Erythropoietin increase

It is produced primarily by peritubular cells in the proximal tubule of the kidney. In anaemia renal secretion of erythropoietin increases rapidly manifold. Erythropoietin levels are always detectable in plasma. 

Erythropoietin therapy has been used in only a limited nnmber of patients with SCD and the clinical results have been inconsistent therefore its rontine use in these patients cannot be recommended. When used in combination with hydroxyurea, erythropoietin increases HbF levels to a greater extent than hydroxyurea alone. This suggests that there may be a role for addition of erythropoietin therapy in patients who do not respond to hydroxyurea alone, although more studies are needed. Other proposed combinations are hydroxyurea combined with either penylbutyrate or clotrimazole, based on their different mechanisms of action. ... 

Bierer R, Roohi M, Peceny C, Ohls RK. Erythropoietin increases reticulocyte counts and maintains hematocrit in neonates requiring surgery. J Pediatr Surg 2009 44(8) 1540-5. 

Erythrocyte-stimulating agents Erjdhrocyte-stimulating agents such as erythropoietin increase BP in as many as 20% of patients with anemia or chronic kidney disease... 

There are undifferentiated stem cells of the blood elements in the bone marrow that differentiate and mature into erythrocytes, (red blood cells), thrombocytes (platelets), and white blood cells (leukocytes and lymphocytes). The production of erythrocytes is regulated by a hormone, erythropoietin (see the section on kidney toxicity), that is synthetized and excreted by the kidney. An increase in the number of premature erythrocytes is an indication of stimulation of erythropoiesis, i.e., increased production of erythrocytes in anemia due to continuous bleeding. 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

Anemia may be present in some patients due to impaired erythropoietin regulation, nutritional factors (vitamin E and iron malabsorption), or chronic inflammation. With chronic pulmonary disease, increased cytokine production can lead to shortened red blood cell survival, reduced erythropoietin response, and impaired mobilization of iron stores. 

The progenitor cells of the kidney produce 90% of the hormone erythropoietin (EPO), which stimulates red blood cell (RBC) production. Reduction in nephron mass decreases renal production of EPO, which is the primary cause of anemia in patients with CKD. The development of anemia of CKD results in decreased oxygen delivery and utilization, leading to increased cardiac output and left ventricular hypertrophy (LVH), which increase the cardiovascular risk and mortality in patients with CKD. 

The first-line treatment for anemia of CKD involves replacement of erythropoietin with erythropoiesis-stimulating agents (ESAs). Use of ESAs increases the iron demand for RBC production and iron deficiency is common, requiring iron supplementation to correct and maintain adequate iron stores to promote RBC production. Androgens were used extensively... 

Studies have shown that in patients with chemotherapy-related anemia, therapy with erythropoietin products (epoetin-alfa and darbepoetin) can increase hemoglobin, decrease transfusion requirements, and improve quality of life.12 Epoetin is recombinant human erythropoietin, and darbepoetin is structurally similar to endogenous erythropoietin. Both bind to the same receptor to stimulate red blood cell production. Darbepoetin differs from epoetin in that it is a glycosylated form and exhibits a longer half-life in the body. The half-lives of a single subcutaneous injection of epoetin or darbepoetin in patients are roughly 27 and 43 hours, respectively. 

The response to erythropoietin products must be monitored closely to prevent adverse effects associated with these agents. The common adverse effects experienced include hypertension and thrombosis. Concomitant drugs with the same adverse-effect profile may increase a patient s risk for these complications. Also, the patient s overall survival may be decreased if the hemoglobin level is titrated to above the recommended 11 to 12 g/dL (110-120 g/L or 6.82-7.44 mmol/L) value. Therefore, it is important to follow the dosing and titration scheme recommended by the NCCN and summarized in... 

Do not exceed more than 1 g/dL (10 g/L or 0.62 mmol/L) every 2 weeks when using erythropoietin products to increase hemoglobin. Otherwise, decrease the dose of the erythropoietin product. 

Very limited information is available on the use of combination therapy for potentiation of HbF production. Erythropoietin has shown inconsistent results in small numbers of patients. When used with hydroxyurea, erythropoietin has been shown to increase HbF to a greater extent than hydroxyurea alone, and although more studies are needed, this may provide an option for patients who do not respond to hydroxyurea alone.27... 

In the beginning of the eighties, the clinical application of DFO expanded to a new type of patient, namely those on maintenance dialysis. As we will see in Chapter 12, some patients suffered from aluminium overload, mostly due to the use of aluminium salts as phosphate binders, while others had obvious transfusional iron overload in the pre-erythropoietin era. DFO was therefore used either to remove aluminium, excess iron or both. Nephrologists established that DFO therapy did not increase the overall incidence of bacterial infections but that it slightly increased the risk of bacteraemia caused by Y. enterocolitica or Y. pseudotuberculosis, as had been previously observed in thalassaemic patients (Boelaert et ah, 1987 Tielemans et ah,... 

To date, three pharmaceutical companies have entered clinical trials with PHD inhibitors for the treatment of anemia with the most advanced being FG-2216. In clinical studies, compound 2 (likely FG-2216) showed a dose- and time-dependent elevation of plasma erythropoietin after oral administration [66]. Healthy volunteers were orally administered various doses of compound 2 and serum erythropoietin (EPO) concentrations were measured at various times. Compound 2 increased serum EPO levels in a dose-dependent manner and, following administration of the 20 mg/kg dose, a 5-fold increase of EPO levels was observed after 12 h. In the same patent application, the effect of 2 on anemic predialysis patients with no previous rh-EPO exposure was also disclosed. Patients were treated with 2 three times/week for 4 weeks (no dose reported) and the hemoglobin levels were assessed on day 42. The patients who received treatment showed a mean increase in hemoglobin of 1.9 g/dL from baseline values, whereas subjects who received placebo showed a mean decrease of 0.35 g/dL from baseline levels. These data suggest for the first time that an oral PHD inhibitor could be effective for the treatment of anemia. 

Further details of the above study were discussed in U.S. EPA (1994). After the last exposure, methemoglobin levels were elevated in a dose-dependent manner 17 ppm, 0% to 2.9% (no different from controls) 45 ppm, 2.2% to 5.4% and 87 ppm, 4.2% to 23%. The animals exposed at 45 and 87 ppm were anemic with decreases in RBC counts, hemoglobin content, MCHb concentration, and hematocrit, and accompanying increases in erythropoietin foci, reticuloendothelial cell hypertrophy, and hemosiderin deposition in the spleen. The animals in the 87-ppm exposure group were judged cyanotic. In the 17-ppm exposure group, effects were limited to mild splenic congestion. 

The pathogenesis of hypertension in patients with CKD is multifactorial and includes fluid retention, increased sympathetic activity, an endogenous digitalis-like substance, elevated levels of endothelin-1, erythropoietin use, hyperparathyroidism, and structural arterial changes. 

Erythropoeitins are used to treat symptomatic anaemia associated with erythropoietin deficiency in chronic renal failure and to shorten the period of symptomatic anaemia in patients receiving cytotoxic chemotherapy. It is not recommended for use in cancer patients who are not receiving chemotherapy. In cancer patients, the risk of thrombosis and related complications might be increased. The haemoglobin concentration should be maintained within the range of 10-12 g/100 ml - higher concentrations should be avoided to reduce risk of complications of therapy. 

Erythropoietin release is stimulated by hypoxia (low PO2). Within hours, the hormone ensures that erythrocyte precursor cells in the bone marrow are converted to erythrocytes, so that their numbers in the blood increase. Renal damage leads to reduced erythropoietin release, which in turn results in anemia. Forms of anemia with renal causes can now be successfully treated using erythropoietin produced by genetic engineering techniques. The hormone is also administered to dialysis patients. Among athletes and sports professionals, there have been repeated cases of erythropoietin being misused for doping purposes. 

Pharmacology Erythropoietin is a glycoprotein that stimulates red blood cell production. It is produced in the kidney and stimulates the division and differentiation of erythroid progenitors in bone marrow. Hypoxia and anemia generally increase the production of erythropoietin, which in turn stimulates erythropoiesis. In patients with CRF, erythropoietin production is impaired this deficiency is the primary cause of their anemia. Epoetin alfa stimulates erythropoiesis in anemic patients on dialysis and those who do not require regular dialysis. 

The impact of anemia on outcomes in heart failure is well documented. Horwich et al. documented a 16% increased risk of death with each 1 g/dL decrease in hemoglobin [53]. Secondary to these findings, erythropoietin (EPO) has been used in... 

The kidney normally manufactures erythropoietin, the growth factor for the production of red blood cells. In fact, erythropoietin was first isolated from the urine of patients with anemia, a condition characterized by too few red blood cells. Red cells carry oxygen to the body s tissues, and if too little oxygen is delivered to them, certain kidney cells produce erythropoietin. Most of this substance goes into the blood, where it circulates to the bone marrow and other tissues and triggers increased production of red cells from immature cells. Some erythropoietin spills into the urine. The concentration of erythropoietin in the blood is very low. The concentration is even lower in urine, but urine is easy, safe, and cheap to collect, and it does not contain a large number of other proteins. 

Patients are initially grouped by independent measurements of red cell mass and plasma volume. Where the latter is contracted the increase in packed red cell volume or haemoglobin in the peripheral blood is spurious or relative. In true erythrocytosis the red cell mass, and often the plasma volume, are both expanded. These individuals are further subdivided, depending upon whether tissue oxygenation is impaired, with consequent activation of normal physiological mechanisms. Conversely, this situation may reflect pathological production of erythropoietin or uncontrolled overgrowth of red cells in the chronic myeloproliferative syndrome. 

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