Iron deficiency and heart failure

Heart failure (HF) is a common and with poor prognosis disease that impairs quality of life. There are many causes of symptomatic worsening, but lately particular attention has been paid to iron deficiency and anemia as a cause. The reduced iron content in the body has turned to be a new important target for treatment in patients with HF. The aim of this study is to search for the prevalence of iron deficit in patients with HF hospitalized for exacerbation of existing or newly developed symptoms, and to establish its relationship with important prognostic parameters of patients. Patients and Methods: 209 consecutive patients with different etiology of HF were examined and hospitalized at the Cardiology Clinic of the University Hospital "St. Marina", Varna, at an average age of 68,89±12,06 (30-94 years), 58% of them male. Basic demographic variables, creatinine and eGFR were investigated, as well as an echocardiographic study, and a 6-minute walking test was performed. Iron deficit (ID) is formulated at ferritin values ​​<100 µg/l, or if values ​​are 100-300µg/l, then transferrin saturation should be <20%. An alternative method for determining ID was also used, correlating the two methods. Statistical methods include descriptive methods and Cohen&#39;s method of calculating the coefficient κ (Kappa) for determining agreement between two diagnostic methods. Results: There were 146 (70%) patients presenting with ID, with isolated deficiency without anemia occurring in 38% of patients. Anaemic syndrome is found in 87 (41.6%) of all patients, with 76% of anemia cases being iron deficient. Isolated ID is more common in women - 42 (48%) than in men - 38 (31%), p=0.014. There is no significant difference in age, EF, physical capacity, and glomerular filtration rate between patients with and without ID. The incidence of ID is similar in patients with different types of HF - with preserved, mid-range, or decreased EF. There is not a very good agreement between the different methods of determining ID, with coefficient κ=0.31. Conclusions: Iron deficit is common in patients with HF of various etiology and different forms, regardless of the presence of anemia. Females are more vulnerable to this disorder. Its significant presence and role in the prognosis and symptomatology of the patients require that patients be screened for ID and corrected consequently after its detection.

Two Clinical Cases: Severe Hypoglycemia and Then Hyperglycemia in Children with Anemia in Iron Therapy

Diabetes type 1 in children could be present in emergency with hypoglycemia acute episode like an absent or similar to an epilepsy seizure. Blood examinations give evidence of microcytosis iron anemia in a little group of these patients. This disease is often diagnosed when diabetic ketoacidosis occurs. Classical symptoms are frequent urination, increase thirst and hunger with weight loss and iron anemia and with a future risk of osteoporosis in adult age. Moreover, an early diagnostic of iron deficit in DMT1 may be a potential preventive therapeutic possibility with specific nutritional indication in case of confirm with a hyperglycemia and insulin deficit.

Hto, Tritiated Amino Acid Exposure and External Exposure Induce Differential Effects on Hematopoiesis and Iron Metabolism

The increased potential for tritium releases from either nuclear reactors or from new facilities raises questions about the appropriateness of the current ICRP and WHO recommendations for tritium exposures to human populations. To study the potential toxicity of tritium as a function of dose, including at a regulatory level, mice were chronically exposed to tritium in drinking water at one of three concentrations, 10 kBq.l−1, 1 MBq.l−1 or 20 MBq.l−1. Tritium was administered as either HTO or as tritiated non-essential amino acids (TAA). After one month’s exposure, a dose-dependent decrease in red blood cells (RBC) and iron deprivation was seen in all TAA exposed groups, but not in the HTO exposed groups. After eight months of exposure this RBC decrease was compensated by an increase in mean globular volume - suggesting the occurrence of an iron deficit-associated anemia. The analysis of hematopoiesis, of red blood cell retention in the spleen and of iron metabolism in the liver, the kidneys and the intestine suggested that the iron deficit was due to a decrease in iron absorption from the intestine. In contrast, mice exposed to external gamma irradiation at equivalent dose rates did not show any change in red blood cell numbers, white blood cell numbers or in the plasma iron concentration. These results showed that health effects only appeared following chronic exposure to concentrations of tritium above regulatory levels and the effects seen were dependent upon the speciation of tritium.

Impact of Parenteral Iron Therapy on Hemoglobin Normalization: A Retrospective Analysis

Introduction Parenteral iron therapy is often necessary for patients with iron deficiency anemia who cannot tolerate or are nonresponsive to oral iron. Parenteral iron therapy is also used in patients with chronic diseases when oral iron is poorly absorbed or when rapid iron repletion is desirable. Several parenteral iron therapies are currently available in the US. They vary in the amount of iron dose per administration and the number of infusions required to achieve complete iron repletion. The objective of this analysis was to evaluate complete repletion of iron deficit and its effect on the likelihood of serum hemogloblin (Hgb) normalization among patients receiving various parenteral iron therapies in real world clinical practice. Methods Data was obtained from the Decision Resources Group (DRG) Real World Evidence US Data Repository. Patients (≥18 years) who were treated with parenteral iron therapy from 3/1/2015-2/28/2017 were included. Patients were required to have their most recent baseline Hgb level recorded &lt;30 days prior to or on the date of their index (first) parenteral iron therapy claim and below the normal Hgb level (&lt;12 g/dL for females and &lt;13.5 g/dL for males). Patients were excluded if they received parenteral iron therapy 6 weeks prior to the date of their index iron injection (index date); received dialysis or had insufficient data to identify comorbidities 1 year prior to index date. Iron deficit was calculated using the modified Ganzoni equation. The proportion of patients receiving parenteral iron dose required for complete repletion during the 3 weeks after index date, and the proportion of patients achieving normalized Hgb levels within 1 year after index date were summarized for patients receiving ferric carboxymaltose (FCM), ferumoxytol (FM) and other parenteral iron products (OTH). Multivariable logistic regression was used to assess the likelihood of complete iron repletion within 3 weeks of index date while controlling for gender, age, comorbidities, prescription oral iron use and iron deficit level. The likelihood of Hgb normalization within 1 year of index date was assessed using multivariable logistic regression while controlling for gender, age, comorbidities, prescription oral iron use, baseline Hgb and if the patient received the complete iron repletion dose within 3 weeks of index date. Results A total of 2,966 patients were included (female [68.2%], ≥65 years [58.4%]; CKD [60.1%], congestive heart failure [50.1%], IBD [64.4%], and cancer [59.5%]). Most (95%) patients did not receive prescription oral iron therapy within 3 months before or after index date. Iron sucrose was the most commonly used parenteral therapy (46.2%), followed by FCM (23.1%), FM (13.7%), iron dextran (13.6%), and sodium ferric gluconate complex in sucrose (3.4%). Mean (SD) iron deficit in mg was 966 (303) for FCM, 1007 (317) for FM and 1011 (313) for OTH patients. FCM had the highest proportion of patients received the full iron repletion dose within the 3 weeks after index date (73.1%), followed by FM (41.4%) and OTH (18.0%). Mean (SD) total iron dose in mg received by FCM, FM and OTH patients within 3 weeks of index date was 1277.1 (446.9), 842.5 (357.6), and 534.2 (584.8), respectively. The proportion of patients who had normalized Hgb within 1 year of index date was 66.6%, 40% and 51.9% for FCM, FM and OTH, respectively. Patients treated with FCM were significantly more likely to have received their full repletion dose within 3 weeks of index date than patients treated with FM [adjusted odds ratio (AOR)] (95% CI) = 5.10 (3.66, 7.11)] or OTH [AOR (95% CI) = 17.46 (13.59, 22.42)] after adjusting for differences in iron deficit level and other covariates. Patients treated with FM also had higher likelihood of receiving full repletion dose within 3 weeks compared to OTH [AOR (95% CI) = 3.71 (2.82, 4.88)]. After adjusting for full repletion dose and other covariates, patients treated with FCM were significantly more likely to have normalized Hgb within 1 year of index date than patients treated with FM [AOR (95% CI) = 1.88 (1.38, 2.56) or OTH [AOR (95% CI) = 1.40 (1.11, 1.77). However, patients treated with FM had lower likelihood to have normalized Hgb within 1 year of index date than patients treated with OTH [AOR (95% CI) = 0.69 (0.53, 0.89)]. Conclusion The results of this analysis suggest that the choice of iron replacement product may affect the likelihood of Hgb normalization for some patients in real world practice. Disclosures Kwong: Daiichi Sankyo, Inc.: Employment. Boccia:Bristol Myers Squibb: Consultancy, Speakers Bureau; SecuraBio: Consultancy; Rigel: Speakers Bureau; Daiichi Sankyo, Inc.: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; AMAG: Consultancy.

SIDEROPENIC SYNDROME IN STUDENTS

The latent iron deficit is always preceded to iron-deficient anaemia. A research aim was to study occurrence rate of clinical signs of latent iron deficit in adolescents. 280 individuals aged from 17 to 21 were involved into study. A questionnaire method with a series of questions was used to identify signs of sideropenic and anaemic syndromes, as well as questions to identify the causes of iron deficiency. Statistical processing was carried out by applying the Microsoft office Excel 2013. Among the clinical signs of syderopenic syndrome in the students we observed the predominance of olfactory perversion (33,21%), muscular weakness, pain gastrocnemius muscles (29,64%), taste perversion (16,79%), changes in the state of hair and nails (46,79%). This was mainly typical for female individuals. 33,75% of women had polymenorea, and 37,2% out of the were diagnosed to have a syderopenic syndrome. The individuals complaining on gastrointestinal problems (two or more) demonstrated a sharp increase in the frequency syderopenic syndrome occurance (by 26,8%) as compared to the respondents without the complaints.

Importance of Complete Parenteral Iron Replacement on Hemoglobin Normalization: A Retrospective Analysis

Introduction Iron deficiency anemia (IDA) is the most common cause of anemia in the United States (US) and occurs most often in patients with chronic diseases and inflammation. Although oral iron therapy is often prescribed for iron deficiency anemia, parenteral iron therapy is necessary for patients who cannot tolerate or are nonresponsive to oral iron. Parenteral iron therapy is also used in patients with chronic diseases such as inflammatory bowel disease, cancer or chronic kidney disease when rapid iron replacement is desirable. Currently, several parenteral iron therapies are available in the US and they vary in dose strengths and administration schedules. There are limited data on the dosing patterns of parenteral iron therapy and its effectiveness in the real world setting. The objective of this analysis was to assess the importance of parenteral iron dosing on serum hemoglobin (Hgb) level normalization in real world clinical practice. Methods Data was obtained from the Decision Resources Group (DRG) Real World Evidence Data Repository US database, which includes medical and pharmacy claims, and electronic health record data representing more than 300 million patient lives. Adult patients (≥18 years of age) who were treated with parenteral iron between 3/1/2015 and 2/28/2017 were included in the analysis. Eligible patients were required to have their most recent baseline Hgb level below normal (Hgb <12 g/dL for females and <13.5 g/dL for males) and recorded <30 days prior to or on the date of their index (first) parenteral iron therapy claim. Patients were excluded from the study if they received parenteral iron 6 weeks prior to the index date, received dialysis, or had insufficient data to identify comorbidities one year prior to index date. Parenteral iron dose required to correct for iron deficit was calculated using the Ganzoni formula. Patients were categorized based on whether or not they received the full amount of parenteral iron required to correct for iron deficit during the 3 weeks after the index date. Patients were assessed to determine the proportions of patients achieving normalized Hgb levels (≥12 g/dL for females and 13.5 g/dL for males) within 8 weeks after index date and until the end of data availability. Logistic regression was used to estimate the effect of receiving the full amount of required parenteral iron dose within 3 weeks of treatment initiation on the likelihood of Hgb level normalization while controlling for gender, age, comorbid conditions, and use of prescription oral iron therapy. Results A total of 2,966 patients were included in the analysis (68.2% female, 58.4% ≥65 years; 60.1% chronic kidney disease, 50.1% congestive heart failure, 64.4% inflammatory bowel disease, and 59.5% cancer). Most (95%) patients did not receive prescription oral iron therapy within 3 months before or after index date. Mean (SD) number of injections during the 3-week period after index date was 2.5 (1.4). Parenteral iron dose required to correct for iron deficit ranged from 343.7mg to 1915.0mg. Parenteral iron dose received during the first three weeks ranged from 600mg to 2000mg. About a third of patients (33.9%, n=1,006) received the full amount of required parenteral iron dose within the 3-week treatment course. A total of 582 (19.6%) patients had normalized Hgb levels within 8 weeks of treatment initiation and 53.9% (n=1,599) had normalized Hgb levels at any time during the entire study period (median study follow-up=108 weeks). Patients who received the full amount of required dose to correct for iron deficit within 3 weeks of treatment initiation were significantly more likely to have normalized Hgb levels within 8 weeks of treatment initiation than those patients who did not receive the full amount of required dose over the same time period [adjusted odds ratio (95% CI) =2.67 (2.20, 3.24)]. Similarly, when normalized Hgb levels were analyzed using data available for the entire study period, patients who received the full amount of required dose within 3 weeks of treatment initiation were significantly more likely to have normalized Hgb levels than those patients who did not receive the full amount of required dose within 3 weeks of treatment initiation [adjusted odds ratio (95% CI) =2.32 (1.96, 2.75)]. Conclusion The results of this analysis underscore the importance of initial complete iron replacement on rapidly improving clinical outcomes for IDA patients receiving parenteral iron therapy. Disclosures LaVallee: Daiichi Sankyo, Inc.: Research Funding. Cronin:Daiichi Sankyo, Inc.: Research Funding. Bansal:Daiichi Sankyo, Inc.: Research Funding. Kwong:Daiichi Sankyo, Inc.: Employment.

Evaluating and Correcting Iron Deficit in Atypical Hemolytic Uremic Syndrome (HUS)

Introduction: Atypical hemolytic uremic syndrome (HUS), in the absence of Shiga toxin producing E. coli, is most often complement mediated and is associated with microangiopathic hemolytic anemia (MAHA). And while this association is well understood, it is less common to encounter concurrent pre-existing iron deficiency anemia. In such patients, apart from correcting anemia with supportive blood transfusions, the calculation and correction of iron deficit is a valuable but underutilized management strategy, and is highlighted in the presented case. Example case: A 33 year-old Hispanic female with no significant past medical history other than iron deficiency anemia with a baseline hemoglobin of 5.4 g/dL presented to the hospital for abnormal renal function seen on outside laboratory studies. She was found on admission to have a creatinine of 15.47, BUN of 94 (baselines unknown), LDH of 451, haptoglobin of 44, hemoglobin of 6.9 (MCV 87) and platelets of 107 x 10³/µL. Vital signs were stable. Peripheral smear revealed approximately 1 schistocyte/hpf. She complained of a recent but resolving upper respiratory infection and a 10 day history of new-onset blurry vision; she self-identified as a Jehovah's Witness. The patient was tentatively diagnosed with atypical HUS in light of MAHA, Cr >1.5, platelets>30 with only occasional schistocytes and no antecedent diarrheal illness. To definitely rule out pre-existing intrinsic renal disease and/or IgA nephropathy, however, the patient required a kidney biopsy, but was unable to undergo the procedure because of her anemia, thrombocytopenia and refusal to receive whole blood if needed. The patient's desired hemoglobin in order to undergo biopsy was set at 10 g/dL, and iron deficit was calculated as 677 mg. The patient was administered intravenous iron sucrose along accordingly along with epoetin, which resulted in gradual improvement in anemia during hospitalization. Decision to biopsy was deferred to her outpatient care provider. Discussion: Atypical HUS responds best to supportive care with blood transfusions and dialysis, if accompanying symptomatic uremia is present. Definitive therapy is with eculizumab. Patients who will not receive blood for religious purposes, however, present a challenge to providers in the acute setting of HUS, as gradual hemolysis can result in tissue hypoxia, hemodynamic instability and even death. Should patients have concurrent iron deficiency, however, even in the setting of active hemolysis, replacing iron can result in meaningful hemoglobin recovery. Iron deficit is calculated by the following equation: Body weight (in kg) x [target Hb - actual Hb] + depot iron (which is 500 mg if patient >35 kg). Iron deficit as a clinical tool is seldom discussed in the literature, with a particular paucity in studies pertaining to atypical HUS. One potential explanation for this absence is that atypical HUS is an already rare diagnosis, and is a disorder of peripheral red blood cell destruction rather than a disorder of decreased hemoglobin-to-oxygen binding, as is seen in iron deficiency. Regardless, the utility of iron replacement is evident in the presented case of atypical HUS, and should be explored further in larger scale retro- and prospective studies. Conclusions: While disease-directed therapy in atypical HUS (i.e. eculizumab) is required to effectively manage acute, complement-mediated hemolytic anemia and renal failure, correction of the calculated iron deficit in co-existing iron deficiency anemia, if present, can result in gradual but marked improvement in hemoglobin. Conversely, patients with atypical HUS who are actively hemolyzing with a normocytic anemia should still be evaluated for iron deficiency and undergo iron transfusions for any calculated deficit. Disclosures No relevant conflicts of interest to declare.