The Newest Research Information for EPO Clinical Application
The erythropoietin(EPO) is a kind of active glycoprotein, mainly synthesized by the kidney. It binds to its receptors that express in erythrocyte surface to stimulate the proliferation and differentiation of hematopoietic cells in macaques bone marrow. Recombinant human erythropoietin (rhuEPO) is one of first use clinical genetic engineering drugs. Initially it was used mainly for chronic renal anemia. Since then, the clinical application of EPO was extended progressively as researchers gain deeper understanding of the pathophysiological processes correlation between anemia with diseases, and the relationships among the EPO, iron and formation red blood cells.
Hepatitis C Virus Infection
Interferon-α combined with ribavirin treatment of HCV infection has become the standard first-line program. However, ribavirin caused a dose-dependent, reversible anemia and interferon α-induced bone marrow suppression often influence the course of treatment, and even interrupt the treatment. Combination with EPO in the treatment stage can mitigate the degree of anemia and avoid interruption of antiretroviral treatment. Clinical study results suggest that after a weekly subcutaneous injection of 40,000UEPO, the hemoglobin level of patients becomes higher than the control group, and there is no need to reduce the ribavirin dose.
Acquired Immunodeficiency Syndrome (AIDS)
The AIDS anemia is the most common hematologic abnormalities. It aggravated with the development of the disease. The first anti-retroviral drugs - AZT (zidovudine) is bone marrow inhibition, particularly in the role of high-dose applications. Therefore, simultaneous application of the anti-HIV infective treatment combined EPO treatment has potential advantages. 4 results of total 255 cases of acceptance of zidovudine therapy in patients with AIDS to participate in the randomized, placebo-controlled clinical studies have shown that subcutaneous injection of EPO 3 times a week, every time 150 ~ 300U can significantly increase the hematocrit (HCT), and reduce the demand for blood transfusion .
Chronic Kidney Disease
Chronic kidney disease is often accompanied by normocytic normochromic anemia. It can lead to cardiac dysfunction, decline in cognitive function, reduce immune response, children with development retardation, decrease quality of life and shorten survival time of physiological and pathological abnormalities. Since 1986 EPO has been successfully used in clinical treatment to adults and children with chronic renal anemia, there are significantly improvements including the survival rate of pre-dialysis and dialysis patients, hospitalization risk, disability rates, the progress of disease, and the quality of life. In order to ensure the safety of oxygen usage, the normal physiological function and quality of life, the National Kidney Fund recommended target hemoglobin in patients with chronic kidney disease should be set at the value of 110 ~ 120 g / L, hematocrit 33% ~ 36%. The results of recent studies suggested that when patients with mild chronic kidney disease showed clinical hemoglobin decline that should be given EPO treatment, in order to reduce its evolution to congestive heart failure, stroke and other serious complications of the process.
Malignant tumor
Anemia associated with tumors is mainly chronic anemia. Serum EPO levels are higher than normal, but still lower than a similar hemoglobin concentration of patients with iron deficiency anemia and hemolytic anemia. The above-mentioned symptoms are related to reducing synthesis of EPO or decreasing the response to anemia, and high doses of exogenous EPO may help to improve the symptom. The study also confirmed that, EPO can improve hemoglobin levels of patients treated with radiotherapy and radiotherapy plus chemotherapy reduce transfusion needs and improve patients’ life quality. Studies have shown that the model mouse of multiple myeloma administered with EPO can significantly prolong their life cycle, and reduce fatality rate, suggesting that, in addition to play a role in promoting the features, EPO erythropoietin may also have anti-tumor biological effects.
Central nervous system disease
The recent study shows that EPO can protect the brain from brain trauma, stroke, epilepsy, and patients with autoimmune encephalitis from neuronal damage. When the central nervous system is is-chemia and anoxic state, the macroglia cell and neurons can produce EPO, therefore the physiological EPO can not provide enough oxygen refer to cardio-cerebral vascular events, blunt brain trauma and status epilepticus of ischemia and hypoxia. Thus, exogenous EPO on these patients has important clinical significance. Traditionally, it is thought difficult for EPO glycoprotein macromolecules to go through the blood-brain barrier, but by using the capillary endothelial receptor expression in the combination of technology, it will be possible for EPO to enter the central nervous system.
Improving Cognitive Function
Some of interventions treatments, such as coronary artery bypass grafting, thoracic tumor combined with chemotherapy can often lead to impair cognitive function, which may be related to the reduction of oxygen supply in central nervous system. Based on experiments, the EPO has neuroprotective effect and can improve the life quality of anemia patients with cancer. Clinical research that focuses on tumor patients after chemotherapy investigates the relationship between hemoglobin decrease and the cognitive function. EPO delayed those patients’ cognitive function. The results showed that as hemoglobin decreases, the cognitive function would be damaged indeed, during which the use of 40000UEPO weekly subcutaneous administration of 1, patients with cognitive function will be improved.
Congestive heart failure
Patients with congestive heart failure often suffer anemia, and the heart failure is positively related to severity of anemia. Animal experiments and clinical studies have shown that ischemic heart hypertrophy is highly sensitive to the anemia. Chronic severe anemia often leads to water-sodium retention, which can be improved with the improvement of anemia. A retrospective analysis including 142 cases of patients showed that cardiac function in patients with I-class for the 9% risk of anemia, and cardiac function grade Ⅳ anemia incidence as high as 79%. Of which 26 cases of cardiac function in patients with grade Ⅳ accepted (7.2 ± 5.5) months, including the intervention of EPO and iron therapy, hemoglobin and cardiac function improved significantly than that before treatment, left ventricular ejection fraction increased over 28% before treatment. At the same time reducing the demand for furosemide, 92 percent lower risk of hospitalization, renal failure delayed the process, and did not find any significant adverse reaction.
Critical illness.
Anemia is a common complication of patients with critical illness, and directly casuse blood transfusion requirements, as well as a direct result of the increase in fatality rate, about 40% of intensive care unit (ICU) patients who have received blood transfusion therapy. Aged patients, as well as longer ICU stay patients have a higher proportion of blood transfusion. Patients with critical illness cure weaken of endogenous EPO companied by compensatory function and iron metabolism disorders, may reduce the number of such patients needs blood transfusion by timely given some exogenous EPO.A number of randomized, double-blind, placebo-controlled clinical studies have shown that a daily 300 units / kg subcutaneous injection of EPO and 1 times per week subcutaneous injection of 40,000 units of EPO able to reduce the number of red blood cell transfusion, increased HCT, but the study did not assessed the relationships of the number of blood transfusion reduced and clinical findings.
Adverse reactions and Instruction.
The common adverse reactions of EPO is including fever, vomiting, diarrhea, shortness of breath, paresthesia, and upper respiratory tract infection. Anemia associated with chronic kidney disease, after treatment with EPO, will often have high blood pressure, so if it has not been a good control of blood pressure of hypertensive patients should be banned. A prospective randomized clinical study found that with heart disease in hemodialysis patients receiving EPO treatment, the hematocrit patients rose to 42%, fatality rate of hematocrit patients is higher than 29%, and non-fatal myocardial infarction and other thrombotic event rate are higher. When perioperative patients are given EPO, the potential of thrombotic events shall be discussed. A small number of patients with renal failure can occur pure red cell aplasia after EPO treatment.