Oral Iron Replacement Therapy Research Articles

#406 High ferritin is not needed in hemodialysis patients: a retrospective study of total body iron and oral iron replacement therapy

Abstract Background and Aims In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. Although serum ferritin is useful as an indicator of iron stores, it does not necessarily reflect body iron levels in HD patients with unstable hematopoiesis since iron metabolism is a semi-closed system in vivo. In this study, we investigated total body iron (TBI), new index calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. Method We analyzed data on 105 courses of low-dose iron replacement therapy (50–120 mg of iron daily) administered to 83 patients with serum ferritin <60 ng/mL and Hb <12 g/dL undergoing maintenance hemodialysis at our institution. Low-dose oral iron replacement therapy was initiated between August 2016 and June 2023 and continued for at least seven months. All blood samples were collected at the start of hemodialysis at the beginning of the week. Blood examinations were performed twice a month, and patients were given darbepoetin alfa (DA), long-acting ESAs to maintain Hb at the target level of 10–12 g/dL, in accordance with the guidelines of the Japanese Society for Dialysis Therapy. Iron-related parameters were determined based on blood samples collected once a month, with TSAT calculated from serum iron (Fe) and total iron-binding capacity (TIBC), using the following equation. TSAT=Fe/TIBC × 100. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7, in two groups of patients, namely, iron-therapy responders and non-responders. Furthermore, we investigated factors associated with steady-state TBI. TBI was regarded as achieving a steady state during the course of therapy when the trend shifted from an increase and the difference from the value at one month was less than or equal to zero. TBI was calculated using the formula proposed by Cable et al (Transfusion. 2016, 56, 2005). Results Mean age was 68.1±12.6 years and median time on hemodialysis was 6.6 years. Of the 105 courses of therapy, 75 were delivered to men and 30 to women, and 66.7% of the patients had diabetic nephropathy. The patients had a mean Hb level of 10.4±0.7 g/dL, a mean serum ferritin level of 27.3±12.5 ng/mL, mean transferrin saturation (TSAT) of 18.1%±5.9%, and a median C-reactive protein level of 0.1 mg/dL at the start of each course. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900±447 vs. 1900±408 mg, Fig. 1). As for RBC iron, iron-therapy responders showed significant monthly increases up to month 3, whereas non-responders showed constant values. Regarding iron stores, iron-therapy responders showed significant monthly increases up to month 5, while non-responders showed a significant increase only at month 1. DA per body weight showed a significant decrease at month 3 and 4 in the effective group, but a slight increase in the non-responder group. Steady-state TBI did not correlate with Hb or serum ferritin, but was strongly correlated with body surface area (BSA) using the Du Bois formula [TBI=−791.914 + 1628.606 × BSA (m2); R2=0.88, p<0.001, Fig. 2]. Conclusion This study showed that hemodialysis patients can increase their body iron levels during oral iron replacement therapy and maintain them at the same level after sufficiency has been achieved, suggesting activation of a “mucosal block.” Furthermore, this result also suggests that determining iron sufficiency based on serum ferritin alone is difficult in HD patients with fluctuations in Hb. However, regression equations using steady-state TBI and BSA showed a high degree of fit. Therefore, BSA might potentially be used in estimations of TBI sufficiency, which may be useful for avoiding excessive iron dosage.

Role of Intravenous Iron in Current Era

Iron is an essential trace mineral necessary for life, and iron deficiency anaemia (IDA) is one of the most common haematological problems worldwide. Oral iron replacement therapy is a simple, inexpensive treatment option for the treatment of iron deficiency in stable patients, but there are many populations for whom IV iron is more effective. Therefore, IV iron should be considered when there are no contraindications, when poor response to oral iron is anticipated, when rapid hematologic responses are desired. Third generation intravenous (IV) iron therapies allow rapid and complete replacement dosing without the toxicity issues inherent with older iron preparations. This review provides an updated overview on diagnosis and management of IDA in patients with chronic conditions, preoperative and considers the properties of the different IV irons, and how differences might impact current and future clinical practice. We will discuss the benefits and limitations of oral versus intravenous iron replacement. Keywords: Anaemia; Intravenous Iron; Iron Deficiency; Oral Iron

High Ferritin Is Not Needed in Hemodialysis Patients: A Retrospective Study of Total Body Iron and Oral Iron Replacement Therapy.

In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. In this study, we investigated total body iron (TBI), calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. We analyzed data on 105 courses of low-dose iron replacement therapy administered to 83 patients on maintenance HD over 7 months. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7 in two groups of patients, namely, iron-therapy responders and non-responders. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900 ± 447 vs. 1900 ± 408 mg). Steady-state TBI was strongly correlated with body surface area (y = 1628.6x - 791.91, R2 = 0.88, p < 0.001). We observed constant TBI during oral iron replacement therapy suggesting the activation of a "mucosal block". The results suggest that body surface area has utility for estimating the required TBI with regression equations.

Association of oral iron replacement therapy with kidney failure and mortality in CKD patients.

Oral iron is the predominant route of iron replacement (IRT) but its benefits and safety are unclear in patients with chronic kidney disease (CKD). We examined the association of oral IRT vs no IRT with end-stage kidney disease (ESKD) and mortality in a national cohort of US Veterans. We identified 17413 incident new users of oral IRT with estimated glomerular filtration rates <60mL/min/1.73 m2 and 32530 controls who did not receive any IRT during 2004-18. We used propensity score-overlap weighting to account for differences in key baseline characteristics associated with the use of oral IRT. We examined associations using competing risk regression and Cox models. In the cohort of 49943 patients, 1616 (3.2%) patients experienced ESKD and 28711 (57%) patients died during a median follow-up of 1.9 years. Oral IRT was not associated with ESKD [subhazard ratio (HR) (95% confidence interval, CI) 1.00 (0.84-1.19), P=.9] and was associated with higher risk of all-cause mortality [HR (95% CI) 1.06 (1.01-1.11), P=.01]. There was significant heterogeneity of treatment effect for mortality, with oral IRT associated with higher mortality in the subgroups of patients without congestive heart failure (CHF), anemia or iron deficiency. In patient with blood hemoglobin <10g/dL oral IRT was associated with significantly lower mortality. Oral IRT was associated with lower mortality only in patients with anemia. In patients without anemia, iron deficiency or CHF, the risk-benefit ratio of oral IRT should be further examined.

Pica sebagai Manifestasi Anemia Defisiensi Besi: Suatu Laporan Kasus

Prevalence of anemia in Indonesia based on Basic Health Research (2018) was 23.7%. Symptoms of iron deficiency anemia were pallor, malaise, palpitation, shortness of breath, headache, sore tongue. But sometimes can be found abnormal behavior in the form of PICA. This article reports on a-52-year-old man who sought medical treatment and was diagnosed with iron deficiency anemia with pica manifestation. The pica manifestation was characterized by a repeated desire to consume raw rice due to bleeding from hemorrhoids. Patient was given oral iron replacement therapy contain 100 mg of Fe (III) hydroxide polymaltose complex and folic acid 0.35 mg alternating with vitamin C 500 mg daily. Total iron daily dose given were 200 mg, divided in two doses. The patient received dietary education and was advised to consult a Gastroenterohepatology Subspecialist for the management of hemorrhoids, but it has not been done yet. The desire for raw rice consumption disappeared and the hemoglobin level increased to 12.4 g/dL after six weeks of therapy. The patient continued to take iron supplements until January 2023 but did not have follow-up visits to the clinic. In January 2023, the patient underwent hemorrhoid surgery due to bleeding accompanied by and a non-reducible lump that had been present for three days. Iron supplements continued for one month post-operation and then discontinued. The latest hemoglobin level was 15.3 g/dL without iron supplements. The symptoms of pica in this patient disappeared along with an increased hemoglobin level, and the management of severe anemia in this patient showed an adequate response. Bleeding has never occurred again after the surgery. Curative measures for hemorrhoidal bleeding are crucial, while iron supplementation is only a supportive therapy.

Ferric Carboxymaltose Versus Ferrous Glycine Sulfate For Treatment of Iron Deficiency Anemia and Their Effect On Vitamin B12 And Folic Acid: A Retrospective Study

Aim Anemia is a major public health problem, affecting about one-third of the world's population, and is most commonly caused by iron deficiency. Iron deficiency anemia requires oral or intravenous iron replacement therapy. The purpose of this study was to assess the change in several hematological parameters, vitamin B12, and folic acid from baseline to the first month of follow-up following therapy with oral ferrous glycine sulfate or intravenous ferric carboxymaltose. Methods: All patients who received oral ferrous glycine sulfate or intravenous ferric carboxymaltose for the treatment of iron deficiency anemia between January 1, 2016, and December 31, 2018, were included in the trial. Along with age and gender information, values of hemoglobin, ferritin, transferrin saturation, mean corpuscular volume, vitamin B12, and folic acid were derived from patients’ records at the beginning of treatment and first month follow-up. Results: Laboratory values obtained after treatment showed statistically significant improvement in both groups (intra group, p&amp;lt;0.001). When the percentage of change between groups was compared: Percentage-based increases in hemoglobin, mean corpuscular volume, transferrin saturation and ferritin values were significantly higher in the ferric carboxymaltose group (p&amp;lt;0.001). The percentage decrease in vitamin B12 and folic acid values was higher in the ferric carboxymaltose group (p=0.005 and p=0.01, respectively) when compared with oral ferrous glycine sulfate group. Conclusions: According to the findings of our study, iron deficiency anemia can be treated very successfully using ferric carboxymaltose; however, it should be remembered that concurrent supplementation of elements such vitamin B12 and folic acid is necessary for the appropriate progression of erythropoiesis.

Red Blood Cell Function and Disorders of Iron Metabolism

The red blood cell, or erythrocyte, is an anucleate biconcave disk, approximately 7 µm in diameter. The principal function of the red blood cell is to exchange carbon dioxide for oxygen while in the pulmonary circulation, exchange that oxygen for carbon dioxide in the peripheral tissue, and carry that carbon dioxide back to the lungs. The physicochemical composition of the red cell is aligned to optimize that function. The state of tissue oxygenation, in turn, regulates the production of red cells. This review covers red blood cell function, iron metabolism, iron deficiency, iron overload, and primary iron overload. Figures show a model of the hemoglobin molecule showing the relative alignment of the α chains and β chains; the normal oxygen-hemoglobin dissociation curve shifted by changes in temperature, pH, and the intracellular concentration of 2,3-diphosphoglycerate; body iron supply and storage; regulation of hepcidin expression and its role in disease; blood smear from a patient with iron deficiency; and mechanisms contributing to iron overload in iron-loading anemias. Tables list laboratory results associated with decreased iron balance, causes of iron deficiency, oral iron replacement therapy, parenteral iron replacement therapy, primary iron overload syndromes, secondary iron overload syndromes, laboratory results associated with increased iron stores, and other rare disorders of iron overload. This review contains 6 figures, 20 tables, and 111 references Keywords: Red blood cell, iron deficiency anemia, iron overload, hemochromatosis, hemoglobin, iron balance

Red Blood Cell Function and Disorders of Iron Metabolism

The red blood cell, or erythrocyte, is an anucleate biconcave disk, approximately 7 µm in diameter. The principal function of the red blood cell is to exchange carbon dioxide for oxygen while in the pulmonary circulation, exchange that oxygen for carbon dioxide in the peripheral tissue, and carry that carbon dioxide back to the lungs. The physicochemical composition of the red cell is aligned to optimize that function. The state of tissue oxygenation, in turn, regulates the production of red cells. This review covers red blood cell function, iron metabolism, iron deficiency, iron overload, and primary iron overload. Figures show a model of the hemoglobin molecule showing the relative alignment of the α chains and β chains; the normal oxygen-hemoglobin dissociation curve shifted by changes in temperature, pH, and the intracellular concentration of 2,3-diphosphoglycerate; body iron supply and storage; regulation of hepcidin expression and its role in disease; blood smear from a patient with iron deficiency; and mechanisms contributing to iron overload in iron-loading anemias. Tables list laboratory results associated with decreased iron balance, causes of iron deficiency, oral iron replacement therapy, parenteral iron replacement therapy, primary iron overload syndromes, secondary iron overload syndromes, laboratory results associated with increased iron stores, and other rare disorders of iron overload. This review contains 6 figures, 20 tables, and 111 references Keywords: Red blood cell, iron deficiency anemia, iron overload, hemochromatosis, hemoglobin, iron balance

Comparison of daily oral iron replacement therapy with every other day treatment in female reproductive age patients with iron-deficiency anemia

Iron-deficiency anemia (IDA) is accepted as the most common cause of anemia in the world. The main goals of iron replacement therapy are to normalize the hemoglobin level and to replace iron stores. Current guidelines for treating iron deficiency recommend daily divided doses of iron to increase absorption. Hepcidin is a key regulator of systemic iron balance and acts in harmony with intracellular iron metabolism. Daily dosing and divided doses may increase serum hepcidin and decrease iron absorption. In this study, it was aimed to compare the effectiveness of daily and every other day oral iron replacement therapy in women of reproductive age with iron-deficiency anemia. We included premenopausal female patients aged between 18 and 50years with iron-deficiency anemia. Forty patients were given oral iron therapy at a daily dose of 2*80mg (iron sulfate). Forty-three patients were given iron treatment at a dose of 2*80mg (iron sulfate) every other day. After 2months of oral iron therapy, there was a significant improvement in hemoglobin, mean corpuscular volume, serum iron, total iron-binding capacity, and transferrin saturation in both groups. The values of hemoglobin, serum iron, transferrin saturation, and ferritin significantly increased at the end of the treatment for both groups. Although the median hepcidin level on the 15th-day measurement in the every other day treatment group was higher than that in the daily treatment group, there was no significant difference. As a result, the patients' compliance with the treatment can be increased by offering treatment every other day instead of daily, since it provides similar treatment effectiveness.

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

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. 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. 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. 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.

Iron Replacement Therapy with Oral Ferric Maltol: Review of the Evidence and Expert Opinion

Iron deficiency is the most common cause of anemia globally and is frequently reported in patients with underlying inflammatory conditions, such as inflammatory bowel disease (IBD) and chronic kidney disease (CKD). Ferric maltol is a new oral iron replacement therapy designed to optimize iron absorption while reducing the gastrointestinal adverse events associated with unabsorbed free iron. Ferric maltol has been studied in clinical trials involving almost 750 adults and adolescents with iron-deficiency anemia associated with IBD, CKD, and other underlying conditions, and it has been widely used in clinical practice. It is approved for the treatment of adults with iron deficiency with or without anemia, independent of the underlying condition, and is commercially available in Europe and the United States. We review the published evidence for ferric maltol, which demonstrates consistent and clinically meaningful improvements in hemoglobin and measures of iron availability (ferritin and transferrin saturation) and shows that it is well-tolerated over long-term treatment for up to 64 weeks—an important consideration in patients with chronic underlying conditions such as IBD and CKD. We believe that ferric maltol is an effective, convenient, and well-tolerated treatment option for iron deficiency and iron-deficiency anemia, especially when long-term management of chronic iron deficiency is required. Writing support was provided by Shield Therapeutics (Gateshead, UK).

Lactoferrin versus iron hydroxide polymaltose complex for the treatment of iron deficiency anemia in children with cerebral palsy: a randomized controlled trial.

Iron deficiency anemia (IDA) is common among children with cerebral palsy (CP), and studies on the efficacy of lactoferrin (Lf) in the treatment of IDA are limited. This study aimed to compare the efficacy of Lf with that of iron hydroxide polymaltose complex (IPC) in the treatment of IDA in children with CP. This randomized controlled study, conducted at Alexandria University Children's Hospital, enrolled 70 children aged 1-10 years with CP and IDA; 35 children randomly received IPC, whereas the other 35 received Lf. Four children withdrew from the study; thus, only 66 children were analyzed (32 in the IPC group and 34 in the Lf group). At baseline, the hemoglobin level and other blood parameters were similar between the two intervention groups. After four weeks of treatment, both the IPC and Lf groups showed significant improvements in hemoglobin (Hb), serum ferritin (SF), serum iron, total iron-binding capacity, mean corpuscular volume, and mean corpuscular hemoglobin from baseline. Upon comparing the two treatment groups, adjusted mean Hb and SF changes in the Lf group were significantly higher than that of the IPC group (p =0.001and p= 0.033, respectively), and constipation was less likely to occur in the Lf group than the IPC group (p = 0.049 ).Conclusion: Lactoferrin is effective and superior to IPC as an oral iron replacement therapy in children with CP and IDA, as it has fewer side effects. What is Known: • Lactoferrin (LF) is a natural glycoprotein capable of treating iron deficiency anemia (IDA). • Studies on the efficacy of Lf in the treatment of IDA in children with cerebral palsy (CP) are limited. What is New? • This trial compared the efficacy of Lf and iron hydroxide polymaltose complex (IPC) as treatments of IDA in children with CP. • Lf is effective and even better than IPC as a treatment of IDA in children with CP, as it has fewer side effects.

Oral Ferric Maltol for the Treatment of Iron-Deficiency Anemia in Patients With CKD: A Randomized Trial and Open-Label Extension

Iron-deficiency anemia is common in patients with chronic kidney disease (CKD) not requiring kidney replacement therapy (KRT). We evaluated effects of oral iron replacement therapy with ferric maltol in these patients. Phase 3, double-blind, randomized, placebo-controlled trial (AEGIS-CKD) and open-label extension. Adults with stage 3 or 4 CKD and iron-deficiency anemia at 30 US centers. Oral ferric maltol at 30mg or placebo twice daily for 16 weeks (2:1 randomization) followed by ferric maltol at 30mg twice daily for up to 36 weeks (all patients). Change from baseline in hemoglobin (primary end point at week 16), ferritin, transferrin saturation, and serum iron; safety. 167 patients were randomized (ferric maltol, n=111; placebo, n=56). At week 16, hemoglobin had increased significantly with ferric maltol versus placebo (least-squares mean difference: 0.5±0.2 [SE] g/dL; 95% CI, 0.1-0.9; P=0.01). Ferritin, transferrin saturation, and serum iron increased with ferric maltol but declined with placebo (all P<0.05). Hemoglobin levels were sustained up to week 52 in patients continuing ferric maltol and increased in patients switching from placebo to ferric maltol. The most frequent adverse events were gastrointestinal (randomized phase: 41% vs 30% [ferric maltol vs placebo]; open-label phase: 56% vs 46%, respectively). Adverse events led to treatment withdrawal in 7 patients (6%) receiving ferric maltol and 5 patients (9%) receiving placebo during double-blind treatment, and 11 patients (9%) during the open-label extension. Heterogeneity in baseline ferritin levels; high proportion of female participants; single-arm open-label extension. Ferric maltol was associated with statistically significant (week 16) and sustained (up to week 52) increases in hemoglobin and iron indices in patients with CKD and iron deficiency, and was well tolerated during treatment for up to 52 weeks. Funded by Shield Therapeutics (UK) Ltd. Registered at ClinicalTrials.gov with study number NCT02968368.

Comparison of Efficacy of Oral and Intravenous Iron Replacement Therapy in Children with Systolic Heart Failure and Iron Deficiency

Purpose Iron deficiency (ID) is associated with increased risk of ventricular assist device implantation, transplant, or death in children with systolic heart failure (HF). Oral iron replacement is standard therapy for ID. However retrospective studies in children with HF estimate its efficacy at ∼50%. There are no data comparing the efficacy of oral and intravenous (IV) iron therapy in children with systolic HF. Methods In July 2019, we instituted a screening and treatment protocol for ID in children with systolic HF. We performed a retrospective analysis of patients who were screened with this protocol between 07/2019 and 10/2020. ID was defined as the presence of ≥2 of the following 4 criteria on serum iron testing: iron 300 ng/mL, transferrin saturation Results Forty patients with systolic HF (21 male, median age 4.5 years, 28 cardiomyopathy and 12 congenital heart disease) met inclusion criteria. Nine received oral iron while 31 received IV iron. Post-therapy iron studies were available for 6/9 of the oral iron cohort and 28/31 of the IV iron cohort. The oral and IV iron cohorts were similar in terms of demographics, etiology or chronicity of HF, renal dysfunction, and mechanical ventilation. Pre-treatment serum BNP was higher in the IV iron cohort (median 1092 vs 55, p = 0.028) compared to the oral iron cohort. At 3 months, iron therapy was effective in 50% (3/6) of the oral iron cohort, compared to 86% (24/28) of those on IV iron (p = 0.086). By 6 months, ID was effectively treated in 50% (3/6) of patients on oral iron, compared to 89% (25/28) of patients on IV iron (p = 0.053). Demographics, etiology or chronicity of HF, BNP, renal dysfunction, and mechanical ventilation were not associated with efficacy of iron therapy at 3 or 6 months. Conclusion IV iron tended to be more effective than oral iron in treating ID in children with systolic HF, despite the IV iron cohort having higher BNP levels and being presumably sicker. This is the first pediatric data on the topic, although statistical significance was limited by small sample size. Larger studies are needed to guide effective therapy for ID in children with systolic HF.

Preoperative intravenous iron therapy and survival after colorectal cancer surgery: long-term results from the IVICA randomised controlled trial.

Preoperative iron is frequently used for the correction of anaemia in colorectal cancer surgery. However, enteral iron intake may promote tumour growth and progression which could influence cancer recurrence and patient survival. We explore the long-term outcomes of patients receiving either oral or intravenous iron replacement therapy as part of a previous randomized controlled trial. The IVICA trial randomized anaemic colorectal cancer patients to receive either oral (OI, control) or intravenous (IVI, treatment) iron prior to their elective operation. Follow-up analysis of all patients recruited to this multicentre trial who underwent surgical resection with curative intent was performed. Kaplan-Meier survival estimates and Cox proportional hazard models were used to compare groups. A pooled group multivariable analysis comparing patients who achieved resolution of anaemia preoperatively to those who did not was also undertaken. In all, 110 of the 116 patients previously enrolled were eligible for analysis (OI n=56, IVI n=54). Median overall follow-up duration was 61months (interquartile range 46-67). No significant difference in 5-year overall survival (hazard ratio (HR) 1.22, 95% CI 0.65-2.28, P=0.522) or disease-free survival (HR 1.08, 95% CI 0.61-1.92, P=0.79) was observed between OI and IVI. A pooled analysis of treatment groups found that preoperative resolution of anaemia led to improved 5-year overall survival on multivariable analysis (HR 3.38, 95% CI 1.07-11.56, P=0.044). We recommend IVI for the preoperative correction of anaemia. Route of iron therapy did not significantly influence survival. Preoperative anaemia correction may lead to an overall survival advantage following elective colorectal cancer surgery.

Efficacy of Oral Iron Replacement Therapy in Pediatric Patients with Heart Failure

Iron deficiency (ID) is associated with worse outcomes in children with systolic heart failure (HF). Oral iron replacement therapy (IRT) is first line therapy for ID in children but the efficacy of oral IRT in children with HF is unknown. We hypothesized that less than half of children with HF and ID would have replenishment of their iron stores with oral IRT. We performed a single center retrospective cohort study of patients aged ≤ 21 years with systolic HF and ID who received oral IRT (2-5mg/kg/day) between 01/2017 and 12/2018. ID 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 hematologic indices pre and post IRT were compared in patients who received ≥6 weeks of therapy (to allow adequate duration of IRT to assess response) using paired-samples Wilcoxon test. Forty-two independent courses of oral IRT (in 40 patients) met inclusion criteria. The cohort was 52% male with median age 13 yrs (IQR 5 - 16 yrs). HF etiologies included cardiomyopathy (57%), congenital heart disease (31%), and history of heart transplantation with graft dysfunction (12%). Patients received ferrous sulfate (40/42) or ferrous gluconate (2/42). Median duration of IRT was 68d (IQR 32 - 145d). Twenty-nine patients received ≥6 weeks of IRT and were included for the analysis for response to oral IRT. Post IRT iron testing was available in 18 patients and post IRT hemogram was available in 26 patients. Serum iron and hematologic indices of the overall cohort as well as comparison of indices pre and post oral IRT are shown (Table). While there was an improvement in serum iron studies, 50% (9/18) of the patients remained iron deficient. This is the first report about oral IRT in children with HF. Though median values of some iron parameters increased after 6weeks of oral IRT, half of the children with HF remained iron deficient and hence non-responsive to oral IRT. Further studies are needed to find the most suitable IRT for children with HF.

Iron deficiency anemia induced by magnesium overuse: a case report

BackgroundAlthough in vitro studies show that iron absorption can be inhibited by magnesium laxatives such as magnesium oxide, taking oral iron supplements with magnesium laxatives is not considered a clinical problem.Case presentationA 28-year-old woman diagnosed with anorexia nervosa who overused magnesium laxatives was admitted to our hospital to evaluate her refractory iron deficiency anemia (IDA), despite having taken oral iron replacement therapy for nine months. She had had amenorrhea for years and her fecal occult blood tests were negative. Furthermore, upper gastrointestinal endoscopy showed no suspected gastroduodenal bleeding or gastroenteritis. We considered her IDA to be induced by malabsorption of iron due to magnesium laxative overuse. Psychoeducational intervention stopped the overuse and oral iron replacement therapy was switched to the intravenous route. During outpatient follow-up, her anemia gradually improved; however, when her magnesium laxative overuse began again, her hemoglobin levels suddenly decreased.ConclusionsClinicians should be attentive to the interactions between iron and magnesium laxatives.

PB2045 EFFICACY &amp; SAFETY OF INTRAVENOUS FERRIC CARBOXYMALTOSE IN IRON DEFICIENCY ANEMIA: A PROSPECTIVE STUDY

Background:Iron deficiency anemia (IDA) is the most common nutritional anemia globally. Goal of iron replacement therapy are correction of anemia and repletion of body iron stores. Oral iron replacement is the preferred route in general. However, response to oral iron replacement therapy is often suboptimal due to poor compliance to treatment resulting from gastrointestinal intolerance and prolonged duration of oral iron therapy. Ferric carboxymaltose is a relatively recently approved parenteral iron formulation which can be administered in large doses of upto 1000 mg in a single infusion.Aims:The present study describes the efficacy &amp; safety of intravenous ferric carboxymaltose for treatment of iron deficiency anemia in a tertiary institution in India.Methods:This non‐randomised prospective study included 77 patients of age ≥ 12 years with confirmed diagnosis of iron deficiency anemia between January 2018 &amp; January 2019. Detailed history was taken &amp; examination performed for signs &amp; etiology of IDA. The cut‐off serum ferritin level for IDA diagnosis was &lt; 15 ng/ml. Pregnant females and patients with concurrent vitamin B12 deficiency were excluded. All patients were treated with Injection Ferric Carboxymaltose (FCM) by I.V. infusion over 30 minutes in day care. Total dose of parenteral iron was calculated according to Ganzoni Formula: Total iron deficit (mg) = 2.4 x body weight (kg) x [target haemoglobin – actual haemoglobin (g/dl)] + 500 mg (depot iron). The maximum dose of FCM administered in a single infusion was 1000 mg. Patients with total iron dose &gt; 1000 mg received two divided doses one week apart. Patients also received oral folic acid at 5 mg/day dose for at least 3 weeks. Appropriate workup for etiology of IDA was performed in all patients. Therapeutic response was assessed after 3 weeks of first FCM dose &amp; was defined as hemoglobin increase of ≥ 2 g/dl from baseline.Results:The median age of patients was 33 years (range 16 ‐ 75 years) and majority (78%) were females. The median baseline hemoglobin was 5 g/dl (range 2.0 ‐ 8.6 g/dl). Therapeutic response was achieved in 100% patients. Mean increase in haemoglobin at 3 weeks was 4.2 g/dl (range 2.8 ‐ 5.5 g/dl). One patient had mild headache during FCM infusion. There was no infusion‐related toxicity or any other adverse event.Summary/Conclusion:In our study, intravenous ferric carboxymaltose was found to be highly effective &amp; safe alternative to oral iron for treatment of iron deficiency anemia, with excellent patient compliance. It is ideally suited for patients who require rapid replenishment of iron stores.

Intravenous Irons: From Basic Science to Clinical Practice.

Iron is an essential trace mineral necessary for life, and iron deficiency anaemia (IDA) is one of the most common haematological problems worldwide, affecting a sixth of the global population. Principally linked to poverty, malnutrition and infection in developing countries, in Western countries the pathophysiology of IDA is primarily linked to blood loss, malabsorption and chronic disease. Oral iron replacement therapy is a simple, inexpensive treatment, but is limited by gastrointestinal side effects that are not inconsequential to some patients and are of minimal efficacy in others. Third generation intravenous (IV) iron therapies allow rapid and complete replacement dosing without the toxicity issues inherent with older iron preparations. Their characteristic, strongly-bound iron-carbohydrate complexes exist as colloidal suspensions of iron oxide nanoparticles with a polynuclear Fe(III)-oxyhydroxide/oxide core surrounded by a carbohydrate ligand. The physicochemical differences between the IV irons include mineral composition, crystalline structure, conformation, size and molecular weight, but the most important difference is the carbohydrate ligand, which influences complex stability, iron release and immunogenicity, and which is a unique feature of each drug. Recent studies have highlighted different adverse event profiles associated with third-generation IV irons that reflect their different structures. The increasing clinical evidence base has allayed safety concerns linked to older IV irons and widened their clinical use. This review considers the properties of the different IV irons, and how differences might impact current and future clinical practice.

Analiza bolnikov z anemijo zaradi pomanjkanja železa v hematološki ambulanti

Background: Iron deficiency anaemia (IDA) is the most prevalent type of anaemia and a common cause for patient referrals to the haematology outpatient clinic. The aim of this study was to determine the number of patients with IDA treated at the Haematology Outpatient Clinic of the UMC Ljubljana in the period of two years, as well as to inquire into the causes for their referrals to the clinic, patient characteristics, their complete blood count results at initial examination, the prescribed therapy, the number and the causes of their follow-up visits. We draw special attention to the IDA onset mechanism, the microcytic anaemia therapy principles and the indications prompting a referral of an IDA patient to the haematology specialist.Methods: We undertook a retrospective analysis of the medical records of patients who were referred to the Haematology outpatient clinic of the UMC Ljubljana for examination in the two-year period between 1 January 2014 and 31 December 2015 and had been diagnosed with IDA on the basis of their clinical picture and their CBC values. Data were collected with the Hipokrat IT system and statistically evaluated with Microsoft Excel.Results: In the period relevant for our research, 277 patients of those who were referred to the Haematology outpatient clinic for medical examination were diagnosed with IDA. 11.6 % of these patients were male and 88.4 % female; 62.1 % of the female patients were of childbearing age. IDA was specified as the referral diagnosis in the cases of no more than 39 % of the patients referred to the specialist outpatient clinic, whilst the medical condition of the remaining percentage of patients was not identified by the referring doctor. Comorbidities were observed in 50.2 % of the patients, and for 62.5 % of the patients a follow-up appointment was scheduled by the treating haematologist. Of all patients, 63.5 % were treated with an intravenous iron preparation during their first examination at the outpatient clinic and a transfusion of erythrocytes was administered during such an examination to 4.3 % of the patients.Conclusion: Patients with IDA were often treated at our Haematology Outpatient Clinic in the relevant two-year period. The data indicates a poor recognition rate of this prevalent type of anaemia. IDA is not a blood disorder and the referral of IDA patients to the Haematology Outpatient Clinic is justified in the case of severe microcytic anaemia, when the patient does not respond to the oral or intravenous iron replacement therapy or if a concomitant change in the CBC persists despite the effective treatment with iron preparations.