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Chronic renal failure is almost invariably accompanied by symptomatic anemia. It has been demonstrated that the primary cause of this anemia is inadequate production of erythropoietin by the diseased kidneys. The isolation of erythropoietin, followed by the cloning and expression of the human erythropoietin gene, made possible clinical trials of rHuEPO in uremic patients. rHuEPO produced dramatic increases in the hematocrit in almost all patients treated and also ameliorated many symptoms, such as lethargy, dizziness, and poor appetite, that had long been attributed to the effect of uremic toxins. Adverse effects of treatment with rHuEPO noted in the early clinical trials included hypertension, seizures, arteriovenous fistula or shunt thrombosis, and hyperkalemia. Further study of rHuEPO has shown that many of these side effects may be no more frequent in patients receiving rHuEPO than in other uremic patients not receiving rHuEPO. Reduction of the rHuEPO dosage and subcutaneous administration produce less rapid increases in the hematocrit and may lessen the incidence and severity of these side effects. rHuEPO therapy places great demands on both the body's iron stores and the capacity to rapidly transfer iron from storage sites to the erythroid progenitor cells. Thus, almost all patients treated with rHuEPO become iron deficient and require oral or parenteral iron replacement. Response to rHuEPO in uremic patients is diminished if the anemia is complicated by iron deficiency, inflammatory disorders, aluminum overload, or deficiency of folate or vitamin B12. rHuEPO therapy is safe and effective in the treatment of the anemia of chronic renal failure. The use of rHuEPO leads to enhanced quality of life and eliminates the need for red cell transfusions. In addition to hemodialysis patients, predialysis patients and those on CAPD benefit from and are candidates for rHuEPO therapy.
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PMID:Anemia of renal failure. Use of erythropoietin. 157 66

In order to examine the efficacy and safety of long-term erythropoietin (rHuEPO) therapy, 103 hemodialysis patients were treated with rHuEPO for their renal anemia and the effects were observed for 1 year. Within 3 or 4 months after starting the rHuEPO therapy, the hematocrit (Ht) value rose up to nearly 30% and the level was maintained thereafter by approximately 4500 IU per week of rHuEPO. Tachyphylaxis did not occur even after 1 year of rHuEPO treatment. Symptoms such as headache, dizziness or palpitation were markedly reduced with the improvement of anemia. Although blood pressure was modestly elevated (systolic by 9 mmHg, p < 0.01 and diastolic by 5 mmHg, p < 0.01 at 6-month-stage), only 1 patient was forced to stop the therapy. Moreover, the blood pressure was successfully controlled to the original level after 11 months. This blood pressure elevation was not related to the increase of Ht level nor the dose of rHuEPO. Serum protein, lipid, electrolytes and liver enzymes did not change during 1 year of rHuEPO therapy. These results indicate that rHuEPO treatment is effective and innocuous as a long-term therapy of renal anemia in hemodialysis patients.
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PMID:[Efficacy and safety of long-term erythropoietin therapy in chronic hemodialysis patients with renal anemia]. 831 80

Many patients are donating their own blood before surgery to avoid blood-borne infections, often on the advice of their physicians. But autologous blood transfusion, while safer than allogeneic transfusion, is not completely risk-free. It is also expensive, its benefits are difficult to assess, and its increasing popularity raises many difficult ethical issues, such as whether the benefit of allogeneic transfusion supports its additional expense. Record-keeping, collection, and transfusion errors are occasional risks of autologous transfusions. In addition, risks associated with blood donation, from mild dizziness to precipitation of angina, should be considered when high-risk patients are referred for autologous collection. Only approximately half of autologous units collected are actually used, and the cost per quality-adjusted year of life saved may be as high as $1 million, depending on the type of surgical procedure. Although recombinant human erythropoietin can stimulate red blood cell production before autologous donation and decrease the need for transfusion, it is not clear whether this strategy, which can cost thousands of dollars per patient, will be cost-effective. Perioperative hemodilution may become an important component in efforts to reduce patient exposure to allogeneic blood, but its use remains controversial.
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PMID:Preoperative autologous blood donation: clinical, economic, and ethical issues. 887 Mar 40

Anaemia, manifesting as fatigue, dizziness, dyspnoea and anorexia, is common among patients with cancer. A host of factors, such as neoplastic bone marrow infiltration, impaired haematopoiesis, autoimmune haemolysis, impaired endogenous erthropoietin production and treatment with cytotoxic agents contribute to the underlying pathology. Traditionally, blood transfusions have formed the mainstay of therapy for the treatment of cancer-related anaemia. Numerous clinical trials have subsequently confirmed the safety and therapeutic utility of recombinant human erythropoietin (rHuEPO) in anaemic cancer patients, including those with haematological malignancies, such as multiple myeloma and non-Hodgkin's lymphoma. Indeed, well over 50% of unselected patients treated with rHuEPO can be expected to respond with increases in haemoglobin level and/or elimination of transfusion need. In addition, a low baseline serum erythropoietin level can identify those patients with haematological malignancies having a very high likelihood of responding to rHuEPO therapy. These findings, in combination with the possibility of titrating to a lower, maintenance dose, have improved the cost-benefit relationship and thus support the use of rHuEPO as an appropriate alternative to blood transfusions for the management of anaemic patients with lymphoma and myeloma.
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PMID:The role of recombinant human erythropoietin in the management of anaemic cancer patients: focus on haematological malignancies. 1118 81

Combination drug therapy and enhanced patient management techniques result in increased survival for many AIDS patients. This phenomenon has brought the issue of fatigue, a common and difficult side effect of HIV/AIDS treatment, to the forefront. Three-quarters of the AIDS patients surveyed in a recent study indicated that fatigue negatively affects their quality of life and influences their willingness to continue aggressive treatment. New advances for combating fatigue include the use of nutritional therapy, anti-depressants, anti-infectives, medications that boost the production of red blood cells, hormone replacement, exercise, massage, and acupuncture. The most common source of fatigue in HIV-positive patients is anemia, which also causes shortness of breath and dizziness. Anti-HIV medications may inhibit red blood cell production. An alternative treatment, Epoetin alfa, works by increasing low levels of naturally producing erythropoietin, a protein manufactured in the kidneys. Fatigue resulting from low testosterone levels can be treated with anabolic steroids. Poorly functioning adrenal glands can be the cause of fatigue in patients with advanced disease. Taking hydrocortisone pills is often effective. Depression is the fourth most common cause of fatigue. Antidepressants work well without traditional side effects.
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PMID:More awareness needed in treatment of fatigue. 1136 53

The symptoms and severity of anemia depend on various factors, including the degree of anemia, the rapidity of its onset, and the age and physiologic status of the patient. Although the human body tries to counterbalance the effects of anemia by various mechanisms, almost every organ system of the human body is eventually affected. The symptoms experienced by patients vary from cold skin, dizziness, and palpitations to pulmonary edema, heart failure, depression, and severe impairment of cognitive function. Anemia substantially impacts patients' quality of life, a fact that has been shown in several clinical trials in patients with renal disease as well as in patients suffering from various malignancies undergoing chemotherapy. These studies evaluated the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) to anemic patients, and it was shown that raising hemoglobin levels with epoetin alfa ameliorated the symptoms of anemia and significantly improved the functional status and overall quality of life in cancer patients. Furthermore, preliminary data indicate that the correction of anemia in cancer patients may in addition improve treatment efficacy and possibly overall survival.
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PMID:Symptomatology of anemia. 1139 46

Anemia is a common complication in patients with hematologic malignancies, and is caused by a variety of mechanisms, including neoplastic cell infiltration into the bone marrow, hemolysis, nutritional deficiencies, and defects in erythropoiesis as a result of the disease itself or cytotoxic therapy. The anemia associated with multiple myeloma is caused by inadequate erythropoietin levels consequent to renal impairment and the effect of inflammatory cytokines. The degree of anemia can have prognostic importance, as is the case with multiple myeloma, or be a significant indicator of disease stage, as noted with chronic lymphocytic leukemia. Anemia results in fatigue, exhaustion, dizziness, headache, dyspnea, and decreased motivation, seriously affecting a patient's quality of life. Since anemia is so prevalent in hematologic malignancy patients, its treatment must be an integral part of disease management, to improve quality of life and to possibly increase potential survival. Clinical studies have shown that effectively treating anemia and increasing hemoglobin levels using recombinant human erythropoietin (rHuEPO, epoetin alfa) has a significant effect on transfusion requirements and quality of life.
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PMID:The effects of anemia in hematologic malignancies: more than a symptom. 1208 53

Posttransplant erythrocytosis (PTE) is defined as a persistently elevated hematocrit to a level greater than 51% after renal transplantation. It occurs in 10% to 15% of graft recipients and usually develops 8 to 24 months after engraftment. Spontaneous remission of established PTE is observed in one fourth of the patients within 2 years from onset, whereas in the remaining three fourths it persists for several years, only to remit after loss of renal function from rejection. Predisposing factors include male gender, retention of native kidneys, smoking, transplant renal artery stenosis, adequate erythropoiesis prior to transplantation, and rejection-free course with well-functioning renal graft. Just as in other forms of erythrocytosis, a substantial number (approximately 60%) of patients with PTE experience malaise, headache, plethora, lethargy, and dizziness. Thromboembolic events occur in 10% to 30% of the cases; 1% to 2% eventually die of associated complications. Posttransplant erythrocytosis results from the combined trophic effect of multiple and interrelated erythropoietic factors. Among them, endogenous erythropoietin appears to play the central role. Persistent erythropoietin secretion from the diseased and chronically ischemic native kidneys does not conform to the normal feedback regulation, thereby establishing a form of "tertiary hypererythropoietinemia." However, erythropoietin levels in most PTE patients still remain within the "normal range," indicating that erythrocytosis finally ensues by the contributory action of additional growth factors on erythroid progenitors, such as angiotensin II, androgens, and insulin-like growth factor 1 (IGF-1). Inactivation of the renin-angiotensin system (RAS) by an angiotensin-converting enzyme (ACE) inhibitor, or an angiotensin II type 1 AT1 receptor blocker represents the most effective, safe, and well-tolerated therapeutic modality.
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PMID:Posttransplant erythrocytosis. 1263 34

Cancer-related anemia often develops from the infiltration of marrow by malignant cells, impaired hemoglobin (Hb) production related to chemotherapy or radiation therapy, iron deficiency, or low endogenous erythropoietin levels. Patients with cancer-related anemia may experience cognitive dysfunction including decreased mental alertness, poor concentration, and memory problems. Anemia-mediated cerebral hypoxia may cause symptoms such as headache, vertigo, tinnitus, and dizziness. These symptoms often are exacerbated in the elderly patient with cancer and related to underlying low Hb concentrations. Restoring Hb levels via the administration of iron supplements, blood transfusions, or, more recently, erythropoiesis-stimulating therapy (epoetin alfa) results in significant improvement of cognitive function. The use of epoetin alfa as a treatment option for patients with chemotherapy-associated anemia and an Hb concentration less than 10 g/dL has been recommended by the American Society of Clinical Oncology and the American Society of Hematology. Erythropoiesis-stimulating therapies are a promising treatment option for cancer-related anemia that may improve cognitive function and quality of life for patients with cancer.
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PMID:Anemia in the oncology patient: cognitive function and cancer. 1502 12

Anemia is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) that is commonly overlooked, despite its significant impact on quality of life. Characteristic symptoms include chronic fatigue, headache, and subtle impairment of cognitive function, although some less common symptoms include dyspnea, dizziness, pica, angular stomatitis, shortened attention span, and esophageal webs. Several types of anemia are associated with IBD, but iron deficiency anemia (IDA) accounts for the majority of cases and others include anemia of chronic disease, anemia associated with vitamin deficiency (vitamin B12 and folate), autoimmune anemia, and anemia caused by medication used to treat IBD. The diagnosis of IDA relies on laboratory blood tests. Therefore, these tests should be obtained on a regular basis because characteristic symptoms may be absent or not readily recognized by patients and their clinicians. Complete blood count may suffice; however, iron studies and serum vitamin levels may be necessary to differentiate between specific types of anemia. During the diagnostic process, it is important to consider coexistence of different types of anemia, especially if no response to therapy is noted. The therapy for anemia is directed towards treatment of the underlying inflammatory process and supplemental therapy, depending on the type of deficiency. Iron deficiency anemia is treated with iron preparations, first orally, and if unresponsive or if associated with untoward adverse events leading to decrease in adherence with the therapeutic regimen, with intravenous preparations. Intramuscular therapy has been abandoned due to high rate of complications. Intravenous therapy may be administered as a multiple-dose regimen (intravenous iron sucrose and gluconate) or as a single intravenous dose (iron dextran), which is associated with a higher risk of allergic infusion reactions and requires obligatory test dose administration. Treatment with erythropoietin is reserved for a select subgroup of patients with anemia of chronic disease. With appropriate treatment, the majority of patients with IBD will have significant improvement or resolution of anemia, which can lead to a better quality of life. However, a high index of suspicion should be maintained in order to identify the precise cause of anemia and to prescribe the appropriate therapy.
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PMID:Treatment of iron deficiency anemia in pediatric inflammatory bowel disease. 1616 7


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