losartan-potassium and Vitamin-B-12-Deficiency

Anemia, a common complication associated with inflammatory bowel disease (IBD), is frequently overlooked in the management of IBD patients. Unfortunately, it represents one of the major causes of both decreased quality of life and increased hospital admissions among this population. Anemia in IBD is pathogenically complex, with several factors contributing to its development. While iron deficiency is the most common cause, vitamin B12 and folic acid deficiencies, along with the effects of pro-inflammatory cytokines, hemolysis, drug therapies, and myelosuppression, have also been identified as the underlying etiology in a number of patients. Each of these etiological factors thus needs to be identified and corrected in order to effectively manage anemia in IBD. Because the diagnosis of anemia in IBD often presents a challenge, combinations of several hematimetric and biochemical parameters should be used. Recent studies underscore the importance of determining the ferritin index and hepcidin levels in order to distinguish between iron deficiency anemia, anemia due to chronic disease, or mixed anemia in IBD patients. With regard to treatment, the newly introduced intravenous iron formulations have several advantages over orally-administered iron compounds in treating iron deficiency in IBD. In special situations, erythropoietin supplementation and biological therapies should be considered. In conclusion, the management of anemia is a complex aspect of treating IBD patients, one that significantly influences the prognosis of the disease. As a consequence, its correction should be considered a specific, first-line therapeutic goal in the management of these patients.

Topics: Anemia; Anemia, Iron-Deficiency; Cytokines; Dietary Supplements; Erythropoietin; Ferritins; Folic Acid Deficiency; Hemolysis; Hepcidins; Humans; Inflammatory Bowel Diseases; Iron; Prognosis; Quality of Life; Vitamin B 12 Deficiency

The formation of red blood cells (RBCs) in the bone marrow is regulated by erythropoietin in response to a cascade of events. Anemia in the intensive care unit can be caused by a host of factors. Patients in the intensive care unit may have decreased RBC production and a blunted response to erythropoietin. Administration of recombinant human erythropoietin may stimulate erythropoiesis, increase hematocrit levels and hemoglobin concentration, and reduce the need for RBC transfusions.

Topics: Anemia; Anemia, Iron-Deficiency; Blood Specimen Collection; Bone Marrow Cells; Comorbidity; Erythrocytes; Erythroid Precursor Cells; Erythropoietin; Hemorrhage; Humans; Incidence; Intensive Care Units; Vitamin B 12 Deficiency

Iron deficiency anaemia is one of the most common disorders in the world. Also, one third of inflammatory bowel disease (IBD) patients suffer from recurrent anaemia. Anaemia has significant impact on the quality of life of affected patients. Chronic fatigue, a frequent IBD symptom itself, is commonly caused by anaemia and may debilitate patients as much as abdominal pain or diarrhoea. Common therapeutic targets are the mechanisms behind anaemia of chronic disease and iron deficiency. It is our experience that virtually all patients with IBD associated anaemia can be successfully treated with a combination of iron sucrose and erythropoietin, which then may positively affect the misled immune response in IBD.

Topics: Anemia, Iron-Deficiency; Chronic Disease; Erythropoietin; Fatigue; Folic Acid; Humans; Inflammatory Bowel Diseases; Iron; Quality of Life; Recombinant Proteins; Vitamin B 12 Deficiency

Topics: Erythropoietin; Ferritins; Hematologic Tests; Hemoglobinometry; Humans; Nuclear Medicine; Radionuclide Imaging; Schilling Test; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia, Hypochromic; Arthritis, Rheumatoid; Erythropoiesis; Erythropoietin; Ferritins; Hemosiderin; Humans; Transferrin; Vitamin B 12 Deficiency

In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of "anemia of unknown etiology" and whether this trend persists after accounting for confounders.. This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index.. A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities.. We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology.

Topics: Aged; Aged, 80 and over; Anemia; Anemia, Iron-Deficiency; Biomarkers; Chronic Disease; Comorbidity; Erythropoietin; Female; Folic Acid Deficiency; Glomerular Filtration Rate; Hematologic Tests; Hemoglobins; Humans; Linear Models; Male; Middle Aged; Myelodysplastic Syndromes; Renal Insufficiency, Chronic; Retrospective Studies; Vitamin B 12 Deficiency

Topics: Adult; Anemia, Hypochromic; Arthroplasty, Replacement, Hip; Chronic Disease; Colitis; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Ferric Compounds; Folic Acid; Humans; Intestinal Polyps; Leucovorin; Malabsorption Syndromes; Male; Methotrexate; Osteoarthritis, Hip; Preoperative Care; Recombinant Proteins; Rectal Diseases; Remission Induction; Spondylitis, Ankylosing; Time Factors; Vitamin B 12; Vitamin B 12 Deficiency

In rats, in contrast with human subjects who develop megaloblastic anaemia due to vitamin B12 deficiency, haematological abnormalities with anaemia were not observed under normoxic conditions even though plasma vitamin B12 concentration was reduced to <15 % of a normal concentration by depleting dietary vitamin B12. To elucidate whether erythropoiesis was affected by vitamin B12 deficiency in rats, these vitamin B12-deficient rats were exposed to hypoxia (10.5 % O2) to stimulate erythropoiesis. In the vitamin B12-sufficient control rats, erythrocyte count was significantly (P<0.05) increased 1 week after starting the hypoxic exposure. However, the hypoxia-induced erythropoiesis was affected by vitamin B12 deficiency, and no significant increase in the erythrocyte count was observed even after 6-week exposure to hypoxia in the vitamin B12-deficient rats. In the vitamin B12-deficient rats in hypoxia, erythrocytes became abnormally enlarged, and haemoglobin concentration in peripheral blood was increased in proportion to the increase of mean corpuscular volume. However, the level of the increase in the haemoglobin concentration was significantly (P<0.05) lower in the vitamin B12-deficient rats compared with that in the -sufficient controls. In addition, in the vitamin B12-deficient rats, in contrast to the -sufficient rats, serum erythropoietin concentration was not normalized even after 6-week exposure to hypoxia. These results indicate that a megaloblastic anaemia-like symptom is induced when the vitamin B12-deficient rats are exposed to hypoxia.

Topics: Analysis of Variance; Anemia, Megaloblastic; Animals; Erythrocyte Count; Erythropoietin; Hypoxia; Male; Methylmalonic Acid; Models, Animal; Rats; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Iron-Deficiency; Chronic Disease; Cytokines; Erythropoietin; Humans; Inflammatory Bowel Diseases; Intestinal Absorption; Quality of Life; Vitamin B 12 Deficiency

Human recombinant erythropoietin (rHu-Epo) is now extensively used in chronic renal failures; this treatment, resulting in a correction of the severe anemias seen in hemodialysed patients, may in turn lead to a resistance to rHu-Epo therapy by reason of the shortage of erythropoiesis factors, such as iron, vitamin B12 and folates. The utility of the red cell indices (MCV, MCH, RDW) for detection of early iron, folate and B12 deficiencies was studied in eighteen hemodialysed patients with end-stage renal failure treated with rHu-Epo; Microcytosis (MCV < 80 fl) was found ineffective in detecting iron deficiencies as well as macrocytosis (MCV > 100 fl) in folate and B12 deficiencies, partly due to the high incidence of associated iron and folate deficiencies. Lowered MCH (< 27 pg) was not more efficient than microcytosis in detecting early iron deficiencies. Increased RDW was the most sensitive feature for folate, iron and B12 deficiencies with respective sensitivities of 62.5%, 72% and 75%. The global specificity for detecting all deficiencies was 74%. However, high RDW values were not indicative of any type of deficiency; it may thus be concluded that RDW is a non expensive, non invasive and sensitive test, which allows a selection of hemodialysed patients treated with rHu-Epo for a complete investigation program, in order to detect early iron, B12 and folate deficiencies.

Topics: Anemia, Hypochromic; Drug Resistance; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Folic Acid Deficiency; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Renal Dialysis; Treatment Failure; Vitamin B 12 Deficiency

Iron deficiency involvement in the results of long-term replacement therapy of renal anemia with recormon, a preparation of recombinant human erythropoietin, has been studied in chronic renal failure patients on programmed hemodialysis. The effect of recormon subcutaneous administration to 51 patients was found reduced in 9 patients; in 5 of them the decreased sensitivity to recormon was attributed to iron deficiency. During a year of treatment the percentage of iron-deficient patients rose from 9.1% to 45% as a result of intensive uptake of iron in the course of erythropoiesis. Iron preparation as a corrective treatment contributed to hematocrit increment reducing effective doses of erythropoietin. In addition to routine control of ferritin and iron it is recommended to trace the degree of transferrin saturation in the course of recombinant erythropoietin therapy.

Topics: Anemia, Hypochromic; Drug Evaluation; Erythropoietin; Ferritins; Folic Acid; Folic Acid Deficiency; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Transferrin; Vitamin B 12; Vitamin B 12 Deficiency

We describe the first reported case of resistance to human recombinant erythropoietin (rhEPO) treatment caused by vitamin B12 deficiency in a chronic hemodialysis patient. Despite a normal B12 level before rhEPO treatment, resistant anemia together with a low B12 level and a megaloblastic bone marrow developed after only 8 months of rhEPO. There was a rapid reticulocyte response to B12 supplements, and transfusion requirements dropped from 2 units monthly to nothing. Atrophic gastritis was diagnosed through endoscopy and biopsy. Because of the fall in B12 level after 8 months of rhEPO treatment, we analyzed the results of routinely measured B12 levels in 30 hemodialysis patients treated with rhEPO, and found the mean B12 levels to be unchanged before and after rhEPO treatment. Although we found screening for B12 deficiency of little benefit, any patient with rhEPO resistance should have B12 levels tested, given the potentially serious extra-hematological effects of B12 deficiency.

Topics: Aged; Anemia; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Vitamin B 12; Vitamin B 12 Deficiency

In order to further study the relation between transferrin receptor and erythropoiesis we examined serum receptor levels in megaloblastic anemia, which is the classic example of ineffective erythropoiesis. We studied 33 patients with unequivocal cobalamin deficiency, only 22 of whom were anemic. High serum transferrin receptor levels were found in 12 patients, all of whom were anemic and had high lactate dehydrogenase (LDH) levels; in contrast, only 10 of the 21 patients with normal receptor levels were anemic. Receptor correlated most strongly with LDH (r = 0.573, p < 0.001) and, inversely, with hemoglobin values (r = -0.560, p < 0.001); it also correlated with ferritin and total bilirubin levels, but not with cobalamin, MCV or erythropoietin. No association was found with the hemolytic component of megaloblastic anemia, represented indirectly by haptoglobin levels. Changes induced by cobalamin therapy were also examined in 13 patients. Transferrin receptors rose in all 6 patients who initially had high levels and in 2 of 3 patients who had borderline levels, but not in the 4 patients with initially normal levels. The receptor levels began to rise within 1-3 days, peaked at about 2 weeks and returned to normal at about the 5th wk. The findings indicate that serum transferrin receptor levels reflect the severity of the megaloblastic anemia. The elevated receptor levels rise further with cobalamin therapy, however, as effective erythropoiesis replaces ineffective erythropoiesis, and these persist until the increased erythropoiesis returns to normal.

Topics: Anemia, Megaloblastic; Bilirubin; Biomarkers; Blood Volume; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; L-Lactate Dehydrogenase; Male; Middle Aged; Receptors, Transferrin; Transferrin; Vitamin B 12; Vitamin B 12 Deficiency

Erythroid alterations were studied in 136 patients with rheumatoid arthritis (RA). Anemia was present in 75 cases. A definite diagnosis was determined in 65. The most frequent anemia was that of chronic disease (ACD) (43 cases); 14 patients with ACD presented with moderate to severe anemia. Prevalence of deficiencies were also high (15 cases had iron deficiency anemia, IDA). Serum erythropoietin levels were different in patients with RA compared with a healthy control group (p < 0.00001). Serum erythropoietin was increased in ACD (49 +/- 28.8 U/l) with respect to both RA (38.6 +/- 12.7 U/l, p = 0.0036) and controls (18.2 +/- 7.6 U/l, p < 0.00001). Although hemoglobin (Hb) was similar in ACD and IDA, serum erythropoietin in ACD was lower than in IDA (p = 0.01). There was a negative relationship between Hb and serum erythropoietin in ACD (r = -0.42, p = 0.005). In conclusion, almost 50% of patients with RA have anemia and ACD is the most frequent. As serum erythropoietin in ACD is blunted, patients with moderate to severe ACD are possible candidates for erythropoietin treatment.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Arthritis, Rheumatoid; Chronic Disease; Erythropoietin; Female; Folic Acid Deficiency; Humans; Male; Middle Aged; Prevalence; Prospective Studies; Vitamin B 12 Deficiency

The major stimulus for erythropoietin secretion is the circulating hemoglobin level, but other poorly understood factors appear to influence the erythropoietin level as well. Therefore, the effect of cobalamin deficiency was studied in patients who were not anemic, even though many of them had macrocytosis or metabolic deficiency of the bone marrow cells. All 15 cobalamin-deficient patients without anemia had normal erythropoietin levels, including the 4 patients with macrocytosis and 3 in whom metabolic cobalamin deficiency of the marrow cells was documented with the deoxyuridine suppression test. Moreover, among 21 cobalamin-deficient patients with anemia, the 4 least anemic patients also had normal erythropoietin levels. The other 17 anemic patients had elevated erythropoietin levels. Erythropoietin levels correlated with the severity of the anemia (r = 0.423, p less than 0.05). However, wide individual variations were observed; 4 patients with hemoglobin levels of 37-43 g/l had erythropoietin levels ranging from 69 to 3300 units/l, for example. These observations support the hypothesis that the hemoglobin level is the major, but not the sole factor that determines erythropoietin levels. As long as it does not produce anemia, however, cobalamin deficiency does not raise erythropoietin levels even when it induces metabolic deficiency of the bone marrow and macrocytosis.

Topics: Anemia; Anemia, Pernicious; Erythropoietin; Hemoglobins; Humans; Vitamin B 12 Deficiency

Topics: Anemia; Animals; Arthritis, Rheumatoid; Chronic Disease; Erythrocyte Aging; Erythropoietin; Female; Folic Acid Deficiency; Humans; Lupus Erythematosus, Systemic; Male; Recombinant Proteins; Vitamin B 12 Deficiency

Thirty six patients with rheumatoid arthritis (RA) (25 with anaemia) were studied to establish the role of iron, vitamin B12, and folic acid deficiency, erythropoietin responsiveness, and iron absorption in the diagnosis and pathogenesis of anaemia in RA. Iron deficiency, assessed by stainable bone marrow iron content, occurred in 13/25 (52%), vitamin B12 deficiency in 7/24 (29%), and folic acid deficiency in 5/24 (21%) of the anaemic patients. Only 8/25 (32%) had just one type of anaemia. The iron deficiency of anaemia of chronic disease (ACD) was distinguished by ferritin concentration, which was higher in that group. Mean cell volume (MCV) and mean cell haemoglobin (MCH) were lower in both anaemic groups, but most pronounced in iron deficient patients. Folic acid, and especially vitamin B12 deficiency, masked iron deficiency by increasing the MCV and MCH. Iron absorption tended to be highest in iron deficiency and lowest in ACD, suggesting that decreased iron absorption is not a cause of ACD in RA. No specific causes were found for vitamin B12 or folic acid deficiency. Haemoglobin concentration was negatively correlated with erythrocyte sedimentation rate in the group with ACD. Erythropoietin response was lower in ACD than in iron deficient patients. It was concluded that generally more than one type of anaemia is present simultaneously in anaemic patients with RA. The diagnosis of each type may be masked by another. Studies on pathogenesis of the anaemia are difficult as deficiencies generally coexist with ACD. Disease activity and, possibly, erythropoietin responsiveness are major factors in ACD pathogenesis.

Topics: Aged; Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Bone Marrow; Chronic Disease; Erythropoietin; Female; Folic Acid Deficiency; Humans; Iron Deficiencies; Male; Middle Aged; Vitamin B 12 Deficiency

Various factors are involved in the pathogenesis of anemia in dialysis patients. Reduced erythropoiesis is mainly attributed to erythropoietin deficiency. Stimulation of erythropoiesis may be promoted by androgens. Substitution of iron is recommended in case of iron deficiency. As a rule, supplementation of vitamin B12 is not necessary, but administration of folic acid is recommended. Treatment of anemia in renal failure is rendered more effective by increased technical efficiency in hemodialysis permitting a relatively protein-rich diet. Blood transfusions are not necessary during routine treatment of dialysis. Since bilateral nephrectomy will always provoke severe anemia, it should be reserved to special cases of severe hypertension. Until now, no conservative therapy has been developed which would allow optimal treatment of anemia in dialysis patients. Successful renal transplantation still is, and will be, the best therapeutic intervention.

Topics: Androgens; Anemia, Hypochromic; Blood Transfusion; Erythrocytes; Erythropoiesis; Erythropoietin; Folic Acid; Folic Acid Deficiency; Hemoglobins; Hemolysis; Histidine; Humans; Iron; Kidney Failure, Chronic; Renal Dialysis; Splenectomy; Vitamin B 12 Deficiency

Topics: Anemia, Neonatal; Biological Transport; Birth Weight; Cell Survival; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Folic Acid Deficiency; Hemoglobins; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Iron Deficiencies; Oxygen Consumption; Pregnancy; Reticulocytes; Vitamin B 12 Deficiency; Vitamin E Deficiency

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Macrocytic; Diagnosis, Differential; Erythrocytes; Erythropoietin; Half-Life; Hemorrhage; Humans; Iron; Neoplasms; Vitamin B 12 Deficiency