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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The introduction of recombinant human erythropoietin (rh-Epo, epoetin) as a treatment for the anaemia of renal failure has transformed the management of this condition. Nevertheless, a significant number of patients fail to respond. There are many different possible causes of inadequate response to epoetin. Iron deficiency, whether absolute or functional, is considered to be the most important, and it is widely accepted that maintaining adequate iron levels reduces rh-Epo dosage requirement and improves efficacy in haemodialysis patients. Infection and inflammation have been shown to influence responsiveness to rh-Epo by disrupting iron metabolism and eliciting the release of cytokines that inhibit erythropoiesis. Another factor for consideration is severe hyperparathyroidism, which can lead to a reduced number of responsive erythroid progenitor cells. Inadequate dialysis can also negatively impact on rh-Epo therapy, and aluminium overload interferes with iron metabolism and reduces the efficacy of rh-Epo. Deficiencies in vitamin B(12), folic acid and potentially vitamin C can all reduce the efficacy of treatment with rh-Epo. Optimizing patient response to rh-Epo therapy, therefore, requires consideration of many factors, some well established and others that are more controversial, and the list continues to grow with the identification of new factors.
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PMID:Hyporesponsiveness to recombinant human erythropoietin. 1159 Feb 53

Anemia was induced in weanling Sprague Dawley rats either by feeding an iron-deficient diet or by chronic phlebotomy. The erythroid regenerative response was then evaluated before and after a hemolytic event, and results were compared with those of a third group of control nonphlebotomized rats fed an iron-replete diet. Diet and phlebotomy groups developed a similar degree of anemia (mean hemoglobin concentration 7.9 g/dL and 7.8 g/dL, respectively; controls, 13.9 g/dL) and hypoferremia (mean serum iron concentration 25.4 microgram/dL and 34.9 microgram/dL, respectively; controls, 222.0 microgram/dL). However, the anemia in diet rats was nonregenerative (reticulocyte count, 83.1 X 10(3) cells/microliter) and associated with bone marrow erythroid hypoplasia; whereas the anemia in phlebotomy rats was regenerative (reticulocyte count, 169.6 X 10(3) cells/microliter) and associated with bone marrow erythroid hyperplasia. Thrombocytosis was seen in diet rats (1,580 X 10(3) cells/microliter) but not phlebotomy rats (901 X 10(3) cells/microliter) when compared with controls (809 X 10(3) cells/microliter). To further evaluate the regenerative capability, phenylhydrazine (PHZ) was administered to induce hemolysis. Erythrocyte mass declined approximately 25% in all groups, including controls. The reticulocytosis (265.3 X 10(3) cells/microliter) seen in phlebotomy rats was earlier and significantly greater than that seen in either diet or control rats. Hemoglobin concentration returned to pre-PHZ concentrations (7.9 g/dL) in phlebotomy rats within 4 days posthemolysis. In diet rats, the maximal regenerative response (176.3 X 10(3) cells/microliter) was not seen until 8 days posthemolysis, and hemoglobin (7.5 g/dL) did not return to pre-PHZ concentrations during the 8-day study. In many aspects, the anemia seen following diet- or phlebotomy-induced iron deficiency was similar. However, the erythroid regenerative capability varied depending on the mechanism by which anemia was induced and furthermore altered the efficiency of hemoglobin production following a hemolytic event. These results suggest that the availability of iron in the diet may modulate the pathogenesis of iron deficiency anemia.
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PMID:Evaluation of the erythroid regenerative response in two different models of experimentally induced iron deficiency anemia. 1202 20

The clinical and hematologic features of two cases of probable essential thrombocythemia in the dog are described. Both dogs presented with hepatosplenomegaly, severe nonregenerative anemia, neutrophilia and Thrombocytosis. Mean platelet volume and percentages of large platelets were markedly increased in both dogs. Platelet aggregation studies demonstrated hyperaggregability in one dog; platelets from the other dog aggregated spontaneously, precluding further investigation. Cytologic and histologic examination of bone marrow showed pronounced megakaryocytic hyperplasia, with erythroid hypoplasia and relative myeloid hyperplasia. Megakaryocyte morphology was abnormal, with increased numbers of small mononuclear and binucleate cells. Normal to increased hemosiderin stores suggested that apparent macrocytosis in one dog, rather than being due to iron deficiency, resulted from the hematology analyzer counting large platelets as small red blood cells. Megakaryocytic infiltration of the spleen was evident in both dogs. The hematologic findings in dogs with essential thrombocythemia can mimic those associated with iron deficiency anemia, such that diagnostic investigations should be aimed at ruling out chronic blood loss and other causes of reactive Thrombocytosis.
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PMID:Diagnostic and hematologic features of probable essential thrombocythemia in two dogs. 1207 9

A dog with myelodysplastic syndrome had microcytic hypochromic anemia, with siderocytes, poikilocytosis, hypersegmented neutrophils and giant platelets in peripheral blood. In bone marrow, the erythroid series showed immaturity, asynchronous maturation and sideroblasts. Dysgranulopoiesis and dysthrombopoiesis also were present, and hemosiderin was increased. Serum iron concentration was high, and both iron deficiency and lead toxicity were excluded as the cause of dyscrasia. This case represents a unique variant of myelodysplastic syndrome, best described as sideroblastic myelodysplasia. We propose the terms dyserythropoiesis, sideroblastic dyserythropoiesis, dyserythropoiesis with excess blasts, myelodysplasia and sideroblastic myelodysplasia to describe and categorize myelodysplastic syndromes in dogs.
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PMID:Myelodysplastic syndrome with sideroblastic differentiation in a dog. 1207 26

Our knowledge of erythropoiesis and iron in renal disease is limited. The accepted view of the control of erythropoiesis was founded on observations made in a variety of disorders, but the control mechanism in healthy individuals may not be quite the same. Evidence suggests that mechanisms other than erythropoietic stimulation may play a role in increased red blood cell production. Measuring erythropoiesis is complex. The quantitative reticulocyte count is probably the closest practical assessment of erythropoietic activity we can achieve, yet there is very little correlation between circulating erythropoietin level and reticulocyte count in normal and near normal subjects. Oxygen transport in humans depends entirely upon iron. In renal disease, the failure of the erythropoietin positive feedback mechanism can be readily and directly remedied; recombinant human erythropoietin therapy can replace the missing erythropoietin, but this will be negated if iron supply to the erythroid marrow falls short of demand. Measurement of iron stores is also complex. The use of serum ferritin concentration as a direct quantitative estimate of iron in the stores is not advisable, and in practice we have not found the transferrin receptor assay to be useful in identifying patients who require iron therapy. Use of percentage hypochromia as a measure of iron deficiency is complicated by the fact that hypochromic cells are not exclusively a consequence of functional iron deficiency. There are clearly lessons still to be learned in this field and there is much that we do not yet understand about the control of erythropoiesis and iron metabolism in humans.
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PMID:Iron and erythropoietin in renal disease. 1209 2

Iron appears to exert self-regulatory control over erythroblast iron uptake, iron storage and its incorporation into haem. It does this via iron regulatory proteins (IRPs) which bind reversibly to the iron responsive elements (IREs) on the mRNA of transferrin receptor (TfR), erythroid 5-aminolaevulinic acid synthase (ALA-S2) and ferritin. Iron deficiency leads to the binding of IRP to IRE. This binding inhibits the translation of mRNA for ALA-S2 and ferritin but stabilizes mRNA for TfR expression. Sideroblastic erythropoiesis is highly ineffective and characterized by mitochondrial iron loading. The study of X-linked sideroblastic anaemia has shown that the entry of iron into the mitochondria is poorly controlled and able to occur when protoporphyrin production is reduced, as is seen with the ALA-S2 mutations, or when it is increased as has been seen with ABC7 transporter mutations. Sideropenia characterises both iron deficiency anaemia (IDA) and the anaemia of chronic disease (ACD). Erythroblasts in ACD seem doubly equipped to protect their iron supply with their ability to increase the efficiency of transferrin-iron uptake as well as to activate the IRP/IRE system to increase surface TfR production. This increase in efficiency restricts the need to increase surface TfR production and maintains serum soluble TfR (sTfR) values within the normal range in iron replete ACD. The coexistence of iron deficiency with chronic disease, however, is associated with an increase in both the efficiency and number and a highly significant rise in sTfR values.
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PMID:Erythroblast iron metabolism in sideroblastic and sideropenic states. 1224 84

The anemia of chronic disease traditionally is defined as a hypoproliferative anemia of no apparent cause that occurs in association with an inflammatory, infectious, or neoplastic disorder, and resolves when the underlying disorder is corrected. Disordered iron metabolism as manifested by a low serum iron, decreased serum transferrin, decreased transferrin saturation, increased serum ferritin, increased reticuloendothelial iron stores, increased erythrocyte-free protoporphyrin, and reduced iron absorption, is a characteristic feature of the anemia of chronic disease and has been thought to be a major factor contributing to the syndrome. A mild shortening of red cell life span also occurs. However, we now know that impaired erythropoietin production and impaired responsiveness of erythroid progenitor cells to this hormone are also important abnormalities contributing to the anemia of chronic disease, and appear to be due to the effects of inflammatory cytokines. Increased intracellular iron may also have a role in the inhibition of erythropoietin production, since the oxygen sensor is a hemoprotein. While the role of inflammatory cytokines in the pathogenesis of anemia of chronic disease appears unequivocal, it has become apparent that disordered iron metabolism, while characteristic of this form of anemia, may not be central to its pathogenesis. It is undisputed that iron absorption is reduced, and that iron administered intravenously is rapidly sequestered in the reticuloendothelial system; however, iron delivery to the bone marrow is not impaired, and erythroid iron utilization is not markedly depressed in anemia of chronic disease. Importantly, recombinant erythropoietin therapy can correct the anemia of chronic disease, but it cannot correct the anemia due to iron deficiency. This refutes the concept that the lack of available iron is central to the pathogenesis of the syndrome. Indeed, it is highly likely that abnormalities such as reduced iron absorption and decreased erythroblast transferrin-receptor expression largely result from decreased erythropoietin production and inhibition of its activity by inflammatory cytokines.
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PMID:Iron and the anemia of chronic disease. 1238 Sep 52

Macrophage inflammatory protein-1alpha (MIP-1alpha) is an interesting chemokine because in addition to its variety proinflammatory activities including chemotaxis and immunomodulation, it is a potent inhibitor of hematopoetic stem cell proliferation. Inhibition of erythroid progenitor cells due to MIP-1alpha or other cytokines can play a role in the pathogenesis of anemia which is one of the most common extra-articular features of active rheumatoid arthritis (RA). In 84 patients with RA, serological and immunological parameters were assessed to detect inflammatory mechanisms and anemia in relation to the serum concentrations of MIP-1alpha. All patients fulfilled the ACR criteria for the diagnosis of a definite or classic RA. We used a quantitative enzyme immuno assay for the detection of MIP-1alpha as well as for the measurement of the acute phase protein serum amyloid A (SAA), the erythropoiesis inducer erythropoietin (EPO) and the transferrin receptor (TfR). The immune activation marker neopterin was measured radioimmunologically. Half of the patients with RA were anemic with hemoglobin values below 12 g/dl. MIP-1alpha was found to be elevated significantly in serum of patients with active rheumatoid arthritis and in patients with anemia. Most of the anemic patients with markedly elevated acute phase reactions had an anemia with chronic diseases and not a functional iron deficiency alone. TfR correlated with EPO. The results show that enhanced expression of MIP-1alpha is indicative of systemic inflammation in RA. Moreover, besides the regulation of inflammatory processes, this chemokine may influence the pathogenesis of anemia in RA patients.
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PMID:[Effects of the chemokine MIP-1alpha on anemia and inflammation in rheumatoid arthritis]. 1239 85

Blood transferrin receptor (TR) level is largely determined by the quantum of erythropoiesis and by intracellular iron content of the cells of the erythroid lineage. Hence, a high serum TR level has been found to be useful in distinguishing iron deficiency anemia (IDA) from anemia of chronic disorders (ACD). In order to examine its potential role in the diagnosis of concomitant iron deficiency in ACD, we determined serum TR levels in 130 cases of ACD, in 25 cases of IDA, and in 40 normal adults. As expected, all patients of IDA had significantly higher serum TR levels compared to the normal subjects (4.2-19.2 microg/dL vs. 1.3-3.0 microg/dL) (P < 0.002). In 11/25 cases of IDA, the total iron-binding capacity (TIBC) was in the normal range although bone marrow iron store was absent and serum TR levels were high, thereby highlighting the superiority of TR level in the diagnosis of iron deficiency compared to TIBC. Although 54% (70/130) patients of ACD had normal or low serum TR levels (0.9-3.0 microg/dL) as expected, in 46% (60/130) of ACD patients, serum TR levels were high (3.2-11.0 microg/dL). Mean corpuscular volume, red cell distribution width, and transferrin saturation were significantly lower (P < 0.001) in the latter group of patients compared to the former, and these parameters resembled those in IDA patients. Also, serum iron was lower and TIBC was higher in this group of ACD patients compared to those with normal or low serum TR. All these features point to an "IDA-like" profile of ACD patients with high TR and support the possibility of co-existent iron deficiency in this subgroup of ACD patients. In light of these observations it would be prudent to treat ACD patients with high serum TR levels with iron replacement therapy.
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PMID:High serum transferrin receptor level in anemia of chronic disorders indicates coexistent iron deficiency. 1260 86

In renal failure, severe anemia and associated fatigue, cognitive and sexual dysfunction have a significant impact on the patient's quality of life. Anemia has also been identified as an important etiologic factor in the development of left ventricular hypertrophy. The major cause of anemia in presence of a reduction of glomerular filtration rate is an inadequate production of a glycoprotein hormone, the erythropoietin (EPO). EPO is the primary regulator of the growth and survival of erythroid progenitor. The introduction of recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of anemia in chronic renal failure. The vast majority of patients respond very well to treatment, but 5-10% of patients show some resistance to EPO, the most common cause of which is iron deficiency. Several studies are recently commenced to investigate the effects of preventing renal anemia ever developing. The target of hemoglobin concentration in pre-dialysis and dialysis patients are object of continuous re-examinations.
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PMID:Anemia in renal insufficiency. 1273 11


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