Poor efficacy of oral iron replacement therapy in pediatric patients with heart failure

2021 ◽  
pp. 1-8
Author(s):  
Kriti Puri ◽  
Joseph A. Spinner ◽  
Jacquelyn M. Powers ◽  
Susan W. Denfield ◽  
Hari P. Tunuguntla ◽  
...  
Keyword(s):  
Heart Failure ◽  
Iron Deficiency ◽  
Transferrin Saturation ◽  
Systolic Heart Failure ◽  
Oral Iron ◽  
Wilcoxon Test ◽  
Iron Therapy ◽  
Oral Iron Therapy ◽  
Iron Deficient ◽  
Iron Replacement

Abstract Introduction: Iron deficiency is associated with worse outcomes in children and adults with systolic heart failure. While oral iron replacement has been shown to be ineffective in adults with heart failure, its efficacy in children with heart failure is unknown. We hypothesised that oral iron would be ineffective in replenishing iron stores in ≥50% of children with heart failure. Methods: We performed a single-centre retrospective cohort study of patients aged ≤21 years with systolic heart failure and iron deficiency who received oral iron between 01/2013 and 04/2019. Iron deficiency was defined as ≥2 of the following: serum iron <50 mcg/dL, serum ferritin <20 ng/mL, transferrin >300 ng/mL, transferrin saturation <15%. Iron studies and haematologic indices pre- and post-iron therapy were compared using paired-samples Wilcoxon test. Results: Fifty-one children with systolic heart failure and iron deficiency (median age 11 years, 49% female) met inclusion criteria. Heart failure aetiologies included cardiomyopathy (51%), congenital heart disease (37%), and history of heart transplantation with graft dysfunction (12%). Median dose of oral iron therapy was 2.9 mg/kg/day of elemental iron, prescribed for a median duration of 96 days. Follow-up iron testing was available for 20 patients, of whom 55% (11/20) remained iron deficient despite oral iron therapy. Conclusions: This is the first report on the efficacy of oral iron therapy in children with heart failure. Over half of the children with heart failure did not respond to oral iron and remained iron deficient.

A Head-to-Head Comparison of the Safety and Efficacy of Ferumoxytol to Iron Sucrose for the Treatment of Iron Deficiency Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5157-5157
Author(s):  
Allen Poma ◽  
Karen Diana ◽  
Justin McLaughlin ◽  
Annamaria Kausz
Keyword(s):  
Iron Deficiency ◽  
Oral Iron ◽  
Iron Sucrose ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Safety And Efficacy ◽  
Oral Iron Therapy ◽  
The Us ◽  
Iv Iron ◽  
Iron Replacement

Abstract Abstract 5157 BACKGROUND: Iron replacement therapy is essential for increasing iron stores and raising hemoglobin levels in patients with iron deficiency anemia (IDA). Oral iron supplements have limited absorption and are commonly associated with gastrointestinal (GI) side effects that reduce compliance, resulting in limited increases in hemoglobin. In patients without chronic kidney disease (CKD), oral iron therapy is frequently used to treat IDA. However, when oral iron therapy is unsatisfactory or cannot be tolerated, intravenous (IV) iron therapy may be appropriate. In the US, iron dextrans are the only approved IV iron products indicated for the treatment of IDA in non-CKD patients, and have limitations around convenience because they require a test dose and as many as 10 administrations via a slow infusion; iron dextrans have also been associated with a relatively high rate of serious adverse reactions compared to other IV iron products. Other IV irons, such as iron sucrose and sodium ferric gluconate, are only approved in the US for the treatment of IDA in patients with CKD. Like the iron dextrans, both of these products are limited by administration, requiring 5 to 10 clinic visits for the administration of a full therapeutic dose (1 gram of iron). Feraheme® (ferumoxytol) Injection is an IV iron product approved in the US for the treatment of IDA in adult subjects with CKD. Its carbohydrate coating is designed to minimize immunological sensitivity, and it has less free iron than other IV iron preparations. Ferumoxytol is administered as two IV injections of 510 mg (17 mL) 3 to 8 days apart for a total cumulative dose of 1.02 g. METHODS: To date, there have been a limited number of studies that have examined the safety and efficacy of IV irons in a head-to-head manner for the treatment of IDA, and no study has done so in a large number of subjects or in a broad patient population. AMAG, therefore, has initiated a randomized, controlled trial (ClinicalTrials.gov NCT01114204) to compare ferumoxytol with iron sucrose. Iron sucrose is approved in many countries outside the US for the treatment of IDA in patients intolerant to oral iron therapy, and is considered a safer alternative to IV iron dextran. This open-label trial (n=600) will evaluate the efficacy and safety of a 1.02 g of IV ferumoxytol, administered as 2 doses of 510 mg each, compared with 1.0 g of IV iron sucrose, administered as 5 doses of 200 mg each. Enrolled subjects will have IDA associated with a variety of underlying conditions including abnormal uterine bleeding, GI disorders, cancer, postpartum anemia, and others (eg, nutritional deficiency). Endpoints include changes in hemoglobin and transferrin saturation at Week 5, as well as evaluation of the requirement for erythropoiesis stimulating agent therapy and blood transfusion. Patient reported outcomes instruments will be employed to assess the impact of IV iron therapy on anemia symptoms and health-related quality of life (fatigue, energy, etc). Additionally, detailed information on healthcare utilization will be collected. CONCLUSION In the US, non-CKD patients with IDA who have a history of unsatisfactory oral iron therapy have limited options for iron replacement therapy. Study NCT01114204 will provide novel information comparing the safety and efficacy of two IV iron therapies for the treatment of IDA in a broad patient population. Disclosures: Poma: AMAG Pharmaceuticals, Inc.: Employment. Diana:AMAG Pharmaceuticals, Inc.: Employment. McLaughlin:AMAG Pharmaceuticals, Inc.: Employment. Kausz:AMAG Pharmaceuticals, Inc.: Employment.

Ascertainment of Iron Depletion and Deficiency in Blood Donors Through Screening Questions for Pica and Restless Legs Syndrome.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2283-2283
Author(s):  
Barbara J. Bryant ◽  
Yu Ying Yau ◽  
Sarah M. Arceo ◽  
Julie A. Hopkins ◽  
Susan F. Leitman
Keyword(s):  
Iron Deficiency ◽  
Restless Legs Syndrome ◽  
Blood Donors ◽  
Oral Iron ◽  
Iron Therapy ◽  
Iron Depletion ◽  
Restless Legs ◽  
Iron Deficient ◽  
Screening Questions ◽  
Iron Replacement

Abstract Abstract 2283 Background: Pica and restless legs syndrome (RLS) are associated with iron depletion and deficiency. Pica refers to the compulsive craving for and persistent consumption of non-nutritive substances. Pagophagia, the pathological consumption of ice, is a specific pica strongly associated with iron deficiency. RLS is a neurological movement disorder characterized by uncomfortable sensations in the lower extremities, with a compelling urge to move the extremities to relieve the discomfort. Primary RLS is a central nervous system disorder; however, secondary RLS may be caused or exacerbated by iron deficiency. The purpose of this study was to prospectively assess the prevalence of pica and RLS in blood donors presenting to a hospital-based donor center, to correlate the findings with donor hemoglobin and iron levels, and to study the effects of oral iron replacement on the resolution of symptoms. Methods: During a 39-month period, 1236 blood donors deferred for fingerstick hemoglobin <12.5 g/dL and 400 non-deferred “control” donors underwent health screening and laboratory testing (CBC, ferritin, iron, transferrin). Iron deficiency was defined as a ferritin level below the institutional reference range of 9 mcg/L in females and 18 mcg/L in males. Iron depletion was defined as a ferritin of 9 – 19 mcg/L in females and 18 – 29 mcg/L in males. Pica and RLS were assessed by direct questioning. Deferred donors and iron-deficient control donors were given ferrous sulfate 325 mg daily for 60 days. Reassessments were performed and additional iron tablets dispensed at subsequent visits. Results: Pica was reported in 11% of donors with iron depletion/deficiency, compared with 4% of iron-replete donors (p<0.0001). The prevalence of pica rose to 21% in females with ferritin <9 mcg/L. Pagophagia (ice pica) was most common and was often of extraordinary intensity, with characteristics of an addiction. Donors with pagophagia given iron reported a marked reduction in the desire to eat ice by day 5–8 of therapy, with disappearance of symptoms by day 10–14. RLS was reported in 16% of subjects with iron depletion/deficiency compared with 11% of iron-replete donors (p=0.012). Iron replacement generally resulted in improvement of RLS symptoms, however, at least 4–6 weeks of iron therapy was necessary. The positive predictive values of pica and RLS in iron deficient/depleted blood donors were 73% and 58%, respectively. Conclusion: The presence of pica is highly predictive of iron depletion/deficiency in blood donors; however, RLS lacks a strong correlation in this population. Screening questions for pica, in particular pagophagia, may be useful in the ascertainment of iron depletion and deficiency in blood donors and may identify those who would benefit from oral iron therapy. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efficacy of oral iron therapy in geophagic women with iron deficiency anaemia residing in Botshabelo, South Africa

2020 ◽  
pp. 13-21 ◽  
Author(s):  
LF Mogongoa
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anaemia ◽  
Iron Absorption ◽  
Binding Capacity ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anaemia ◽  
Oral Iron Therapy ◽  
Soil Consumption

Background: Iron deficiency anaemia is the most commonly encountered form of anaemia in females worldwide. This form of anaemia is, amongst others, associated with geophagia that is defined as the consumption of soil. The two main reasons for the association of geophagia with anaemia are that soil is thought to supplement mineral deficiency and geophagia is seen as a symptom of the anaemia. However, it is hypothesised that soil consumption interferes with iron absorption instead of supplementing it. The first line of therapy for iron deficiency anaemia is oral iron. Therefore, if soil consumption interferes with iron absorption it could interfere with oral iron therapy leading to patients being burdened with symptoms of anaemia as treatment is not effective. The aim of the study was to evaluate the efficacy of oral iron therapy in female participants afflicted with iron deficiency anaemia associated with geophagia. Methods: In this prospective randomised intervention study, 84 geophagic women with iron deficiency anaemia were divided into two groups. One group continued with soil consumption while the other stopped consumption. Oral iron therapy was administered for ten weeks at increasing therapy doses for both groups. Red cell and iron study parameters were evaluated at different time intervals to ascertain the efficacy of iron replacement therapy. Results: The group that stopped soil consumption showed a statistically significant change in haemoglobin (9.4 to 10.0 g/dL, p = 0.029), mean corpuscular volume (73.6 to 75.7 fl), mean corpuscular haemoglobin (23.7 to 24.6 pg), serum iron (22.5 to 28 μg/dL, p < 0.001, transferrin saturation (4.8 to 6.9%, p < 0.001) and total iron-binding capacity (467 to 441 μg/L, p = 0.001). These findings were contrary to the group that continued with consumption, where the statistical changes were only observed for the iron study parameters (serum iron: 21 to 28 μg/dL, p = 0.038; transferrin saturation: 4.3 to 6.9%, p = 0.011; total iron-binding capacity: 496 to 421 μg/L, p = 0.002). Nevertheless, the changes for both groups were clinically insignificant. Oral iron therapy did not correct the anaemia in geophagic females of both groups, this could be explained by two hypotheses where soil affected the gastrointestinal lining and soil directly interfered with therapy iron absorption. This is evidenced by the group that continued with consumption showing fewer changes than the group that abstained from soil consumption. These results were consistent with a case study where oral iron therapy was implemented. Conclusion: Oral iron therapy was not effective in geophagia cases of iron deficiency anaemia.

scholarly journals Iron Deficiency: A New Target for Patients With Heart Failure

2021 ◽  
Vol 8 ◽  
Author(s):  
Caterina Rizzo ◽  
Rosa Carbonara ◽  
Roberta Ruggieri ◽  
Andrea Passantino ◽  
Domenico Scrutinio
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Iron Deficiency ◽  
Exercise Capacity ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Peak Oxygen Consumption ◽  
Iron Deficient ◽  
Patients With Heart Failure

Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF). ID is estimated to be present in up to 50% of outpatients and is a strong independent predictor of HF outcomes. ID has been shown to reduce quality of life, exercise capacity and survival, in both the presence and absence of anemia. The most recent 2016 guidelines recommend starting replacement treatment at ferritin cutoff value &lt;100 mcg/l or between 100 and 299 mcg/l when the transferrin saturation is &lt;20%. Beyond its effect on hemoglobin, iron plays an important role in oxygen transport and in the metabolism of cardiac and skeletal muscles. Mitochondria are the most important sites of iron utilization and energy production. These factors clearly have roles in the diminished exercise capacity in HF. Oral iron administration is usually the first route used for iron repletion in patients. However, the data from the IRONOUT HF study do not support the use of oral iron supplementation in patients with HF and a reduced ejection fraction, because this treatment does not affect peak VO2 (the primary endpoint of the study) or increase serum ferritin levels. The FAIR-HF and CONFIRM-HF studies have shown improvements in symptoms, quality of life and functional capacity in patients with stable, symptomatic, iron-deficient HF after the administration of intravenous iron (i.e., FCM). Moreover, they have shown a decreased risk of first hospitalization for worsening of HF, as later confirmed in a subsequent meta-analysis. In addition, the EFFECT-HF study has shown an improvement in peak oxygen consumption at CPET (a parameter generally considered the gold standard of exercise capacity and a predictor of outcome in HF) in patients randomized to receive ferric carboxymaltose. Finally, the AFFIRM AHF trial evaluating the effects of FCM administration on the outcomes of patients hospitalized for acute HF has found significantly fewer hospital readmissions due to HF among patients treated with FCM rather than placebo.

Hepcidin Levels Predict Non-Responsiveness to Oral Iron Therapy in Patients with Iron Deficiency Anemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 484-484
Author(s):  
Lawrence T. Goodnough ◽  
David Morris ◽  
Todd Koch ◽  
Andy He ◽  
David Bregman
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Ferric Carboxymaltose ◽  
Predictive Values ◽  
Oral Iron Therapy

Abstract Abstract 484 Background Treatment options for individuals diagnosed with iron deficiency anemia (IDA) include oral or intravenous iron. Oral iron may not increase patient hemoglobin levels adequately, due to poor compliance and/or suboptimal gastrointestinal absorption due to inflammation-mediated induction of hepcidin, which regulates iron homeostasis. This study evaluated whether hepcidin levels can be used to identify patients with IDA who are unresponsive to oral iron therapy. Methods Hepcidin levels were assessed in a subset of subjects enrolled in a randomized trial comparing oral iron (ferrous sulfate) to intravenous iron (Injectafer®[ferric carboxymaltose, FCM]) in subjects with IDA (Hemoglobin [Hb] ≤ 11 g/dL; and ferritin ≤ 100 ng/mL, or ≤ 300 ng/mL when transferrin saturation (TSAT) was ≤ 30%) (Szczech et al Amer Soc Nephrol 2011; 22:405A). Subjects who met the inclusion criteria underwent a 14-day (run-in) course of ferrous sulfate 325 mg, three times per day. Subjects with an increase in Hb ≥ 1 g/dL were considered to be “responders” and not randomized. “Non-responders” were randomized to ferric carboxymaltose (2 injections of 750 mg given on Day 0 [day of randomization] and Day 7) or oral iron for 14 more days. Hb levels and markers of iron status were assessed at screening (day-15), day-1 and day 35. Hepcidin levels were analyzed at screening (Day -15) in an initial Cohort (I) of 44 patients, 22 responders and 22 non-responders. A hepcidin value of >20 ng/mL was identified for further analysis for predictive values for non-responsiveness to 14 day oral iron run-in in 240 patients (Cohort II). Hepcidin levels were also analyzed at Day -1 and Day 35 in a Cohort (III) of patients who were then randomized to FCM vs. oral iron therapy. Results Hepcidin screening levels in Cohort I were significantly higher in the non-responders vs. responders (33.2 vs. 8.7 ng/mL, p < 0.004). Twenty one of 22 non-responders had hepcidin values > 20 ng/mL. For Cohort II, mean hepcidin levels were again significantly higher in the non-responders vs. responders (38.4 vs. 11.3 ng/mL, p = 0.0002). Utilizing a hepcidin criterion of > 20 ng/mL, we found a sensitivity of 41.3% (26 of 150), specificity of 84.4% (76 of 90), and a positive predictive value (PPV) of 81.6% (62 of 76) for non-responsiveness to oral iron (Figure: The Receiver Operator Characteristic curves present plots of sensitivity vs. (1-specificity) for hepcidin, ferritin, and TSAT at the various cutoff levels indicated near the respective curves in the same color as the respective curves). While ferritin < 30ng/mL or TSAT <15% had greater sensitivity (77.3% and 64.7%, respectively), their PPVs (59.2% and 55%) were inferior to PPVs for hepcidin. Patients subsequently randomized to FCM vs. oral iron responded with Hgb increases of ≥1 g/dL for 65.3% vs. 20.8% (p <0.0001)and mean Hgb increases of 1.7 ± 1.3 vs. 0.6 ± 0.9 g/dL (p = 0.0025), respectively. Conclusion Our analysis provides evidence that non-responsiveness to oral iron in patients with iron deficiency anemia can be predicted from patients' baseline hepcidin levels, which have superior positive predictive values compared to transferrin saturation or ferritin levels. Furthermore, non-response to oral iron therapy does not rule out iron deficiency, since two thirds of these non-responders to oral iron responded to IV iron. Disclosures: Goodnough: Luitpold: Consultancy. Off Label Use: ferric carboxymaltose for treatment of iron deficiency anemia. Morris:Luitpold: Consultancy. Koch:Luitpold: Employment. He:Luitpold: Employment. Bregman:Luitpold: Employment.

Impact Of Oral Iron Therapy In Iron Deficient Patients With Heart Failure And Coronary Artery Disease

2019 ◽  
Vol 287 ◽  
pp. e159
Author(s):  
O. Sirbu ◽  
V. Sorodoc ◽  
A. Stoica ◽  
A. Ceasovschih ◽  
L. Vata ◽  
...  
Keyword(s):  
Heart Failure ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Oral Iron ◽  
Iron Therapy ◽  
Oral Iron Therapy ◽  
Iron Deficient ◽  
Patients With Heart Failure ◽  
Artery Disease

scholarly journals Oral Iron Therapy-Induced Neutropenia in Patient with Iron Deficiency Anemia

2020 ◽  
Vol 13 (2) ◽  
pp. 721-724 ◽  
Author(s):  
Mohammad N. Kloub ◽  
Mohamed A. Yassin
Keyword(s):  
Iron Deficiency ◽  
Replacement Therapy ◽  
Iron Deficiency Anemia ◽  
Male Patient ◽  
Hematological Parameters ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Oral Iron Therapy ◽  
Iron Replacement

Iron deficiency anemia is common and worldwide distributed, particularly among females; however, it can also occur among males. Iron deficiency anemia is commonly associated with thrombocytosis; little is known about the effect of iron therapy (oral or intravenous) on other hematological parameters. We report a 29-year-old male patient with iron deficiency anemia, who received oral iron replacement therapy and developed neutropenia which recovered spontaneously 1 month later.

scholarly journals IRON ABSORPTION AND RESPONSE TO ORAL IRON THERAPY IN IRON DEFICIENCY ANEMIA ASSOCIATED TO ASYMPTOMATIC GIARDIASIS.

1993 ◽  
Vol 33 (6) ◽  
pp. 661-661
Author(s):  
Helena U Suzuki ◽  
Mauro B Morais ◽  
Jose N Corral ◽  
Ulisses Fagundes-Neto ◽  
Nelson L Machado
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Absorption ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Oral Iron Therapy

scholarly journals Comparative Study of the Effects of Lactoferrin versus Oral Iron Therapy in Obese Children and Adolescents with Iron Deficiency Anemia

2021 ◽  
pp. 104-114
Author(s):  
Manal Mahmoud Atia ◽  
Rasha Mohamed Gama ◽  
Mohamed Attia Saad ◽  
Mohammed Amr Hamam
Keyword(s):  
Iron Deficiency ◽  
Children And Adolescents ◽  
Iron Deficiency Anemia ◽  
Interleukin 6 ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Obese Children ◽  
Oral Iron Therapy ◽  
Serum Hepcidin

Greater prevalence of iron deficiency (ID) has been observed in overweight and obese children and adolescents. Hepcidin acts as a key regulator of iron metabolism. Hepcidin synthesis increases in response inflammatory cytokines especially Interleukin-6 (IL-6). Considering that obesity represents a low grade chronic inflammatory state, a high concentration of hepcidin has been found in obese children. Elevated hepcidin level in obese children is associated with diminished response to oral iron therapy. Lactoferrin is an iron-binding multifunctional glycoprotein and has strong capacity to modulate the inflammatory response by its capacity to reduce pro-inflammatory cytokine expression in vivo, including IL-6 and hepcidin. Aim of the Work: To compare the efficacy of lactoferrin versus oral iron therapy in treatment of obese children and adolescents with iron deficiency anemia and the effect of therapy on serum hepcidin and interleukin 6 levels. Methodology: This prospective randomized clinical trial was conducted on 40 obese children and adolescents aged between 6 –18 years suffering from iron deficiency anemia (IDA). They were equally randomized into one of 2 groups. Group A received regular oral lactoferrin in a dose of 100 mg/day. Group B received regular oral iron supplementation (Ferric hydroxide polymaltose) in a dose of 6 mg elemental iron/kg /day.Baseline investigations included complete blood count (CBC), iron profile (Serum ferritin, serum iron, total iron binding capacity (TIBC), transferrin saturation), serum Interleukin 6, and serum hepcidin. Reevaluation of CBC was done monthly while iron status parameters, serum IL-6 and serum hepcidin were reevaluated after 3 months of receiving regular therapy. Results: Significant elevations in hemoglobin, MCV, MCH, Serum ferritin, serum iron and transferrin saturation with lactoferrin therapy compared to oral iron therapy. Significantly Lower TIBC after 3 months of lactoferrin therapy while the decrease in TIBC was insignificant in the iron therapy group.Lower serum hepcidin and IL6 after 3 months of lactoferrin therapy with no significant change in serum hepcidin and IL6 after iron therapy. Conclusion: This study clearly demonstrated the superiority of lactoferrin over iron use as oral in the treatment of iron deficiency anemia in obese children not only for the better response of hematological and iron status parameters and less gastrointestinal side effects but also for its effect on decreasing inflammatory biomarkers as hepcidin and IL6.

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