and fourth quintiles were 0.83, 0.82, and 0.86, respectively.
“These data highlight gaps in prenatal care and issues of health equity that warrant harmonization of obstetrical guidelines to recommend routine ferritin testing in pregnancy,” the authors write.
One author disclosed financial ties to the pharmaceutical industry.
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Read more: Iron Deficiency Anemia in Pregnancy
Anemia Updates: Key Takeaways
Key takeaways for clinicians, physicians, epidemiologists, and healthcare professionals include:
- Oral daprodustat is noninferior to injectable erythropoiesis-stimulating agent (ESA) for treating anemia.
- Roxadustat increases hemoglobin levels in red blood cells, reduces need for red blood cell transfusions, and addresses unmet need to treat anemia patients with CKD.
- Significant proportion of children and adults do not receive TCD ultrasound screening and hydroxyurea therapy even when indicated.
- Daily low-dose aspirin increases risks for incident anemia and a decrease in ferritin.
- MRI-based machine learning can distinguish aplastic anemia from myelodysplastic syndromes.
- GERD in children is associated with risks for developing IDA.
- ID common among females aged 12 to 21 years mostly is not associated with IDA.
- Researchers identified a protective association between bacterial pneumonia and IDA.
- Gaps in prenatal care include persons not verifying ferritin levels during pregnancy, even with low iron levels.
Healthcare professionals should apprise themselves of the latest methods to diagnose and treat anemia, and learn how best to communicate this information with patients. Ideally, this knowledge will help clinicians and physicians identify abnormal red blood cells, treat various forms of anemia such as hemolytic anemia and pernicious anemia, and better manage red blood cell production in patients.
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