Subcutaneous Administration Of Erythropoietin Research Articles

CPC-081 Management of Severe Anaemia with Recombinant Human Erythropoietin in a Jehovah’s Witness Patient: Case Report and Review of Literature

BackgroundThe medical care of Jehovah’s Witness patients, because they refuse blood transfusion, becomes problematic in cases of severe life-threatening anaemia.Purpose To describe the case of a patient with severe anaemia...

Anemia in Heart Failure: an Overview of Current Concepts

Chronic heart failure is a substantial public health problem. Anemia is an important comorbidity frequently observed in patients with the disease and, in heart failure, anemia has only recently started to attract systematic epidemiological and therapeutical research endeavor. This article describes the many aspects of anemia in chronic heart failure, starting with the ongoing discussion of how to define anemia, which has important consequences for the estimation of its prevalence and incidence. Further, we discuss prognostic implications of anemia in patients with chronic or acute heart failure, the etiology of anemia in heart failure and treatment possibilities. Such therapeutic avenues embrace intravenous iron preparations and subcutaneous administration of erythropoietin and its derivatives, all of which have been extensively studied over the last several years. Finally, this article describes the potential costs incurred by treating anemic patients with heart failure.

Effect of Route of EPO Administration on Hemodialysis Arteriovenous Vascular Access Failure: A Randomized Controlled Trial

Vascular access failure is a major cause of morbidity and hospitalization in hemodialysis populations worldwide. Erythropoietin (EPO) potentially can contribute to vascular access stenosis and occlusion by promoting intimal hyperplasia and thrombosis. Intravenous administration of EPO results in a severe, but transient, increase in drug concentration within the vascular access, whereas subcutaneous administration leads to a mild, but sustained, increase in the systemic circulation. The effect of route of administration of EPO on vascular access outcomes is uncertain. Randomized controlled trial. 78 Korean hemodialysis patients were randomly assigned to receive either intravenous (n = 40) or subcutaneous (n = 38) EPO. EPO was administered during dialysis, and the dose was titrated to maintain hemoglobin levels between 9 to 12 g/dL. All patients received EPO 2 or 3 times/wk. Study duration was 4 to 77 months. The primary end point was time to vascular access failure. Analysis was performed using Cox regression analysis. The incidence of access failure was 4.7%/patient-year in the intravenous-therapy group and 12.0%/patient-year in the subcutaneous-therapy group, with an unadjusted hazard ratio of 3.24 (95% confidence interval, 1.31 to 8.00; P = 0.01). After adjustment for dialysis access type, vascular access age, previous intervention, serum phosphorus level, and diabetes mellitus, subcutaneous EPO administration was independently associated with increased vascular access failure (hazard ratio, 3.56; 95% confidence interval, 1.20 to 10.58; P = 0.02). There were no significant differences in either hemoglobin concentration or EPO dosage between the 2 groups during the study period. Relatively small sample size and lack of complete symmetry between the 2 groups with respect to some baseline characteristics. This study suggests that the risk of vascular access failure may be greater with subcutaneous compared with intravenous administration of EPO in hemodialysis patients.

Aprotinin and recombinant human erythropoietin reduce the need for homologous blood transfusion in cardiac surgery

The effects of low dose aprotinin (Trasylol) and preoperative administration of recombinant human erythropoietin (EPO) were evaluated in 144 patients undergoing cardiopulmonary bypass divided into four groups. Group I (n = 43) received a subcutaneous administration of EPO (18,000 U) one week before operation and intraoperative administration of low-dose aprotinin (mean; 1.38 +/- 0.26 x 10(6) kallikrein inactivator units; KIU) from extracorporeal circulation, group II (n = 39) received only preoperative administration of EPO, group III (n = 28) received only intraoperative administration of low-dose aprotinin (mean; 1.46 +/- 0.25 x 10(6) KIU), and group IV (n = 34) were not administered either drug. Compared with group IV, the intraoperative blood loss was significantly lower in group I (p < 0.01), and in group II or III (p < 0.05). The postoperative drainage in 24 hours was significantly lower in groups I and III receiving aprotinin than in the other groups. The mean volume of total homologous blood transfusion and the percentage of cases not requiring a homologous blood transfusion in each group was, respectively, 74 +/- 235 ml and 88.4% in group I, 282 +/- 1289 ml and 87.2% in group II, 414 +/- 584 ml and 60.7% in group III, and 976 +/- 1931 ml and 44.1% in group IV. Significant differences were recognized between group I and group IV (p < 0.05). These findings indicate that when used in combination, both drugs reduce blood loss and the need for a homologous blood transfusion more effectively than either drug alone.

Érythropoïétine et hypertension artérielle chez l'insuffisant rénal chronique

The induction or the aggravation of a hypertension is a side effect of recombinant human erythropoietin therapy in 30% of dialysed patients. Clinical manifestations can be severe. Pathogenesis of erythropoietin-induced hypertension is ill known. Peripheral vascular changes were found in most studies. Recently, it was demonstrated that erythropoietin increased endothelin-1 release by endothelial cells. Ambulatory blood pressure recording seems to be the best method for evaluating the modification of blood pressure profile during the interdialytic period. Erythropoietin-induced hypertension is easily controlled by drugs, but also by low dose of erythropoietin. Subcutaneous administration of erythropoietin is an approach to avoid the induction of hypertension. Furthermore economical advantages of subcutaneous administration are proven.

Subcutaneous erythropoietin administration in predialysis patients: a single centre prospective study

Since 1991 we have used subcutaneous administration of recombinant human erythropoietin (rHuEpo) in predialysis patients selected on the basis of chronic anaemia [haemoglobin (Hb) < 7.5 g%] without any extrarenal cause and chronic renal failure with a creatinine clearance of less than 10 ml/min. rHuEpo was given to 16 predialysis patients with nephropathy, due to chronic glomerulonephritis in all 12 of the cases. The sex ratio was 1:1 and mean age was 65 +/- 9 years (range 43-87). Hb was 7 +/- 0.4 g%. rHuEpo was injected subcutaneously thrice weekly while iron was given orally systematically before rHuEpo administration. Follow-up was performed monthly until dialysis (mean 9 months). Anaemia was corrected in all cases (Hb 11 +/- 0.5 g%). Mean Epo dose was 53 +/- 26 IU/kg/week in males and 47 +/- 11 IU/kg/week in females. Iron was systematically added (Fe2+ 8.2 mg/kg/week). Every patient had improved physical and intellectual ability after rHuEpo within the first month. No adverse side effects were noted but all patients were under antihypertensive therapy (one to three drugs). Serum potassium was unchanged. Mean creatinine before treatment was 507 mumol/l, and was 820 mumol/l after the treatment. Progression of renal failure was only affected by rHuEpo in one patient. In this case renal failure progression decreased. There was no significant alteration in the slope of the creatinine curve from 12 months before to after rHuEpo. Ten patients underwent dialysis (five CAPD, five haemodialysis), while six remained dialysis free. From January 1991 to December 1993 rHuEpo was given to 12.3% of the end-stage renal failure patients on dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet Intracellular Calcium Is not Modified by Subcutaneous Administration of Erythropoietin

Platelet Intracellular Calcium Is not Modified by Subcutaneous Administration of Erythropoietin

Hemopoietins in Clinical Oncology

Despite major advances in supportive care, neutropenic infections and thrombopenic bleedings remain major lethal treatment- and disease-related complications in patients with malignancy. Moreover, complications of platelet (Plt) and erythrocyte transfusion therapy have become a cause of great concern and shortages of homologous blood products are a constant problem. Suggestions that the application of recombinant human hemopoietins may provide an alternative treatment modality in this patient population is currently being evaluated in clinical trials. Erythropoietin (EPO) has been shown to be effective in the treatment of anemia in patients with bone marrow, infiltrating low-grade non-Hodgkin's lymphoma, multiple myeloma, and in some patients with myelodysplastic syndrome. Preliminary data suggest that subcutaneous administration of EPO results in a higher slope of increasing erythropoietic parameters compared to intravenous administration. Protective effects on normal erythropoiesis have been attributed to EPO in patients receiving chemotherapy. The finding of EPO receptors on megakaryocytes supports the clinical observation of increased Plt production associated with decreased bleeding and transfusion frequencies in a substantial number of patients receiving EPO. Clinical trials with granulocyte-macrophage (GM-CSF) and granulocyte colony stimulating factor (G-CSF) have reached phase III trials. Both factors show high efficacy to shorten or improve neutropenia related to chemotherapy, bone marrow transplant, or underlying disease. Mechanisms responsible for mucosa protection and improved healing of mucositis observed with both factors remain undetermined yet phase I/II evaluation of IL-3 shows multilineage hemopoietic responses including myeloid, erythroid, and megakaryocyte lineages. Possible anti-cancer effects of hemopoietins achieved by direct action or by increased chemotherapy intensity are currently under investigation.

STUDIES ON DETERMINATION OF ERYTHROPOIETIN USING FE59 INCORPORATION IN STARVED RATS.

A description is given of an investigation into the estimation of erythropoietin by means of the Fe59 -incorporation in starving rats after the subcutaneous administration of the test material. The preparation used has been produced with the aid of polyphosphoric acid and DEAE-sephadex. On registration of the hemoglobin concentration and weight loss in the starving rats, it is found that there is hemoconcentration, and this is considered to be of importance for the increased sensitivity to erythropoietin found in the starved animals. The response is found to be the same after the subcutaneous administration of erythropoietin in partially purified form, and in combination with plasma.