Research Reviews
NAAC Research Reviews contain summaries and commentaries of recently published clinical trials regarding prevalence, diagnosis, consequences and treatment of anemia. We provide a quick overview of the recently published article from a peer reviewed journal and also include an expert commentary written by our Council Members. The commentary discusses the study's results, authors’ conclusions and helps explain how this study or the questions raised may impact you, your practice or medical organization.
Nov 2009
Although the benefit of erythropoiesis-stimulating agents (ESAs) has long been assumed, investigators do not know whether an increase of hemoglobin (Hb) levels through the use of ESAs will lower the risk for cardiovascular events and end-stage renal disease. The Trial to Reduce Cardiovascular Events with Aranesp therapy (TREAT) was designed to test this hypothesis in patients with type 2 diabetes, chronic kidney disease, and anemia who were not on dialysis. Unique in its comparison of an ESA to placebo, the results from the study by Pfeffer et al are likely to impact clinical practice to reduce risks associated with ESAs and maximize transfusion avoidance and quality of life benefits. [ full review ]
Oct 2009
Pergola et al conducted a randomized, open label, multicenter study to test the hypothesis that extended dosing regimens of epoetin alfa would be as safe and effective as approved dosing regimens, concluding that extended dosing regimens were not inferior to the standard three times per week dosing regimen when used to treat anemia in subjects with stage 3-4 CKD. Unfortunately, the increased dose required for significant extension of the dosing interval would make this approach untenable in the anticipated environment of bundled payments for dialysis services. Until our understanding of the basic physiology improves, we will be continuing to use ESAs in a largely empirical fashion rather than based on the important and distinctive pharmacokinetics and pharmacodynamics of individual agents. [ full review ]
Sep 2009
Several previous studies have reported a concurrence of osteoporosis and anemia in certain conditions, including sickle cell anemia, chronic inflammatory conditions, and renal failure. The study by Laudisio et al assessed the association of Hb levels with bone density testing and was able to identify Hb cutoff levels that could potentially be used to identify participants with osteoporosis, which may heighten our awareness that anemia may be a significant contributor to osteoporosis. [ full review ]
Adverse effects of bariatric surgery are not uncommon, but less is known about nutritional complications. The study by Coupaye et al prospectively compared the prevalence of nutritional deficiencies after adjustable gastric banding and gastric bypass procedures. Of most importance, was the observation that anemia remains a chronic problem in this population with iron deficiency as the primary cause of anemia, which has been reported by several other authors. [ full review ]
In their study, Cardenas-Turnanzas and colleagues describe both the incidence and prevalence of anemia in adult cancer patients admitted to the ICU at the University of Texas M.D. Anderson Cancer Center. The prevalence of anemia reflects the current published data that reports astonishingly high rates of this condition. Development of anemia in this population is also comparable to previous incidence reports. Studying anemia in this population has the potential to yeild insight into the correlation anemia has with cancer and survival, along with address the controversy of anemia as marker of survival or reflection of the severity of underlying diseases. [ full review ]
Aug 2009
A recent study tested the hypothesis that normal Hb targets can reduce transfusion rates compared with conventional targets in 596 incident hemodialysis patients without symptomatic cardiac disease. This was a randomized, controlled trial comparing normal Hb targets to partial correction of anemia, when treating with epoetin alfa resulting in authors Foley et al concluding that based on the data, normal target Hb levels can lower blood transfusion requirements in incident hemodialysis patients without symptomatic cardiac disease, in which the mortality rates are low. [ full review ]
A retrospective analysis by Kulnigg et al evaluated the use of intravenous iron sucrose with and without ESAs to treat anemic patients with Crohn’s Disease and ulcerative colitis. Analysis notably indicated that achieving a post treatment ferritin level of 400 mcg/L resulted in the prevention of iron deficiency within 1-5 years of treatment. Close follow up of Hb and iron levels, as well as prompt treatment with iron with or without ESA therapy can help physicians provide a better quality of life for patients with inflammatory bowel disease. [ full review ]
Jul 2009
To reevaluate the benefits and risks of ESAs in clinical settings, Ludwig et al conducted the first pooled analysis of all randomized, placebo-controlled trials that involved the ESA darbepoetin alfa. Analysis included six studies and 2,122 patients with CIA, with lung and hematologic cancers being the most frequent primary tumor type. The study's results reaffirm the value of ESAs in a clinical setting and suggest further reasons why other trials have shown contradictory results. [ full review ]
Jun 2009
A study by Boudville et al examined the relationship of hemoglobin variability and mortality in nondialysis chronic kidney disease patients receiving erythropoiesis-stimulating agents to identify specific factors that are associated with hemoglobin variability. The results suggest an association between hemoglobin variability and adverse clinical outcomes, suggesting that future carefully designed controlled trials should search for better understanding of hemoglobin variability as a marker of illness and comorbidity. [ full review ]
In the study by Bohlius et al, patients receiving epoetin or darbepoetin plus red blood cell transfusion were compared to patients receiving only transfusion. Upon analysis, ESAs increased overall mortality by 17% in all patients compared to control groups, and by 10% in patients undergoing chemotherapy compared to control groups. Although methodologically more rigorous, including 13,933 patients from 53 trials, this trial shows similar results to other meta-analyses or reviews. To further elucidate the clinical benefits of the findings, specific patient sub-groups need to be investigated, and more uniform survival endpoints need to be defined to assess the long-term effects of ESA treatment. [ full review ]
May 2009
The observational study by Rath et al, investigating the use of subcutaneous epoetin beta as an alternative to epoetin alfa for treatment of anemic patients on hemodialysis in Europe, provided further support for the use of epoetin beta in patients on hemodialysis and was well tolerated in CKD patients or patients on forms of renal replacement therapy. These findings suggest that switching to subcutaneous epoetin beta is a safe and effective treatment method, however, it is important to recognize the role concomitant iron therapy may have played in this study to contribute to the stability of target hemoglobin levels. [ full review ]
Within the context of blood donation reducing donors' iron stores, Pedrazzini et al have designed a trial in which the primary goal is to determine whether iron supplementation for one month following blood donation will reduce symptoms of fatigue in female donors with iron deficiency and no anemia. The investigators will also assess whether the iron therapy increases aerobic capacity and enhances mood and quality of life. It is possible that the results of this study, scheduled for publication in the summer of 2010, will provide additional data supporting the practice of providing iron supplementation to regular blood donors. [ full review ]
Apr 2009
A recent study by Zygun et al evaluated the effect of packed red blood cell transfusion on cerebral oxygenation and metabolism in patients with evere traumatic brain injury. The rationale has been to prevent cerebral ischemia by maximizing the oxygen carrying capacity of blood to protect vulnerable neuronal tissues. Although the authors concluded that transfusion of red blood cells acutely results in improved brain tissue oxygen, several limitations which should be considered when evaluating this data and the relation of PbtO2 changes to clinical outcomes. [ full review ]
Mar 2009
Recent guidelines recommend risk stratification and the established use of risk scores for patients with acute coronary syndromes. However, these guidelines have not yet accounted for the impact of anemia on ACS stratification and categorization strategies. A study by Meneveau et al analyzed the impact of anemia on in-hospital and 30-day mortality, as well as the predictive value of anemia for determining prognosis parameters. [ full review ]
Proper treatment is an essential component of anemia management because the prevalence of iron deficiency is extremely high in hemodialysis patients. Exploring the efficacy and safety of ferumoxytol compared to oral iron in hemodialysis patients was a recent Phase III trial by Provenzano et al. The findings of this study, that IV iron is more effective than oral iron, are not unexpected. Yet, direct head-to-head comparisons with other IV irons in less highly selected patients are needed. [ full review ]
The co-existence of iron deficiency and thyroid disease is a common clinical observation, but one that has lacked full explanation or definitive study. A study by Cinemre et al was designed to assess this association, as well as to explore whether thyroid replacement would reverse unresponsiveness to treatment in these patients. The authors concluded that patients with anemia and subclinical hypothyroidism can significantly benefit from treatment with ferrous sulfate and levothyroxine, but whether this marked improvement is due to the effect of the levothyroxine or simply the addition of iodine to iodine-deficient patients is not known. The authors also stress the need for testing thyroid function in patients with resistance to oral iron treatment. [ full review ]
Feb 2009
This review of literature by Minton et al is the first to assess the effects of common pharmacological treatments on cancer-related fatigue, most notably that of methylphenidate and hematopoietic treatments. In conclusion, it is encouraging to know from this study that the correction of anemia and the use of psychostimulants may improve fatigue, however studies are still needed to determine the mechanism of fatigue and the benefits of treating this symptom. [ full review ]
This trial by Seid et al evaluated the efficacy, safety, and tolerability of intravenous ferric carboxymaltose therapy compared to that of oral ferrous sulfate administration in postpartum women, a population in which the replenishment of iron stores is such a critical factor in preventing reoccurrence of iron deficiency anemia. Because this intravenous therapy can be administered more quickly and efficiently than oral therapies, it may, after more studies the drug's sustained benefits, prove to be an attractive agent when intravenous iron is warranted. [ full review ]
The study by Khorana et al suggest caution in using transfusions as an alternative treatment to ESAs and reports that red cell and platelet transfusions are associated with an increased risk of venous and arterial thrombosis and increased mortality in hospitalized cancer patients. Although this type of study cannot establish causality, it does establish a baseline from which to operate and moreover reminds us that red cell transfusions are not a benign alternative to recombinant erythropoietin. [ full review ]
Jan 2009
Trauma patients represent a complex array of physiologic derangements and multiple confounders making them a difficult population to study. In addition, severe injuries may continue to bleed and result in significant anemia. A recent retrospective study examined the effect of anemia in traumatic brain injury patients, and demonstrated that anemia is detrimental (independent risk factor for negative outcome) and that transfusion therapy for anemia compounds the problem. Therefore, reassessment of any transfusion decision is sorely needed and slowly gaining acceptance. [ full review ]
Anemia is highly prevalent in adult patients with CKD, but the prevalence and consequences are less well documented in pediatric patients. This study by Staples et al assessed the prevalence of anemia in children with predialysis CKD, described the association between anemia and morbidity (hospitalization), and adds significant new, hypothesis-generating information to help us better understand the association of anemia and outcomes in younger patients. [ full review ]
Although anemia is common in PICU patients, little is known about its etiology and the use and efficacy of transfusion therapy. This study by Bateman et al places further scrutiny on the dilemma of how to optimize the use of transfusion therapy to maximize clinical utility and minimize adverse impact. Yet, it is clear, based on the information in this paper, and until further studies are forthcoming, that efforts should be made to reduce blood draws to a minimum and to use blood transfusion therapy judiciously. [ full review ]
Dec 2008
There has been much debate and discussion over the last two years about the quality of life (QOL) impact of ESA use in CKD patients. The results of this study by Finkelstein et al supports prior conclusions and clinical judgment that a hemoglobin level of 11-13 g/dL is associated with better QOL compared to lower Hb levels, and that even higher Hb levels are associated with continued, but perhaps, less improvement in QOL. Yet, readers of this study cannot conclude that raising Hb levels causes an increase in QOL, nor should they draw conclusions about any relationship between ESA use and QOL. [ full review ]
Although anemia is typically diagnosed by measuring hemoglobin levels, anemia can also be diagnosed using red cell deficit or hemodilution with plasma volume expansion. A study by Abramov et al examined whether patients with anemia, heart failure and preserved ejections have a similar prevalence of dilutional anemia as patients with low ejection fractions, and whether a correlation exists between hemoglobin values and red cell volume. Although the results point to some important implications in the treatment of anemic patients with heart failure, the study would be more compelling if the authors had used a direct measurement of red cell volume or if the indirect method had been validated in heart failure patients. [ full review ]
Without question, the greatest advance in the last decade of rheumatology therapeutics has been the introduction of TNFα blockade. The study by Doyle et al evaluated the effects of TNFα inhibition by analyzing three trials – ATTRACT, ASPIRE, and START – of RA patients with anemia who were randomly assigned to receive a combination of methotrexate therapy and infliximab or placebo. The results demonstrated that a therapy targeting a major proinflammatory cytokine produced improvement in anemia, but did so independently of a reduction in joint pain. [ full review ]
Nov 2008
Although the transfusion of allogeneic red blood cells can correct anemia by raising hemoglobin levels, some research points to ineffective and even harmful effects from liberal transfusions. This study of the impact of anemia and transfusion in patients with ischemic brain injury from subarachnoid hemorrhage is an important contribution to our understanding of not only which patients may or may not benefit from blood transfusion, but also of the relationship of anemia and transfusion to adverse outcomes. [ full review ]
Using a multivariate analysis, Jädersten et al sought to confirm recent findings that suggest a positive impact of growth factors on survival in MDS without affecting the rate of progression to AML. Although this report offers some reassurance regarding the use of growth factors and cancer progression, definitive conclusions regarding survival are best drawn from randomized, prospective studies. [ full review ]
Although the recommended initiation dosage of epoetin alfa is within 50-100 IU/kg three-times-weekly, several studies reported that the epoetin alfa is still effective in achieving and maintaining hemoglobin target levels in CKD patients when given subcutaneously up to every four weeks. This prospective, open-label, randomized, multicenter study of 39 adult patients receiving one of four different dosing regimens gives some scientific basis to support the practice of extended dosing schedules. [ full review ]
Oct 2008
A competitive enzyme-linked immunoassay for human hepcidin has been developed, giving clinicians a highly improved means of detecting physiological and pathological changes in both serum and urine hepcidin levels. For now, serum ferritin and iron indices will remain the first-line tests to gauge iron stores, but serum hepcidin may augment these studies by shedding light on iron metabolism. [ full review ]
This Phase III clinical trial by Spinowitz et al described the effects of the intravenous iron product, ferumoxytol, in CKD patients. Intravenous iron is recommended for patients with CKD, but is infrequently used before a patient initiates dialysis. It is very likely that if this agent is approved for use in CKD, ferumoxytol will be eagerly incorporated as part of the armamentarium of CKD anemia management. [ full review ]
In this review by Da Silva et al, relative or absolute iron deficiency may play an important role in heart failure patients as indicated in bone marrow studies by the low levels of iron available for erythropoiesis, despite normal ferritin and iron studies from the peripheral blood. The authors contend that by determining the effectiveness of different combinations of clinical therapies, clinicians will be able to develop specific treatment strategies. [ full review ]
Sep 2008
The authors hypothesize that anemia of chronic disease is a beneficial and adaptive response to an underlying disease state rather than a disorder patients would be better off without. [ full review ]
A study of ferrous sulfate administered mid-pregnancy at various dosages - which tracked hemoglobin level, incidence of anemia, and side effects - provides good information toward identifying an ideal protocol for iron replacement in pregnant women with iron deficiency anemia. [ full review ]
An examination of IV iron administration (as compared to no iron or oral iron) in conjunction with darbepoetin alpha in treating chemotherapy-induced anemia confirms its effectiveness in this population, but is unlikely to change current clinical practice until the safe utilization of ESAs is demonstrated. [ full review ]
Aug 2008
This retrospective study examined the impact of post-transplantation anemia on patient and graft survival, and the rate of acute graft rejection. [ full review ]
The DRIVE studies explored the efficacy of intravenous iron (ferric gluconate) to improve hemoglobin levels of hemodialysis patients receiving epoetin doses. [ full review ]
Jul 2008
Recently, a study hypothesized that the changes in white blood cell (WBC) count and serum albumin levels—along with other experimental biomarkers such as monocyte chemoattractant protein 1 (MCP1) and malondialdehyde (MDA)—could predict EPO sensitivity. [ full review ]
The Study of Anemia in Heart Failure Trial was designed to test the efficacy of using a long-acting ESA, darbepoetin alfa, to treat patients with heart failure in a multicenter (65 centers), double-blind, randomized, placebo-controlled, phase II study. [ full review ]
Jun 2008
In order to provide strong evidence of causality, children with ADHD would need to demonstrate a clear benefit from iron supplementation. Therefore, the following double-blind, placebo-controlled, randomized pilot study tested the effects of iron supplementation on iron deficient, nonanemic children with ADHD. [ full review ]
The study population consisted of 205 consecutive patients with IDA and 40 patients with TM who were admitted to the Internal Medicine Outpatient Clinic located in Edirne, Turkey. Also included were 196 patients with FM diagnosed at the Rheumatology Outpatient Clinic. The control group consisted of 100 hospital employees (89 females and 11 males). All patients and healthy subjects were obtained for the study during the period of 2003 to 2005. [ full review ]
The study described below evaluates VTE and mortality rates of ESA use in phase 3 trials comparing ESAs with placebo or standard of care treatment to treat chemotherapy-associated anemia in cancer patients. Data were extracted from trials reviewed in the Cochrane Collaboration (January 1, 1985 - April 1, 2005) and MEDLINE and EMBASE databases (April 1, 2005 - January 17, 2008). [ full review ]
May 2008
An observational study of elderly patients (65-84 years old) to determine the prevalence of dementia, cognitive impairment, functional disability, and health problems. [ full review ]
The data suggests that obesity-related hypoferremia is not explained by differences in reported intake of iron or dietary factors that can affect iron absorption. [ full review ]
The study suggests that the iron-loss in these patients may be due Celiac disease. [ full review ]
Apr 2008
Role of Erythropoietin Treating Anemia in Chronic Heart Failure [ full review ]
Impact of Delayed Erythropoietin Treatment in Critically Ill Patients [ full review ]
A recent study assessed the success of vitamin supplementation to avoid iron, folate, and vitamin B12 deficiency anemia in bariatric surgery patients. [ full review ]
Mar 2008
Costs and Outcomes of ESA Treatment for Non-dialysis Patients [ full review ]
Anemia Management with Erythropoietin in Diabetic Patients [ full review ]
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Feb 2008
Partial Trial Stabilizing Hemoglobin Levels in Cervical Cancer [ full review ]
Clinical Efficacy and Economic Burden of Iron Chelation Therapy [ full review ]
Symptom Assessment Scale Helps Clinicians Treat Anemia of Cancer [ full review ]
Jan 2008
Iron Deficiency Anemia and Stroke in Young Children [ full review ]
Anemia Management for Patients with Lymphoid Malignancies [ full review ]
Hemoglobin variability and mortality in ESRD [ full review ]
Dec 2007
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Anemia Prevalence and Correlates in HIV Patients in the HAART Era [ full review ]
Nov 2007
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Oct 2007
Hypochromic erythrocytes as marker and predictor in myeloma and lymphoma patients [ full review ]
Clinical Guidelines and Evidence-based Management of Anemia in Cancer Patients [ full review ]
Long-term Outcomes of Kidney Transplant Patients with Anemia [ full review ]
Sep 2007
Patient Handgrip Strength and Vigor After Total Joint Arthroplasty [ full review ]
Improved Patient Outcomes in Appropriate Clinical Settings [ full review ]
Careful Treatment for Acute Coronary Syndrome Patients [ full review ]
Aug 2007
Study Shows For-Profit Facilities Give Higher Doses of Epoetin [ full review ]
Restrictive Hemoglobin Strategy May Safely Reduce Transfusion Requirements [ full review ]
Preoperative Anemia is Associated with Increased Risk of Postoperative Mortality and Cardiac Events [ full review ]
Association Between Post-Transplant Anemia and Mortality is Strengthened [ full review ]
Jun 2007
Epoetin alfa study of quality of life outcomes in lung cancer patients with disease-related anemia halted after unplanned safety analysis: Highlights the need to monitor overall survival [ full review ]
Darbepoetin alfa and epoetin alfa achieved similar rates of transfusion independence in critically ill patients [ full review ]
A ferritin cutoff of 100 ng/mL may help identify at-risk men with unexplained anemia for colonoscopy [ full review ]
Diabetic kidney disease is associated with lower hemoglobin, especially at GFR less than 60 ml/min [ full review ]
Hemoglobin level predicts one-year-survival and hospitalization in hemodialysis patients: The MAR Study [ full review ]
IV Ferric Gluconate Provides Greater Increases In Hemoglobin And Hemoglobin Response [ full review ]
After Kidney Transplantation, Anemia Not Entirely Explained by Kidney Function [ full review ]
EORTC Guideline Update for Erythropoietic Protein Use in Cancer Patients with Anemia [ full review ]
Mar 2007
Epoetin delta effective in anemia of chronic kidney disease [ full review ]
Communication Between Patient and Provider Regarding Anemia and Fatigue Studied [ full review ]
Physiologic Model of Iron Status in Infancy Used to Predict Risk of Iron Deficiency [ full review ]
Iron Deficiency Anemia May Be Presenting Sign of Pouchitis Post-Surgery [ full review ]
Epoetin Beta Prevents Anemia in Platinum-Based Chemotherapy Treated Patients [ full review ]
Darbepoetin Alfa Safe and Effective with Once Monthly Dosing in CKD with Anemia [ full review ]
Jan 2007
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Anemia Risk Tool Developed for Chemotherapy Treated Nonsmall Cell Lung Cancer [ full review ]
Anemia is Risk Factor in Patients with Ileal Pouch-Anal Anastomoses [ full review ]
Intravenous Iron Correction of Anemia in CKD Increases Oxidative Stress Complications [ full review ]
Challenge to RBC Transfusion in Hemodynamically Stable Critically Ill Patients [ full review ]
Anemia Associated with Decline in GFR in Adolescents with Chronic Kidney Disease [ full review ]
Correction of Anemia to Higher Hb Levels Increases Adverse Outcome Risk in CKD [ full review ]
Correction of Anemia Does Not Reduce Risk of Cardiovascular Events in CKD [ full review ]
Darbepoetin pharmacokinetics studied in pediatric chemotherapy-induced anemia [ full review ]
Oct 2006
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Sep 2006
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Mar 2006
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Oct 2005
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Aug 2005
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Jul 2005
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May 2005
Researchers report a low hematocrit predicts contrast-induced nephropathy after percutaneous coronar
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Feb 2005
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Dec 2004
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Sep 2004
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Aug 2004
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Prevalence Of Sickle Cell Anemia And Thalassemia Increase By About 45% In England Over Last 10 Years
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Jul 2004
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Jun 2004
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Last Updated: November 19, 2009
