Are we giving too much iron? Low-dose iron therapy is effective in octogenarians

PURPOSE: Elderly patients are vulnerable to the dose-dependent adverse effects of iron replacement therapy. Our study examines whether low-dose iron therapy can efficiently resolve iron-deficiency anemia in patients over the age of 80 years and reduce adverse effects. SUBJECTS AND METHODS: Ninety hospitalized patients with iron-deficiency anemia were randomized to receive elemental iron in daily doses of 15 mg or 50 mg as liquid ferrous gluconate or 150 mg of ferrous calcium citrate tablets for 60 days. Thirty control patients without anemia were given 15 mg of iron for 60 days. A 2-hour iron absorption test was performed after the initial dose. Hemoglobin and ferritin levels were measured on day 1, 30, and 60 after initiating therapy. Each patient completed a weekly questionnaire regarding drug-induced adverse effects. RESULTS: Serum iron rose significantly in the anemic patients beginning 15 minutes after the first dose but not in nonanemic patients. Two months of iron treatment significantly increased hemoglobin and ferritin concentrations similarly in all 3 groups of iron-deficiency anemia patients (for example, hemoglobin levels rose from 10.0 g/dL to 11.3 g/dL with 15 mg/d of iron therapy and from 10.2 g/dL to 11.6 g/dL with 150 mg/d). Abdominal discomfort, nausea, vomiting, changes in bowel movements, and black stools were significantly more common at higher iron doses. CONCLUSIONS: Low-dose iron treatment is effective in elderly patients with iron-deficiency anemia. It can replace the commonly used higher doses and can significantly reduce adverse effects.     

Serum Ferritin in Ascorbic Acid Deficiency

S ummary Serum ferritin levels were monitored in guinea-pigs rendered scorbutic by dietary deprivation of ascorbic acid (AA). Hepatic and splenic concentrations of AA fell rapidly during the first 8 d of deprivation, and then declined more slowly to reach approximately 10% of control values after 14 d. Normal levels of serum ferritin (geometric mean, 324 μg/1) were observed for 20 d but a significant fall occurred between days 20 and 23 of deficiency (143 γg/1; P <0·05).
Intramuscular administration of iron dextran to scorbutic animals (75 mg Fe per kg body weight) resulted in a non-significant elevation of serum ferritin levels (geometric mean, 470 μg/1; P >0·1). In control animals, the same dose of iron dextran caused a 10-fold rise in serum ferritin levels (3400 μg/1). A single subcutaneous dose of AA (75 mg/kg weight) given to scorbutic animals caused a significant rise in serum ferritin levels to 599 μg/1 ( P <0·001) but had no effect in control animals. The same dose of AA given to iron loaded, scorbutic animals elevated serum ferritin levels from 554 μg/1 to 1297 μg/1 ( P <0·025).
Thus, AA deficiency in guinea-pigs caused serum ferritin levels to fall and blocked the rise in serum ferritin levels observed in response to acute iron loading in control animals. Adequate tissue concentrations of AA appeared to be necessary for the maintenance of a quantitative correlation between tissue iron stores and serum ferritin levels. The mechanisms by which AA influences serum ferritin levels are at present unknown.     

Single values of serum transferrin receptor and transferrin receptor ferritin index can be used to detect true and functional iron deficiency in rheumatoid arthritis patients with anemia

OBJECTIVE: To elucidate the use of serum transferrin receptor (sTfR) to distinguish between iron-deficiency anemia (IDA) and anemia of chronic disease (ACD), and to establish an improved scheme to identify functional iron deficiency (FID) in rheumatoid arthritis (RA) patients with anemia. METHODS: We studied 30 anemic RA patients whose iron status was confirmed by bone marrow examination and determination of the sTfR level, serum ferritin level, and sTfR-log ferritin index (TfR-F Index). All patients with diminished or exhausted iron stores (n = 18) received oral iron supplementation. RESULTS: Baseline values of sTfR and the TfR-F Index predicted the response correctly in all patients who received supplementation treatment and were normal in 10 of 11 patients with normal initial iron stores (ACD). CONCLUSION: The results of this study elucidate the roles of sTfR and the TfR-F Index in the differential diagnosis between IDA and ACD and provide direct evidence that these parameters are useful in detecting FID, irrespective of the concurrent iron storage status.     

Iron deficiency in inflammatory bowel disease

The prevalence of iron-deficiency anemia was defined in 105 patients with inflammatory bowel disease and an appraisal made of the diagnostic value of serum ferritin for the assessment of iron stores. Iron deficiency, defined by the absence of bone-marrow hemosiderin was found with anemia in 36% of 41 patients with ulcerative colitis (UC) and 22% of 64 patients with Crohn's disease (CD). Iron deficiency without impaired erythropoiesis was detected in an additional 32% of patients with UC and 2% with CD. Anemia with plentiful bone-marrow iron was present in 33 (51%) of patients with CD, only one of whom had vitamin B₁₂ deficiency. Red blood cell morphology, RBC indices, serum iron, and percent transferrin saturation correlated poorly with stainable marrow iron. Serum ferritin, assayed in samples from 45 patients, was <18 ng/ml in 4/12 with iron-deficiency anemia and 0/5 with absent marrow iron and a normal hemoglobin level; values >55 ng/ml were invariably associated with the presence of marrow hemosiderin. Based on a lower normal limit of 18 ng/ml, the serum ferritin had an excellent predictive value (100%) but a high predictive error (32%) in the diagnosis of iron deficiency in inflammatory bowel disease. Serum ferritin >55 ng/ml ruled out iron deficiency as the basis for anemia.     

Influence of food iron absorption on the plasma iron level in idiopathic hemochromatosis.

The relationship between food iron absorption, iron stores, and plasma iron level was studied. On a low iron diet subjects with idiopathic hemochromatosis (IH) during reaccumulation of iron after phlebotomies showed a fall in plasma iron. Fortification of the diet with 22--135 mg of iron/day for 3 days caused little or no change in the plasma iron in subjects with normal iron stores, whereas in subjects with iron deficiency a significant rise in plasma iron occurred with the addition of 45 mg of iron/day. In subjects with IH with normal iron stores, plasma iron increased with the addition of 22.5 mg/day. These studies indicate that iron absorption is an important determinant of the elevated plasma iron in IH and that the plasma iron tolerance test combined with the serum ferritin may be used to detect excessive absorption of iron.     

Role of Intravenous Iron Sucrose in Correction of Anemia in Antenatal Women with Advanced Pregnancy

The aim of this study is to observe rise in haematological parameters after treatment with iron sucrose in antenatal patients with moderate anemia with period of gestation 32 to 35 weeks. The study included 45 antenatal patients with period of gestation from 32 to 35 weeks having iron deficiency anemia with haemoglobin levels 7–9 g% and serum ferritin levels less than 12 ng/mL. Intravenous iron sucrose was given in the dose of 200 mg on alternate days, according to the calculated dose. The mean haemoglobin and red blood cell indices were compared on days 7, 14, 21, 28 and at the time of delivery from the baseline value. There was a statistically significant rise in haemoglobin value from baseline on days 14, 21, 28 as well as at the time of delivery (p value <0.0001). The mean rise in haemoglobin values was 0.56 g% on day 14, 1.44 g% on day 21 and 2.0 g% on day 28. At the time of delivery, mean haemoglobin was 11.24 g%. After 28 days of treatment, there was a statistically significant rise in the levels of serum ferritin from 10.33 ± 3.8 ng/mL to 36.89 ± 5.7 ng/mL. Thus, earlier response achieved by iron sucrose can be utilised in the patients presenting at an advanced period of gestation with iron deficiency anemia.     

Relationship between serum ferritin,anemia, and disease activity in acute and chronic rheumatoid arthritis

Summary The assessment of anemia in patients with rheumatoid arthritis may be difficult, especially when iron deficiency and the anemia of chronic disease coexist. The development of a radioimmunoassay for serum ferritin concentration has aided the detection of reduced body iron stores in uncomplicated iron deficiency, but its use is compromised in clinically active rheumatoid arthritis by the tendency of serum ferritin to behave as an acute phase reactant. In this latter role it correlated well with disease activity in the patients we studied. Followed serially, serum ferritin levels fell in patients whose disease activity improved after institution of appropriate therapy. In anemic patients with clinically inactive disease, supplemental iron was associated with a significant rise in hemoglobin when compared to untreated patients. Serum ferritin levels behaved independently of hemoglobin levels. Therefore even in clinically inactive rheumatoid arthritis, serum ferritin does not accurately reflect an iron deficiency.     

Iron disorders can mimic anything, so always test for them.

Routinely measuring iron status is necessary because not only are about 6% of Americans in significant negative iron balance, but about 1% have iron overload. Serum ferritin is in equilibrium with body iron stores, and is the only blood test that measures them. Barring inflammation, each one ng (0.0179 pmol) ferritin/ml of serum indicates approximately 10 mg (0.179 mmol) of body iron stores. Very early Stage I positive balance is best recognized by measuring saturation of iron binding capacity. Conversely, serum ferritin best recognizes early (Stage I and II) negative balance. Deviations from normal are: 1. Both stages of iron depletion (i.e. low stores, no dysfunction). Negative iron balance Stage I is reduced iron absorption producing moderately depleted iron stores. Stage II is severely depleted stores, without dysfunction. These stages include over half of all cases of negative iron balance. Treated with iron, they never progress to dysfunction, i.e. to disease. 2. Both stages of iron deficiency. Deficiency is inadequate iron for normal function, i.e. dysfunction, disease. Negative balance Stage III is dysfunction without anemia; Stage IV is with anemia. 3. Positive iron balance: Stage I is a multi-year period without dysfunction. Supplements of iron and/or vitamin C promote progression to dysfunction (disease). Iron removal prevents progression. Stage II is iron overload disease, encompassing years of insidiously progressive damage to tissues and organs from iron overload. Iron removal arrests progression.     

Monitoring of intensive phlebotomy therapy in iron overload by serum ferritin assay

Four patients with idiopathic hemochromatosis were treated with intensive phlebotomy therapy. In 1 to 2 years, 8.8-16.7 g iron was removed. In three out of four patients hemoglobin levels fell at the end of therapy. Serum ferritin was continuously measured during therapy. The greatly elevated serum ferritin levels normalized or decreased to subnormal levels in all patients after therapy. Despite some fluctuations in the first phase of therapy, the fall in serum ferritin was regular with halving of the ferritin levels after about 50% of the excess iron was removed. The normalization of serum ferritin occurred in advance of the hemoglobin decrease at the end of therapy, indicating that in the later stages of therapy the normal iron stores are also depleted. It is emphasized that serum ferritin measurements are useful for monitoring of intensive phlebotomy therapy, and in particular to indicate the end of therapy before anemia develops.     

Serum Ferritin and Erythrocyte 2,3-DPG during Quantitated Phlebotomy and Iron Treatment

Serum ferritin and erythrocyte 2,3-DPG levels were followed in 3 healthy males who were phlebotomized to iron depletion and a moderate anaemia. In 2 of the subjects, the expected rise in DPG levels was seen but not in the third, in spite of a Hb concentration of 95 g/1. Serum ferritin levels were found to reflect changes in iron stores, and subnormal serum ferritin indicated depleted iron stores. However, there was no correlation between pre-phlebotomy ferritin levels and calculated iron stores. The conclusion is that no fixed ratio can be established between serum ferritin and iron stores. A single ferritin value within the normal range does not tell how large iron stores a person has. Changes in an individual's iron stores can, however, be detected by repeated ferritin estimations.     

Parenteral iron supplementation for the treatment of iron deficiency anemia in children

Iron-deficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or iron-deficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from iron-deficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of iron-deficiency anemia is a rapid, easy, and definitive solution to a long-troubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe iron-deficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of long-lasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores.     

Utility of serum ferritin as a measure of iron deficiency in normal males undergoing repetitive phlebotomy

Hematologic indices and iron balance data were obtained on 22 normal male volunteers who were subjected to a mean +/- SD phlebotomy of 164 +/- 34 ml whole blood/mo while living in a controlled environment. Over an average stay of 5 mo, volunteers did not develop anemia, but did display a reduction in iron stores that was quantitated by measurement of serum ferritin and iron balance. The percent saturation of transferrin and the usual erythrocyte parameters did not reflect changes in iron status. Loss of iron, which was calculated from quantitative phlebotomy and iron balance data, showed that a decrease of 1 ng of serum ferritin represented a loss of 4.5 +/- 5.3 mg of iron in 10 men whose initial serum ferritins were greater than 25 ng/ml, and 25.3 +/- 58.8 mg of iron in 7 men whose initial serum ferritins were less than 25 ng/ml. The period required for 3 volunteers who consumed a self-selected mixed diet at home to replace their depleted iron stores to prephlebotomy levels was about 4.5 mo. The sensitivity of serum ferritin as an index of iron stores was affirmed. In addition it was found that normal men who were consuming a mixed diet containing about 15 mg of iron daily and losing blood at a rate of 164 +/- 34 ml/mo did not increase their iron absorption sufficiently to compensate for the iron loss.     

Efficacy for Anemia and Changes in Serum Ferritin Levels by Long‐Term Oral Iron Administration in Hemodialysis Patients

Oral iron preparations are useful for the treatment of anemia in hemodialysis patients; however, long‐term changes in the iron dynamics and effects of anemia are unknown. Serum ferritin levels and erythropoietin‐stimulating agent (ESA)/hemoglobin (Hb) ratios were investigated for 750 days in the following four groups: patients treated with sodium ferrous citrate (SF) (de novo 50 mg/day and 150 mg/day switched from 50 mg/day) and patients treated with 1500 mg/day of ferric citrate (FC) (de novo and switched from 50 mg/day of SF). Compared with the other groups, serum ferritin levels increased less apparently with de novo 50 mg/day SF. ESA/Hb ratios did not change in groups switched from 50 mg/day SF. Conversely, in groups with de novo iron, ESA/Hb ratios decreased and ultimately reached the same levels in all groups. Although more iron results in higher serum ferritin levels, 50 mg/day SF has an equivalent effect for anemia treatment.     

Increased plasma transferrin, altered body iron distribution, and microcytic hypochromic anemia in ferrochelatase-deficient mice

Patients with deficiency in ferrochelatase (FECH), the last enzyme of the heme biosynthetic pathway, experience a painful type of skin photosensitivity called erythropoietic protoporphyria (EPP), which is caused by the excessive production of protoporphyrin IX (PPIX) by erythrocytes. Controversial results have been reported regarding hematologic status and iron status of patients with EPP. We thoroughly explored these parameters in Fechm1Pas mutant mice of 3 different genetic backgrounds. FECH deficiency induced microcytic hypochromic anemia without ringed sideroblasts, little or no hemolysis, and no erythroid hyperplasia. Serum iron, ferritin, hepcidin mRNA, and Dcytb levels were normal. The homozygous Fechm1Pas mutant involved no tissue iron deficiency but showed a clear-cut redistribution of iron stores from peripheral tissues to the spleen, with a concomitant 2- to 3-fold increase in transferrin expression at the mRNA and the protein levels. Erythrocyte PPIX levels strongly correlated with serum transferrin levels. At all stages of differentiation in our study, transferrin receptor expression in bone marrow erythroid cells in Fech(m1Pas) was normal in mutant mice but not in patients with iron-deficiency anemia. Based on these observations, we suggest that oral iron therapy is not the therapy of choice for patients with EPP and that the PPIX-liver transferrin pathway plays a role in the orchestration of iron distribution between peripheral iron stores, the spleen, and the bone marrow.     

Response in serum ferritin and haemoglobin to iron therapy in blood donors

Seven hundred seventeen healthy male blood donors regularly donating four or more units a year were surveyed for haemoglobin and serum ferritin levels. One hundred fifty-one (21%) had a haemoglobin less than 13.5 g/dl and were therefore disqualified from further blood donation, having a mean serum ferritin of 28 micrograms/liter. Of the remaining 566 donors with haemoglobin levels equal to or greater than 13.5 g/dl, the mean serum ferritin was 33 micrograms/liter, although in 299 (53%) the value was less than 28 micrograms/liter. To document response to iron therapy 46 donors with haemoglobin levels equal to or greater than 13.5 g/dl were stratified into those with the lowest iron stores (group 1; n = 23), defined as a serum ferritin less than 20 micrograms/liter, and controls (group 2; n = 23), with serum ferritin between 50 and 150 micrograms/liter. Within each stratum donors randomly received ferric polymaltose at a dose of 100 mg elemental iron twice daily for 56 days (groups 1a and 2a) or an identical iron-free placebo tablet administered on the same schedule (groups 1b and 2b). Iron therapy in the iron-deficient group (group 1a:n = 11) resulted in a significant rise in haemoglobin (p = .03) and iron stores reflected in serum ferritin (p = .002) compared to those receiving placebo (group 1b). In the control group iron therapy or placebo was without significant effect. Thus, ferric polymaltose preparation is bioavailable and is notable for the virtual absence of gastrointestinal tract side effects.     

The clinical significance of ferritinuria

Urinary ferritin levels were measured by a "2-site" immunoradiometric assay in normal volunteers and in patients with various hematologic disorders. The mean urinary ferritin concentration in normal subjects averaged 2.2 microgram/liter, only 3% of the serum ferritin level. Elevated urinary ferritin levels averaging 45 microgram/liter were observed in patients with hematologic malignancies, but there was a proportional increase in serum ferritin so that the urinary level still averaged only 7% of the serum value. The highest urinary ferritin values (mean 170 microgram/liter) were associated with chronic hemolytic anemia, and in these patients, urinary ferritin rose disproportionately in relation to the serum, averaging 82% of it. This higher urinary level apparently reflects increased ferritin in renal tubular cells due to glomerular filtration of unbound hemoglobin, a mechanism that is supported by a highly significant correlation between urinary ferritin and serum haptoglobin levels. In normal subjects and in patients with malignancy, the source of urinary ferritin appears different, since a highly significant correlation was observed between urinary ferritin and reticuloendothelial iron stores as measured by serum ferritin or total iron-binding capacity. In this setting, the most likely source of urinary ferritin is the iron contained in renal tubular cells, which is apparently in equilibrium with body iron stores.     

The usefulness of serum transferrin receptor and ferritin for assessing anemia in rheumatoid arthritis: comparison with bone marrow iron study

OBJECTIVES: This study was aimed at investigating the usefulness of serum transferrin receptor (sTfR) and ferritin in anemic patients with rheumatoid arthritis (RA) compared with bone marrow storage iron and other tests for anemia. METHODS: Fifty-five anemic RA patients underwent anemia study. Bone marrow iron stain was performed in 18 patients. sTfR and serum ferritin levels were compared with bone marrow iron stores. RESULTS: (1) Mean sTfR concentration was 2.63+/-1.91 mg/L, (2) sTfR correlated with most indicators of anemia, (3) sTfR showed no correlation with CRP and ESR, whereas ferritin did, and (4) sTfR was higher in the "iron depleted" subgroup than in the "iron nondepleted" subgroup in bone marrow study. CONCLUSION: The measurement of sTfR and ferritin is useful in finding the cause of anemia in RA and is a possible substitute for invasive bone marrow iron study.     

Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease--a randomized, controlled, open-label, multicenter study

OBJECTIVES: Anemia is a frequent complication in patients with inflammatory bowel disease (IBD). The optimal route for iron supplementation to replenish iron stores has not been determined so far. We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia (IDA) in patients with IBD. METHODS: A randomized, prospective, open-label, multicenter study was performed in 46 patients with anemia and transferrin saturation 相似文献   

Serum Ferritin in the Regulation of Iron Therapy in Blood Donors

Abstract. 12 regular blood donors were selected on the basis of subnormal serum ferritin levels as a criterion for iron deficiency. It was found that all had high transferrin levels but only 5 had subnormal serum iron or transferrin saturation. The donors were given oral iron therapy in a dose of 2,800 mg between each phlebotomy, and the donation interval was standardized to 8 weeks. Test samples were collected every 4th week. After an initial rise in ferritin during the first 2 months, 6 of the donors again had subnormal serum ferritin levels, and the iron dose was therefore doubled after 32 weeks. Following this, all subjects taking the higher dose had normal ferritin values and stainable marrow iron was found at the end of the study, after 92 weeks. 3 subjects did not take the higher dose, had no raised serum ferritin level or stainable hemosiderin. It is concluded that serum ferritin estimation can be used to monitor the therapy in blood donors so that a satisfactory amount of iron is stored.     

A Randomised Controlled Trial to Compare Intravenous Iron Sucrose and Oral Iron in Treatment of Iron Deficiency Anemia in Pregnancy

The aim of this study was to compare the efficacy and safety of intravenous iron sucrose with oral iron therapy in pregnant patients with anemia. The primary outcome of the study was increase in haemoglobin on day 7, 14 & 28 and rise of serum ferritin over 28 days. The study population consisted of 100 patients with singleton pregnancy between 24 and 34 weeks, hemoglobin levels between 7.0–9.0 gm/dL and serum ferritin levels less than 15 ng/mL. The participants in the oral group were given daily 180 mg elemental iron in three divided oral doses for 4 weeks. Total calculated dose of iron sucrose with a target hemoglobin of 11 gm %, was given in 200 mg dose on alternate days. Mean haemoglobin rise was 0.58 gm/dL in the IV group as compared to 0.23 gm/dL in the oral group on day 14 and 1.9 gm/dL in the IV group & 1.3 gm/dL in the oral group on day 28, (p <0.05). In the IV group, 76% of the subjects achieved haemoglobin levels of ≥11 gm% at the time of delivery, as compared to only 54% of the subjects in the oral group who achieved these levels. Serum ferritin value was significantly higher in the IV group, 37.45 ± 5.73 ng/mL as compared to 13.96 ± 1.88 ng/mL in the oral group at 4th week (p <0.001). There was no major side effect in the IV group. 36% subjects in the oral group developed gastrointestinal side effects & 10% of the subjects were non compliant. The rate of hemoglobin rise is faster with intravenous iron sucrose therapy as compared to oral iron therapy which can be beneficial in pregnant women presenting with anemia at a later period of gestation. Intravenous iron sucrose is very well tolerated during pregnancy.