Severity Of Anemia In Patients Research Articles

Luspatercept: A Gigantic Step in the Treatment of Transfusion-Dependent β-Thalassemia Patients-a Quick Review.

Some studies have indicated that the use of luspatercept may be a novel and efficient treatment for β-thalassemia patients. In this article, we aimed to review the current evidence related to luspatercept prescription and its clinical effectiveness in patients with β-thalassemia. PubMed, Web of Science, Scopus, Trip and CENTRAL were searched up to June 2020. The inclusion criteria were English-language articles that studied the effects of luspatercept on improving anemia severity in patients with β-thalassemia in a clinical setting. The search strategy yielded 273 potentially relevant articles. After searching the databases, scanning of titles, abstracts and full texts for relevancy was performed to identify suitable articles. A total of 77 articles were confirmed for full text analysis. The estimated number of patients needed to treat (NNT) for luspatercept treatment, using data derived from conducted clinical trials, according to a reduction in transfusion need of ≥ 33% or ≥ 50 from baseline, during week 13-24/week 37-48/any 12- and 24-week intervals as outcomes, was 3-5 in patients with β-thalassemia. Based on the conducted studies, the effectiveness of luspatercept on transfusion burden and hemoglobin levels was outstanding in β-thalassemia patients. Further large and well-designed clinical studies are needed to identify any unforeseen complications subsequent to use of luspatercept, particularly when used with other treatments with potentially serious adverse effects such as anti-osteoporotic and iron chelator agents.

Morphological and biochemical profile of anaemia- Does it help a step further in under diagnose cases in a hospital based study

Introduction: Anaemia is one of the preventable disease burden worldwide, especially in developing nations like India. There are varied aetiologies for anaemia; Iron deficiency being the most common cause. Age, sex, geographical and comorbid factors play important role in the morphological patterns of anaemia. Anaemia, if undetected can cause morbidity and mortality which can be prevented. Aims and objectives: To identify morphological patterns and severity of anaemia in patients of all age groups andcorrelate the findings of automatic hemoanalyser, peripheral smear and biochemical parameters like iron studies, vitamin B 12 and folic acid; to correlate these findings with age, sex, morphological type and to find out the commonest pattern. Materials and Methods: This cross sectional study comprised of 300 anaemic patients over a period from December 2015 to July 2017 in Mahatma Gandhi Medical College and Research Institute, Pondicherry. Results: In our study of 300 cases, microcytic hypochromic anaemia was the commonest anaemia in all age groups (66%), followed by dimorphic anaemia (23%). Also, prevalence of microcytic hypochromic anaemia was highest in our study (p value

Drug treatment patterns and work productivity in chronic kidney disease patients with anemia in China: Cross sectional analysis of real-world data.

BackgroundWe explored the association of anemia severity in patients with chronic kidney disease (CKD) and anemia treatment with work productivity in China.MethodsCross-sectional survey data from Chinese physicians and their CKD patients were collected in 2015. Physicians recorded demographics, disease characteristics, and treatment. Patients completed the Work Productivity and Activity Impairment questionnaire. Data were stratified by dialysis-dependence, hemoglobin (Hb) level, and anemia treatment.ResultsBased on data from 1,052 patients (704 non-dialysis-dependent [NDD] and 348 dialysis-dependent [DD] patients), prescribed anemia treatment differed significantly across Hb levels (P < 0.001). In NDD patients, anemia treatment also differed significantly by on-treatment Hb level (P < 0.001). In treated NDD patients with Hb < 10 g/dL, Hb 10 to 12 g/dL, and Hb > 12 g/dL, 31%, 59%, and 38% of patients, respectively, were prescribed oral iron, and 34%, 19%, and 0% of patients, respectively, were prescribed oral iron with erythropoiesis-stimulating agents (ESA). NDD patients were less likely to be prescribed any anemia treatment, and ESA specifically, than DD patients. When treated, 67% and 45% of NDD and DD patients, respectively, had Hb ≥ 10 g/dL (P < 0.001). Overall work and activity impairment differed significantly across Hb levels in NDD and DD patients, with the least impairment observed at the highest Hb level.ConclusionApproximately 40% of NDD patients and 60% of DD patients receiving anemia treatment had Hb < 10 g/dL. Compared with mild anemia patients, severe anemia patients were more likely to be treated for anemia and have impaired work productivity. Chinese CKD patients could benefit from improved anemia treatment.

SARS CoV 2 infection in chronic myelogenous leukemia: Severe hematological presentation

Infection with SARS-CoV-2, the cause of coronavirus infectious disease-19 (COVID-19), has caused a pandemic. Few data are available about the risk of COVID-19 infection in persons with hematological cancer, but controversy whether these persons have the same clinical signs and outcomes. We describe a case of life‐threatening COVID-19 infection complicated by severe anemia in patients affected also by chronic myelogenous leukemia. The screening for RBC antibodies and the direct antiglobulin test (DAT) turned positive. The identification of the antibodies, showed the presence of an alloantibody with anti-Lewis b specificity, which was reactive at room temperature, in the anti-human globulin phase (AGH) and with papain-treated red blood cells. At the same time hemophagocytic lymphohistiocytosis (HLH), on the basis of major laboratory findings including hyperferritnemia, increase of triglicerides levels and according to the HLH score was suspected. Patients received antiviral therapy, steroids and intravenous immunoglobulins. Hemolysis resolved and ferritin dramatically decreased after administration of Ig and a Afull recovery was achieved after viral infection resolution.This case highlights the novel and multifaceted hematological findings during sever COVID 19 infection. COVID 19-related pneumonia is mediated by hyper activation of effector T cells and excessive production of inflammatory cytokines, such as IL-6, IL-1, interferon-gamma, and TNF. This inflammatory process called "cytokine storm" is a life-threatening complication of COVID 19 infection. In this case severe immunohematological consequences are reported for the first time and recognition of this complications are probably underestimated.

Lower hemoglobin concentration decreases time to death in severely anemic patients for whom blood transfusion is not an option.

Anemia in patients who decline transfusion has been associated with increased morbidity and mortality. We hypothesized that the time to death decreases with increasing severity of anemia in patients for whom transfusion is not an option. With institutional review board approval, a retrospective review of registered adult blood refusal patients with at least one hemoglobin (Hb) value of 12.0 g/dL or less during hospital admission at a single institution from January 2004 to September 2015 was performed. The association of nadir Hb category and time to death (all-cause 30-day mortality) was determined using Kaplan-Meier plots, log rank tests, and Cox proportional hazard models. We investigated if there was a nadir Hb level between the values of 5.0 and 6.0 g/dL at which mortality risk significantly increased and then categorized nadir Hb by the traditional cut points and the newly identified "critical" cut point. The study population included 1,011 patients. The Cox proportional hazard models showed a more than 50% increase in hazard of death per 1 g/dL decrease in Hb (adjusted hazard ratio [confidence interval], 1.55 [1.40-1.72]; p < 0.001). A Hb value of 5.0 g/dL was identified as defining "critical anemia." We found a strong association between anemia severity level and mortality (p < 0.001). Time to death was shorter (median, 2 days) in patients with critical anemia than in those having higher Hb (median time to death of 4 or 6 days, in severe or moderate anemia). In anemic patients unable to be transfused, critical anemia was associated with a significantly and clinically important reduced time to death. Prognostic, level III.

Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes

BackgroundPatients with anemia and lower-risk myelodysplastic syndromes in whom erythropoiesis-stimulating agent therapy is not effective generally become dependent on red-cell transfusions. Luspatercept, a recombinant fusion protein that binds transforming growth factor β superfamily ligands to reduce SMAD2 and SMAD3 signaling, showed promising results in a phase 2 study.MethodsIn a double-blind, placebo-controlled, phase 3 trial, we randomly assigned patients with very-low-risk, low-risk, or intermediate-risk myelodysplastic syndromes (defined according to the Revised International Prognostic Scoring System) with ring sideroblasts who had been receiving regular red-cell transfusions to receive either luspatercept (at a dose of 1.0 up to 1.75 mg per kilogram of body weight) or placebo, administered subcutaneously every 3 weeks. The primary end point was transfusion independence for 8 weeks or longer during weeks 1 through 24, and the key secondary end point was transfusion independence for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48.ResultsOf the 229 patients enrolled, 153 were randomly assigned to receive luspatercept and 76 to receive placebo; the baseline characteristics of the patients were balanced. Transfusion independence for 8 weeks or longer was observed in 38% of the patients in the luspatercept group, as compared with 13% of those in the placebo group (P<0.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point (28% vs. 8% for weeks 1 through 24, and 33% vs. 12% for weeks 1 through 48; P<0.001 for both comparisons). The most common luspatercept-associated adverse events (of any grade) included fatigue, diarrhea, asthenia, nausea, and dizziness. The incidence of adverse events decreased over time.ConclusionsLuspatercept reduced the severity of anemia in patients with lower-risk myelodysplastic syndromes with ring sideroblasts who had been receiving regular red-cell transfusions and who had disease that was refractory to or unlikely to respond to erythropoiesis-stimulating agents or who had discontinued such agents owing to an adverse event. (Funded by Celgene and Acceleron Pharma; MEDALIST ClinicalTrials.gov number, NCT02631070; EudraCT number, 2015-003454-41.)

Undiagnosed tuberculosis in patients with HIV infection who present with severe anaemia at a district hospital.

BackgroundTuberculosis (TB) is a major cause of severe anaemia in patients with human immunodeficiency virus (HIV) infection in South Africa. However, TB can be difficult to diagnose as it may be extra pulmonary and paucibacillary.AimThe aim of this study was to investigate undiagnosed TB in patients with HIV infection and severe anaemia and to identify the optimal investigations for diagnosing TB.SettingMthatha General Hospital, a district hospital.MethodsThe study was a case series.ResultsHaemoglobin levels ranged from 3.6 g/dL to 7.9 g/dL, the mean CD4 count was 176 cells/μL and 80% of patients had a positive TB symptom screen. Forty-three (86%) patients had either clinical or bacteriologically proven TB of whom 33 had pulmonary TB, 34 had extra pulmonary TB and 24 had both types. The diagnostic yield for TB was: chest X-ray (CXR) 91%; ultrasound (US) abdomen pericardium and lower chest 62%; sputum Xpert MTB/RIF 35%; TB blood culture 21% and TB urine culture 15%. Blood and urine cultures did not identify any additional cases over those identified by CXR and US. The laboratory turnaround times were as follows: sputum Xpert, 1.6 days; blood culture, 20 days and urine culture, 28 days. CXR and US were done within one day of initial patient assessment.ConclusionsThe majority of HIV patients with severe anaemia had TB disease, and extra pulmonary TB was as prevalent as pulmonary TB. CXR, US and sputum Xpert were the optimum tests for rapid diagnosis of TB. South African national TB/HIV guidelines should incorporate these specific tests to diagnose TB in patients with HIV and severe anaemia.

Clinical outcomes of patients with acute coronary syndrome and moderate or severe chronic anaemia undergoing coronary angiography or intervention.

There are limited data on the impact of chronic moderate or severe anaemia on the clinical outcomes of patients with acute coronary syndrome undergoing coronary angiography or percutaneous coronary intervention. We retrospectively compared two groups of consecutive patients with acute coronary syndrome according to their haemoglobin level on admission. The research group ( n=89) had a haemoglobin level of 10.9 g/dl or less and a control group ( n=79) of age-matched patients had a haemoglobin level greater than 10.9 g/dl. We studied drug therapy before, during and after intervention, and performed 1-year follow-up of bleeding complications according to the Bleeding Academic Research Consortium criteria, all-cause mortality and re-infarction, as well as haemoglobin level on discharge, 6 and 12 months after admission. Compared to controls, a haemoglobin level less than 10.9 g\dl on admission is associated with a higher rate of major bleeding: 26 patients (32%) versus none in the control group ( P<0.001); and the use of packed red blood cell (RBC) transfusion: nine patients (11.7%) versus none in the control group ( P=0.003) within the first 6 months post-catheterisation. However, the re-infarction rate and mortality were similar in the study and control groups: 9.2% versus 9.7% ( P=0.915) and 12.6% versus 8.9% ( P=0.434), accordingly. Chronic moderate or severe anaemia in patients with acute coronary syndrome undergoing coronary angiography or percutaneous coronary intervention is associated with a substantially increased risk of bleeding in the first 6 months. However, rates of mortality and re-infarction were similar.

The Ferumoxytol for Anemia of CKD Trial (FACT)\u2014a randomized controlled trial of repeated doses of ferumoxytol or iron sucrose in patients on hemodialysis: background and rationale

BackgroundIron deficiency anemia (IDA) is a common manifestation of chronic kidney disease (CKD), affecting most patients on hemodialysis and imposing a substantial clinical burden. Treatment with iron supplementation increases hemoglobin levels and can reduce the severity of anemia in patients with CKD. While correcting anemia in these patients is an important therapeutic goal, there is a lack of long-term trials directly comparing intravenous iron therapies in patients with CKD receiving hemodialysis.Methods/DesignThe Ferumoxytol for Anemia of CKD Trial (FACT) is a 13-month, open-label, randomized, multicenter, international, prospective study with 2 substudies. Entry criteria for the main study include adults with IDA (defined as hemoglobin <11.5 g/dL [<115.0 g/L] and a transferrin saturation <30%), serum ferritin <800 ng/mL (<1798 pmol/L), and receiving hemodialysis for ≥3 months. Patients are randomized to receive ferumoxytol (1.02 g over 2 doses) or iron sucrose (1.0 g over 10 doses) during the initial 5-week treatment period. Those with persistent/recurrent IDA over the 11-month observation period will receive additional 5-week treatment periods, as appropriate. The primary efficacy endpoint of the main study is the mean change in hemoglobin from Baseline to Week 5 for each treatment period. The secondary efficacy endpoints include the mean change in transferrin saturation from Baseline to Week 5 and the proportion of patients with a hemoglobin increase of ≥1.0 g/dL at any time from Baseline to Week 5. Safety will be assessed through an examination of the adverse event profile over the course of the study. An “oxidative stress” substudy in approximately 100 patients will assess the effects of treatment on biomarkers of oxidative stress/inflammation during the initial 5-week treatment period, and a magnetic resonance imaging substudy in approximately 70 patients will assess the potential for iron deposition in target tissues over 24 months.DiscussionFACT fulfills the need for a long-term comparative trial in patients with IDA and CKD receiving hemodialysis. The efficacy and safety results will provide useful information for guiding therapy in this population. Two hundred ninety-six patients have been enrolled, and completion of the main study is expected soon.Trial registrationClinicalTrials.gov identifier: NCT01227616 (registered October 22, 2010); EudraCT number: 2010-022133-28

HSP70 Is Increased in Circulating Extracellular Vesicles from Transfusion-Dependent β-Thalassemia Patients: Potential Biomarker for Ineffective Erythropoiesis

Heat-shock protein 70 (HSP70) is a chaperone protein involved in cellular protein homeostasis. It protects proteins from, or targets them for degradation, regulates the cellular response against stress injury, and has a key role in erythropoiesis. In β-thalassemia (β-TM) erythroblasts, HSP70 is retained in the cytoplasm by free α-globin chains; the transcription factor GATA1 is unprotected in the nucleus and therefore degraded, resulting in erythroblast apoptosis, which further aggravates the ineffective erythropoiesis observed in β-TM (Arlet et al, Nature 2014). Extracellular vesicles (EVs) are secreted from cells and are involved in intercellular communication and transport of biologically active molecules. The current study aimed to explore HSP70 in EVs as a potential biomarker in β-TM.EVs of 35 transfusion-dependent β-TM children and adults and matched healthy controls were characterized. Patients were treated under a standard protocol at Emek Medical Center. Clinical and laboratory data were collected from patients' files.EV count, cellular origin and membrane antigens were evaluated in platelet-poor plasma (PPP) by nanoparticle tracking analysis to assess concentration and size distribution of particles in the diameter range of 50-1000 nm, and by FACS to visualize >500 nm particles.Protein content was evaluated in EV pellets (obtained from centrifugation of PPP for 1 h, 18,000g at 4°C, washing in PBS and recentrifugation). Human protein antibody arrays for angiogenesis, inflammation and apoptosis were used to evaluate pooled EV pellets obtained from controls and patient subgroups: hypersplenism (Hy), No-Hy and splenectomized (Sp). The level of HSP70 was evaluated by ELISA.Nanoparticle tracking analysis demonstrated a sharp increase in EV concentration in patients vs. controls (2.15 ± 1.1 vs. 0.66 ± 0.2 E+9 particles/μl; P< 0.001), with mean sizes of 91.9 ± 22 nm and 80.1 ± 6.4 nm, respectively. The concentration of annexin-V-labeled EVs was slightly higher in patients than in controls (7.5 ± 11 vs. 2 ± 0.6 E+5 particles/μl), with mean sizes of 261.6 ± 74 nm and 295.6 ± 140 nm, respectively.FACS analysis showed significantly lower RBC (CD235+) EV and CD14+ EV levels in patients vs. controls. Similar percentages of platelet EVs (CD41+), activated platelet EVs (CD62P+), endothelial cell EVs (CD31+41-) and leukocyte EVs (CD11+) were found in patients and controls.We found significant differences in several angiogenic/inflammatory proteins between the patients and controls. Increased levels (over 200%) of 11 proteins were observed in the Sp group, among them growth-regulated oncogene and platelet-derived growth factor BB, while levels of only 3 proteins were increased in Hy and No-Hy groups. Levels of 14 proteins seemed to decrease (less than 75%) in Hy and No-Hy groups, whereas 5 proteins decreased in the Sp group. Several differences in the apoptotic protein profile were found between patients and controls; however a uniform pattern was observed in the patient subgroups. Increased levels of insulin-like growth factor-binding protein (IGFBP) 2 and caspase 8, decreased levels of IGFBP 3 and 6, and a high increase in HSP70 were found.The increased HSP70 levels were validated in the study cohort: patients (n = 32) 3.46 ± 3 ng/ml vs. healthy controls (n = 11) 1.7 ± 0.2 ng/ml; P< 0.0001. HSP70 showed a moderate positive correlation with patients’ reticulocyte count and lactate dehydrogenase (n = 31, R = 0.47 and n = 32, R = 0.43, respectively) and a moderate negative correlation with hemoglobin (Hb) levels (study Hb n = 32, R = -0.4 and mean 5-yr Hb n = 31, R = -0.51) and annual transfusion requirement (mL /kg weight) (n = 29, R = -0.48). Thus HSP70 reflects the degree of ineffective erythropoiesis, hemolysis and severity of anemia in patients. However, no correlation was found with iron-overload parameters (iron, transferrin saturation and ferritin).Overall, important differences were found between the properties of patient and control EVs, probably reflecting and affecting the pathophysiology of β-TM. We show that circulating EVs in β-TM contain high levels of HSP70 that are correlated with hematological disease severity but not with iron-overload status. These results create a foundation for the potential use of HSP70 in circulating EVs as a novel biomarker for monitoring ineffective erythropoiesis in β-TM. Further studies are required to explore the consequences of high HSP70 in β-TM EVs. DisclosuresNo relevant conflicts of interest to declare.

IL-34 is associated with the presence and severity of renal dysfunction and coronary artery disease in patients with heart failure.

Pro-inflammatory mediators are identified in patients with heart failure (HF), some of which may be used as biomarkers with diagnostic or prognostic value. As an additional ligand of Colony Stimulating Factor-1 Receptor (CSF-1R), interleukin-34 (IL-34) has been identified as a pro-inflammatory cytokine participating in chronic heart failure (CHF). However, the potential impact of IL-34 in CHF complications remains unknown. In order to determine the clinical significance of serum IL-34 in CHF patients, especially those with kidney dysfunction and coronary artery disease (CAD) comorbid conditions, serum IL-34 was measured in 510 consecutive patients with CHF in a cross-sectional study. The present study demonstrated that higher serum IL-34 levels were associated with poorer renal function and more severe anemia in patients with CHF. After adjusting for age, gender, conventional risk factors, and other significant covariates, IL-34 positively correlated with the presence and severity of renal dysfunction (as measured by eGFR and cystatin C) on multivariable linear and logistic regression analysis. IL-34 was also demonstrated to be an independent risk factor for CAD among HF patients. In conclusion, elevated serum IL-34 levels were demonstrated to be independently associated with renal insufficiency and CAD in patients with CHF, regardless of the systolic function.

Iron Therapy Challenges for the Treatment of Nondialysis CKD Patients.

The clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing debate regarding oral versus intravenous administration of iron. Compared with oral iron therapy, which often leads to gastrointestinal adverse events, low patient adherence, and low efficacy, intravenous iron administration has been associated with potential serious adverse events, such as anaphylaxis. New iron-based compounds and drugs currently under development are reviewed to describe their potential benefits in the treatment of anemia in patients with CKD. New oral compounds, including iron-based phosphate binders, heme iron polypeptide, and liposomal iron, show different rates of absorption with possibly different efficacy and improved tolerability. These new potential therapies offer health care providers additional anemia treatment options for their patients with CKD; however, the management of anemia in the CKD population continues to present challenges that require prospective studies to identify the optimal iron therapy for patients.

Association between hypoxemia and anemia following arthroplasty: A pilot clinical study.

Hypoxia and anemia are common complications following joint arthroplasty. Whether hypoxia indicates that a patient is anemic and whether anemia causes a decline in arterial oxygen pressure accompanied by hypoxemia are not completely understood. The aim of the present study was to determine the association between hypoxemia and anemia following arthroplasty. A total of 135 patients who underwent arthroplasty at the China-Japan Friendship Hospital between January and May 2013 were retrospectively analyzed. The patients were divided into five groups depending on the type of arthroplasty they had experienced: Unilateral total knee arthroplasty (TKA), bilateral TKA, unilateral total hip arthroplasty (THA), bilateral THA or unilateral unicompartmental knee arthroplasty. Perioperative peripheral oxygen saturation (SpO2) and hemoglobin (Hb) levels were assessed, and the associations between the changes in SpO2 (ΔSpO2) and hemoglobin (ΔHb) levels on the first and third postoperative days (PODs) were analyzed using Pearson's correlation test for each group. The perioperative SpO2 curves for the various groups were typically at their lowest on the day of surgery. Significant hypoxemia was observed on POD 0-2, although a stable recovery curve was observed on POD 3-5. Trends in ΔHb were observed among the 5 groups, with the lowest Hb value observed predominantly on POD 2 and 3. By POD 4 and 5 Hb levels had recovered, with a steadily and consistently increasing curve. There was no statistically significant correlation between ΔSpO2 and decrease in Hb levels (P>0.05). SpO2 levels should not serve as a clinical indicator of the incidence and severity of anemia in patients who have undergone primary arthroplasty. To a point, the degree of postoperative anemic status does not affect SpO2 levels.

Prevalence of Oxaliplatin-induced Chronic Neuropathy and Influencing Factors in Patients with Colorectal Cancer in Iran.

The chemotherapeutic agent oxaliplatin can cause acute and chronic forms of peripheral neuropathy. The aim of this study was to evaluate the incidence of chronic neuropathy and its risk factors in colorectal cancer (CRC) patients treated with FOLFOX or XELOX regimens in the Oncology Ward of Hazrat-e-Rasoul Hospital in Tehran. A total of 130 patients with CRC were entered into our study, aged over 18 years, without history of receiving other neurotoxic agents or other predisposing factors such as diabetes or neurologic diseases and kidney and liver dysfunction. For the FOLFOX regimen, patients received oxaliplatin, 85 mg/m2, every 2 weeks for 12 courses and with the XELOX regimen, oxaliplatin was 130 mg/m(2), every 3 weeks for 8 courses. Based on Common Toxicity Criteria (CTC or NCI-CTC v.3), the patients were divided into 5 groups (grades) based on the severity of their symptoms. Fifty-seven patients (43.8%) were male and 73(56.2%) female. Some 19 patients (14.7%) had BMI<20, 97(74.6%) were between 20-25 and 14 (10.8%) ≥ 25. In 105 patients (80.7%) neuropathy was found. There was significant correlation between BMI, hypomagnesaemia and especially, severity of anemia in patients with neuropathy compared to those without. Oxaliplatin regimens can induce chronic neuropathy in CRC patients, with anemia, high BMI and hypomagnesaemia as risk factors that can predispose to this kind of neurotoxicity.

Association between HRP-2/pLDH rapid diagnostic test band positivity and malaria-related anemia at a peripheral health facility in Western Uganda.

The detection of severe malaria in resource–constrained settings is often difficult because of requirements for laboratory infrastructure and/or clinical expertise. The aim of this study, therefore, was to explore the utility of a multiple antigen (HRP–2/pLDH) rapid diagnostic test (RDT) as a low–cost, surrogate marker of patients at high risk for complications of severe malaria. We reviewed programmatic data at a peripheral health center in Western Uganda. Available demographic and clinical data on all individuals presenting to the center who underwent an RDT for suspected malaria infection were reviewed. We fit logistic regression models to identify correlates of two outcomes of interest: 1) severe malaria–related anemia, defined here as hemoglobin ≤7g/dL and 2) receipt of parenteral quinine. 1509 patients underwent malaria testing with an SD FK60 RDT during the observation period. A total of 637 (42%) RDTs were positive for at least one species of malaria, of which 326 (51%) exhibited a single HRP–2 band and 307 (48%) exhibited both HRP–2 and pLDH bands, while 4 exhibited only a single pLDH band. There was a trend towards more severe anemia in patients with a HRP–2/pLDH positive RDT compared to a HRP–2 only RDT (β = –0.99 g/dl, 95% CI –1.99 to 0.02, P = 0.055). A HRP–2/pLDH positive RDT was associated with an increased risk of severe malaria–related anemia compared to a negative RDT (adjusted odds ratio (AOR) 18.8, 95% CI 4.32 to 82.0, P < 0.001) and to a HRP–2 only RDT (AOR 2.46, 95% CI 0.75 to 8.04, P = 0.14). There was no significant association between RDT result and the administration of parenteral quinine. These results offer preliminary evidence that specific patterns of antigen positivity on RDTs could be utilized to identify patients at an increased risk for complications of severe malaria.

The test characteristics of physician clinical gestalt for determining the presence and severity of anaemia in patients seen at the emergency department of a tertiary referral hospital in Tanzania

ObjectivesTo evaluate the test characteristics of clinical gestalt for detecting the presence and severity of anaemia in emergency department patients at a tertiary referral hospital in Tanzania.MethodsThis prospective study enrolled...

Update on intravenous iron choices

Iron deficiency is a major factor in the prevalence and severity of anemia in patients with chronic kidney disease (CKD). We review the pathophysiology impairing normal intestinal iron absorption in CKD and compare the characteristics of newer intravenous (i.v.) iron agents to the longstanding i.v. iron products in the market. The newer iron products, ferumoxytol, ferric carboxymaltose, and iron isomaltoside, more avidly bind iron, minimizing the release of labile iron during infusions, thus permitting large dose infusions. These irons also have more complex carbohydrate shells than their predecessors, which may also diminish reactions. Newer agents can be routinely administered at higher single doses, in as little as 15 min, with an acceptable safety profile. Newer i.v. iron products permit the rapid, and sometimes complete, repletion of iron-deficient patients with a single dose. However, further studies examining the long-term risks and benefits of i.v. iron repletion are needed.

The Impact of CDA A79C Gene Polymorphisms on the Response and Hematologic Toxicity in Gemcitabine-Treated Patients: A Meta-Analysis

To investigate the impact of the cytidine deaminase (CDA) A79C polymorphism on both the response to gemcitabine in non-small cell lung cancer (NSCLC) patients and the risk of hematologic toxicities in patients bearing any kind of cancer taking gemcitabine. The PubMed and Embase databases were searched from the first available article to January 2013. Eligible studies included clinical trials that contained the keywords "gemcitabine" or "cytidine deaminase" and information about response rate of NSCLC patients or hematologic toxicities in patients with any kind of cancer. Relative risk (RR) of different genotypes and 95% confidence intervals (CI) were calculated. A total of 7 articles (623 patients from 6 studies) were included. The results showed that patients with wild type CDA (AA and AC) had a significantly lower rate of severe anemia than the homozygote mutant type CC (RR=0.308; 95%CI, 0.113-0.021, p=0.021). However, the rate of severe neutropenia, thrombocytopenia, and the response rate were identical between different CDA genotypes. The A79C CDA polymorphism did not show a significant impact on the response rate to gemcitabine in NSCLC patients, while the wild type CDA genotype was indeed correlated to a lower rate of incidence of severe anemia in patients taking gemcitabine.

Effective Iron Chelation Practice for Patients With β-Thalassemia Major

Chronic blood transfusion is the only treatment for severe anemia in patients with β-thalassemia major. However, red blood cell transfusions lead to iron overload and subsequent organ damage because of the toxic effects of iron. The heart is particularly vulnerable to iron toxicity, and heart failure is the leading cause of death among these patients. Iron chelation therapy prevents or reverses iron loading, thereby reducing the risk of complications from excess iron. Serum ferritin and liver iron concentration often are used to gauge the risk of organ iron overload, but these measurements may not correlate well with cardiac iron load. Magnetic resonance imaging (MRI) is a noninvasive diagnostic tool that can provide a more direct measure of iron concentration in both the heart and liver. Cardiac iron determined by MRI is expressed as a function of T2*, in which higher values represent lower concentrations. Changes in T2* are used to assess the effectiveness of iron chelation and to adjust therapy. Early treatment and compliance are keys to successful therapy. Nursing strategies to optimize chelation therapy include identifying patients who are at risk for developing organ damage, developing chelation plans, promoting compliance, and educating patients. The efficacy and safety of iron chelators, as well as nursing best practices, are reviewed.

Hemoptysis in patients of celiac disease with disproportionately severe anemia: tip of the iceberg?

Idiopathic Pulmonary Hemosiderosis (IPH) is characterized by the triad of iron deficiency anemia, pulmonary infiltrates and haemoptysis with no recognizable cause. Since the first description of its association with Celiac Disease (CD) by Lane and Hamilton in 1971, only a few isolated cases have been reported in literature. Although it has been considered an uncommon association of two disease entities, recent reports indicate that prevalence of celiac disease is as high as one percent. Further, individually both celiac disease and IPH are known to present as refractory anemia only. We are reporting a young adult with Lane Hamilton Syndrome, who realized that he was having significant gastrointestinal complaints only when they disappeared on gluten free diet (GFD). This case report reiterates the fact that celiac disease should be considered in all patients of IPH because of the therapeutic implications. Further on review of literature, we believe that covert hemoptysis may be responsible for disproportionately severe anemia in patients of celiac disease. Thus, prevalence of this association may be more than currently believed. Further research in this regard may improve our understanding of pathogenesis of celiac disease.