Anemia Of Chronic Disorders Research Articles

Myeloperoxidase activity of polymorphonuclear leukocytes in iron deficiency anemia and anemia of chronic disorders.

Myeloperoxidase (MPO) activity was studied in adults with iron deficiency anemia (IDA) or anemia of chronic disorders (ACD). MPO activity (biochemical quantitation) was found to be decreased in IDA when compared to the control group (p less than 0.05); ACD subjects also had lower values although the difference was not significant (p less than 0.05). MPO scores (MPO staining) were significantly lower in IDA and ACD subjects than in the healthy control group (p less than 0.05). A significant positive correlation was noted between ferritin (R = 0.40) and percent transferrin saturation (R = 0.37) and MPO activity (p less than 0.001) in IDA and for the healthy controls.

Anemia of Chronic Disorders

Anemia of chronic disorders is a common anemia found in many clients with long-term illnesses. It is a normocytic, normochromic anemia and is usually mild. It is frequently overlooked, though, in the general workup of the underlying disease or misdiagnosed as other common forms of anemia. However, the treatments for these anemias are either ineffectual or harmful to the client with anemia of chronic disorders. Therefore, it is important to be aware of and to differentiate anemia of chronic disorders from other anemias.

Giant lymph node hyperplasia (Castleman's disease) of the mesentery

Abstract A mesenteric mass, histologically characterized as giant lymph node hyperplasia was found in an 18-yr-old man with at least 11 yr of growth retardation and anemia. The anemia was characterized by iron deficiency from selective malabsorption of iron, and by features of the anemia of chronic disorders. In contrast with a previous report, no inhibitor of erythropoietin was found and there was no abnormality of erythropoietin secretion. Resection of the mass was followed by rapid correction of the anemia and catch-up growth. The mass had histologic features of the hyaline vascular and plasma cell types of Castleman's disease with multinucleate giant cells probably of macrophage origin. Immunologic studies of the mass showed that the B lymphocytes were polyclonal and the T lymphocyte helper/suppressor cell ratio was normal, suggesting that giant lymph node hyperplasia is a local inflammatory reaction.

The anaemia of chronic disorders. A bag of unsolved questions.

The anaemia of chronic disorders. A bag of unsolved questions.

The anaemia of chronic disorders.

Summary Chronic disease can cause anaemia in a number of ways, such as poor nutrition, chronic blood loss and as a result of drug therapy. Leaving aside these factors, however, there is a specific type of anaemia associated with chronic infection, chronic inflammatory diseases and malignancy. This anaemia is characterised by decreased plasma iron and iron-binding capacity in the presence of normal or increased reticulo-endothelial iron stores, and has been termed the anaemia of chronic disorders (Cartwright and Lee, 1971). Although the anaemia of chronic disorders is one of the most common anaemias encountered in medical practice, its aetiology remains unclear and treatment unsatisfactory.

In-vitro studies of ineffective erythropoiesis in rheumatoid arthritis.

Ineffective erythropoiesis was assessed in a series of 32 patients with rheumatoid arthritis by means of a new in-vitro method which measures the release of haem from a labelled cohort of erythroblasts in culture. Haem release was significantly increased in patients with the anaemia of chronic disorders but was normal in those who were not anaemic or who had an iron-deficiency anaemia. In 2 patients with anaemia of chronic disorders haem release returned to normal after successful antirheumatic therapy. The increased ineffective erythropoiesis in patients with rheumatoid arthritis and anaemia of chronic disorders appeared to be unrelated to functional iron deficiency and was not attributable to a serum factor.

Turnover of human lactoferrin in the rabbit.

Lactoferrin turnover was studied in the rabbit with 125I- and 131I-labelled human lactoferrin. Plasma lactoferrin activity showed a rapid decrease during the first 24 h, followed by a 'final slope' with a T1/2 of about 25 h. Turnover studies after transfer of plasma from one rabbit (A) 3 h after injection to another rabbit (B), showed a recovery of 100% compared to 30% in A rabbits but otherwise a similar disappearance curve. The rapid turnover was confirmed in whole body studies. Concomitantly with the initial dissapearance from the plasma, there was a marked accumulation of proteinbound activity only in the liver in both A and B rabbits. From these results, the rate of synthesis in normal man can be estimated at around 25 mg per d. The disappearance pattern and hepatic uptake are discussed in relation to knowledge about lactoferrin receptors in macrophages, asialo elimination, and fucose group recognition. Concerning the significance of lactoferrin turnover for iron metabolism it is concluded that the plasma turnover results are insufficient to explain the disturbance in iron kinetics seen in the anaemia of chronic disorders; however, it is likely that lactoferrin plays a role in iron metabolism within the extravascular space.

Immunochemical determination of serum transferrin. Reference values, correlation with serum total iron-binding capacity and value in the diagnosis of iron deficiency anaemia and anaemia of chronic disorders.

Immunologically determined reference values of serum transferrin are presented for adults and children. A good correlation between serum transferrin and total iron-binding capacity values was found. In 2 groups of anaemic patients - 51 patients with iron deficiency anaemia and 45 patients with anaemia of chronic disorders - serum transferrin determination distinguishes the two groups of anaemic patients from normals somewhat better than TIBC determination.

Is the Anemia of Chronic Disorders Normocytic-Normochromic?

Is the Anemia of Chronic Disorders Normocytic-Normochromic?

Serum ferritin, free erythrocyte protoporphyrin, and urinary iron excretion in patients with iron disorders

Tests to evaluate body iron stores were compared in patients with iron deficiency and the anemia of chronic disease. The serum ferritin assay separated these disorders in 20 of 22 patients. One discrepancy was explained by the concomitant association of both disorders. From this study and review of literature a low serum ferritin level is a good indication for iron therapy. The serum ferritin assay is a clinically useful test in lieu of bone marrow estimation of body iron stores to detect patients with iron deficiency. Total iron binding capacity levels when high-normal or elevated are sometimes helpful as a screening test in separating iron deficiency from the anemia of chronic disorders. Free erythrocyte protoporphyrin values were elevated in both conditions but were higher in iron deficiency than in the anemia of chronic disorders with considerable overlap of values. Urinary iron excretion with deferoxamine was not helpful in separating these disorders but is a useful test to establish iron overload. An elevated serum ferritin level is usually found with disease of iron overload but serum iron levels, deferoxamine iron excretion tests, and liver biopsy for estimation of iron stores are still beneficial diagnostic aids.

Automated red cell indices and marrow iron reserves in geriatric patients.

The marrow iron reserves, automated red cell indices, serum iron, and total iron binding capacity of 69 geriatric patients were recorded. A fall in the mean red cell volume (MCV) to between 71 and 82 fl failed to distinguish between iron deficiency and the 'anaemia of chronic disorders'. However, there was no reserve of marrow iron in the eight patients with an MCV of 70 fl or less.

The anaemia of chronic disorders: studies of iron reutilization in the anaemia of experimental malignancy and chronic inflammation.

The purpose of this study was to evaluate the contribution of defective reutilization of iron in the pathogenesis of the anaemia of chronic disease (ACD). Normal rats with or without splenectomy and rats with Walker 256 carcinosarcoma with or without splenectomy were studied. The reutilization of 59Fe labelled heat‐damaged red cells (59Fe DRBC), the sequestration of 59Fe DRBC in major organs, red cell mass, 51Cr red cell survival, serum iron, plasma erythropoietin and routine haematological parameters were measured.Three weeks after tumour implantation in rats a moderate degree of anaemia was noted. The maximum 59Fe reutilization in the tumour group and tumour with splenectomy group (63 ± 6% and 56 ± 9%, respectively) was not significantly different than observed in the normal group (64 ± 6%) or normal with splenectomy group (53 ± 7%). Excessive iron sequestration in liver and spleen was not observed in animals with cancer. Red cell survival in the tumour group was slightly decreased as compared to normal. Plasma erythropoietin levels were appropriately increased for the degree of anaemia in rats with cancer. This type of experiment was repeated in a second group of anaemic animals with turpentine induced abscesses. Reutilization of 59Fe DRBC in rats with inflammation was normal.These results indicate that adult rats with anaemia of malignancy or chronic inflammation do not have a decreased reutilization of red cell iron. Thus RE blockade of iron is not a major factor in anaemia of chronic disease in this experimental model. Furthermore, these experiments confirm the importance of decreased red cell production in the anaemia of malignancy.

Quantitation of Ineffective Erythropoiesis from the Incorporation of [15N]Delta‐aminolaevulinic Acid and [15N]Glycine into Early Labelled Bilirubin: II. ANAEMIC PATIENTS

The incorporation of [15N]delta-aminolaevulinic acid and [15N glycine into haemoglobin haem and early labelled bilirubin was measured in subjects with various haematological disorders. The clearance of [14C bilirubin was used to measure bilirubin production rate, and the magnitude of the various sources of bilirubin production and the percentage ineffective erythropoiesis were calculated. Ineffective erythropoiesis was found to be a major factor in the production of the anaemia in patients with the following disorders: megaloblastic anaemia associated with the Lesch-Nyhan syndrome, thalassaemia intermedia, sideroblastic anaemia, and the anaemia of chronic disorders. In three patients with iron-deficiency anaemia ineffective erythropoiesis was increased, but was of minor importance in the production of the anaemia, while in two patients with aplastic anaemia and one with macrocytosis of alcoholism there was no increase in ineffective erythropoiesis.

Hematologic changes in chronic arthritis of mice induced by Mycoplasma arthritidis.

The arthritis caused by iv injection of M. arthritidis in mice was found to be associated with neutrophilia and lymphopenia without a change in the total WBC concentration. A mild anemia developed which was characterized by hypoferremia and plentiful RE iron but with an increased plasma total iron-binding capacity. This anemia therefore differs from the anemia of chronic disorders and indeed from any anemia which occurs in man.

The anemia of chronic disorders: studies of marrow regulation and iron metabolism

Marrow regulation and iron metabolism were evaluated in 17 patients with mild or moderate anemia associated with chronic disorders. In addition, whole blood P50 and red cell 2,3-diphosphoglycerate (DPG) levels were measured. The study group consisted of seven patients with non-hematologic malignancies, nine with infection or inflammation, and one with idiopathic hypoproliferative anemia. The mean whole blood P50 and DPG levels were elevated to 28.5 +/- 1.9 mm Hg and 7.03 +/- 0.83 mumole/ml packed RBC, respectively, as compared to normal values of 26.6 +/- 0.6 mm Hg and 4.83 +/- 0.33 mumole/ml packed RBC. Erythropoietin (ESF) excretion was variable (1.1–28.7 IRP U, day), clearly elevated above normal in only three patients and, within the study group, bore no relation to hematocrit. While nine of the 17 subjects had ESF excretion rates within the 95% limits predicted by hematocrit, the remaining eight had lower than expected values. No significant differences in ferrokinetics, ESF excretion, or hematologic profile were found between patients with malignancy and those with inflammation. Marrow transit times correlated inversely with both serum and urine ESF activity (r = -0.57, p less than 0.02; and r = -0.63, p less than 0.01, respectively), indicating that the marrow reticulocyte release response to ESF stimulation was unimpaired. Erythroid iron turnovers were unrelated to serum or urinary ESF activity but were significantly correlated with serum iron levels expressed as microgram/100 ml whole blood (r = 0.56, p less than 0.02). These studies suggest that there is an intraerythrocytic response to the anemia in this group of patients, document that reduced ESF production is not a uniform finding with the anemia of chronic disorders, and provide evidence that the marrow proliferative response to anemia is limited in many patients primarily by the availability of iron.

The Anemia of Chronic Disorders: Studies of Marrow Regulation and Iron Metabolism

Marrow regulation and iron metabolism were evaluated in 17 patients with mild or moderate anemia associated with chronic disorders. In addition, whole blood P50 and red cell 2,3-diphosphoglycerate (DPG) levels were measured. The study group consisted of seven patients with non-hematologic malignancies, nine with infection or inflammation, and one with idiopathic hypoproliferative anemia. The mean whole blood P50 and DPG levels were elevated to 28.5 +/- 1.9 mm Hg and 7.03 +/- 0.83 mumole/ml packed RBC, respectively, as compared to normal values of 26.6 +/- 0.6 mm Hg and 4.83 +/- 0.33 mumole/ml packed RBC. Erythropoietin (ESF) excretion was variable (1.1-28.7 IRP U, day), clearly elevated above normal in only three patients and, within the study group, bore no relation to hematocrit. While nine of the 17 subjects had ESF excretion rates within the 95% limits predicted by hematocrit, the remaining eight had lower than expected values. No significant differences in ferrokinetics, ESF excretion, or hematologic profile were found between patients with malignancy and those with inflammation. Marrow transit times correlated inversely with both serum and urine ESF activity (r = -0.57, p less than 0.02; and r = -0.63, p less than 0.01, respectively), indicating that the marrow reticulocyte release response to ESF stimulation was unimpaired. Erythroid iron turnovers were unrelated to serum or urinary ESF activity but were significantly correlated with serum iron levels expressed as microgram/100 ml whole blood (r = 0.56, p less than 0.02). These studies suggest that there is an intraerythrocytic response to the anemia in this group of patients, document that reduced ESF production is not a uniform finding with the anemia of chronic disorders, and provide evidence that the marrow proliferative response to anemia is limited in many patients primarily by the availability of iron.

The anaemia of chronic disorders.

Although the anaemia associated with chronic disorders is one of the most frequently encountered forms of anaemia, particularly in hospital patients, it has not received the distinction which it deserves, in part, perhaps, because of the lack of an appropriate name. The term ‘simple chronic anaemia’ is most inappropriate because the pathogenesis of the anaemia involves the delicate control mechanisms of erythropoiesis and these are not simple. The title ‘anaemia of chronic infections’ is much too restrictive, for the anaemia occurs in patients with cancer, lymphoma, rheumatoid arthritis, collagen vascular diseases, fractures, severe tissue injury and many other disorders. ‘Anaemia of chronic disorders’, though a less restrictive title, is unsatisfactory because many other types of anaemia occur in these disorders, such as blood loss, overt haemolytic anaemia of various types, reactions to drugs, myelophthisic anaemia, and the anaemia of renal failure. Furthermore, the name gives no hint as to the diagnostic features or pathogenesis of the anaemia. A more descriptive, but somewhat more cumbersome, title might be ‘sideropenic anaemia with reticuloendothelial siderosis.’

The anemia of chronic disorders due to renal cell carcinoma: ferrokinetic and morphologic documentation of its surgical correction.

The anemia of chronic disorders due to renal cell carcinoma: ferrokinetic and morphologic documentation of its surgical correction.

Serum level of erythropoietin in anemias associated with chronic infection, malignancy, and primary hematopoietic disease.

The serum level of erythropoietin was measured in 31 patients with anemia secondary to chronic infection or malignancy and compared with erythropoietin levels in 23 patients with iron-deficiency anemia and 14 patients with primary hematopoietic diseases. Erythropoietin levels varied directly with the degree of anemia in patients with iron deficiency or primary hematopoietic disorders. There was no correlation of erythropoietin and the degree of anemia in patients with chronic infection or malignancy and the erythropoietin levels were significantly lower than in patients with iron deficiency or primary hematopoietic disease and the same degree of anemia. A major factor in the anemia of chronic disorders is a decrease in levels of erythropoietin.

The anemia of chronic disorders: experimental abscess, spleen transplantation, and red cell iron reutilization.

AbstractStudies of Fe59 incorporation into blood, liver, and spleens utilizing ‘cooked’ red blood cells labeled with 59‐ferrous citrate were undertaken to evaluate iron reutilization. Intraperitoneal transplantation of intact spleens was performed from mice both with and without turpentine abscess to similarly prepared mice. Presence or absence of abscess in the recipient mouse determined ‘compartmentalization’ of reutilizable iron between the recipient reticuloendothelial system (spleen and liver) and blood. Reduced iron reutilization induced by chronic inflammation seems to be predominantly due to alteration of reticuloendothelial system function as measured by Fe59 incorporation into blood from labeled ‘cooked’ red blood cells. The model studied shows that chronic inflammation is sufficient systemic cause for reduced iron reutilization and thereby a major contributor to the anemia of chronic diseases.