Microcytic anemia with iron malabsorption: An inherited disorder of iron metabolism

Two siblings were identified with severe hypoproliferative microcytic anemia and iron malabsorption, in the absence of any gastrointestinal disorder or blood loss. These children had severe microcytosis (MCV 48 fl, hemoglobin 7.5 g/dl) with decreased serum iron, elevated serum TIBC, and decreased serum ferritin, despite prolonged treatment with oral iron. An iron challenge study with an oral dose of 2 mg/kg elemental iron as ferrous sulfate documented iron malabsorption. After treatment with intravenous iron dextran, there was an absence of the expected reticulocytosis and only a partial correction of the hemoglobin, hematocrit, and microcytosis. The bone marrow was hypocellular with abnormal iron incorporation into erythroid precursor cells. This appears to be a rare form of inherited anemia characterized by iron malabsorption and disordered iron metabolism that only partially corrects after the administration of parenteral iron. These features resemble those found in the microcytic mouse (mk/mk), which also has severe microcytic anemia and iron malabsorption that partially responds to parenteral iron. © 1996 Wiley-Liss, Inc.     

Serum ferritin in evaluation of iron status in children

The value of serum ferritin in assessing iron status was studied in 192 preschool age children between the ages of 3 and 60 months. Children were considered to have iron deficiency if the transferrin saturation was less than 16% and the peripheral smear revealed microcytosis and hypochromia. Anemia was present when hemoglobin level was 10.5 g/dl. According to this criteria, 46% of children screened had either iron deficiency (11.5%) or iron deficiency anemia (34.4%). Mean serum ferritin for the iron deficiency anemia group was 39.1 ng/mg as compared to 41.7 ng/ml for the iron deficiency group and 84.7 ng/ml for the normal group. Even though the serum ferritin level was lower in the iron deficiency group, the difference in the means did not reach statistical significance. Furthermore, only 30% of children who had either iron deficiency or iron deficiency anemia had serum ferritin level of less than 12 ng/ml, the level considered diagnostic for iron deficiency. It can be concluded that serum ferritin cannot be used alone for iron status determination. Multiple parameters will make the assessment more reliable.     

Serum Ferritin Levels in Male Blood Donors

Serum ferritin estimation has been shown to be a reliable test to reveal iron deficiency. Such estimations have been made in groups of male blood donors with a varying number of previous phlebotomies and a mean interval between donations of 9.9 +/- 1.7 SD weeks. It was found that the mean ferritin level was significantly (p less than 0.001) lower in the blood donors than in nondonors. After 6-8 phlebotomies it was about 40% lower. Subnormal ferritin values were found in 10% of the donors, almost exclusively among those who had taken less than 1,000 mg of iron supplementation since the last donation. It is concluded that with a donation interval of about 10 weeks, there is a considerable risk for iron deficiency after about 6 donations. This risk is far less if more than 1,000 mg of iron supplementation is taken between phlebotomies. A role for serum ferritin estimation in monitoring donation intervals and/or iron therapy is suggested.     

Patient compliance with phlebotomy therapy for iron overload associated with hemochromatosis

OBJECTIVE: The aim of this study was to evaluate patient compliance with phlebotomy therapy of hemochromatosis-associated iron overload. METHODS: We reviewed medical records of white adults with hemochromatosis and iron overload diagnosed during medical care. We defined three elements of compliance: 1) achieving iron depletion (serum ferritin 相似文献   

Free erythrocyte protoporphyrin assay in the diagnosis of iron deficiency in the anemic aged subject. A prospective study of 103 anemic patients

We determined the relative value of the free erythrocyte protoporphyrin (FEP) assay compared to those of total iron-binding capacity (TIBC) and serum ferritin in the diagnosis of iron deficiency in a population of elderly anemic subjects. One hundred and three patients, 65 to 98 years old (mean +/- SD: 81.5 +/- 8.8), with hemoglobin levels of less than 110 milligrams (mean +/- SD: 97 +/- 12, range 53-109) were included in the study. In the patients with iron-deficiency anemia due solely to chronic bleeding, mean values for the three parameters were highly different from those in patients without chronic bleeding. In the patients with anemia due to an association of chronic bleeding and chronic inflammation, the mean FEP value was very significantly different (p less than 0.001) from that in the patients with chronic inflammation but without bleeding, whereas this was not the case for TIBC or serum ferritin. The sensitivity of FEP in the diagnosis of iron deficiency due to chronic bleeding in this population of anemic subjects was 60% (specificity 90%), compared to 13% (specificity 96%) for TIBC and 20% (specificity 100%) for serum ferritin. The FEP assay thus emerges as being highly suitable for the diagnosis of iron-deficiency anemia in the elderly subject, particularly when bone marrow is not examined.     

Microcytic and hypochromic anemias

In the majority of cases, microcytosis is the result of impaired hemoglobin synthesis. Disorders of iron metabolism and protoporphyrin and heme synthesis, as well as impaired globin synthesis, lead to defective hemoglobin production and to the generation of microcytosis and microcytic anemia. Iron deficiency anemie, anemia of chronic diseases, thalassemias, congenital sideroblastic anemias and homozygous HbE disease are the main representatives of microcytosis and microcytic anemias. Serum iron, total iron binding capacity, transferrin saturation, serum ferritin, serum transferrin receptor, transferrin receptor-ferritin index, and zinc-protoporhyrin concentration in erythrocytes are tests used for assessment of iron deficiency. The convention laboratory test for diagnosing iron deficiency is the measurement of serum ferritin. The most precise method for evaluating body iron stores is the examination for iron on aspirated bone marrow or marrow biopsy. Increased content of Hb A2 over 3.5% is diagnostic for beta-thalassemia. Presence of ringed sideroblasts is characteristic of sideroblastic anemias. Hemoglobin electrophoresis is required for the diagnosis of hemoglobinopathy E. The optimal therapeutic regimen in iron deficiency anemia used in this country is to administer 100 mg of elemental iron twice daily separately from meals. Ferrous sulphate (Ferronat Retard tbl. or Sorbifer Dulures tbl.) which are slow-releasing iron formulations are preferred because of their low cost, high bioavailability and low side-effects. Parenteral iron therapy is justified only in patients who cannot absorb iron, who have blood losses that exceed the maximal absorptive capacity of their intestinal tract or who are totally intolerant of oral iron. However, parenteral iron therapy may be associated with serious and even fatal side-effects.     

Comparison of a Combination Ferrous Fumarate Product and a Polysaccharide Iron complex as Oral Treatments of Iron Deficiency Anemia: A Taiwanese Study

Despite efforts to improve iron supplements for iron deficiency anemia, there is no consensus on products that balance efficacy, safety and tolerability, and cost. Ferrous products are effective, but they are associated with more gastrointestinal side effects than ferric products. Ferric products tend to have lower absorption. We present results from a 12-week study that randomized 72 people with uncomplicated iron deficiency anemia to receive a ferrous iron supplement (Ferall, a combination of ferrous fumarate with ascorbic acid, folic acid, and cyanocobalamin) or a ferric iron polysaccharide complex (Niferex, ferro-glycine sulfate) plus ascorbic acid. The ferrous product was significantly more effective, the primary and secondary endpoints including changes in levels of hemoglobin and serum ferritin. There was a slightly higher frequency of gastrointestinal side effects in patients taking the ferrous product, but both supplements were well tolerated. No participant withdrew from the study because of side effects. We concluded that the ferrous product is safe and effective for use in uncomplicated iron deficiency anemia. The lack of direct comparison between single-agent ferrous fumarate and the combination ferrous product limited interpretation of results in terms of possible effects due to other components, such as ascorbic acid.     

Possible ameliorative effect of taurine in the treatment of iron-deficiency anaemia in female university students of Gaza,Palestine

The aim of the study was to evaluate the haematological effects of adding the antioxidant taurine to iron sulfate in the treatment of iron-deficiency anaemia (IDA). A sample of 730 students from Al-Azhar University, Gaza, in Palestine underwent screening with complete blood counts and serum samples. In subjects with microcytosis/hypochromasia, Alpha2 delta2 (HbA2) and serum concentrations of iron, total iron binding capacity (TIBC), ferritin and taurine were determined. Samples from 17 normocytic, normochromic, and non-anaemic subjects were used as baseline controls. At base-line, 81 of the 730 subjects (11.1%) had microcytosis/hypochromasia, 26 (3.6%) were diagnosed as beta-thalassemia carriers, none of which was iron deficient. Four subjects had microcytosis of unknown cause. Fifty-one subjects (all females) had iron-deficiency anaemia and were included in the therapeutic study, which lasted for 20 wk. They were matched for Hb into pairs and were treated with oral iron (325 mg of slow-release iron sulfate). In addition, they were, in a double-blind procedure, randomised to additional oral taurine (1000 mg d(-1) at a cost comparable to that of adding ascorbic acid) or placebo. Mean S-taurine was significantly lower in the IDA subjects than in the controls. After 20 wk of iron supplementation, both the taurine and placebo group significantly improved their Hb concentrations and normalised the markers of iron deficiency. Apart from the expected, albeit in this study mild side-effects of oral iron, no significant side-effects were noted. In the taurine group, there was a statistically significant additive positive change from the baseline values on Hb (2.67 +/- 1.24 g dL(-1)), red blood cell (RBC) count [(0.57 +/- 0.25) x 1012 L(-1)] and serum ferritin (30.33 +/- 17.99 microg L(-1)) as compared to placebo group values, which were 1.80 +/- 1.10 g dL-1, (0.39 +/- 0.36) x 1012 L(-1), and 20.11 +/- 7.34 microg L(-1), respectively. Oral taurine appears to increase the effectiveness of oral iron in the treatment of IDA, and has no significant side-effects. This merits further cost-benefit and clinical analyses.     

Effect of iron therapy on serum ferritin levels in iron-deficiency anemia

The level of serum ferritin is a reliable indicator of body iron stores. Exceptions include liver disease, malignant diseases, and treatment of iron-deficiency anemia. The latter was noted in iron- deficient infants who showed a rise of serum ferritin to normal levels in the first week of treatment. To evaluate this in adults, 14 patients with iron-deficiency anemia were studied prior to and after beginning treatment with oral ferrous sulfate in standard dose, 300 mg t.i.d., or double dose, 600 mg t.i.d. Serum ferritin was assayed by radioimmunoassay. No rise occurred in the first 3 wk in 5 patients treated with standard dose, although hematologic response occurred. With double dose, 7 of 9 showed a ferritin rise in 2 days with return to subnormal levels within 6 days of discontinuing iron. This study indicates that standard treatment of iron deficiency anemia in adults does not cause a rise in serum ferritin until hemoglobin levels are normal. The early rise seen with double dose is most likely due to absorption of iron in excess of utilization for erythropoiesis resulting in temporary storage. When iron is discontinued, stores are rapidly depleted as reflected by the prompt decrease in serum ferritin.     

Clinical and laboratory manifestations of congenital dyserythropoietic anemia type I in young adults

OBJECTIVES: Congenital dyserythropoietic anemia (CDA) type I is a rare autosomal recessive macrocytic anemia whose natural history is not well documented. The aim of the present study was to evaluate the clinical picture of the disease in young adults. METHODS: The study sample consisted of 17 patients of mean age 11.9 +/- 5.4 yr (range 18-33 yr) and one older patient (age 44 yr), all Israeli Bedouins. The degree of anemia was evaluated as well as the extent of development of gallstones and iron overload. In each subject we determined the hemochromatosis gene mutations and the uridine dyphosphate-glucoronosyltransferase (UGT-1A) gene polymorphism associated with Gilbert's syndrome. RESULTS: The patients were found to have moderate anemia, with the women displaying lower mean hemoglobin levels than the men (8.2 +/- 0.9 g dL(-1) vs. 10 +/- 1.3 g dL(-1); P=0.0059). The majority of patients (59%) had received at least one blood transfusion, with the women having a significantly higher transfusion requirement. Although delayed puberty was noted, final height and weight were within normal limits, and eight patients had progeny. Biliary stones were found in three of 16 patients, two of whom were homozygous for UGT-1A gene polymorphism. None of the patients carried the common hemochromatosis gene mutation, although serum ferritin levels were moderately elevated (788 +/- 332 ng mL(-1)). CONCLUSIONS: CDA type I in young adults is characterized by moderate macrocytic anemia, more severe in women, and a tendency to cholelithiasis and secondary progressive iron overload. We suggest that iron overload in this patient population should be monitored and chelation therapy initiated when indicated to prevent organ damage     

Strategy for diagnosis and management in iron overload.

When suspecting an iron overload condition, the transferrin saturation levels should be determined. Levels higher than 45% and serum ferritin in men and postmenopausal women exceeding 200 microg/l confirm the iron overload. Afterwards, the HFE protein genotype should be determined. If it is C282Y or C282Y/H63D, the diagnosis of hereditary hemochromatosis can be accepted as the cause of the iron overload. In the absence of said genotypes, the overload is secondary or not related to the HFE protein. In hereditary hemochromatosis, the degree of iron overload and organic lesions must be established. Liver biopsies are very useful for obtaining said information and for the first case, the determination of serum ferritin is very useful. When less than 1000 microg/l, normal transaminases and no hepatomegalies, a treatment can be started without the need for a liver biopsy. In absence of anemia, the treatment is based on phlebotomies, 400-500 ml a week until obtaining depletion of excess iron. In presence of anemia, the treatment is based on chelating agents, preferably subcutaneous administered 8 hours a day.     

Intravenous iron dextran therapy in patients with iron deficiency and normal renal function who failed to respond to or did not tolerate oral iron supplementation

PURPOSE: To evaluate the safety and effectiveness of using 500-mg doses of iron as intravenous iron dextran after premedication with diphenhydramine, cimetidine, and dexamethasone.SUBJECTS AND METHODS: We treated 135 iron-deficient adults (26 men, 109 women) with normal renal function (serum creatinine level 相似文献   

Clinical evaluation of iron deficiency

While the prevalence of iron deficiency has remained relatively constant, there has been continuing refinement in its laboratory recognition, especially with the recent introduction of serum ferritin and FEP measurements. It is helpful to classify iron deficiency into three stages. Storage iron depletion is identified by marrow examination or serum ferritin, iron deficient erythropoiesis by TS, FEP, or MCV, and iron deficiency anemia by hemoglobin concentration or therapeutic iron trial. Combinations of these measurements have been used in prevalence studies to obtain a quantitative measure of body iron stores. The optimal laboratory approach to diagnosing iron deficiency depends on the clinical setting. In the office or outpatient clinic, iron depletion is best recognized by the serum ferritin, although the TS, FEP, and MCV are helpful in gauging its severity. In hospitalized patients with overt anemia, the TS, FEP, and MCV are much less helpful because similar changes are seen in the anemia of chronic disease. Examination of marrow iron remains the method of choice, especially in patients with infection, chronic disease, malignancy, or liver disease, although in many clinical situations the same information can be obtained from a serum ferritin. Serial measurements of serum ferritin have been particularly useful in monitoring patients at high risk of iron deficiency such as those with rheumatoid arthritis, chronic inflammatory bowel disease, or chronic renal failure.     

Ret-Y a measure of reticulocyte size: a sensitive indicator of iron deficiency anemia

In this study the size of reticulocytes was measured, reticulocyte-Y (Ret-Y), to distinguish iron deficiency anemia from the anemia of chronic disease using a Sysmex XE2100 cell counter. We evaluated this parameter prospectively in 100 patients seen for the evaluation of anemia. A clinical diagnosis of iron deficiency anemia or anemia of chronic disease was made on the basis of a complete blood count, examination of the peripheral smear, and serum ferritin along with a history and physical examination. We analyzed the sensitivity and specificity of the Ret-Y in relationship to the clinical diagnosis. We also measured serum transferrin receptor levels to use as the gold standard laboratory test for iron deficiency against which we compared the Ret-Y. In 40 normal individuals with normal serum ferritin and transferrin receptor levels the mean Ret-Y was 1874 +/- 178 (1 SD). The mean Ret-Y in the anemia of chronic disease group (n=62) was 1722 +/- 162, not significantly different from normal. The mean Ret-Y value among iron-deficient patients (n=38), was 1407 +/- 136 (P <0.01 vs. the anemia of chronic disease group's Ret-Y value). Receiver operator curves showed that Ret-Y correlated closely to the serum transferrin receptor and was superior to the mean corpuscular volume, and ferritin level, in differentiating the type of anemia. The Ret-Y parameter has the highest overall sensitivity and specificity of the panel of tests routinely used in differentiating iron deficiency anemia from anemia of chronic disease.     

Immunohistochemistry of the Hfe protein in patients with hereditary hemochromatosis, iron deficiency anemia, and normal controls

In 1996 two mutations in Hfe, the gene affected in hereditary hemochromatosis, were identified as C282Y (c.845G. A) and H63D (c.187C. G). Immunohistochemical studies have localized the protein product of Hfe to the deep crypts of the duodenum, the maximum site of iron absorption. To date, there are no published data on the cellular location and regulation of Hfe in patients with hemochromatosis who are homozygous for C282Y. The aim of this study was to identify the cellular localization of Hfe in genotyped individuals and to study possible regulation of this protein by the mutations described in the Hfe gene locus and iron deficiency. Duodenal biopsy specimens and serum for iron, ferritin, and transferrin saturation were taken from controls (n = 10) and patients with hereditary hemochromatosis (n = 10) and iron deficiency anemia (n = 10). All participants were genotyped for C282Y and H63D mutations. Expression of Hfe in the duodenum was demonstrated by immunohistochemistry. Hfe was expressed in the deep crypts of the duodenum in all three groups in a perinuclear fashion. Hfe staining was weaker in the hemochromatosis and iron deficiency patients (mean transferrin saturation 69.6%, SD 23% and 15%, SD 11%, respectively) when compared to controls (mean transferrin saturation 33.1%, SD 15%). There was no difference in the intensity of Hfe staining within the hemochromatosis group who were iron overloaded when compared to their iron-depleted counterparts. In summary, Hfe is expressed strongly in the deep crypts of the small intestine of normal subjects. Homozygosity for C282Y and conditions of iron deficiency result in a downregulation of Hfe. Furthermore, Hfe is not regulated by therapeutic iron depletion in patients with hemochromatosis who are homozygous for the C282Y mutation.     

Serum transferrin receptor: a quantitative measure of tissue iron deficiency

This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency.     

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   

Transfusion iron overload in adults with acute leukemia: manifestations and therapy

BACKGROUND: Hepatic dysfunction occurs commonly among persons successfully treated for acute leukemia, and iron overload is a possible cause of hepatic and other abnormalities in these patients. METHODS: We identified 5 adults 40+/-13 (mean +/- S.D.) years of age who developed transfusion iron overload in association with successful chemotherapy of de novo acute leukemia. None had evidence of hemochromatosis, viral hepatitis, or other primary hepatic disorders. RESULTS: The mean serum ferritin concentration of our patients was 1531+/-572 ng/mL. Other abnormalities associated with transfusion iron overload were increased stainable iron in bone marrow macrophages, elevated serum concentrations of hepatic enzymes, hyperpigmentation, hyperferremia, elevated iron saturation of serum transferrin, and increased stainable iron in Kupffer cells and hepatocytes. Rheumatologic, endocrinologic, or cardiac abnormalities attributable to iron overload were not observed. Therapeutic phlebotomy was initiated after chemotherapy; recovery of hemoglobin concentrations after phlebotomy permitted weekly treatment in each case. This yielded an average of 28+/-9 units per patient (range 15-35 units). Abnormalities associated with transfusion iron overload resolved after iron depletion therapy. The mean leukemia-free survival of our patients is 96+/-36 months (range 40-125 months). Conclusions: Our data and those of others suggest that 15 to 20% of adults who are long-term survivors of acute leukemia develop iron overload, often with hepatic abnormalities. Iron overload is a relatively common sequela to successful management of acute leukemia in adults for which routine evaluation should be performed and for which therapeutic phlebotomy should be used as treatment.     

The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic

BACKGROUND: The gene that causes most cases of hereditary hemochromatosis is designated HFE. Three mutations exist at this locus at a relatively high gene frequency. OBJECTIVE: To determine the gene frequency of the three HFE mutations and to relate genotypes to various clinical and laboratory variables. DESIGN: Observational study. SETTING: Health appraisal clinic. PATIENTS: 10,198 adults who registered for health appraisal and consented to DNA examination for hemochromatosis. Consenting patients were slightly older and had attained a slightly higher educational level than nonconsenting patients. MEASUREMENTS: Extensive medical history and laboratory tests, including complete blood count, transferrin saturation, and other chemistries; serum ferritin levels; and HFE genotype. RESULTS: In white participants, the gene frequencies were 0.063 for the C282Y mutation, 0.152 for the H63D mutation, and 0.016 for the S65C mutation. Gene frequencies were lower in other ethnic groups. In participants with HFE mutations, the average serum transferrin saturation and ferritin levels were slightly increased, as were mean hemoglobin levels and mean corpuscular volume. A transferrin saturation of 50% had a sensitivity of only 0.52 (95% CI, 0.345 to 0.686) and a specificity of 0.908 (CI, 0.902 to 0.914) for detection of homozygosity. A ferritin level of 200 microg/L in women and 250 microg/L in men had a sensitivity of 0.70 (CI, 0.540 to 0.854) and a specificity of 0.803 (CI, 0.796 to 0.811). The prevalence of iron deficiency anemia was lower in women who carried HFE mutations. CONCLUSIONS: Screening for transferrin saturation and ferritin levels does not detect all homozygotes for the major hemochromatosis mutation. Heterozygotes for HFE mutations had a lower prevalence of iron deficiency anemia.     

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.