losartan-potassium and Anemia--Hypochromic

Topics: Anemia, Hypochromic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Small Cell; Clinical Protocols; Darbepoetin alfa; Data Interpretation, Statistical; Erythropoietin; Female; Filgrastim; Follow-Up Studies; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematinics; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Lung Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Male; Multicenter Studies as Topic; Neoplasms; Neutropenia; Platelet Aggregation Inhibitors; Polycythemia Vera; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Survival Analysis; Thrombocythemia, Essential; Treatment Outcome

In recent years, the question of hemoglobin (Hb) stability in patients with chronic renal failure has attracted the interest of medical experts. One of the most important reasons behind this interest is that maintaining the hemoglobin level within the new narrower target range is highly challenging in clinical practice. According to the results available from observational trials, instability of inter-patient hemoglobin levels may be associated with increased morbidity and mortality. To clarify the questions and answers related to this topic and to prepare an updated summary, we reviewed the scientific literature. With the help of the PubMed portal, the incidence, clinical importance, and reasons of Hb variability were summarized according to the available scientific literature. Hb variability is affected by multiple factors which are connected to the general condition of the patient as well as medical interventions and treatments. Also the fluctuation of serum Hb level is a physiological process and is a healthy sign of the capability of the normal human body to adapt. The characteristics and extent of Hb variability vary in patients with chronic renal failure and this topic requires further clinical research. More precise studies are needed in order to explore the differences in possible Hb variability as well as the change in variability caused by particular treatment methods. Finally, based on the available data, the results of future research, and on board scientific consensus, in a strategy for treatment of renal anemia, we should take into account the questions related to Hb stability and variability.

Topics: Anemia, Hypochromic; Comorbidity; Erythropoietin; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Risk Factors

The cardiovascular state and life quality of patients suffering from chronic renal insufficiency is primarily determined by their haemostatic status. Renal anemia can positively be diagnosed if the glomerular filtration rate diminishes significantly (<60 ml/min/1,73 m 2 ). Other causes of anemia besides renal insufficiency can be excluded in these instances. The primary aim of erythropoietin treatment is to abolish the transfusion demand of patients suffering from renal insufficiency as this could lead to antibody formation and the transduction of viral infections. In case the existence of renal anemia is proved, the target values must be determined. A target value of >11 g/dl hemoglobin should be achieved for at least 85% of the patients in order to get an average hemoglobin level of 12-12,5 g/dl for the whole patient population. During the treatment of renal anemia regulating the iron metabolism of patients is of primary importance. A >5% rate of the hypochromic red blood cells in the blood circulation implies iron deficiency; but a value above 10% positively indicates iron deficiency. The transferric saturation values under 20% indicate functional iron deficiency and this indicator is a good means of following iron treatment. In the case of patients receiving dialysis parenteral input is advised because of poor iron absorption. In national clinical practice several erythropoietin products are available (erythropoietin-alpha, erythropoietin-beta, alpha-darbepoetin and continuous erythropoietin receptor activator, a new product now being introduced). When selecting the appropriate treatment strategy for each patient, the application method, the effect range and cost efficiency of the selected erythropoietin product must be taken into consideration.

Topics: Anemia, Hypochromic; Darbepoetin alfa; Drug Resistance; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kidney Failure, Chronic; Quality of Life; Recombinant Proteins; Renal Dialysis

This is an updated systematic review of 57 trials and 9353 cancer patients from articles, abstracts, and reports published between January 1, 1985, and April 30, 2005, on the effects of epoetin alfa and beta (i.e., epoetin) and darbepoetin alfa (i.e., darbepoetin). We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusion with red blood cell transfusion alone for prophylaxis or treatment of anemia in cancer patients with or without concurrent antineoplastic therapy. The Cochrane Library, MEDLINE, EMBASE, and conference proceedings were searched. Effect estimates and 95% confidence intervals (CIs) were calculated with fixed-effects models. Treatment with epoetin or darbepoetin statistically significantly reduced the risk for red blood cell transfusions (relative risk [RR] = 0.64, 95% CI = 0.60 to 0.68; 42 trials and 6510 patients) and improved hematologic response (RR = 3.43, 95% CI = 3.07 to 3.84; 22 trials and 4307 patients). Treatment with epoetin or darbepoetin increased the risk of thrombo-embolic events (RR = 1.67, 95% CI = 1.35 to 2.06; 35 trials and 6769 patients). Uncertainties remain as to whether and how epoetin or darbepoetin affects overall survival (hazard ratio = 1.08, 95% CI = 0.99 to 1.18; 42 trials and 8167 patients). Caution is advised when using epoetin or darbepoetin in combination with thrombogenic chemotherapeutic agents or for cancer patients who are at high risk for thrombo-embolic events.

Topics: Anemia, Hypochromic; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Incidence; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Risk Assessment; Thromboembolism; Treatment Outcome

Deletions of the long (q) arm of chromosome 5 [del(5q)]occur in patients with myelodysplastic syndromes (MDS) including, but not limited to, those who meet the WHO definition of the 5q- syndrome. Del(5q) MDS patients frequently have symptomatic anemia, and its treatment has traditionally consisted of RBC transfusions and, for some, iron chelation therapy. Erythropoietin, darbepoetin, hypomethylating agents, and lenalidomide can enhance erythropoiesis in MDS patients with anemia, increasing hemoglobin levels and abrogating RBC transfusion requirements. Lenalidomide is particularly active in treating the anemia of del(5q) MDS, which is especially relevant given the low response rate to erythropoietin in this group of patients. In a recent study of 43 MDS patients, 10 of 12 patients (83%) with del(5q) MDS achieved sustained RBC transfusion independence (or a > 2 g/dL increase in hemoglobin), compared with 57% of those with a normal karyotype and 12% of those with other karyotypic abnormalities. Complete cytogenetic remissions were achieved in 75% (nine of 12) of the del(5q) MDS patients, suggesting that lenalidomide targets a fundamental pathogenetic feature of MDS that is more pronounced in the presence of chromosomal 5q deletions. This review highlights some issues about the classification and treatment of del(5q) MDS.

Topics: Anemia, Hypochromic; Azacitidine; Bone Marrow; Chromosome Aberrations; Chromosomes, Human, Pair 5; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Gene Deletion; Hematinics; Hematopoietic Stem Cell Transplantation; Humans; Karyotyping; Lenalidomide; Myelodysplastic Syndromes; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Recombinant Proteins; Thalidomide

Pegylated (PEG)-interferon and ribavirin combination therapy are the standard of care for the treatment of chronic hepatitis C and are associated with a high rate of sustained virologic response. However, there is a high incidence of hematologic side effects with this therapeutic regimen. Hematologic side effects are particularly common; bone marrow suppression caused by interferon may result in neutropenia and thrombocytopenia. Ribavirin is directly toxic to red blood cells and is associated with hemolysis, which is usually dose-related but self-limited. Historically, the traditional management of hematologic side effects of interferon therapy has been dose reduction. However, recent studies have shown that response to therapy is strongly influenced by adherence to optimal doses of interferon and particularly ribavirin. Therefore, there is increasing emphasis on the use of growth factors such as filgrastim and erythropoietin to stimulate bone marrow production of erythrocytes and leukocytes to allow patients to receive the optimal doses of interferon and ribavirin. The incidence, magnitude, and possible mechanisms of hematologic complications associated with interferon and ribavirin are described in this review.

Topics: Anemia, Hypochromic; Antiviral Agents; Clinical Trials as Topic; Drug Therapy, Combination; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematologic Diseases; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Thrombocytopenia

Hematologic side effects (anemia, neutropenia, and thrombocytopenia) of combination therapy with pegylated (PEG)-interferon alfa and ribavirin are commonly encountered during antiviral therapy for chronic hepatitis C (HCV). An important consequence of these side effects is dose modification of PEG-interferon alfa, ribavirin, or both. Dose modification (including discontinuation) diminishes the efficacy of optimal treatment regimen for HCV and may have a negative impact on sustained virologic response. Additionally, fatigue associated with anemia may impair patients' quality of life. The clinical implications of neutropenia or thrombocytopenia are less clear than for anemia; nevertheless, severe infection and bleeding are uncommon. Dose adjustments effectively treat these hematologic side effects, but the resulting suboptimal dosing and potential impact on virologic response are major concerns. Recent attempts to maximize adherence to the optimal treatment regimen have used hematopoietic growth factors rather than dose adjustment to treat side effects. Research on growth factor support has focused on anemia and neutropenia. Epoetin alfa and darbepoetin alfa are erythropoietic growth factors that effectively increase hemoglobin while maintaining the optimal ribavirin dose and improving patients' quality of life. Preliminary work suggests that filgrastim, granulocyte colony stimulating factors, may be an effective treatment of interferon-induced neutropenia. Although this early work shows tremendous promise for managing hematologic side effects of combination therapy for HCV, and potentially enhancing adherence, further research is needed to clarify the efficacy, safety, and cost-effectiveness of growth factors in the management of patients with chronic HCV.

Topics: Anemia, Hypochromic; Antiviral Agents; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Growth Substances; Hematinics; Hematologic Diseases; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Thrombocytopenia

Many patients with breast cancer suffer from anaemia, as a consequence of the disease itself or its treatment. Anaemia has a negative impact on treatment outcome and overall survival, and affects the quality of life (QoL) of patients with cancer. Previously, cancer-related anaemia was treated with blood transfusion, but this is inconvenient, offers only temporary improvement in haemoglobin (Hb) level and is associated with several risks. Consequently, blood transfusion is usually reserved for patients with severe anaemia (Hb levels <8 g/dl). Recombinant human erythropoietin (epoetin) is an effective and convenient treatment for cancer-related anaemia without the risks associated with red blood cell transfusion. Epoetin therapy effectively increases Hb levels, thereby reducing the need for emergency blood transfusion and improving the QoL of patients with anaemia and breast cancer. Epoetin beta is also effective for the prevention of anaemia and reduction of transfusion requirements in patients with a high risk of developing anaemia during chemotherapy. With the increased use of dose-intensified chemotherapy in an attempt to improve response rates, administration of epoetin to prevent anaemia could potentially benefit many patients with breast cancer.

Topics: Adult; Age Distribution; Aged; Anemia, Hypochromic; Breast Neoplasms; Combined Modality Therapy; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Humans; Incidence; Middle Aged; Neoplasm Staging; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Sex Distribution; Survival Rate; Treatment Outcome

The number of diabetic patients with renal disease increased significantly in the last years worldwide. Anemia is an important and frequent component of diabetic nephropathy that may begin early in the course of the chronic renal disease of diabetics, and is more severe in diabetic patients with renal disease than in non - diabetic renal patients controlled for the same level of renal function. The reason for the anemia is decreased erythropoietin level caused by diminished production and, in a lesser degree, by increased excretion of erythropoietin in the urine. There is a close connection between diabetic nephropathy, anemia and cardiovascular complications. On the basis of small studies correction of anemia may decrease the progression of diabetic nephropathy and cardiovascular complications. However, the result of ongoing large randomised controlled studies are required to get "evidence-based" data to prove that correction of anemia has beneficial effects on microvascular and macrovascular diabetic complications, particularly cardiac disease, and on progression of diabetic nephropathy.

Topics: Anemia, Hypochromic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Epoetin Alfa; Erythropoietin; Heart Failure; Humans; Kidney Failure, Chronic; Randomized Controlled Trials as Topic; Recombinant Proteins; Time Factors

Cancer-related anemia is a cytokine-mediated disorder resulting from complex interactions between tumor cells and the immune system. Overexpression of certain inflammatory cytokines results in shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin production. Numerous other factors may also contribute to the development of anemia in cancer patients. The European Cancer Anaemia Survey (ECAS) has provided the most current, comprehensive, prospectively collected data on the incidence and prevalence of anemia among cancer patients, as well as important perspectives on anemia treatment and relationship of hemoglobin and performance status. ECAS enrolled over 15,000 treated and untreated patients with various malignancies from cancer centers in 24 European countries and followed them for up to 6 months. The initial analysis of the ECAS data revealed that 39% of the total cancer patient population was anemic (hemoglobin <12.0 g/dl) at enrollment, although the rate varied according to tumor type, disease status, and cancer treatment status. Of the patients who were not anemic at enrollment and started cancer treatment during the survey, those undergoing chemotherapy--either alone or in combination with radiotherapy--had the highest incidence of anemia (63 and 42%, respectively). Low hemoglobin levels correlated with poor performance status and only 40% of patients who were anemic at some time during the survey received treatment for their anemia. These findings are noteworthy, since a growing body of clinical evidence indicates that the treatment of anemia can significantly improve patients' quality of life and may also improve the clinical outcome.

Topics: Anemia, Hypochromic; Chemotherapy, Adjuvant; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Prevalence; Prospective Studies; Radiotherapy, Adjuvant; Recombinant Proteins

The introduction of recombinant human erythropoietin (rHuEPO) has proven to be a major advance in the therapeutic options available for managing anemia in cancer patients. The results of placebo-controlled clinical trials and large, community-based, open-label studies have confirmed that epoetin alfa, a recombinant human erythropoietin, significantly reduces transfusion requirements, and reliably increases hemoglobin (Hb) levels in anemic (Hb level <12 g/dl) cancer patients undergoing chemotherapy. Increased Hb improves patients' energy level and their ability to perform the activities of daily living, as well as their overall quality of life (QOL). These findings are independent of tumor type and disease status and are comparable in patients receiving nonplatinum- and platinum-based chemotherapeutic regimens. Furthermore, more than a decade of use in clinical trials and by physicians in routine clinical practice has demonstrated that epoetin alfa is safe and well tolerated when used to treat cancer patients with anemia. The availability of epoetin alfa as an alternative to transfusion has changed practices in anemia management; physicians can now treat anemia with the goal of achieving adequate Hb levels to relieve anemia-related fatigue, a major symptom contributing to decreased QOL in cancer patients. Incremental benefit analysis has shown that increasing Hb level from 11 g/dl to 12 g/dl yields the greatest improvement in QOL per 1 g/dl increase in Hb. The demonstrated efficacy of epoetin alfa for increasing Hb levels and improving patient QOL have made this agent a rationale choice for management of cancer-related anemia. Ongoing research will continue to provide new insights into best management of anemia with epoetin alfa in cancer patients.

Topics: Anemia, Hypochromic; Controlled Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Severity of Illness Index

Anemia is common in cancer patients, but its impact is often poorly appreciated. As well as the negative effect of anemia on the quality of life, there is strong evidence that it is associated with poor treatment outcome and reduced survival. The introduction of recombinant human erythropoietin (epoetin) has provided an effective treatment of anemia, without the risk associated with blood transfusion. A recent randomized study of patients with hematological malignancies showed that once-weekly epoetin beta has comparable efficacy at the same overall weekly dose as three-times-weekly treatment. This once-weekly regimen of epoetin beta (NeoRecormon) has been approved by European Regulatory Authorities for patients with lymphoproliferative malignancies and relative erythropoietin deficiency, who are receiving anti-tumor therapy. Darbepoetin alpha (Aranesp) has also recently been approved for once-weekly treatment of anemia in patients with nonmyeloid malignancies receiving chemotherapy. The improved convenience and reduced administration costs associated with a once-weekly treatment may result in more patients receiving the benefits of epoetin therapy.

Topics: Anemia, Hypochromic; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Recombinant Proteins

Anaemia is the most common haematological abnormality encountered by cancer patients. A large European survey of cancer patients (n = 15,367) reported that 67% had anaemia at some point during the survey, and that over 60% of these patients did not receive any treatment for their anaemia. Two other surveys (the FATIGUE surveys) showed that over 75% of cancer patients experienced fatigue at least monthly, with over 30% reporting this symptom on a daily basis. Significantly, patients regarded fatigue as having a greater negative impact on their daily lives than many other cancer- or treatment-related complications, with important emotional and mental consequences including lack of self-motivation, sadness, frustration, and mental exhaustion. Indeed, fatigue was considered so debilitating, 12% of patients felt their quality of life (QoL) was so reduced that they did not wish to continue living. Anaemia is also recognised as an independent predictor of poor prognosis in cancer patients. A systematic review evaluating survival showed a 65% overall increase in the risk of mortality in cancer patients with anaemia. Increasing physicians' awareness of the importance of effectively treating anaemia in cancer patients therefore has the potential to improve prognosis as well as QoL.

Topics: Activities of Daily Living; Anemia; Anemia, Hypochromic; Cost of Illness; Erythropoietin; Fatigue; Humans; Neoplasms; Predictive Value of Tests; Prognosis; Quality of Life; Recombinant Proteins; Risk Assessment; Risk Factors; Survival Analysis; Time Factors; Treatment Outcome

Anaemia is a condition that frequently occurs in patients with cancer, but a recent survey has cast doubt over whether it is being appropriately treated. These findings are disappointing considering the wealth of data showing the effectiveness of epoetin therapy in patients with cancer. Recently, evidence-based guidelines have been published that aim to provide physicians with the latest information required for optimal management of anaemia in patients with cancer. By increasing physician awareness of the appropriate therapy for anaemia management, more patients may receive the benefits of epoetin therapy.

Topics: Anemia, Hypochromic; Erythropoietin; Evidence-Based Medicine; Humans; Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Recombinant Proteins

Recombinant human erythropoietin (epoetin) has become the standard of care in the treatment of anaemia resulting from cancer and its treatment, and chronic kidney disease. The discovery that erythropoietin and its receptor are located in regions outside the erythropoietic system has led to interest in the potential role of epoetin in other tissues, such as the central nervous system. Animal studies have shown that systemically applied epoetin can cross the blood-brain barrier, where it reduces tissue injury associated with stroke, blunt trauma and experimental autoimmune encephalomyelitis. Pilot studies in humans have shown that epoetin treatment given within 8 h of stroke reduces infarct size and results in a significantly better outcome when compared with placebo treatment. Studies also suggest that epoetin has the potential to improve cognitive impairment associated with adjuvant chemotherapy in patients with cancer. Anaemia is a major factor causing tumour hypoxia, a condition that can promote changes within neoplastic cells that further tumour survival and malignant progression and also reduces the effectiveness of several anticancer therapies including radiotherapy and oxygen-dependent cytotoxic agents. Use of epoetin to prevent or correct anaemia has the potential to reduce tumour hypoxia and improve treatment outcome. Several therapeutic studies in anaemic animals with experimental tumours have shown a beneficial effect of epoetin on delaying tumour growth. Furthermore, clinical observations in patients with multiple myeloma and animal studies have suggested that epoetin has an antimyeloma effect, mediated via the immune system through activation of CD8+ T cells. Therefore, the role of epoetin may go well beyond that of increasing haemoglobin levels in anaemic patients, although additional studies are required to confirm these promising results.

Topics: Anemia, Hypochromic; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Hypoxia; Central Nervous System Diseases; Chemotherapy, Adjuvant; Cognition; Erythropoietin; Humans; Multiple Myeloma; Neoplasms; Pilot Projects; Recombinant Proteins

Erythropoietin (EPO) is a hematopoietic growth hormone that regulates survival, proliferation, and differentiation of erythroid progenitor cells. A reduction in tissue oxygenation stimulates EPO production, through a complex feedback mechanism. Patients with cancer-related anemia have an inadequate EPO response that is further impaired by cancer treatments such as chemotherapy. Cancer-related anemia substantially impairs patient functioning and may contribute to poor treatment outcomes. A significant number of studies demonstrates that treatment of anemia in cancer patients using recombinant human EPO (rHuEPO, epoetin alfa) significantly increases haemoglobin (Hb) levels, reduces transfusion requirements, and improves quality of life, particularly by relieving fatigue. Recent data also show that epoetin alfa therapy may improve cognitive function in patients receiving chemotherapy. In addition, the correction of anemia may prolong survival by enhancing tumor oxygenation, thus increasing tumor sensitivity to chemotherapy or radiation. The indicated dose of epoetin alfa is 150-300 IU/kg three times per week, but it is commonly dosed at 40,000-60,000 IU once weekly based on trial data and extensive clinical use. Determining the timing of initiation of epoetin alfa is a clinical judgement; however, data suggest that patient functioning declines and the risk of transfusion increases when the Hb level falls under 12 g/dL.

Topics: Anemia, Hypochromic; Antineoplastic Agents; Cognition; Decision Trees; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Practice Guidelines as Topic; Quality of Life; Recombinant Proteins; Survival Rate; Treatment Outcome

The presence of anaemia in patients with cancer is correlated with poor clinical outcome, a reduced tumour response to anticancer therapy and an increased risk of mortality. This observation has led to speculation as to whether treatment of anaemia can enhance survival rates. The majority of studies have suggested that erythropoietic therapy either does not change or improves disease-free and/or overall survival. Only two studies, one in breast cancer and the other in head and neck cancer, both of which used epoetin outside its approved indications, have observed a decrease in survival in epoetin-treated patients compared with controls. Methodological issues and baseline imbalances between groups in prognostic factors for survival that may have favoured placebo treatment have complicated the interpretation of these studies. In contrast, a Cochrane meta-analysis of randomised, controlled trials of epoetin in anaemic patients with cancer that reported survival identified 19 trials up to the end of 2001 with 2,865 patients. This meta-analysis reported a hazard ratio for overall survival of 0.81 (95% CI 0.67-0.99) for adjusted data and a hazard ratio of 0.84 (95% CI 0.69-1.02) for unadjusted data. A recent meta-analysis of nine randomised, controlled trials of epoetin beta (n = 1,413) suggests that use of this therapy is associated with a reduced risk of tumour progression. This meta-analysis also showed that no association existed between the risk of overall mortality or thromboembolic mortality and epoetin beta therapy. These results suggest that treatment of anaemic patients with cancer with epoetin beta is effective and safe.

Topics: Anemia, Hypochromic; Erythropoietin; Hematinics; Humans; Meta-Analysis as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate

The contribution of epoetin beta to the management of cancer-related anaemia over the past decade has been a significant one; increased haemoglobin (Hb) levels, reduced transfusion need and improved patient quality of life (QoL) have been well documented in patients across a wide range of malignancies. In recent years, concerns have been raised over the inconvenience and costs associated with the conventional three-times weekly (tiw) epoetin dosing regimen. As a result, optimising therapy through less frequent dosing (i.e. once weekly) has become a focus of research. The NeoRecormon Once Weekly (NOW) study compared the efficacy and tolerability of epoetin beta 30,000 IU once weekly with a standard 10,000 IU tiw regimen in patients with lymphoproliferative malignancies. The study showed that the once weekly regimen was equally effective as the tiw regimen in increasing Hb levels and reducing transfusion need. Furthermore, the response to once weekly treatment was rapid, with 1 and 2 g/dl increases in Hb level seen at approximately 4 and 8 weeks, respectively. Studies with other erythropoietic agents have also shown the efficacy of the once weekly dosing strategy. Epoetin beta 30,000 IU is now approved for once weekly administration in patients with lymphoproliferative malignancies receiving antitumour therapy, and can be administered using a new 30,000 IU pre-filled syringe. Once weekly administration of epoetin beta offers greater convenience and should reduce administration costs compared with the tiw regimen.

Topics: Anemia, Hypochromic; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

Epoetin represents the standard of care in the management of cancer therapy-related anaemia, increasing haemoglobin levels, reducing transfusion need and improving patient quality of life (QoL). Recent research aimed at improving convenience and ease of use has involved all epoetins. In particular, it has confirmed that epoetin beta 30,000 IU once weekly is equally effective as the conventional 10,000 IU three-times weekly regimen in alleviating cancer-related anaemia. Ongoing research aimed at improving still further the effectiveness of epoetins in anaemia treatment is examining the role of concomitant intravenous iron during epoetin beta therapy. With the recent debate over whether epoetin therapy has an effect on treatment outcome and survival, well-designed trials specifically powered to assess survival are required. The BReast cancer-Anaemia and the Value of Erythropoietin (BRAVE) trial is such a study, assessing the impact of epoetin beta on survival and QoL of patients with metastatic breast cancer scheduled to receive anthracycline- and/or taxane-based chemotherapy. The findings of such studies are expected to lead to a greater understanding of the optimal use of epoetins in cancer-related anaemia.

Topics: Anemia, Hypochromic; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Administration Schedule; Erythropoietin; Hematinics; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Survival Analysis; Treatment Outcome

Topics: Anemia, Hypochromic; Disease Progression; Erythropoietin; Humans; Kidney Failure, Chronic; Peritoneal Dialysis; Recombinant Proteins

Iron and erythropoiesis are inextricably linked. Erythropoiesis is a dynamic process that requires 30-40 mg of iron per day. In normal circumstances this is met from red cell destruction but in anaemia this will not be the case. Reduced iron stores will limit iron supply to erythroblasts but normal or raised iron stores may not be able to supply iron fast enough. This is particularly true when the marrow is stimulated by erythropoietin therapy; the most common cause of failure to respond is "functional iron deficiency"'. This entity can only be effectively addressed by intravenous iron therapy. While haemoglobin and serum ferritin concentrations reflect the major iron pools, iron supply to erythroid cells can only be assessed by measuring effective haemoglobinization through the percentage of hypochromic red cells in the circulation.

Topics: Anemia, Hypochromic; Erythrocytes; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Iron

Iron plays an essential role in immunosurveillance, because of its growth promoting and differentiation inducing properties for immune cells and its interference with cell mediated immune effector pathways and cytokine activities. At the same time, iron is crucial for the proliferation of tumour cells and micro-organisms, due to its role in mitochondrial respiration and DNA synthesis. Thus, gaining control over iron homeostasis is of vital importance for the course of an infection or a tumour disease, since increased iron availability or iron overload of the immune system are associated with an unfavourable course of many of these diseases. The most frequent clinical condition demonstrating this interaction of iron and immunity is anaemia of chronic disease (ACD). ACD develops in patients with chronic activation of cellular immunity such as subjects suffering from malignancies, auto-immune disorders or infections. ACD may be seen as an immune driven disease since cytokines and their products cause (i) a diversion of iron traffic into the reticuloendothelial systems, thus limiting the availability of the metal to erythroid progenitor cells for haem biosynthesis, (ii) an inhibition of erythroid progenitor cell proliferation and (iii) blunted production and activity of erythropoietin (EPO). However, ACD may also hold some benefit by reducing iron availability to invading pathogens, thus limiting their growth, and by stimulating cell mediated immune function. The latter can be referred to the correction of an inhibitory effect of iron towards IFN-gamma induced immune effector pathways in macrophages. Whereas ACD can be easily diagnosed based on the characteristic changes of iron homeostasis, therapy of ACD is much more controversial. Where a cure of the underlying disease is impossible, transfusions for rapid correction of haemoglobin levels and human recombinant EPO can be used with varying success. The sole application of iron should be strictly avoided due to promotion of pathogen growth and impairment of immune function.

Topics: Anemia, Hypochromic; Bacterial Infections; Cytokines; Erythroid Precursor Cells; Erythropoietin; Heme; Hemochromatosis; Humans; Immune Tolerance; Immunity, Cellular; Iron; Macrophages; Neoplasms

Topics: Anemia, Hypochromic; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Iron Compounds; Kidney Failure, Chronic; Male; Prognosis; Quality of Life; Renal Dialysis; Treatment Outcome

Automated counting of reticulocytes has markedly increased the precision and accuracy of this assay compared with the traditional manual counts. In addition, several new reticulocyte parameters are now available to clinicians and pathologists. This review examines the potential role of these parameters in the diagnosis and management of anemias. Reticulocyte maturity can now be assessed based on the staining intensity of reticulocytes, which is proportional to their RNA content. However, the clinical value of the numerical estimate of the immature reticulocyte fraction has not been yet demonstrated. In the bone marrow transplant setting, there is no clear evidence that the use of this index results in improved care of these patients, and many studies have failed to show its superiority compared with the traditional white cell count, especially for autologous transplants. Direct measurement of reticulocyte volume, hemoglobin concentration, and hemoglobin content are now available. Studies have shown that these parameters, and hemoglobin content in particular, allow a real-time assessment of the functional state of the erythroid marrow. In the setting of recombinant human erythropoietin therapy, studies of hemoglobin content have shown that this index allows an early detection of functional iron deficiency. Preliminary studies have also shown that this index may be helpful in the diagnosis of iron deficiency and in the monitoring of iron replacement therapy.

Topics: Anemia, Hypochromic; Anemia, Megaloblastic; Anemia, Sickle Cell; Bone Marrow; Bone Marrow Diseases; Bone Marrow Transplantation; Cell Size; Cellular Senescence; Erythropoietin; Graft Survival; Hematologic Diseases; Hemoglobins; Humans; Iron Deficiencies; Recombinant Proteins; Reference Values; Reticulocyte Count; Reticulocytes; RNA; Staining and Labeling

Topics: Anemia; Anemia, Hypochromic; Antihypertensive Agents; Blood Transfusion; Cardiovascular Diseases; Combined Modality Therapy; Erythropoietin; Hemoglobins; Humans; Hypertension; Immunocompromised Host; Immunosuppressive Agents; Iron; Iron Deficiencies; Kidney Failure, Chronic; Nutrition Disorders; Recombinant Proteins; Renal Dialysis

Erythropoietin (EPO) plays a central role in the regulation of red blood cell (RBC) production. Since iron is an essential element for erythropoiesis and hemoglobin (Hb) synthesis, its importance is heightened in patients treated with epoetin alfa. Stimulation of erythropoiesis following the administration of epoetin alfa is associated with several changes in iron metabolism; indeed, plasma ferritin levels fall as a result of increased utilization of iron by the expanding erythroid marrow. The administration of epoetin alfa can therefore lead to a state of relative iron deficiency. Thus, iron supplementation is essential to maximize the effect of epoetin alfa-induced erythropoiesis.

Topics: Adult; Anemia, Hypochromic; Bone Marrow; Epoetin Alfa; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Inflammation; Iron; Iron Deficiencies; Iron Overload; Male; Middle Aged; Recombinant Proteins

Erythropoietin, a glycoprotein, is synthesized mainly in the kidney. With the destruction of renal tissue, erythropoietin production decreases; this is a major factor in the development of anemia in patients with renal failure. For about ten years now, recombinant human erythropoietin has been available for the treatment of renal anemia. All patients with renal insufficiency, independent of their plan for future renal replacement therapy, may benefit from erythropoietin. At what extent of anemia erythropoietin therapy should be started is still discussed and is certainly dependent on the degree of the patient's impairment by his anemia. Before beginning a therapy with erythropoietin, other forms of anemia observed in patients with renal failure, i.e. mainly iron deficiency, have to be excluded. A strict monitoring of hematocrit during treatment with erythropoietin is mandatory. Hypertension, seizures and cardiovascular complications have been observed with overdosing of erythropoietin. Special emphasis of this review is therefore put on the discussion of the dynamics of the erythropoietin-red cell system.

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Hypertension; Kidney Failure, Chronic; Recombinant Proteins

Anemia is an inevitable and potentially serious complication of chronic renal failure and one of the most important limiting factors in patient rehabilitation. Although adequate dialysis can control many of the symptoms of uremia, dialysis does not reverse anemia-associated fatigue, and thus, many patients are not rehabilitated. Human recombinant erythropoietin (epoetin) therapy has proven to be effective in reversing anemia and increasing hematocrit levels in the majority of patients with chronic renal failure. Among this patient population, increases in hematocrit level have resulted in improvements in the symptomatology of organ hypoxia, neurobehavioral indices, anorexia, insomnia, depression, and sexual disinterest and dysfunction, as well as a reduction in cardiomegaly. However, despite the availability of epoetin and the dramatic improvements in the complications associated with the anemic state observed following therapy, it appears that patient rehabilitation remains a challenge. One aspect of the continuing problem of rehabilitation appears to be the reluctance of the medical community to increase hematocrit levels above 30%, despite the fact that higher hematocrit levels are associated with greater improvements and that potential adverse events related to hemodynamic adaptation are manageable. Indeed, a comparison of the results from two Epoetin alfa clinical trials, one in which hematocrit levels were maintained at 35% and a large phase IV study in which the target hematocrit level appears to have been approximately 30%, clearly demonstrate the benefits of optimizing hematocrit levels and thus improving the potential for rehabilitation.

Topics: Anemia, Hypochromic; Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Quality of Life; Renal Dialysis

The anemia of chronic disease may be viewed simply as the anemia that accompanies chronic inflammatory, infectious, or neoplastic disorders. Because these conditions are very common, the anemia of chronic disease is one of the most frequent anemias encountered, and is only second in incidence to iron-deficiency anemia. The anemia of chronic disease is primarily an anemia due to underproduction of red cells, with low reticulocyte production, and is most often a normochromic, normocytic anemia. However, in 30% to 50% of patients, the red cells are hypochromic and microcytic and, most often, the serum iron, total iron-binding capacity, and transferrin saturation are reduced in the presence of adequate iron stores. Although the differential diagnosis includes other underproduction anemias, such as those caused by vitamin and mineral deficiencies, renal failure, endocrinopathies, and myelodysplasia, it generally is easily distinguished from these conditions. Nevertheless, an understanding of the pathogenesis of this condition, as well as a means of alleviating the anemia when the chronic disorder persists, has remained elusive. Recently, major advances have occurred toward understanding the pathogenesis of the anemia of chronic disease and its treatment, and these advances are reviewed.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Anemia, Hypochromic; Animals; Arthritis, Rheumatoid; Bone Marrow; Chronic Disease; Cytokines; Erythropoietin; Humans; Incidence; Neoplasms; Recombinant Proteins

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

It is apparent that exercise can influence erythropoiesis and red cell survival in a variety of fascinating ways. A number of mechanisms have been reviewed that could lead to mild changes in the Hb or red cell mean corpuscular volume. In addition, athletes may be at high-risk to develop decreased iron stores. Nevertheless, iron deficiency anemia is uncommon and the ritual of routine iron supplementation is not recommended. Clearly, most of the mechanisms discussed lead to only subtle changes in the overall red cell numbers and indices. Yet there is a small subset of athletes who will have red cell changes that can only be attributable to participation in sports. The diagnosis of sports anemia, however, remains one of exclusion.

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Erythropoietin; Exercise; Humans; Sports; Water-Electrolyte Balance

In successful renal transplant recipients, transient and modest increases in endogenous erythropoietin (Epo) reverse anemia, whereas in dialysis patients, sustained administration of large doses of exogenous Epo is required for the correction of uremic anemia. Moreover, in transplant recipients, serum Epo returns to normal as the hematocrit level increases to greater than 32%. Thereafter, the hematocrit continues to increase to normal levels, while serum Epo remains in the normal range. Thus, the restoration of renal function may improve the erythropoietic response to Epo, and/or erythropoiesis in transplant patients may be stimulated by factors other than, or in addition to, Epo. In early posttransplant patients who develop erythrocytosis, serum Epo levels are often elevated, while in long-term transplant recipients, erythrocytotic patients (with normal serum ferritin) have normal serum Epo levels. On the other hand, in long-term transplant recipients with low serum ferritin, circulating Epo levels are elevated, even in patients with no overt anemia. This suggests a possible interaction between body iron store status and the synthesis of Epo.

Topics: Anemia; Anemia, Hypochromic; Animals; Erythropoiesis; Erythropoietin; Humans; Kidney Failure, Chronic; Kidney Transplantation

The treatment of renal anaemia by recombinant human erythropoietin (EPO) is now well established. Several studies have examined the pharmacokinetics and efficacy of the drug given intravenously, intraperitoneally and subcutaneously and there is increasing evidence that the subcutaneous route has several advantages including the requirement for a lower dose. It is also important to stress the need for careful determination of baseline iron status of all patients before commencing EPO therapy. In the long term the extremely high iron stores of transfusion dependent patients will disappear. In the short term, however, the majority of the patients whose serum ferritin is less than 100 micrograms/l will require iron supplementation to allow an appropriate haemoglobin response. Alternatively, a fall in transferrin saturation to less than 20% is certainly an indication for iron supplementation and if oral iron therapy is not adequate then intravenous preparations may have to be considered. Although the anaemia of renal failure can be fully corrected by EPO, partial correction may be sufficient to reverse the problems of reduced exercise capacity, myocardial ischaemia and cardiomegaly which are frequently associated with end-stage renal disease. Partial correction will also result in a lesser rise in whole blood viscosity and, in turn, possibly reduce hypertension, thrombosis and increased peripheral resistance and thus lessen the side effects of EPO therapy.

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Hypertension; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Thrombosis

Topics: Anemia; Anemia, Hypochromic; Animals; Drug Hypersensitivity; Erythropoietin; Humans; Hyperkalemia; Hypertension; Peritoneal Dialysis, Continuous Ambulatory; Phosphates; Recombinant Proteins; Renal Dialysis; Seizures; Thrombosis; Uremia

Iron deficiency frequently complicates both acute and chronic phases of recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) therapy for dialysis-associated anemia. During acute correction of anemia, iron needed for new hemoglobin production may outstrip available body iron stores. During maintenance r-HuEPO therapy, blood lost both through the dialysis process and the uremic predisposition to gastrointestinal bleeding promotes ongoing negative iron balance. Failure to recognize and treat iron deficiency may lead to impaired efficacy of r-HuEPO in the anemic patient by converting the anemia associated with chronic renal failure to the anemia associated with iron deficiency. The risk of iron deficiency is assessed by weighing available iron stores, as reflected by the level of serum ferritin, against anticipated iron needs for new hemoglobin synthesis, as measured by the difference between the current and target hemoglobin. Using this approach, body iron reserves can be determined, iron deficits predicted, and appropriate iron replacement therapy planned. Once patients are identified as being at risk for iron deficiency, they are treated prophylactically with oral iron supplements. Parenteral iron therapy is reserved for those at greatest risk for iron deficiency during acute r-HuEPO treatment and those intolerant or unresponsive to oral iron supplements during chronic r-HuEPO treatment. Although no dose-response relationship has been observed in the restoration of iron balance with oral iron supplements, those taking supplements show distinctly higher projected iron stores and daily iron balance than those not given supplements.

Topics: Anemia; Anemia, Hypochromic; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Sideroblastic; Animals; Erythrocytes; Erythropoietin; Humans; Kidney Failure, Chronic; Rats; Renal Dialysis

PTH may participate in the genesis of the anemia of uremia through at least three pathways. These include inhibition of erythropoiesis, shortening survival of RBCs and inducing fibrosis of bone marrow cavity. A possible fourth mechanism through which PTH may contribute to the anemia of uremia is its effect on platelets. PTH inhibits platelet aggregation [53] and, as such, may play an important role in the genesis of the bleeding tendencies and the consequent blood loss in uremia.

Topics: Anemia; Anemia, Hypochromic; Anemia, Sideroblastic; Animals; Colony-Forming Units Assay; Erythrocyte Aging; Erythropoiesis; Erythropoietin; Folic Acid Deficiency; Hematopoietic Stem Cells; Hemolysis; Hemorrhage; Humans; Hyperparathyroidism, Secondary; In Vitro Techniques; Mice; Parathyroid Hormone; Uremia

Topics: Anemia; Anemia, Hypochromic; Blood Cell Count; Bone Marrow Cells; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Hematopoietic Stem Cells; Hemoglobins; Humans; Iron; Oxygen; Reticulocytes

Topics: Adolescent; Adult; Anemia; Anemia, Hypochromic; Anemia, Megaloblastic; Animals; Child; Child, Preschool; Dapsone; Drug Combinations; Erythropoietin; Female; Hookworm Infections; Humans; Infant; Iron-Dextran Complex; Leishmaniasis, Visceral; Macaca mulatta; Malaria; Male; Mice; Middle Aged; Protein-Energy Malnutrition; Pyrimethamine; Schistosomiasis; Socioeconomic Factors; Tropical Medicine; Trypanosomiasis, African

Topics: Anemia; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Myelophthisic; Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Erythrocyte Count; Erythropoiesis; Erythropoietin; Reticulocytes

Uremia interferes with erythropoiesis, granulocyte, platelet, and immune functions. As a result, uremic patients are almost invariably anemic, and have a high incidence of infections and hemorrhagic complications. The anemia of renal failure, which is caused primarily by damage to the site of erythropoietin production is often complex, and complicated by hemolysis from a variety of mechanisms, iron deficiency, and so forth. Although hemodialysis ameliorates some of the hematologic complications to a variable degree, they remain a serious hinderance to the well being of this group of patients. Progress in understanding the mechanism of these problems and their therapy has been reviewed here.

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Blood Transfusion; Erythrocytes; Erythropoiesis; Erythropoietin; Folic Acid Deficiency; Hemorrhage; Humans; Kidney; Kidney Failure, Chronic; Renal Dialysis; Testosterone; Testosterone Congeners

Topics: Absorption; Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Bone Marrow; Erythropoiesis; Erythropoietin; Hemolysis; Humans; Iron; Iron-Dextran Complex; Synovial Membrane; Synovitis

Topics: Anemia, Hypochromic; Animals; Biological Transport; Erythropoietin; Ferritins; Humans; Intestinal Absorption; Intestinal Mucosa; Iron; Mitochondria; Pancreas; Rats

Topics: Anemia, Hypochromic; Animals; Bile; Chelating Agents; Chemical Phenomena; Chemistry; Diet; Erythropoietin; Gastric Mucosa; Heme; Hemoglobins; Humans; Hydrogen-Ion Concentration; Hypoxia; Intestinal Absorption; Intestinal Mucosa; Iron; Iron Isotopes; Kinetics; Models, Biological; Pancreas; Transferrin

Topics: Anemia; Anemia, Hypochromic; Bone Marrow; Bone Marrow Cells; Erythrocyte Aging; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Hematocrit; Hemoglobins; Hemolysis; Humans; Iron; Reticulocytes

Topics: Anemia; Anemia, Hypochromic; Anemia, Sideroblastic; Animals; Arthritis, Rheumatoid; Bone Marrow; Chronic Disease; Copper; Disease Models, Animal; Endotoxins; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Freund's Adjuvant; Hematocrit; Humans; Infections; Iron; Mononuclear Phagocyte System; Neoplasms; Porphyrins; Protein Binding; Rats; Transferrin

Topics: Adult; Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Blood Platelets; Blood Urea Nitrogen; Bone Marrow Cells; Chronic Disease; Erythrocytes; Erythrocytes, Abnormal; Erythropoiesis; Erythropoietin; Feedback; Female; Hemolysis; Hemostasis; Humans; Hypertension, Malignant; Iron; Kidney; Kidney Concentrating Ability; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Oxygen Consumption; Plasma Volume; Uremia

The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response.. We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response.. Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 μg once weekly and ribavirin 1,000-1,200 mg/day; 174 were responders. Forty individuals completed treatment with no hemoglobin reduction; 134 developed anemia during therapy. Anemic responders were distributed randomly into two groups: group 1 continued therapy with epoetin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only.. Patients in group 1 achieved better control of hemoglobin levels (13.8 ± 1.2 g/dl at the end of therapy) than those in group 2 (11.5 ± 0.8 g/dl). Sustained virological response was 59.7% in group 1 compared with 34.4% in group 2 (p<0.01).. In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment, administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence.

Topics: Adult; Anemia, Hypochromic; Antiviral Agents; Drug Administration Schedule; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Ferritins; Hematinics; Hemoglobins; Hepacivirus; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Longitudinal Studies; Male; Middle Aged; Polyethylene Glycols; Prospective Studies; Quality of Life; Recombinant Proteins; Ribavirin; RNA, Viral; Treatment Outcome; Viral Load

The percentage of hypochromic red blood cells (RBCs) (%HYPO) has been demonstrated as the best predictor of response to iron loading in haemodialysis patients treated with recombinant human erythropoietin (rHuEPO). However, we have previously shown that this parameter is positively influenced by erythropoietic activity since reticulocytes are considered hypochromic by cell counters. New cell counters are able to determine cell volume and haemoglobin (Hb) concentration separately on reticulocytes and mature erythrocytes. The aim of this study was to assess the sensitivity and specificity of mature erythrocyte parameters in detecting functional iron deficiency (FID).. A total of 32 stable chronic haemodialysis patients in the maintenance phase of rHuEPO therapy were included. Classical parameters of iron monitoring and mature erythrocyte parameters were measured after a 4-week iron-free period. Patients were classified as responders (R) or non-responders (NR) to an iron load of 100 mg iron sucrose at each dialysis session for 4 weeks, according to whether their Hb increased by >1 g/dl at the end of iron loading.. Twelve patients were identified as responders. Receiver operating characteristic (ROC) curve analysis demonstrated %HYPO and its corresponding parameter on mature erythrocyte, %HYPOm, as the best predictors of FID. The other parameters were ordered as follows: tranferrin saturation (TSAT), ferritin (FRT), mature RBC Hb content (CHm), mean corpuscular Hb concentration (MCHC), percentage of mature erythrocytes with a low CHm (%lowCHm), mean content in Hb (MCH) and reticulocyte Hb content CHr. Comparing the parameters at different cut-offs, the best sensitivity, specificity and efficiency were demonstrated for %HYPOm> 6%.. The best efficiency to predict FID was found for %HYPOm> 6%. The predictive value of %HYPO was quite similar. The clinical impact of %HYPOm in iron monitoring should also be tested in the induction phase of rHuEPO treatment because of its independence from erythropoietic activity.

Topics: Aged; Aged, 80 and over; Anemia, Hypochromic; Anemia, Iron-Deficiency; Biomarkers; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Renal Dialysis; Sensitivity and Specificity

Patients with cancer who are receiving chemotherapy often experience chemotherapy-induced anemia (CIA), which is associated with symptoms that reduce quality of life. The M. D. Anderson Symptom Inventory (MDASI) is a brief, self-rating assessment scale that measures the severity of core symptoms and symptom interference with function. The current study used the MDASI to prospectively assess the correlation between hemoglobin and self-perceived cancer-related symptoms in a large patient population with CIA who were receiving darbepoetin-alpha at a dose of 200 mug every 2 weeks.. Eligible patients enrolled in this multicenter, open-label study were age > or =18 years, had a nonmyeloid malignancy, were receiving multicycle chemotherapy, and were anemic (hemoglobin < or = 11 g/dL). Hemoglobin was measured every 2 weeks; the MDASI was administered weekly. For hemoglobin-based endpoints, patients were stratified by baseline hemoglobin (< 10 g/dL or > or =10 g/dL).. Of 2422 enrolled patients, 2401 received > or =1 dose of darbepoetin-alpha. Eighty percent of patients (95% confidence limit, 78-82 patients) achieved target hemoglobin levels (> or =11 g/dL) during the study. Patients with a baseline hemoglobin < 10 g/dL had a greater increase in hemoglobin, took longer to achieve the target hemoglobin, and received more red blood cell transfusions than patients with a baseline hemoglobin > or =10 g/dL. The percentage of patients with moderate to severe MDASI scores (> or =5 points) for fatigue, distress, loss of appetite, disturbed sleep, and interference with function was reduced during the study. Improvement in symptom burden was associated with an increase in hemoglobin concentration.. Treatment with darbepoetin-alpha at a dose of 200 mug every 2 weeks is associated with improvement in symptom burden as measured by the MDASI, a simple tool that may improve symptom management for cancer patients with CIA.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Cost of Illness; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Fatigue; Female; Hematinics; Humans; Male; Middle Aged; Surveys and Questionnaires; Treatment Outcome

In the United States, darbepoetin alfa (Aranesp) is often used to treat patients with chemotherapy-induced anemia using weekly or every-2-week administration schedules. In Europe, darbepoetin alfa is used either weekly or in every-3-week dosing. The every-3-week schedule can be synchronized with many chemotherapy regimens, resulting in fewer visits and reducing burden to patients, but the safety and efficacy of this regimen have not been clear.. A randomized, double-blind, double-dummy, active-controlled phase 3 trial was performed in 110 European centers. Eligible patients (age > or = 18 years) were anemic (hemoglobin level < 11 g/dL), had a nonmyeloid malignancy, and were to receive at least 12 weeks of chemotherapy. Patients were randomly assigned 1:1 to darbepoetin alfa treatment every 3 weeks (500-microg dose) or weekly (2.25-microg/kg) for 15 weeks. We compared red blood cell transfusion incidence among the two arms from week 5 to the end of the treatment phase using a noninferiority study design. Noninferiority was determined if the upper limit of the 95% confidence interval (CI) for the difference in blood transfusions between groups, calculated using Kaplan-Meier methods, did not exceed 12.5%, a margin based on previous placebo-controlled studies.. A total of 705 patients were randomly assigned, and 672 remained in the study at week 5. Fewer patients in the every-3-week arm than in the weekly arm received blood transfusions from week 5 to the end of the treatment phase (unadjusted Kaplan-Meier estimates = 23% versus 30%, difference = -6.8%; 95% CI = -13.6 to 0.1). Percentages of patients achieving the target hemoglobin level (> or = 11 g/dL, consistent with evidence-based practice guidelines) were 84% (every 3 weeks) and 77% (weekly). The frequency of cardiovascular/thromboembolic adverse events was 8% in both groups, and safety was comparable.. Patients with chemotherapy-induced anemia can safely and effectively be treated with 500 microg of darbepoetin alfa every 3 weeks.

Topics: Adult; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Darbepoetin alfa; Double-Blind Method; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Europe; Female; Humans; Male; Middle Aged

To compare maintenance epoetin alfa administered once every 3 weeks with continued weekly epoetin alfa for patients with cancer-associated anemia.. Eligible patients were randomly assigned at enrollment to receive three weekly doses of epoetin alfa 40,000 U subcutaneously (SC), followed by either standard weekly epoetin alfa (40K arm) or 120,000 U of epoetin alfa (120K arm) SC every 3 weeks for 18 additional weeks.. Three hundred sixty-five patients were enrolled. One hundred eighty-three patients were assigned to the 40K arm, and 182 were assigned to the 120K arm. There was no difference in the proportion of patients requiring transfusions during the study (23% in 40K arm and 18% in 120K arm, P = .22) or specifically during the maintenance phase (13% in 40K arm v 15% in 120K arm, P = .58). Patients randomly assigned to the 40K arm were more likely to have a > or = 2 or > or = 3 g/dL hemoglobin (Hb) increment, were more likely to have a drug dose held because of high Hb, and had higher mean end-of-study Hb levels. Toxicities, including thromboembolism, and overall survival were similar. Patients in the 40K arm had a higher global quality of life (QOL) at baseline for unclear reasons, whereas patients in the 120K arm had a greater global QOL improvement during the study, so end-of-study QOL was equivalent.. After three weekly doses of epoetin alfa 40,000 U, a dose of 120,000 U can be administered safely once every 3 weeks without increasing transfusion needs or sacrificing QOL. The Hb increment is somewhat greater with continued weekly epoetin alfa. Lack of blinding as a result of different treatment schedules may have confounded results.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Antineoplastic Agents; Confounding Factors, Epidemiologic; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Quality of Life; Recombinant Proteins; Research Design; Treatment Outcome

To evaluate the effects of once-weekly epoetin alfa (EPO) on health-related quality of life (HRQOL), hemoglobin (Hb), transfusions, and tolerability in children with cancer.. Anemic patients 5 years to 18 years of age receiving myelosuppressive chemotherapy for nonmyeloid malignancies, excluding brain tumors, received intravenous EPO 600 units/kg to 900 units/kg or placebo once-weekly for 16 weeks. Patients and parents completed the pediatric health-related quality-of-life generic scales (GS) and cancer-specific scales (CS).. One hundred eleven patients received EPO and 111 patients received placebo. Mean final values for GS total score (P = .763 among patients; P = .219 among parents) and CS domain scores (P > or = .238; P > or = .081, respectively) were not significantly different between treatment groups. EPO-treated patients had greater increases in Hb overall (P = .002) and were more likely to be transfusion free after 4 weeks (38.7% v 22.5%; P = .010). Change in Hb was correlated with change in PedsQL-GCS total score in the EPO group (r = 0.242; P = .018), but was not in the placebo group (r = 0.086; P = .430). Adverse events were comparable between treatment groups.. This study confirmed the tolerability and hematologic benefits of once-weekly EPO in children with cancer. No significant difference in HRQOL was detected between treatment groups, but a significant positive correlation was observed between Hb changes and HRQOL changes in the EPO group. Additional studies are warranted to assess HRQOL when anemia is managed optimally in children with cancer.

Topics: Adolescent; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Child; Child, Preschool; Double-Blind Method; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Health Status; Hematinics; Hemoglobins; Humans; Male; Neoplasms; Quality of Life; Recombinant Proteins

The effectiveness of every-three-week administration of darbepoetin alfa in women with chemotherapy-associated anemia was evaluated.. Women receiving chemotherapy for gynecological tumors who had a hemoglobin concentration of <10 g/dL were recruited from an obstetrics and gynecology service. Study patients received subcutaneous darbepoetin alfa 6.75 microg/kg, followed by 4.5 microg/kg every three weeks for a total of up to six doses. Hematopoietic response and mean changes in hemoglobin concentrations were evaluated. The Functional Assessment in Cancer Therapy-Anemia (FACT-An) survey was self-administered before and after study completion to evaluate the patients' quality of life.. The mean+/-S.D. age and weight for the 14 patients recruited (12 of whom were assessable) were 52.1+/-14 years and 64.6+/-19.8 kg, respectively. The mean initial and maintenance doses were 442 and 301.6 microg, respectively. The overall hematopoietic response was 64.3%, of which 35.7% were complete and 28.6% were partial. Peak response occurred at weeks 9 and 12. The mean+/-S.D. change in hemoglobin concentration was 1.6+/-1.51 g/dL. Treatment failure was predicted by week 9 (n=2). Maintenance doses were withheld if a patient's hemoglobin concentration exceeded 12 g/dL (n=3). The mean+/-S.D. point differential for FACT-An pretreatment and posttreatment scores was 5.8+/-4.71 (n=6).. Every-three-week administration of subcutaneous darbepoetin alfa produced a complete or partial hematopoietic response in 11 of 14 women with chemotherapy- associated anemia. A quality-of-life indicator generally improved among the 6 patients for whom posttreatment quality-of-life data were available.

Topics: Adult; Aged; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Female; Hematopoiesis; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Ovarian Neoplasms; Pilot Projects; Prospective Studies; Quality of Life; Time Factors

Intravenous iron supplementation is an integral part of the management of anemia in patients with chronic kidney disease. Traditionally, this has been administered as an infusion over 1 or more hours, which requires the use of intravenous fluids and administration tubing, along with extra demands on patient and nursing time.. We prospectively investigated the safety and practicality of administering iron sucrose, 200 mg, as a bolus injection over 2 minutes in patients with chronic kidney disease. A total of 2,297 injections were administered to 657 patients. Any adverse events were recorded, including acute anaphylactoid reactions to the iron injection, along with the presence or absence of metallic taste and phlebitis, and these were classified as "serious" and "nonserious.". The most common adverse event was a mild and transient metallic taste that occurred during 412 injections (17.9%); in no case was this of significant distress to the patient. Excluding this, 2,240 injections (97.5%) proceeded uneventfully, and no case of phlebitis was recorded. Adverse events other than metallic taste were recorded in association with 57 injections (2.5%). Seven of these were caused by an acute anaphylactoid reaction to the intravenous iron. All 7 acute reactions resolved completely within 30 minutes with no sequelae, and none required hospitalization. The remaining 50 adverse events consisted of pain during the injection (n = 31), pain after the injection with or without some bruising (n = 9), nausea/gastrointestinal symptoms (n = 3), lethargy (n = 4), and lightheadedness (n = 3).. Administration of 200 mg of iron sucrose as an intravenous bolus injection over 2 minutes is a practical dosing regimen in patients with chronic kidney disease, resulting in considerable savings in time and cost.

Topics: Adult; Aged; Anaphylaxis; Anemia, Hypochromic; Chronic Disease; Cohort Studies; Dysgeusia; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Graft Rejection; Humans; Hypotension; Injections, Intravenous; Kidney Diseases; Kidney Transplantation; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies

Platinum compounds are commonly associated with significant anemia. Erythropoietin administration has been found effective in correcting anemia in patients with solid tumors receiving chemotherapy. We conducted a randomized, open label study to assess the efficacy of erythropoietin in preventing transfusions and significant anemia (hemoglobin <10 g/dl) in patients with solid tumors receiving platinum-based chemotherapy.. One hundred forty-four patients with hemoglobin <13 g/dl were included in this study (72 in each arm). Patients in the treatment arm received 10,000 U of recombinant human erythropoietin (rHuEPO) thrice weekly s.c. during platinum-based chemotherapy, while patients in the control arm received no treatment.. All patients were evaluable for efficacy. Transfusions were reduced by the administration of rHuEPO (15.3 vs. 33.3%, p = 0.019), and fewer patients developed significant anemia (16.6 vs. 45.8%, p < 0.0001). Subgroup analysis showed that patients with observed to predicted (O/P) serum erythropoietin levels 0.9 or non-responders.. rHuEPO at a dose of 10,000 U thrice weekly prevents transfusions and development of significant anemia in patients with solid tumors receiving platinum-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Erythropoietin; Female; Greece; Humans; Male; Middle Aged; Neoplasms; Organoplatinum Compounds; Prognosis; Prospective Studies; Quality of Life; Recombinant Proteins; Risk Factors; Treatment Outcome

The religious beliefs of Jehovah's Witnesses who refuse homologous and autologous blood transfusion poses serious problems for surgeons when operating on patients requiring a mean transfusion requirement of =/>2 units of blood.. After a number of encouraging studies in a randomised sample of patients 2-3 and after the treatment of some Jehovah's Witnesses 1, a group of 45 patients (23 females and 22 males) underwent elective heart surgery between June 1998 and December 2000. The patients, who were all Jehovah's Witnesses, received pre-treatment with epoetin alpha and ferrous sulphate. In the light of recent studies, it was also decided to repeat medullary preconditioning using the same intervals but with a higher dose. The patients underwent surgery involving myocardial revascularisation, mitral and/or aortic valve replacement, associated interventions, valvuloplasty and ascending aortic aneurysms. After obtaining informed and signed consent, the treatment protocol comprised the administration of 140 IU/kg epoetin alpha three times a week for 3 weeks associated with oral ferrous sulphate 3 times a day. Hematochemical levels (hemoglobin, free hemoglobin, hematocrit, ferritin, transferrin, haptoglobin, reticulocytes, iron levels) were monitored from admission to Day Hospital to discharge.. No patient in the study required blood transfusion.. The short, medium and long-term follow-up reconfirmed the substantial reliability of this drug linked to the absence of collateral effects.

Topics: Administration, Oral; Aged; Anemia, Hypochromic; Blood Transfusion; Christianity; Coronary Artery Bypass; Elective Surgical Procedures; Epoetin Alfa; Erythropoietin; Female; Ferrous Compounds; Heart Valve Prosthesis Implantation; Heart Valves; Hematinics; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Recombinant Proteins; Religion and Medicine; Treatment Outcome; Vascular Surgical Procedures

Topics: Anemia, Hypochromic; Doping in Sports; Erythropoietin; Humans; Iron; Male; Recombinant Proteins; Time Factors

Impaired erythropoiesis in continuous ambulatory peritoneal dialysis (CAPD) or continuous cyclic peritoneal dialysis (CCPD) patients receiving recombinant human erythropoietin (rHuEPO) is most often secondary to iron deficiency, either as a result of poor intestinal absorption or failure to take oral supplements as prescribed. The inconvenience of giving intravenous (i.v.) iron dextran (ID) to CAPD/CCPD patients precluded its use in this population. We therefore examined the efficacy of bolus intraperitoneal (i.p.) iron dextran (1000 mg) on erythropoiesis in a pilot study of 14 CAPD/CCPD patients. The patients ranged in age from 23-81 years, and all had iron deficiency (transferrin saturation 6%-23%; mean: 15.2% +/- 1.34%). Of the 14 patients studied, 13 were receiving rHuEPO. Pre-treatment hematocrit (Hct) ranged from 21%-38% (mean: 30.2% +/- 1.37%). After infusion of 2 L Dianeal (Baxter Healthcare Corp., Deerfield, Illinois, U.S.A.), 500 mg of undiluted ID was administered directly into the Tenckhoff catheter and subsequently flushed with 30 mm3 normal saline. The peritoneal dialysis (PD) exchange containing ID then dwelled for a period not < 6 hours before standard PD resumed. A second 500 mg dose ID was given to each patient by the same protocol 3-86 days later (mean: 14 days). No complications were seen. No patient complained of abdominal pain or other subjective symptoms during infusion or during the dwell. Repeat iron studies done 1-7 months post ID (mean: 2.8 months) showed a 1.1-fold to 4.9-fold increase (mean: 1.4-fold) in mean iron levels (40.4 +/- 3.9 mg/dL versus 57.5 +/- 5.5 mg/dL, p = 0.036); a 1.1-fold to 5.2-fold increase (mean: 1.6-fold) in mean transferrin saturation (15.2% +/- 1.3% versus 24.5% +/- 2.6%, p = 0.008); a 1.01-fold to 1.60-fold increase (mean: 1.12-fold) in mean Hct (30.2% +/- 1.37% versus 33.8% +/- 1.5%; p = 0.042). The mean dose of rHuEPO was statistically unchanged (170.0 +/- 47.4 U/kg body weight versus 178.8 +/- 49.6 U/kg body weight per week; p = 0.841). Peritoneal equilibration test (PET) score 1-4 months post ID (mean: 2 months) was 0.778 +/- 0.02 compared with a PET score at baseline of 0.767 +/- 0.03 (p = 0.734). No significant delta was observed in blood urea nitrogen (BUN) or creatinine values. We conclude that use of bolus i.p. ID is safe, effective, and convenient, and demonstrates no short-term negative effect on peritoneal membrane integrity. Long-term effects have yet to be determined.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Erythropoietin; Female; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Pilot Projects; Recombinant Proteins; Treatment Outcome

Although erythropoietin (EPO) is known to be useful in treating chemotherapy-induced anemia, few data are available on its potential preventive role. The aim of this study was to evaluate the ability of EPO in preventing the development of clinically significant anemia in patients treated with chemotherapy.. Sixty-two early-stage breast cancer patients undergoing accelerated adjuvant chemotherapy were randomized to receive EPO 150 U/kg three times a week or no additional treatment. Chemotherapy consisted of six cycles of cyclophosphamide 600 mg/m2, epirubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF) intravenously on day 1, every 2 weeks with the support of granulocyte colony-stimulating factor (G-CSF), 5 microg/kg subcutaneously from day 4 to day 11.. Throughout the six cycles of chemotherapy, EPO-treated patients maintained stable values of hemoglobin, whereas control patients developed a progressive anemia. At the end of chemotherapy, the mean (+/- SD) hemoglobin decrease in the control group was 3.05 g/dL (+/- 1.0; 95% confidence interval [CI], 2.6 to 3.5), whereas in the EPO group it was 0.8 (+/- 1.4; 95% CI, 0.3 to 1.4). Clinically significant anemia (hemoglobin < or = 10 g/dL) occurred in 16 patients (52%; 95% CI, 33 to 69) in the control arm and in no patient (0%; 95% CI, 0 to 14) in the EPO arm (P = .00001).. EPO prevents anemia in patients undergoing chemotherapy. Further trials are required to identify subsets of patients in which the preventive use of this drug could be cost-effective.

Topics: Adult; Aged; Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drug Administration Schedule; Erythropoietin; Female; Humans; Iron; Middle Aged; Treatment Outcome

Serum erythropoietin (EPO) and its relationship to hemoglobin (Hb), iron status markers and iron supplementation during normal pregnancy was assessed in a longitudinal, placebo-controlled study on 118 women, 61 took daily tablets containing 66 mg ferrous iron from the second trimester until delivery and 57 took placebo. Blood samples were obtained at 4-week intervals until delivery as well as post-partum. In the placebo-treated women, median serum EPO rose from 22.5 U/l at inclusion to 35.0 U/l at delivery (P = 0.0001). In the iron-treated women, median serum EPO rose from 23.9 to 29.9 U/l (P = 0.0001). Serum EPO showed a steeper increase in the placebo-treated women than in the iron-treated women (P < 0.05). After delivery, serum EPO became normal in both groups (P = 0.0001). Median Hb was lower in placebo-treated (iron depleted) than in iron-treated (iron repleted) women (P < 0.05). In the placebo-treated women there was a negative correlation and in the iron-treated women a positive correlation between serum EPO and Hb. In the placebo-treated women, inverse correlations existed between serum EPO and serum transferrin saturation and serum ferritin, reflecting the consequences of iron deficiency, whereas the iron-treated women displayed no correlation. A physiological, nonhypoxia-induced increase in EPO production accounts for the basic expansion of the red cell mass during pregnancy. In placebo-treated women, iron deficient erythropoiesis constitutes an additional hypoxic stimulus, which induces a further increase in serum EPO.

Topics: Anemia, Hypochromic; Double-Blind Method; Erythropoiesis; Erythropoietin; Female; Ferritins; Ferrous Compounds; Hemoglobins; Humans; Hypoxia; Iron; Iron Deficiencies; Longitudinal Studies; Placental Lactogen; Postpartum Period; Pregnancy; Pregnancy Complications, Hematologic; Transferrin

In order to reveal whether serum transferrin receptor (sTfR) can serve as an index in erythropoiesis during recombinant human erythropoietin (rHuEpo) therapy for anemia in pre-dialysis patients with chronic renal failure, we analyzed hematopoietic parameters and sTfR levels in 26 patients who were newly administered rHuEpo. sTfR was determined as sTfR transferrin complex (TRC) using the enzyme linked immunosolvent assay (ELISA) and the latex agglutination nephelometric immunoassay (LA). The therapeutic effect of rHuEpo was expressed as the change in the Ht from the start of treatment to 8 weeks later. (delta Ht). Ht, RBC and Hb levels were significantly increased at 4 and 8 weeks after initiating rHuEpo treatment. Furthermore, sTfR levels were significantly increased at 2 and 4 weeks after the start of rHuEpo treatment. Absolute changes in the sTfR level (sTfR before - sTfR after) and rates of change (absolute change/sTfR before x 100) at, 2, 4 weeks after the start of rHuEpo treatment showed a significant positive correlation with delta Ht. These results indicate that sTfR is a useful marker as an index of therapeutic effect of rHuEpo for anemia in pre-dialysis patients with chronic renal failure.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Biomarkers; Erythropoiesis; Erythropoietin; Humans; Kidney Failure, Chronic; Middle Aged; Receptors, Transferrin; Recombinant Proteins

Intravenous (IV) iron therapy can reduce erythropoietin (EPO) requirements in dialysis patients. Monitoring this response accurately is difficult. Estimation of red blood cell ferritin (RBCFer) and reticulocyte indices may give additional valuable information about iron availability to the erythroblasts (erythron). We evaluated the use of RBCFer, mean hemoglobin content of reticulocytes (CHr), and mean hemoglobin concentration of reticulocytes (CHCMr) in a prospective, nonblinded study of 22 hemodialysis patients (16 men and six women with a mean age of 62 years [range, 24 to 80 years]). All patients had an initial serum ferritin of < or = 60 microg/L. Patients with features known to produce EPO resistance and underlying bleeding/hematologic disorders were excluded. Patients were established on subcutaneous EPO and given IV iron therapy. The mean hemoglobin level remained constant throughout the study (P = 0.087). Serum ferritin and RBCFer increased significantly (P < 0.001 and 0.015, respectively) while a reduction in transferrin saturation became significant at the end of the study (P = 0.0047). A sharp increase in reticulocytes occurred in the first 14 days after commencement of IV iron, and there was an initial decrease in the percentage of hypochromic RBCs. An early decline in RBCFer was apparent. CHr increased with IV iron, indicative of increased iron supply to the developing erythron. Measurement of RBCFer and CHr provide evidence of increased iron supply for erythropoiesis during IV iron therapy. These measures help identify patients with functional iron deficiency and allow more accurate monitoring of response to IV iron therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Anemia, Iron-Deficiency; Biological Availability; Erythroblasts; Erythrocyte Count; Erythrocyte Indices; Erythrocytes; Erythropoiesis; Erythropoietin; Evaluation Studies as Topic; Female; Ferritins; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Injections, Subcutaneous; Iron; Male; Middle Aged; Prospective Studies; Renal Dialysis; Reticulocytes

In a randomized, double-blind, placebo controlled study of the effect of iron supplementation during pregnancy, iron status (hemoglobin (Hb), serum (S-)transferrin saturation, S-ferritin) and S-erythropoietin (EPO) were assessed in 120 healthy pregnant women at 14-16 weeks of gestation, and just before delivery; 63 women were treated with 66 mg iron daily, and 57 with placebo. There were no differences in baseline values in the two groups. At term, the iron treated group had significantly higher Hb, transferrin saturation, S-ferritin (median 22 micrograms/l vs. 14 micrograms/l, (p < 0.0001) and lower S-EPO compared to the placebo treated group. In the iron group, 30.2% had exhausted iron stores (i.e. S-ferritin < 20 micrograms/l), 6.3% latent iron deficiency (S-ferritin < 20 micrograms/l and transferrin saturation < 15%), and no patients had iron deficiency anemia (S-ferritin < 20 micrograms/l and transferrin saturation < 15% and HB < 110 g/l). In the placebo group, 93.0% had exhausted iron stores, 54.4% latent iron deficiency, and 17.5% iron deficiency anemia; S-EPO was inversely correlated to iron status markers: Hb, rs = -0.51, p < 0.001; transferrin saturation, rs = -0.65, p < 0.0001; S-ferritin, rs = -0.31, p < 0.01, suggesting that the elevation in S-EPO was secondary to iron deficient erythropoiesis. Newborns to iron treated mothers had higher cord S-ferritin, median 155 micrograms/l, than newborns to placebo treated mothers, median 118 micrograms/l (p < 0.02); there were no differences in birth weight, transferrin saturation, or S-EPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Anemia, Hypochromic; Biomarkers; Double-Blind Method; Erythropoiesis; Erythropoietin; Female; Ferritins; Humans; Infant, Newborn; Iron; Placebos; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Trimester, Second; Pregnancy Trimester, Third

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.

Topics: Anemia; Anemia, Hypochromic; Blood Pressure; Clinical Trials as Topic; Drug Evaluation; Erythropoietin; Hematocrit; Humans; Hypertension; Kidney Failure, Chronic; Monitoring, Physiologic; Recombinant Proteins; Renal Dialysis; Seizures

Cell surface proteins Hfe, Tfr2, hemojuvelin and Tmprss6 play key roles in iron homeostasis. Hfe and Tfr2 induce transcription of hepcidin, a small peptide that promotes the degradation of the iron transporter ferroportin. Hemojuvelin, a co-receptor for bone morphogenic proteins, induces hepcidin transcription through a Smad signaling pathway. Tmprss6 (also known as matriptase-2), a membrane serine protease that has been found to bind and degrade hemojuvelin in vitro, is a potent suppressor of hepcidin expression. In order to examine if Hfe and Tfr2 are substrates for Tmprss6, we generated mice lacking functional Hfe or Tfr2 and Tmprss6. We found that double mutant mice lacking functional Hfe or Tfr2 and Tmprss6 exhibited a severe iron deficiency microcytic anemia phenotype mimicking the phenotype of single mutant mice lacking functional Tmprss6 (Tmprss6msk/msk mutant) demonstrating that Hfe and Tfr2 are not substrates for Tmprss6. Nevertheless, the phenotype of the mice lacking Hfe or Tfr2 and Tmprss6 differed from Tmprss6 deficient mice alone, in that the double mutant mice exhibited much greater erythropoiesis. Hfe and Tfr2 have been shown to play important roles in the erythron, independent of their role in regulating liver hepcidin transcription. We demonstrate that lack of functional Tfr2 and Hfe allows for increased erythropoiesis even in the presence of high hepcidin expression, but the high levels of hepcidin levels significantly limit the availability of iron to the erythron, resulting in ineffective erythropoiesis. Furthermore, repression of hepcidin expression by hypoxia was unaffected by the loss of functional Hfe, Tfr2 and Tmprss6.

Topics: Anemia, Hypochromic; Animals; Erythropoiesis; Erythropoietin; Female; Hemochromatosis Protein; Histocompatibility Antigens Class I; Hypoxia; Male; Membrane Proteins; Mice; Mice, 129 Strain; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Receptors, Transferrin; Reticulocytosis; Serine Endopeptidases

Hypochromic microcytic anemia associated with ineffective erythropoiesis caused by recessive mutations in divalent metal transporter 1 (DMT1) can be improved with high-dose erythropoietin supplementation. The aim of this study was to characterize and compare erythropoiesis in samples from a DMT1-mutant patient before and after treatment with erythropoietin, as well as in a mouse model with a DMT1 mutation, the mk/mk mice.. Colony assays were used to compare the in vitro growth of pre-treatment and post-treatment erythroid progenitors in a DMT1-mutant patient. To enable a comparison with human data, high doses of erythropoietin were administered to mk/mk mice. The apoptotic status of erythroblasts, the expression of anti-apoptotic proteins, and the key components of the bone marrow-hepcidin axis were evaluated.. Erythropoietin therapy in vivo or the addition of a broad-spectrum caspase inhibitor in vitro significantly improved the growth of human DMT1-mutant erythroid progenitors. A decreased number of apoptotic erythroblasts was detected in the patient's bone marrow after erythropoietin treatment. In mk/mk mice, erythropoietin administration increased activation of signal transducer and activator of transcription 5 (STAT5) and reduced apoptosis in bone marrow and spleen erythroblasts. mk/mk mice propagated on the 129S6/SvEvTac background resembled DMT1-mutant patients in having increased plasma iron but differed by having functional iron deficiency after erythropoietin administration. Co-regulation of hepcidin and growth differentiation factor 15 (GDF15) levels was observed in mk/mk mice but not in the patient.. Erythropoietin inhibits apoptosis of DMT1-mutant erythroid progenitors and differentiating erythroblasts. Ineffective erythropoiesis associated with defective erythroid iron utilization due to DMT1 mutations has specific biological and clinical features.

Topics: Anemia, Hypochromic; Animals; Antimicrobial Cationic Peptides; Apoptosis; Bone Marrow; Caspases; Cation Transport Proteins; Cell Survival; Erythroblasts; Erythrocyte Indices; Erythroid Precursor Cells; Erythropoietin; Hepcidins; Humans; Iron; Mice; Mice, Knockout; Mutation; Signal Transduction

Anemia is common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases patient's quality of life, and worsens the dose-intensity of chemotherapy. The aim of this retrospective data-analysis was to evaluate quality of life and hemoglobin levels in 19 consecutive lung cancer patients receiving beta-erythropoietin, due to chemotherapy induced anemia. A self developed, patient source data based quality of life questionnaire was used. The mean pre-erythropoietin hemoglobin concentration of the patients was 96.31±6.72 g/L (mean±SD), the post-treatment hemoglobin concentration 111.63±14.05 g/L (p<0.05). During the chemotherapy of the 19 patients with lung cancer, transfusion was given only four times. The mean quality of life total score of the patients increased significantly during erythropoietin treatment that was resulted by the improvements of scores determining dizziness, tachycardia, and fatigue. Main limitations of this real life data analysis are low patient number and the lack of validation in the used questionnaire. In summary, according to our experiences, the use of beta-erythropoietin in patients with lung cancer results improved quality of life and a low rate of transfusions.

Topics: Adult; Aged; Anemia, Hypochromic; Antineoplastic Agents; Blood Transfusion; Dizziness; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Quality of Life; Recombinant Proteins; Retrospective Studies; Surveys and Questionnaires; Tachycardia; Treatment Outcome

The primary cause of anemia in HIV-infected patients with ESRD is diminished production of erythropoietin. Although most patients respond to recombinant erythropoietin, the response may be blunted in patients with ESRD and concomitant viral or bacterial infections. Previous studies demonstrated a response to erythropoietin by HIV-infected ESRD patients, but hematocrit levels on average were only 27-29%. We were interested in determining if KDOQI guidelines could be met in these patients. Hematocrits and epogen doses of all HIV-positive patients who were undergoing hemodialysis at the Nassau University Medical Center Dialysis Unit between September 2002 and March 2003 were compared to matched controls in our hemodialysis unit. The hematocrit levels in our population were higher than those reported in earlier papers. In our patient population, the mean hematocrit was 37.5, whereas the mean hematocrit levels in the HIV group in previous papers were 27-29%. HIV-infected patients did require higher erythropoietin dosages than controls, but similar doses were used as compared to previous studies. HIV patients on hemodialysis can achieve KDOQI target hematocrits. The difference in route of iron administration and iron stores may explain the higher hematocrit levels in our HIV patient population as compared to previous trials.

Topics: Anemia, Hypochromic; Black or African American; Drug Administration Schedule; Erythropoietin; Hematocrit; Hemoglobins; HIV Infections; Humans; Kidney Failure, Chronic; Male; Middle Aged; New York; Practice Guidelines as Topic; Renal Dialysis

Anaemia is a common complication of chemotherapy. As anaemia can lead to e.g. fatigue, depression, social isolation and chest pain it diminishes physical capacity and quality of life. It is generally accepted that symptomatic anaemia should be corrected. Treatment options include red blood cell transfusion (RBCT), erythropoietin (EPO) administration or a combination of both.. The objective of this study was to carry out a cost-effectiveness analysis of treatment with EPO (epoetin alfa), compared to treatment with RBCT for patients with chemotherapy-induced anaemia in Sweden from a health care perspective.. A model was developed for estimating incremental costs and QALY gains associated with EPO treatment compared to treatment with RBCTs, based on a model commissioned by the UK National Institute for Health and Clinical Excellence and adjusted to reflect Swedish treatment practice. Data regarding patient characteristics, response rates, and RBCT was derived from a Swedish observational study of EPO treatment in cancer patients with chemotherapy related anaemia. Swedish guidelines and unit costs were used throughout the study. A systematic review of EPO for treatment of anaemia associated with cancer was used to estimate QALY gains associated with changes in Hb-concentrations in our model.. The model's results validate well to real world data from three major hospitals in Sweden. The cost per QALY gained from administration of EPO was estimated at EUR 24,700 in the base case analysis. Practicing an EPO treatment target Hb-level of 12 g/dl yields a cost per QALY about 40% lower than practicing a Hb-target level of 13 g/dl, which is in agreement with updated recommendations of using a 12 g/dl target.. The estimated cost per QALY falls well within the range acceptable in Sweden when practicing a Hb-target level of 12 g/dl. The incremental cost of elevating Hb-levels above 13 g/dl is very high in relation to the incremental QALY gain achieved.

Topics: Adult; Aged; Anemia, Hypochromic; Antineoplastic Agents; Cost-Benefit Analysis; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Male; Markov Chains; Middle Aged; Quality of Life; Quality-Adjusted Life Years; Recombinant Proteins; Severity of Illness Index; Sweden

DMT1 deficiency causes microcytic hypochromic anemia due to decreased erythroid iron utilization. Anemia is present from birth. Transferrin saturation is high and serum ferritin is mildly elevated, despite liver iron overload. DMT1 deficiency must be considered in the differential diagnosis of microcytic hypochromic anemia observed in the newborn period.

Topics: Anemia, Hypochromic; Cation Transport Proteins; Diagnosis, Differential; Erythrocytes; Erythropoietin; Ferritins; Genes, Recessive; Genotype; Humans; Infant, Newborn; Iron Chelating Agents; Mutation; Phenotype; Transferrin

A 3-year-old girl with H. pylori negative duodenal ulcer with hypergastrinemia secondary to chronic renal failure presenting with upper gastrointestinal bleed as the cardinal manifestation is unusual in toddlers and the case is presented for its rarity.

Topics: Anemia, Hypochromic; Anti-Ulcer Agents; Child, Preschool; Drug Therapy, Combination; Duodenal Ulcer; Erythropoietin; Female; Gastric Acid; Gastrointestinal Hemorrhage; Humans; Kidney Failure, Chronic; Omeprazole; Treatment Outcome

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Erythropoiesis; Erythropoietin; Female; Humans; Male; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Sensitivity and Specificity; Survival Analysis; Treatment Outcome

Body iron stores should be assessed regularly and accurately during erythropoietin (r-HuEPO) replacement therapy. To evaluate the accuracy of the current tests, transferrin saturation (TSAT) and serum ferritin levels, in assessing and monitoring body iron stores, we studied 24 regular hemodialysis patients (19 males, mean age 47+/-18 years, and mean duration on hemodialysis 15+/-13 months) on regular erythropoietin therapy over a 12 month period. Patients were classified as having normal, deficient, indeterminate, or overload status depending on the values of TSAT and serum ferritin. Using TSAT and serum ferritin, iron status could be determined in 16 (67%) patients only; 12 (50%) had adequate (or normal) iron status, 3 (12.5%) had iron deficiency, and one (4.2%) had iron overload. In the remaining 8 patients, iron status was indeterminate; six patients had high serum ferritin with low TSAT (functional iron deficiency), and two patients had high TSAT values and low serum ferritin. Serum ferritin alone had very low specificity in diagnosing iron overload. In conclusion, when used together, TSAT and serum ferritin have a low sensitivity for diagnosing the iron status of CKD patients on HD. When TSAT and serum ferritin values diverge, they become unreliable in guiding iron therapy, and this set of findings generally indicates functional iron deficiency. There is a clear need to use the newer indices, like reticulocyte hemoglobin concentration and percentage of hypochromic red cells, which are more sensitive. This is likely to make the diagnosis of iron status more accurate and may reduce the requirements and frequency of iron and r-HuEPO administration.

Topics: Adult; Anemia, Hypochromic; Biomarkers; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematinics; Hematocrit; Hemoglobins; Humans; Iron; Iron Deficiencies; Iron Overload; Kidney Failure, Chronic; Male; Middle Aged; Predictive Value of Tests; Recombinant Proteins; Renal Dialysis; Saudi Arabia; Sensitivity and Specificity; Time Factors; Transferrin; Treatment Outcome

We aimed in this study to evaluate the attitude of physicians in the Kingdom of Saudi Arabia (KSA) towards strategies for treatment of anemia in patients with chronic kidney disease (CKD). A questionnaire was sent to 153 physicians in 148 active dialysis units in the KSA including centers under the Ministry of Health (MOH) (73.6%), centers in the governmental non-MOH sector (12.2%) and centers in private hospitals (14.2%) that together care for a population of more than 7900 chronic dialysis patients. The study was performed between April and June 2006. A total of 137 physicians (89.5%) answered the questionnaire from 129 (87.1%) dialysis centers that catered to 7052 (89.2%) dialysis patients. There were 104 respondents (75.9%) who staged their CKD patients according to the level of glomerular filtration rate (GFR). The estimated mean prevalence of each stage of CKD in the respondents' clinics was 15%, 19%, 29%, 22%, and 29% for the stages 1, 2, 3, 4, and 5, respectively. The estimated prevalence of anemia [hemoglobin (Hb) < 110 g/L] in the different stages of CKD were 11%, 17%, 38%, 59%, and 78% in stages 1, 2, 3, 4, and 5, respectively. However, only 69 respondents (48%) answered these two questions. Sixty-seven respondents (50.4 %) believed that any patient with Hb < 110 g/L should receive r-HuEPO irrespective of the CKD stage, and 133 (99.3%) believed that correction of anemia in the CKD patients has documented impact on morbidity and mortality. In case of availability of a long acting r-HuEPO such as darbepoetin, 88 (66.2%) respondents would use it as their first choice other than the current short acting drug. Our survey suggests that the current practices concerning anemia management in CKD patients in the KSA may not be satisfactory. There are many centers that do not have data on the prevalence of CKD or anemia in their units. More studies are required to explore the quality of services rendered to the CKD patients and guidelines need to be outlined for the management of anemia in the CKD patients.

Topics: Anemia, Hypochromic; Attitude of Health Personnel; Chronic Disease; Darbepoetin alfa; Drug Utilization; Erythropoietin; Glomerular Filtration Rate; Guideline Adherence; Health Care Surveys; Health Knowledge, Attitudes, Practice; Hematinics; Hemoglobins; Humans; Kidney Diseases; Practice Guidelines as Topic; Practice Patterns, Physicians'; Prevalence; Recombinant Proteins; Saudi Arabia; Severity of Illness Index; Surveys and Questionnaires

According to recent data erythropoietin receptor (EPOR) is expressed not only by bone marrow erythroid progenitors but by endothelial- and cancer cells and it was suggested that erythropoietin (EPO) may affect their functions as well. We have analyzed the effects of recombinant human erythropoietin-alpha (rHuEPOalpha) on radiation sensitivity of EPOR+ human epidermoid carcinoma (A431) xenograft model. In vivo rHuEPOalpha treatment was started after tumor cell inoculation into SCID mice. 5 Gy irradiation was performed on day 14, the effect of which was measured on day 22. Hemoglobin level, tumor-associated microvessels and HIF-1alpha expression of the xenograft were monitored during the experiment. rHuEPOalpha administration prevented the development of tumor-induced anemia of SCID mice and reduced the level of HIF-1alpha expression of the xenograft tumor without affecting tumor growth. We have found that rHuEPOalpha treatment significantly increased the efficacy of antitumor effect of irradiation which was partly mediated by complex effects on tumor-associated microvessels. In vitro rHuEPOalpha did not affect proliferation of A431 cells but enhanced the antiproliferative and proapoptotic effects of irradiation. We concluded that rHuEPOalpha administration positively modulated the antitumoral effects of irradiation at least by two pathways, decreasing systemic hypoxia resulting in decreased tumoral HIF-1alpha expression and enhancing direct effects on tumor-associated microvessels.

Topics: Anemia, Hypochromic; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, SCID; Microcirculation; Polymerase Chain Reaction; Radiation-Sensitizing Agents; Recombinant Proteins; Transplantation, Heterologous

Iron-deficiency anemia not only causes insufficient oxygen delivery to the body of the mother, but creates serious conditions in the fetus, such as insufficient oxygen delivery and poor development, and its treatment has become an important issue. To elucidate the mechanism of the anemia-ameliorating action of Tokishakuyakusan, we investigated the effect of administration of Tokishakuyakusan on anemia-related parameters and the serum transferrin and erythropoietin levels, erythrocyte morphology, and bone marrow cells in pregnant rats and in pregnant rats with iron-deficiency anemia. The results showed that Tokishakuyakusan significantly improved the low erythrocyte count, hemoglobin, and hematocrit values of the pregnant rats in the iron-deficient state, increased the proportion of normal erythrocytes in terms of erythrocyte morphology, increased the proportion of erythroblasts among bone marrow cells, and also significantly increased the erythropoietin and transferrin levels in the blood. These findings suggested that Tokishakuyakusan promotes erythrocyte differentiation in iron-deficiency anemia, and that it possesses anemia-ameliorating efficacy.

Topics: Anemia, Hypochromic; Animals; Bone Marrow Cells; Drugs, Chinese Herbal; Erythrocytes; Erythropoietin; Female; Hematocrit; Hemoglobins; Pregnancy; Pregnancy, Animal; Rats; Rats, Wistar; Transferrin

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Confidence Intervals; Disease Progression; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Odds Ratio; Ovarian Neoplasms; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Therapeutic Equivalency; Treatment Outcome

The purpose of this study was to evaluate the sTfR-F index and hypochromic erythrocytes (HYPO%) as potential predictors of response to recombinant human erythropoietin (r-HuEPO) of anemic patients with multiple myeloma (MM) before treatment, as well as early in the course of treatment. Twenty-six newly diagnosed anemic MM patients received r-HuEPO 30,000 IU/wk sc, for six weeks. The sTfR-F index and HYPO% were determined at baseline and at weeks 2 and 6. Patients were classified in 1 of 4 categories of a diagnostic plot, according to erythropoietic state (ES I-IV), defined by the combination of sTfR-F index and HYPO%. Sixteen of 20 patients in ES I and II before treatment responded to r-HuEPO, whereas none of the 6 patients in ES III and IV responded (P < .001). At week 2, 44% of patients who responded and 60% of the nonresponders were in functional iron deficiency (FID) and the proportion increased to 69% and 80%, respectively, by week 6. Seven of the patients who did not respond received in addition 200 mg iron sucrose IV weekly, for the next 4 weeks, and 6 of them responded. These results suggest that combination of sTfR-F index and HYPO% in a diagnostic plot can be used as a predictive model to recognize patients who will benefit from r-HuEPO and identify FID requiring iron supplementation, before treatment and early in the course of treatment, contributing thus to optimization of r-HuEPO therapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Erythrocyte Count; Erythropoietin; Female; Humans; Male; Middle Aged; Monitoring, Physiologic; Multiple Myeloma; Recombinant Proteins

The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production.

Topics: Anemia, Hypochromic; Animals; Antineoplastic Agents; Body Weight; Cadmium Chloride; Cisplatin; Environmental Pollutants; Erythropoietin; Female; Hematologic Tests; Hypoxia; In Situ Hybridization; Kidney Tubules, Proximal; Liver; Organ Size; Rats; Rats, Wistar; RNA, Messenger; Spleen; Time Factors

Topics: Anemia, Hypochromic; Case-Control Studies; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythropoietin; Ferritins; Hemoglobins; Humans; Infusions, Intravenous; Iron; Kidney Failure, Chronic; Prospective Studies; Renal Dialysis

Topics: Anemia, Hypochromic; Antineoplastic Agents; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome

Anemia is very common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases the patient's quality of life. Erythropoietin therapy is accessible in Hungary for the treatment of chemotherapy-induced anemia in patients suffering from small cell lung cancer. In our case report we present the case of a 62-year-old female small cell lung cancer patient with severe anemia, treated by erythropoietin-beta. The erythropoietin treatment provided the possibility of effective chemo- and radiotherapy. The patient's quality of life greatly improved due to the lack of the symptoms of anemia. The adequate use of erythropoietin is of great help to the physician in the management of small cell lung cancer patients, by improving the quality of life.

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Chemotherapy, Adjuvant; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Lung Neoplasms; Middle Aged; Quality of Life; Radiography; Radiotherapy, Adjuvant; Recombinant Proteins; Treatment Outcome

Topics: Anemia, Hypochromic; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins

Two new intravenous (IV) iron products, ferric gluconate and iron sucrose, recently were approved for use in the United States. We report trends in IV iron use in both incident (1994 to 2001) and prevalent (1994 to 2002) Medicare US dialysis patients.. Included patients had Medicare as a primary payer. Recombinant human erythropoietin doses, IV iron use, and hemoglobin data were obtained from Medicare outpatient files. The most recent cohorts included 241,770 prevalent hemodialysis (HD) patients in 2002 and 11,744 incident HD patients in 2001.. For incident HD patients in the first 9 months of dialysis therapy, the percentage of patients administered IV iron increased sharply between 1994 and 1997 and then increased gradually between 1997 and 2001. In 2002, a total of 84.4% of HD and 19.3% of peritoneal dialysis (PD) patients were administered IV iron. Ferric gluconate use increased slowly in 2000, increased from 5.7% to 18.6% from December 2000 to January 2001, increased to 29.8% in April 2002, and was 23.3% in December 2002. Iron sucrose use increased to 26% by December 2002. The absolute monthly percentage of HD patients administered IV iron dextran decreased from 49.6% in January 2000 to 3.6% in December 2002.. In US patients with end-stage renal disease, IV iron use has increased, although slowly, from 1997 to 2002. Ferric gluconate and iron sucrose have become the predominant form of therapy. IV iron therapy was used in a much smaller percentage of PD compared with HD patients, and racial and geographic variability was observed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Child; Child, Preschool; Drug Utilization; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Incidence; Infant; Infusions, Intravenous; Kidney Failure, Chronic; Male; Medicare; Middle Aged; Outpatients; Peritoneal Dialysis; Prevalence; Recombinant Proteins; Renal Dialysis; Retrospective Studies; United States

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

Very few patients with chronic renal failure (CRF) can maintain a hemoglobin concentration > 12 g/dl without rHuEpo treatment. Among 68 patients treated in our Department by CAPD, 12 of them (17.6%) with daily diuresis < 400 ml, for at least 6 months had Hb level over 12 g/dl, Hct > 35% without rHuEpo treatment. In present study we carried out a clinical analysis of 12 patients without anaemia treated CAPD from 12 to 63 months. Mean Hb value was 13.5 +/- 0.97 g/dl (range 12.4-14.9 g/dl). None of 12 patients had acquired cystic kidney disease in ultrasonographic investigation. Nobody of these patients was rHuEpo treated. Mean C-reactive protein as well as ferritin serum concentrations was significantly lower in this group of patients compared to others. Mean endogenous Epo concentration was not significantly different from other CAPD pts. We conclude that spontaneous increase in Hb concentration in CAPD pts was not connected with increase in the serum endogenous Epo concentration. Factors other than Epo probably play a role in regulation of erythropoiesis in these pts.

Topics: Adult; Aged; Anemia, Hypochromic; C-Reactive Protein; Enzyme-Linked Immunosorbent Assay; Erythropoiesis; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Parathyroid Hormone; Peritoneal Dialysis, Continuous Ambulatory; Time Factors

Few studies have assessed treatable factors associated with achieving the Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline of hemoglobin values of 11 to 12 g/dL in anemic hemodialysis patients.. This was a retrospective study of 30,029 prevalent hemodialysis patients with mean hemoglobin values less than 11 g/dL between January 1 and March 31, 1999. We studied the associations between demographic characteristics, comorbid conditions, disease severity, urea reduction ratio, epoetin doses, intravenous iron doses, and mean hemoglobin values in the ensuing 3 months.. Approximately half (51.3%) of patients reached a mean hemoglobin value of at least 11 g/dL. By multiple logistic regression, the major factors showing a positive association with this outcome included a urea reduction ratio greater than 75% (odds ratio [OR], 1.23; P < 0.0001) and intravenous iron (OR: for 0 vials/month, 1; for < 1, 1.22; for 1 to 1.9, 1.36; 2 to 2.9, 1.48; for 3 to 3.9, 1.61; for > or = 4, 1.79; P < 0.0001), while a negative association with hemoglobin response, possibly representing epoetin resistance, was shown for initial severity of anemia (OR: for initial hemoglobin value < 7 g/dL, 0.06; for 7 to 7.9 g/dL, 0.12; for 8 to 8.9 g/dL, 0.23; for 9 to 9.9 g/dL, 0.45; for 10 to 10.9 g/dL, 1; P < 0.0001) and epoetin doses in the highest quintile (OR for > 38,000 units/wk, 0.76; P < 0.0001).. In patients with persistently low hemoglobin values, optimizing urea clearance and a proactive approach to intravenous iron therapy may enhance epoetin responsiveness.

Topics: Adult; Age Factors; Aged; Anemia, Hypochromic; Erythropoietin; Female; Follow-Up Studies; Guidelines as Topic; Hemoglobins; Humans; Iron Compounds; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Multivariate Analysis; Quality of Life; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Sex Factors; Total Quality Management; Treatment Outcome

To assess the effects of erythropoietin (EPO) on bone metabolism in patients receiving chronic hemodialysis (HD).. Forty one patients were divided into two groups whether they required the administration of EPO to treat renal anemia or not. Serial measurements of predialysis blood samples and bone mineral density were performed prospectively over a year.. The administration of EPO was associated with an increased serum creatinine (11.9 +/- 0.4 to 12.5 +/- 0.4 mg/dl, p < 0.05), insulin-like growth factor binding protein (3.0 +/- 0.2 to 3.4 +/- 0.2 micrograms/ml, p < 0.05) as well as decreased iron level (112 +/- 7 to 88 +/- 7 micrograms/dl, p < 0.005). Furthermore, in EPO-treated group, exogenous EPO doses correlated with the increments in 1,25-dihydroxy-vitamin D (r = 0.38, p < 0.05), intact osteocalcin (r = 0.42, p < 0.05) and bone alkali-phosphatase (r = 0.53, p < 0.005), but not intact parathyroid hormone (r = 0.09). Both metacarpal index (0.47 +/- 0.02 to 0.47 +/- 0.02) and the summation of gray scale/diameter (2.68 +/- 0.06 to 2.61 +/- 0.07 mmAl), bone mineral density parameters, remained unchanged.. The present data provide evidence that EPO may modulate the production of 1,25-dihydroxy-vitamin D in HD patients. Furthermore, our findings suggest that EPO therapy activates insulin-like growth factor system in HD patients, possibly through its actions on metabolism.

Topics: Analysis of Variance; Anemia, Hypochromic; Blood Chemical Analysis; Bone Density; Case-Control Studies; Densitometry; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Probability; Prognosis; Prospective Studies; Recombinant Proteins; Reference Values; Renal Dialysis; Risk Assessment; Treatment Outcome

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Recombinant Proteins; Ventricular Function, Left

Recently programs for preoperative autologous blood donation (PABD) have expanded to reduce the need for allogenic blood transfusion. Nevertheless, the ability of the patients's bone marrow to replace the red blood cells (RBCs) mass reduced by phlebotomies determines the efficacy of PABD. In mild anemia, known as iron-deficient erythropoiesis (IDE) or iron deficiency without anemia, precipitated by PABD, the marrow response is suboptimal and needs adjuvant therapy. The aim of this study was to evaluate the use of the serum transferrin receptor (sTfR) for the assessment of IDE in patients undergoing PABD.. Two autologous blood units from 50 consecutive patients scheduled for elective orthopedic surgery were collected preoperatively. Serial measurements of RBCs, haematocrit (Hct), haemoglobin (Hb), serum iron, serum ferritin, reticulocyte count, reticulocyte maturity index (RMI), endogenous erythropoietin (EPO) and sTfR were performed throughout the phlebotomy program.. RBC, Hct, Hb and serum iron significantly decreased although within the normal range. There was no change in serum ferritin levels. Reticulocytes, RMI and EPO significantly increased as did sTfR which significantly exceeds the normal range.. These results demonstrate that the sTfR is a reliable laboratory marker for detecting mild anemia or IDE. In patients undergoing PABD increased sTfR levels may suggest a treatment with recombinant human EPO (rh-EPO) or iron to improve the bone marrow performance.

Topics: Adult; Aged; Anemia, Hypochromic; Biomarkers; Blood Transfusion, Autologous; Erythropoietin; Female; Humans; Iron Deficiencies; Male; Middle Aged; Orthopedic Procedures; Phlebotomy; Preoperative Care; Receptors, Transferrin; Recombinant Proteins

Topics: Aluminum; Anemia; Anemia, Hypochromic; Drug Resistance; Erythropoiesis; Erythropoietin; Humans; Inflammation Mediators; Iron Deficiencies; Isoantibodies; Nutrition Disorders; Primary Myelofibrosis; Recombinant Proteins; Renal Dialysis; Treatment Failure

Topics: Anemia, Hypochromic; Antirheumatic Agents; Autoimmune Diseases; Blood Loss, Surgical; Christianity; Crohn Disease; Erythropoietin; Folic Acid Deficiency; Hepatitis C, Chronic; Hip Fractures; Humans; Iron; Male; Middle Aged; Paraproteinemias; Premedication; Proteus Infections; Recombinant Proteins; Spondylitis, Ankylosing; Sulfasalazine; Urinary Tract Infections; Vitamins

The European best practice guideline [Nephrol Dial Transplant 1999; 14 (Suppl 5)] (5A) for the management of anaemia suggests that > 85% of the CAPD population should have a haemoglobin level of > 11.0 g/dl.. We developed and implemented an outpatient-based protocol for intravenous iron sucrose (IV Fe) and erythropoietin (Epo) in CAPD patients showing iron deficiency despite oral iron therapy. We managed a total of 103 patients over 13 months of study. All CAPD patients were included, regardless of co-morbidity. Treatment developed in two phases: in phase 1 (reactive) (months 1-8), patients with markers of iron deficiency (ferritin < 100 ng/ml or ferritin 100-500 and percentage hypochromic red cells (%HRC) > or =5) were converted from oral iron to IV Fe (300 mg) and reviewed after 4-8 weeks according to haemoglobin (Hb). In phase 2 (proactive) (months 9-13), the criteria for iron therapy were extended: ferritin < 150 ng/ml or ferritin 150-500 and %HRC > or = 2. Patients then received IV Fe (200 mg) and were reviewed after 4 weeks according to Hb.. The median haemoglobin increased from 11.0 (Inter quartile range, IQR, 10.1-12.6) g/dl to 11.7 (11.0-12.7) g/dl (P = 0.06). The proportion of patients with absolute iron deficiency (ferritin < 100 ng/ml) decreased from 24 to 2%. The percentage of hypochromic red cells (%HRC) decreased from 4 (2-7) to 1 (1-4) (P < 0.01).. An integrated Epo and IV Fe policy increased the number of patients reaching the European guideline from 50 to 75% with no increase in the population median Epo requirements (42 (IQR, 25-95) IU/kg/week vs 45 (27-101) (P = NS)). This study demonstrates the benefit of early (proactive) intervention in achieving population compliance within current guidelines for renal anaemia.

Topics: Anemia, Hypochromic; Anemia, Iron-Deficiency; Clinical Protocols; Erythropoietin; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Iron; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins; Time Factors

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Erythropoietin; Female; Hemoglobins; Humans; Male; Neoplasms; Recombinant Proteins; Treatment Outcome

Iron deficiency anemia is a cause of reactive thrombocytosis. A moderate increase in platelet numbers is common but sometimes counts may exceed 1,000 x 10(9)/l. The mechanisms causing reactive thrombocytosis are unclear. In this study, we evaluated 15 women with iron deficiency anemia and thrombocytosis (platelets >450 x 10(9)/l) and 16 women with iron deficiency anemia with normal platelet counts. Serum samples were taken before oral iron replacement therapy, after 1 and 3 months and at the end of replacement therapy. Thrombopoietin, erythropoietin (EPO), leukemia inhibitory factor, interleukin-6 and interleukin-11 levels were assayed. There was no change in the levels of thrombopoietic cytokines except for EPO. The correlation between high EPO levels and high platelet counts may suggest that EPO increases platelet counts, but the same EPO level changes can also be demonstrated in women with iron deficiency anemia but normal initial platelet counts. The fact that the levels of other cytokines remained unchanged during treatment suggests that either these cytokines have no effect on reactive thrombocytosis or the change in platelet counts in our patients is in a narrow range and is thus not affected by the cytokine levels.

Topics: Adolescent; Adult; Anemia, Hypochromic; Cytokines; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Growth Inhibitors; Hematocrit; Hemoglobins; Humans; Interleukin-11; Interleukin-6; Iron; Iron Deficiencies; Leukemia Inhibitory Factor; Lymphokines; Middle Aged; Platelet Count; Thrombocytosis; Thrombopoietin

Topics: Adult; Anemia, Hypochromic; Biomarkers; Erythropoietin; Female; Ferritins; HIV Infections; Humans; Iron; Iron Deficiencies; Male; Predictive Value of Tests; Protoporphyrins; Receptors, Transferrin; Recombinant Proteins; Sensitivity and Specificity; Transferrin

Topics: Anemia, Hypochromic; Erythropoietin; Hematocrit; Humans; Kidney Failure, Chronic; Renal Dialysis

In patients on chronic haemodialysis, because of a non-specific increase in serum ferritin, iron deficiency may be overlooked leading to failure of erythropoietin treatment. A reticulocyte haemglobin content < 26 pg and a percentage of hypochromic red cells > 2.5 have been proposed as markers of iron-deficient erythropoiesis in such subjects, but it is unclear which parameter is superior.. We measured haematocrit, reticulocyte haemglobin content, ferritin and the percentage of hypochromic red cells over 10-150 days in 36 chronic haemodialysis patients in a university hospital. Transferrin saturation was also measured in a subset of 25 patients; iron deficiency was defined as a transferrin saturation < 15%.. The diagnostic sensitivity and specificity of a reticulocyte haemoglobin content < 26 pg in detecting iron deficiency were 100% and 73% respectively, compared with 91% and 54% for a percentage of hypochromic red cells > 2.5. Paradoxical reticulocyte haemglobin concentrations occurred on follow-up in five patients receiving 4000 U erythropoietin per haemodialysis (HD). In three patients, reticulocyte haemglobin content exceeded 26 pg despite a persistent lack of iron. In a fourth, iron gluconate (62.5 mg i.v./HD) increased transferrin saturation to 27% and reduced the percentage of hypochromic red cells from 12 to 4, while reticulocyte haemglobin remained > 30 pg. In the final patient, iron gluconate increased transferrin saturation from 8 to 30% and reduced the percentage of hypochromic red cells from 40 to below 5, but reticulocyte haemglobin content remained < or = 26 pg throughout.. The reticulocyte haemglobin content is superior to the percentage of hypochromic red cells in detecting iron deficiency in haemodialysis patients.

Topics: Adult; Aged; Anemia, Hypochromic; Biomarkers; Erythropoiesis; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Renal Dialysis; Reticulocytes; Transferrin

Topics: Adult; Anemia, Hypochromic; Erythropoietin; Female; Humans; Leiomyoma; Polycythemia; Uterine Neoplasms

Topics: Anemia; Anemia, Hypochromic; Erythropoietin; Ferritins; Humans; Iron; Kidney Failure, Chronic; Recombinant Proteins; Renal Insufficiency

We assessed zinc protoporphyrin (ZPP) and the percentage of hypochromic erythrocytes in patients with advanced acquired immunodeficiency syndrome (AIDS) treated with recombinant erythropoietin (rhEPO).. Patients received 150 IU rhEPO subcutaneously every second day for 10 days, and 150 IU rhEPO plus 62.5 mg of intravenous iron every second day for an additional 10 days.. Before rhEPO therapy, ZPP was at 64.3 +/- 27.3 micromol/mol heme and the percentage of hypochromic erythrocytes was elevated at 9.7%, indicating mild functional iron deficiency. Ferritin was 1,002 +/- 956 microg/L, with transferrin saturation of 19.1 +/- 9.7%. Under rhEPO alone, ZPP rose to 80.1 +/- 21.6 micromol/mol heme and the percentage of hypochromic red cells rose to 22.9 +/- 4.7%; ferritin fell to 705 +/- 601 microg/L and transferrin saturation fell to 12 +/- 6.3%. When rhEPO was supplemented with iron, ZPP fell to 70.4 +/- 20.5 micromol/mol heme, the percentage of hypochromic red cells fell to 14.7 +/- 3.4%; ferritin was unchanged at 771 +/- 62 microg/L and transferrin saturation rose to 20.5 +/- 5.5%.. In contrast to ferritin and transferrin saturation, ZPP and the percentage of hypochromic erythrocytes effectively detect the functional iron deficiency under rhEPO therapy in advanced AIDS.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anemia, Hypochromic; Anemia, Iron-Deficiency; Biomarkers; Erythropoietin; Female; Humans; Iron; Male; Metalloporphyrins; Middle Aged; Protoporphyrins; Recombinant Proteins; Severity of Illness Index

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells.

Topics: Anemia; Anemia, Aplastic; Anemia, Hypochromic; Anemia, Megaloblastic; Antineoplastic Combined Chemotherapy Protocols; beta-Thalassemia; Bone Marrow Transplantation; Erythrocyte Indices; Erythroid Precursor Cells; Erythropoiesis; Erythropoietin; Feedback; Folic Acid; Hodgkin Disease; Humans; Iron; Kidney; Receptors, Transferrin; Transplantation Conditioning; Vitamin B 12

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Iron Deficiencies; Recombinant Proteins; Renal Dialysis

The percentage of hypochromic red blood cells (RBC), defined as those with a cellular haemoglobin < 28 g/dl has been suggested to be a sensitive marker of functional iron deficiency in maintenance haemodialysis (HD) patients. Thus, during rHuEpo therapy an increase in hypochromic RBC to > 10% would indicate that more intensive iron supplementation may be required.. We investigated 70 HD patients 57.1 +/- 15.3 years old and on maintenance HD for 66.3 +/- 47.9 months without blood loss from gastrointestinal bleeding or from the vascular access, without surgery and without infectious disease or malignancy. During the study period of 12 weeks, each patient received in i.v. dose of 800 mg ferrogluconate. Haemoglobin, haematocrit, and the percentage of hypochromic RBC were measured before and every 4 weeks after the start of the study; serum ferritin, zinc protoporphyrin (ZPP) and C-reactive protein (CRP) were measured at the beginning (baseline) and end of the study.. At baseline the percentage of hypochromic RBC was < or = 5.0% in 28 patients, > 5.0 and < or = 10.0% in 25 patients and > 10.0% in 17 patients, suggesting functional iron deficiency in at least 42 patients. Nine patients had serum ferritin values < 100 micrograms/1; nonetheless in these patients the median percentage of hypochromic RBC was 5.9% (range 0.9-14.3%), indicating that an absolute iron deficiency can occur in the presence of normal amounts of hypochromic RBC. There was a significant correlation between serum ferritin levels and hypochromic RBC at the end, but not at the beginning, of the study. However, there was no correlation between ZPP and hypochromic RBC at any time during the study. During i.v. iron supplementation the rHuEpo dose could be reduced by 8.5% in patients with hypochromic RBC < or = 5.0%, by 11.3% in patients with hypochromic RBC > 5.0 and < or = 10.0% and by 23.4% in patients with hypochromic RBC > 10.0%, demonstrating the benefit of i.v. iron in patients with functional iron deficiency. In HD patients in whom serum ferritin levels remained below 290 micrograms/l until the end of the study, a significant reduction of the rHuEpo dosage could be obtained during i.v. iron therapy. This was not the case in patients with serum ferritin > 290 micrograms/l after iron supplementation. We found that the percentage of hypochromic RBC is the most sensitive parameter for predicting hyporesponsiveness in CRP-positive patients. HD patients with hypochromic RBC > 6% and low to moderate increases in serum ferritin levels after i.v. iron supplementation significantly benefit from i.v. iron therapy compared to HD patients with hypochromic RBC < 6%.. Two different aspects should be taken into consideration in HD patients treated with rHuEpo and concomitant i.v. iron therapy: (1) response of the erythropoietic system to rHuEpo, and (2) adequate delivery of the supplemented iron to the erythropoietic system. The patient's percentage of hypochromic RBC and increase in serum ferritin after i.v. iron supplementation should be used to decide whether or not i.v. iron should be given and to monitor this type of therapy in HD patients.

Topics: Anemia, Hypochromic; Erythrocyte Count; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Male; Middle Aged; Protoporphyrins; Recombinant Proteins; Renal Dialysis

Anemia of chronic renal failure (CRF) prior to initiation of dialysis is an important cause of morbidity and requires early therapeutic intervention. The current study was designed to investigate the efficacy and tolerability of a therapeutic algorithm for anemia of CRF in pre-dialysis patients which is based on low dose once-a-week subcutaneous (s.c.) administration of recombinant human erythropoietin (r-HuEPO). Thirty-one patients participated in a prospective open-label multicenter study. At baseline, hemoglobin was 8.8+/-0.1 g/dl, transferrin saturation 27+/-2%, ferritin 207+/-28 ng/ml and serum creatinine 4.7+/-0.2 mg/dl. Treatment with r-HuEPO was started at a fixed s.c. dose of 4,000 units once weekly, irrespective of body weight, and titrated upwards or downwards according to a predetermined algorithm. Hemoglobin rose to levels >10 g/dl within 8 weeks and remained stable throughout the remaining period of the study. By week 24, most patients required

Topics: Adolescent; Adult; Aged; Algorithms; Anemia, Hypochromic; Creatinine; Drug Administration Schedule; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Subcutaneous; Israel; Kidney Failure, Chronic; Leukocyte Count; Male; Middle Aged; Platelet Count; Prospective Studies; Recombinant Proteins; Renal Dialysis; Transferrin; Treatment Outcome

Despite the prevalent use of recombinant human erythropoietin (rhEPO), anemia is a frequent finding in hemodialysis patients. The goal of this study was to evaluate the impact of anemia on patient survival and characterize the determinants of hematopoiesis that may be amenable to therapeutic manipulation to enhance rhEPO responsiveness and reduce death risk. Patient characteristics and laboratory data were collected for 21,899 patients receiving hemodialysis three times per week in dialysis centers throughout the United States in 1993. Hemoglobin concentrations (Hb) < or =80 g/L were associated with a twofold increase in the odds of death (odds ratio = 2.01; P = 0.001) when compared with Hb 100 to 110 g/L. No improvement in the odds of death was afforded for Hb >110 g/L. Using multiple linear regression, variables of rhEPO administration (rhEPO dose and percentage of treatments that rhEPO was administered), variables of iron status (serum iron, transferrin saturation, and ferritin), variables of nutritional status (serum albumin and creatinine concentration), and the dose of dialysis (urea reduction ratio) were found to be significantly associated with hemoglobin concentration (P < 0.001). Age, race, and gender were also found to be significantly associated with hemoglobin concentrations (P < 0.001). From this report, the following conclusions may be made. (1) Anemia may be predictive of an increased risk of mortality in some hemodialysis patients. (2) Hemoglobin concentrations > 110 g/L are not associated with further improvements in the odds of death. (3) Laboratory surrogates of iron stores, nutritional status, and the delivered dose of dialysis are predictive of hemoglobin concentration. Whether manipulation of the factors that improve anemia will also enhance the survival of patients on hemodialysis is unknown and should be evaluated by prospective, interventional studies.

Topics: Adult; Aged; Anemia; Anemia, Hypochromic; Comorbidity; Creatinine; Diabetes Mellitus; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Kidney Failure, Chronic; Male; Middle Aged; Nutrition Disorders; Odds Ratio; Predictive Value of Tests; Prevalence; Recombinant Proteins; Regression Analysis; Renal Dialysis; Risk Factors; Serum Albumin; Survival Analysis; Transferrin; Treatment Outcome; United States

Estimation of red cell ferritin (RCFer) may give a good indication of iron supply to the erythron and it may therefore be clinically useful for the detection of functional iron deficiency. In a cross-sectional study of hemodialysis patients on erythropoietin (EPO) therapy and regular oral iron we have compared the RCFer levels with conventional indicators of iron status. The patients studied, 19 female, 48 male, mean age 62 +/- 3.6 years (range 20-83 years) were characterized by the following mean parameters: aluminum 1.24 +/- 0.12 mumol/L, PTH 115.7 +/- 39 pg/mL, vitamin B12 626 +/- 71.2 ng/L, serum folate 18.8 +/- 2.2 micrograms/L, and hemoglobin 9.8 +/- 0.3 g/dL (range 7.3-12.4). The median serum ferritin (SF), RCFer, total iron binding capacity (TIBC), transferrin saturation (TS), and serum iron were 68 micrograms/L, 14.1 ag ferritin/red cell, 57 mumol/L, 20% and 11.5 mumol/L, respectively. Eleven patients had a reduced RCFer (< 7 ag ferritin/red cell), 5 had a SF of < 15 micrograms/L and 22 a TS of < 16%. The occurrence of functional iron deficiency was suggested by the presence of 10 subjects with reduced RCFer despite normal SF levels (15-240 micrograms/L). Four patients with reduced SF showed acceptable levels of RCFer, suggesting that some patients may maintain an adequate iron supply despite diminished iron stores. Despite oral iron therapy, a significant number of patients (63%) on regular hemodialysis remain relatively iron deficient with a serum ferritin of less than 100 micrograms/L. It has previously been proposed that oral iron provides adequate supplementation during increased demand caused by EPO stimulation. The present study has demonstrated overt iron deficiency in five subjects and suggests functional iron deficiency in a further seven (22% of total patients). We therefore conclude that oral iron therapy cannot maximize the response to EPO.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Aluminum; Anemia, Hypochromic; Biomarkers; Cross-Sectional Studies; Erythrocytes; Erythropoietin; Female; Ferritins; Folic Acid; Hemoglobins; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Renal Dialysis; Vitamin B 12

This study was designed to investigate the effect of intravenous (i.v.) iron dextran (i.d.) on hematocrit (Hct), transferrin saturation (TS), and serum ferritin (SF) in hemodialysis patients treated with a constant dose of erythropoietin (EPO). The sensitivity, specificity, and predictive values of SF and TS for monitoring i.d. therapy were also assessed. All hemodialysis patients with baseline SF < 100 ng/mL or TS < 20%, with EPO dose unchanged 6 weeks before and 4 weeks after dosing with i.d. were included. I.d. (500 mg-1 g) was given as an infusion over 1 h. Patients receiving packed RBC or with active bleeding were excluded. Hct, TS, and SF were measured 2 weeks before and 4 weeks after i.d. Linear correlation coefficients between dose of i.d., changes in Hct, TS, and SF were calculated. The sensitivity, specificity, and predictive values of TS and SF were compared. A positive Hct response was defined as a > 5% increase from baseline 4 weeks after administration of i.d. Thirty-three patients (17 females) received a total of 51 doses of i.d. Mean +/- SD i.d. dose was 770 +/- 278 mg. Hct increased by a mean +/- SD of 4.8% +/- 9.9% (33.4% +/- 3.0% to 34.9% +/- 4.1% [p = 0.028]); SF rose by a median of 208.65% (mean +/- SD of 126.8 +/- 132.1 ng/mL to 325.3 +/- 222.0 ng/mL [p < 0.0001]; TS increased by a median of 53.8% (19.4% +/- 9.4% to 29.3% +/- 11.3% [p < 0.0001]) from baseline values. The correlations between dose of ID and percent changes in SF, TS, and Hct were poor (r2 < 0.02). The sensitivities and specificities were 74% and 36% (TS < 20% alone); 60% and 30% (SF < 100 ng/mL alone); and 33% and 67% (TS < 20% and SF < 100 ng/mL), respectively. The predictive values for positive responses were 48% for TS and 45% for SF when used alone, and 47% when both indices were used together. The predictive value increased to 65% when either SF < 100 ng/mL or TS < 20% were used. At a constant EPO dose, there was a statistically significant increase in Hct 4 weeks after i.d. administration in patients who were diagnosed with iron deficiency by using TS < 20% or SF < 100 ng/mL. The dose of i.d. administered was poorly correlated to changes in Hct, TS, and SF. Both TS and SF are non-specific and insensitive indicators for accurate diagnosis of iron deficiency in hemodialysis patients in EPO.

Topics: Anemia, Hypochromic; Biomarkers; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Injections, Intravenous; Iron Deficiencies; Iron-Dextran Complex; Male; Prospective Studies; Renal Dialysis; Sensitivity and Specificity; Transferrin

A 20-year-old Jehovah's witness patient experienced a femur fracture, with a section of the femoral artery and vein. On admission, haemoglobin concentration was 5.6 g.dL-1 and haematocrit 17%. Because of aponevrotomy, blood losses persisted. As the patient refused blood transfusion, recombinant human erythropoietin and parenteral iron were administered, associated with mild hypothermia, sedation and mechanical ventilation. After 21 days, the haemoglobin concentration increased to 10.9 g.dL-1 and haematocrit to 33% Recombinant human erythropoietin and parenteral iron may provide an alternative safe and effective therapy in life-threatening anaemia when blood transfusions are not accepted by the patient.

Topics: Acute Disease; Adult; Anemia, Hypochromic; Blood Loss, Surgical; Christianity; Erythropoietin; Femoral Artery; Femoral Fractures; Femoral Vein; Hemoglobins; Humans; Male; Recombinant Proteins; Time Factors

Iron deficiency is common in hemodialysis patients, particularly if they are on recombinant human erythropoietin (rHuEPO) therapy. Ten anemic patients (hemoglobin concentration 89 +/- 2.2 g/l, mean +/- SEM) on hemodialysis with either storage (serum-ferritin < 60 mg/l) and/or functional (S-transferrin saturation < or = 17%) iron deficiency were followed for 5 weeks. During the first 3 weeks they were given 100 mg of iron dextran on 10 consecutive dialysis sessions. Half of the patients were concomitantly treated with rHuEPO. Iron therapy resulted in a rapid elevation in serum transferrin iron saturation from 11 +/- 1.5% to 80 +/- 7.2% (p < 0.0001), but it decreased to pre-treatment levels within 2 weeks after discontinuation of iron therapy. Serum ferritin concentration increased from 157 +/- 73 mg/l to 434 +/- 105 mg/l during iron therapy (p < 0.0001). In spite of this only 4 patients (2 rHuEPO treated) responded and had a hemoglobin increment > 10 g/l. In the whole group serum transferrin receptor (TfR) levels remained stable, but increased after the cessation of iron dextran only in the rHuEPO treated patients (p < 0.01). In the responders the TfR levels were higher during iron therapy than in the nonresponders (p < 0.02). In an attempt to explain the resistance to iron therapy, serum concentrations of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1b (IL-1b) were also analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Anemia, Hypochromic; Biological Availability; C-Reactive Protein; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Intravenous; Interleukin-1; Iron; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin; Tumor Necrosis Factor-alpha

In historical studies erythropoietin stimulated bone marrow was shown to produce less stable, macrocytic, "stress erythrocytes". Recent work from our lab suggests that erythropoietin serves as both a growth factor and as a survival factor. To investigate the effects of recombinant human erythropoietin (rHuEPO) on development of red blood cell size of these longer lived erythrocytes, rHuEPO in 50-150 U/kg/dose was administered to patients with the anemia of chronic renal failure (CRF). Mean corpuscular volume (MCV) was determined at control, short term (n = 117, avg. 53 d), intermediate term (n = 73, avg. 136 d) and at long term (n = 66, avg. 221d) for effects of rHuEPO. Statistical evaluation at these time points was made comparing all patients to themselves as their own controls and using contingency tables for distribution of RBC size change. MCV at both short term (p = .02) and intermediate-term (p < .01) was decreased; there was no change (p = .71) at the long term. Analysis of distribution showed a significant (p < .01) trend toward microcytosis at short- and intermediate terms. This decrease of MCV and trend toward microcytosis is consistent with iron deficiency secondary to the early, rapid increase in bone marrow iron utilization and early increased reticulocytosis. Previous reports from our laboratory coupled with data presented in this report refute earlier findings that rHuEPO creates a "stress" mechanism producing less stable macrocytes.

Topics: Anemia, Hypochromic; Erythrocyte Indices; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins

We discussed the problems for autologous blood transfusion particularly in the preoperative blood donation about the patients over 70-year-old who underwent cardiac surgery in contrast with the younger patients. Following results were obtained: 1) Because aged patients have the tendency of anemia before predonation, full storage of blood donation could not be successed. 2 of 8 over 70-year-old patients were able to do the preoperative phlebotomy, and their mean volume were 355 gram as whole blood. On the other hand, 96% patients in younger group were phlebotomized preoperatively, and their mean value of storaged blood volume were 757 gram. 2) As the examinations about the iron-related parameters, not all aged patients were iron deficiency status. Their reticulocyte counts were nearly equal level to the younger group and plasma concentration of erythropoietin were higher in the aged patients than that in the younger group. These results indicate that erythropoiesis in the bone marrow was deteriorated in the aged patients. 3) In aged patients, all of them were required homologous blood transfusion at their perioperative terms. We thought that they have had the anemia before preoperation and our tolerable, allowable level to the postoperative anemia was not lower in the aged patients as against to the younger group. 4) We performed the autologous plasma donation with the membranous plasma separator added to the whole blood donation. It was easy and safe method, and circulatory indices were not changed before and after plasma-separation even in the aged patients. These autologous plasma were usefully administered as the volume expander postoperatively.

Topics: Aged; Anemia, Hypochromic; Blood Transfusion, Autologous; Cardiac Surgical Procedures; Erythropoietin; Female; Humans; Male; Middle Aged; Plasma; Preoperative Care; Reticulocyte Count

Multiple myeloma is very frequently associated with anemia which has the character of hypoproliferative anemia of chronic diseases. In this type of anemia there is often insufficient production of endogenous erythropoietin. According to literature pharmacological doses of erythropoietin result in the increase of blood hemoglobin concentration. Erythropoietin (Eprex Cilag) was given to 11 patients whose hemoglobin concentration in blood was lower than 100 g/l. 10 patients could be evaluated at the end of the study. Within the first month all patients were given erythropoietin in the dose of 150 U/kg 3 times a week. The dose was doubled, when the blood hemoglobin concentration did not increase by more than 10 g/l within the first month. In patients with hemoglobin level above 120 g/l we were trying to find the individual maintenance dose. In patients who had not reached a blood hemoglobin concentration increase of at least 20 g/l, as compared with the initial level, further erythropoietin administration was stopped. The concentration of hemoglobin increased of 20 g/l in 8 (80%) out of 10 patients evaluated. All 5 patients who responded within the first month, had had pretreatment concentration of endogenous erythropoietin below 60 U/l. Three other patients had not been responding before their dose of erythropoietin was increased in the 2nd and 3rd months of therapy. The therapy response appeared only in the 2nd and the 3rd months of treatment. These 3 patients had higher pretreatment concentrations of endogenous erythropoietin, from 100 to 350 U/l. During the treatment no adverse effects of erythropoietin were observed. Erythropoietin is a useful drug for anemic patients with the diagnosis of multiple myeloma. According to the results mentioned above and also according to the data from literature it is evident that in patients with the endogenous blood erythropoietin value below 100 U/l it is possible to expect a sudden rise in hemoglobin concentration already within the first month. Patients with a higher concentration of endogenous erythropoietin (100 to 500 U/l) respond to the therapy less frequently and for the increase in hemoglobin it is necessary to give higher doses of erythropoietin. Patients with the initial value of erythropoietin above 500 U/l are not likely to respond.

Topics: Adult; Aged; Anemia, Hypochromic; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Hemoglobinometry; Humans; Injections, Subcutaneous; Male; Middle Aged; Multiple Myeloma

Topics: Anemia, Hypochromic; Erythrocytes; Erythropoietin; Humans; Iron

We investigated whether determination of serum transferrin receptor (TfR) is useful for detecting iron-deficiency in patients with chronic inflammatory diseases and for differentiating between iron-deficiency anaemia and anaemia of inflammation. Using an immunofluorometric assay, serum TfR was measured in 34 anaemic patients. Of these patients, 23 had a chronic rheumatic disease, 13 with both inflammation and iron-deficiency and 10 with anaemia of inflammation only; the other 11 patients had iron-deficiency anaemia and no evidence of inflammation. Serum TfR concentrations were lower in patients with anaemia of inflammation (2.6 +/- 0.2 mg/l, mean +/- S.E.M.) than in patients with iron-deficiency anaemia (6.7 +/- 1.1 mg/l, P < 0.01) or those with both inflammation and iron deficiency (5.8 +/- 1.0 mg/l, P < 0.01). Among patients with inflammatory disease, correlations between TfR and ferritin concentrations (r = -0.62, P < 0.05) and TfR and erythropoietin concentrations (r = 0.69, P < 0.001) were observed in iron-deficient subjects only. TfR, though not superior to serum ferritin, can help to distinguish between anaemia of inflammation and iron-deficiency anaemia and to identify iron-deficiency in subjects with chronic inflammation.

Topics: Adult; Anemia, Hypochromic; Arthritis, Rheumatoid; Diagnosis, Differential; Erythrocyte Indices; Erythropoietin; Female; Ferritins; Fluoroimmunoassay; Humans; Male; Receptors, Transferrin

In the course of regular dialyzation treatment very frequently iron deficiency develops. The objective of the work was to evaluate the participation of sideropenia in the development of the hypoproliferative component of anaemia and to evaluate the effectiveness of oral iron administration in a group of 24 dialyzed patients whose serum ferritin concentration was lower than 100 micrograms/l. Administration of 105 mg elemental iron per day (1 tablet of Ferronat retard, Spofa) for a period of 6 months led in 17 patients (71%) to a statistically significant increase of erythrocytes, serum ferritin, the iron plasma level and transferrin saturation. In these patients the mean haemoglobin value increased from 65 +/- 6 milligrams to 105 +/- 17 milligrams (increase by 40 milligrams), the mean number of red cells increased from 2.6 +/- 0.4 x 10(12)/l to 3.5 +/- 0.7 x 10(12)/l (increase by 0.9 x 10(12)/l) and the mean haematocrit increased from the initial value of 0.21 +/- 0.02 to 0.31 +/- 0.05 (increase by 0.10). In seven patients (29%) after oral substitution of iron deficiency no significant rise of any of the investigated indicators was observed. Four subjects of this group responded by a rise of red blood cells to intravenous iron administration and in the remaining three patients anaemia was favourably influenced by administration of recombinant erythropoietin (Eprex, Cilag). The results of the investigation provide conclusive evidence that iron deficiency plays a very important part in the development of anaemia in hemodialyzed patients. Substitution treatment with iron preparations extends the opportunities to treat anaemia during regular dialyzation treatment and is at the same time also very important from the economical aspect as it makes more expedient selection of patients suited for recombinant erythropoietin treatment possible.

Topics: Adult; Anemia; Anemia, Hypochromic; Erythropoietin; Female; Humans; Iron; Iron Deficiencies; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

The influence of body iron stores on the concentration of serum erythropoietin was studied in 48 hemodialyzed patients not receiving human recombinant erythropoietin, androgens or iron supplements. The serum erythropoietin concentration was 11.6 +/- 10.4 mIU/ml. There was no correlation between the serum erythropoietin and the hematocrit or hemoglobin concentration; however, there was a correlation between the serum erythropoietin and the log of serum ferritin (r = -0.5699, p < 0.01). Serum erythropoietin levels were higher in the 18 ferropenic patients (serum ferritin < 50 ng/ml) than in the 30 patients with normal serum ferritin concentration (18 +/- 13.8 vs. 7.8 +/- 4.7 mIU/ml, p < 0.01). The administration of intravenous iron to the ferropenic patients resulted in a reduction in serum erythropoietin independent of the response of the anemia (18 +/- 13.8 basal and 7.9 +/- 6.5 mIU/ml at 4 weeks, p < 0.01). Our data would suggest that the concentration of erythropoietin in hemodialyzed patients is influenced by the serum ferritin level.

Topics: Adult; Aged; Anemia, Hypochromic; Erythropoietin; Female; Ferric Compounds; Ferritins; Hematocrit; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Renal Dialysis; Uremia

Iron deficiency severely limits the efficacy of recombinant human erythropoietin (EPO). In order to determine how best to identify and monitor children at risk of developing iron deficiency, we serially measured several parameters of iron status in nine children before and during a 24-week period of EPO therapy. Serum ferritin was the best predictor of development of iron deficiency, five of the nine children developed iron deficiency, characterised by a poor haemoglobin response or evidence of microcytosis and hypochromia; all had a serum ferritin of 60 micrograms/l or less at the start of EPO. Haemoglobin response was also related to change in mean red cell volume (MCV); a falling MCV, irrespective of absolute value, accompanying a poor response to EPO. Iron treatment in five children resulted in significant improvements in haemoglobin and iron status parameters. Although MCV remained low, there was a marked increase in red cell volume distribution width after iron, which may be of value in monitoring the response to iron therapy. We suggest that children with a serum ferritin of 60 micrograms/l or less and those who develop a falling MCV during EPO treatment should receive high-dose oral iron supplementation before and during treatment with EPO.

Topics: Administration, Oral; Anemia, Hypochromic; Biomarkers; Child; Child, Preschool; Erythrocyte Count; Erythrocytes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Injections, Subcutaneous; Iron; Iron Compounds; Kidney Failure, Chronic; Male; Recombinant Proteins; Transferrin

The value of s-Transferrin Receptor (s-TfR) measurements in recognizing simultaneous iron deficiency in anaemia of chronic disease was examined in 35 anaemic patients with active rheumatoid arthritis. Based on a quantification of stainable bone marrow (marrow iron grade 0-4) and serum ferritin concentrations (levels < 60 micrograms l-1) compatible with iron deficiency) the anaemia was found to be aggravated by iron deficiency in 19/35 or 54% of the patients. There was no significant difference between the mean s-TfR concentrations in patients with adequate iron in comparison to patients with iron depletion [2.9 (1.6) mg l-1 v. 2.7 (1.4) mg l-1; t = 0.273; p = 0.786; Student's t-test]. Mean s-TfR levels in both patients with adequate iron and depleted iron stores were within the normal range, but tended to be higher than in normal individuals [mean (SD): 1.54 (0.43) mg l-1]. In patients with no stainable marrow iron (MIG 0; N = 15) a significant inverse correlation was found between s-TfR concentrations and s-ferritin levels (r = 0.57; p < 0.05). 5/15 patients with MIG = 0 exhibited significantly raised concentrations of s-TfR values > 3.05 mg l-1 (the highest normal value of the normal range). Increases of s-TfR levels were consistently moderate, and never exceeded a level of 7 mg l-1, which is markedly lower than concentrations measured in patients with iron deficiency anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Bone Marrow; Erythropoietin; Female; Ferritins; Humans; Iron; Male; Middle Aged; Receptors, Transferrin

The importance of autologous blood donation for elective surgery is recognized, and the method is being used at many hospitals. Not all patients are able to deposit a sufficient amount of blood before surgery because they cannot recover rapidly enough from phlebotomy-induced anemia. The ability to donate sufficient blood for autologous use was studied in patients who are particularly susceptible to phlebotomy-induced anemia.. Of 840 patients who donated blood for autologous use in elective surgery from November 1987 through May 1993, 20 with rheumatoid arthritis, 24 with iron deficiency anemia, and 37 aged 65 years and above with normocytic anemia were compared with 24 nonanemic elderly patients who donated a total of 1000 mL of blood for autologous use. Patients received iron sulfate orally and donated blood once a week until operation.. The amount of blood collected before surgery per control patient was more than that in others. Consequently, there was a tendency to allogeneic blood transfusion in patients with rheumatoid arthritis or elderly patients. The ferritin levels in controls and in patients with iron deficiency anemia during the donation period were almost within the normal range in spite of iron supplementation, which implied a good utilization of iron sulfate for erythropoiesis. On the other hand, the rise in ferritin levels in the elderly and in patients with rheumatoid arthritis suggested inappropriate iron availability for erythropoiesis and resulted in an increase in iron storage. Since an adequate endogenous erythropoietin response to phlebotomy-induced anemia was not observed in these patients, impaired erythropoietin production was considered one of the reasons for anemia.. Patients with iron deficiency anemia are able to continue donating blood for autologous use so long as they have sufficient iron supplementation. However, the elderly or those with rheumatoid arthritis occasionally fail to donate a sufficient volume of blood before surgery as a result of phlebotomy-induced anemia, which is caused in turn by impaired erythropoietin production.

Topics: Adult; Aged; Aged, 80 and over; Anemia, Hypochromic; Arthritis, Rheumatoid; Blood Donors; Blood Transfusion, Autologous; Bloodletting; Erythropoietin; Female; Humans; Iron; Male; Middle Aged; Time Factors

The low plasma erythropoietic (Epo) activity which is non-adequate to manifestation of anemia, and the lack of correlation between Epo activity and the degree of anemia and hypoxia were found in children with sepsis. The lowest Epo activity was determined in plasma of patients after repeatedly blood transfusion and in emaciated children. The non-specific Epo activity inhibitor was determined in acute period of sepsis in majority of patients. We suppose that the low Epo activity was due to the violation of Epo synthesis regulation mechanism or was connected with the presence of non-specific inhibitors. These results suggest recombinant Epo for the treatment of anemia in children with sepsis.

Topics: Anemia, Hypochromic; Animals; Bacterial Infections; Blood Transfusion; Cells, Cultured; Erythropoietin; Hemoglobins; Humans; Hypoxia; Infant; Mice; Mice, Inbred BALB C; Reference Values

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

The peripheral blood was studied in Dolgans, Nganasans and Nenetses, the native population living in Taimyr peninsula. The composition of their blood is really different from the European norm. In Aboriginals of Taimyr the activity of erythropoietin in blood plasma, the concentration of reticulocytes, the circulation in peripheral bed of diskocytes with one and many diverticula, the content of fetal hemoglobin are raised more than two times. The prevalence of iron deficiency anemia among the native population of Taimyr Autonomous Area is larger, than in Russia and in Aboriginals living in Evenkia and Yakutia.

Topics: Adolescent; Adult; Age Factors; Anemia, Hypochromic; Blood Cells; Child; Child, Preschool; Erythrocyte Count; Erythropoietin; Female; Humans; Infant; Iron; Iron Deficiencies; Male; Native Hawaiian or Other Pacific Islander; Population Surveillance; Racial Groups; Sex Factors; Siberia

To analyze the relationship between serum erythropoietin levels and hemoglobin levels in elderly patients with anemia of chronic disorders related to cancer or acute infection when compared with anemic patients with iron deficiency.. Prospective survey with comparison groups.. Tertiary care center.. An elderly group aged 70 and above (mean 84, range 70-96) was divided into subgroups of 45 with anemia of chronic disorders (23 with cancer and 22 with acute infection), 24 with iron-deficiency anemia, and 27 with no anemia. Thirty non-anemic younger adults were also studied.. Serum erythropoietin (radioimmunoassay), complete blood count, serum iron, B12, folate and ferritin, liver and kidney function tests, blood gas analyses, and bacteriological and radiological tests.. The serum erythropoietin levels were significantly lower in the elderly non-anemic hospitalized group than in the healthy younger group. A significant negative relationship between the log serum erythropoietin and hemoglobin levels was found in patients with iron deficiency, but not in the other groups. For any given hemoglobin level, the response of erythropoietin was significantly higher in anemic patients with iron deficiency when compared with the neoplastic and infectious group.. Erythropoietin response to anemia is blunted in elderly patients with anemia of chronic disorders related to cancer or acute infection. Erythropoietin level is lower in non-anemic elderly inpatients than in healthy younger persons.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Anemia; Anemia, Hypochromic; Case-Control Studies; Chronic Disease; Erythropoietin; Female; Hemoglobins; Hospitalization; Humans; Infections; Male; Neoplasms; Prospective Studies

The effect of treatment with recombinant human erythropoietin on skeletal muscle was investigated in 11 anemic transfusion-dependent patients on the hospital hemodialysis program. There were no significant changes in anthropomorphic measurements during the study, but the maximum voluntary contraction increased significantly for each muscle group studied (pre-erythropoietin and post-erythropoietin values, respectively, were as follows: biceps, median 170 N [range, 83 to 220 N] v 189 N [range, 89 to 245 N]; triceps, 88 N [range, 59 to 167 N] v 106 N [range, 95 to 185 N]; deltoid, 168 N [range, 78 to 247 N] v 193 N [range, 93 to 290 N]; and quadriceps, 202 N [range, 165 to 300 N] v 265 N [range, 185 to 335 N]; P < 0.05). There were no significant changes in muscle strength in a control group of regular hemodialysis patients. Programmed electrical stimulation of the quadriceps following erythropoietin treatment resulted in both a greater force generated and a longer duration of contraction. Following cessation of the electrical stimulus the relaxation rate for the type II fibers was quicker following erythropoietin therapy. This suggests that some of the benefit observed in physical well-being following correction of the anemia of chronic renal failure with erythropoietin is due to an improvement in voluntary skeletal muscle function.

Topics: Adult; Anemia, Hypochromic; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Muscles; Recombinant Proteins; Renal Dialysis; Treatment Outcome

Recombinant human erythropoietin (rHuEpo) has been associated with clinical and symptomatic improvements as well as improvements in quality of life in patients with anemia of chronic renal failure. However, resistance to rHuEpo therapy, related to insufficient iron stores, occurs often. Although many patients treated with rHuEpo take oral iron, patients continue to develop iron deficiency. Parenteral iron is a safe and effective alternative in replacing iron stores to sustain erythropoiesis in patients treated with rHuEpo.

Topics: Anemia, Hypochromic; Drug Resistance; Education, Nursing, Continuing; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Patient Education as Topic; Recombinant Proteins

Epoetin alfa stimulates erythropoiesis, thus creating an increased need for iron, and virtually all patients with end-stage renal disease who receive this therapy will eventually require iron supplementation. This article describes the appropriate use of oral and intravenous iron supplementation, including patient assessment, education, and management.

Topics: Aged; Anemia, Hypochromic; Erythropoietin; Female; Humans; Iron; Kidney Failure, Chronic; Patient Compliance; Patient Education as Topic; Recombinant Proteins

The prevalence of anemia in the elderly raises the question of an inappropriate secretion of erythropoietin in response to increased demands. Therefore, the serum erythropoietin concentration of elderly patients (74-95 years) with iron deficiency anemia was measured and compared to that of iron deficiency anemic adults (25-60 years). A lowered erythropoietin secretion in response to anemia was observed in elderly patients in comparison with adults. However, the serum erythropoietin of the anemic elderly was inversely correlated with hemoglobin levels as shown for the anemic adults. The progressive reduction of the renal function observed with aging could explain the decreased capacity of erythropoietin secretion in elderly patients.

Topics: Adult; Aged; Aged, 80 and over; Aging; Anemia, Hypochromic; Creatinine; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Male; Middle Aged

Topics: Anemia, Hypochromic; Erythrocytes; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Male; Protoporphyrins; Sports

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

Previous studies of the erythropoietin response to anaemia in RA have yielded conflicting findings. Some have found the response to be impaired and others have found a normal response. We have compared erythropoietin (EPO) levels measured by radioimmunoassay, in 54 anaemic rheumatoid patients and 55 patients with iron deficiency anaemia but no inflammatory disease. The erythropoietin response in the rheumatoid patients was impaired compared with the control group (P < 0.025) but only seven rheumatoid patients showed a response which fell below the 95% confidence intervals predicted for the control group. Rheumatoid patients who fell within the highest quartile for serum ferritin concentrations (i.e. those most likely to have anaemia of chronic disease) had significantly lower EPO levels compared with the control group (P < 0.01). EPO levels in rheumatoid patients within the lowest quartile for ferritin (i.e. those with iron deficiency anaemia) were not significantly different from the control group (P = 0.670). The difference in EPO response between the RA patients in the upper and lower quartile for ferritin approached but did not achieve significance (P = 0.056). In a second study 15 anaemic RA patients were given a 5-day course of oral prednisolone 1.5 mgkg-1. Hemoglobin did not rise significantly until day 4 but EPO levels fell by day 1 (P < 0.005) and remained lower than pretreatment values throughout the study. Thus, in RA patients, anaemia of chronic disease is associated with inappropriately low EPO concentrations but this does not appear to be the major cause of the anaemia and Hb response to prednisolone does not depend upon an increase in EPO concentration.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Male; Middle Aged; Prednisolone; Radioimmunoassay; Time Factors

We have studied the response of hemoglobin (Hb), hematocrit, reticulocytes, mean corpuscular volume, ferritin, serum iron, total iron-binding capacity (TIBC) and the transferrin saturation index in 9 patients on chronic hemodialysis (HD) with minimal aluminum overload who were treated with recombinant human erythropoietin (rHuEPO) when a single dose of deferoxamine (DFO; 40 mg/kg b.w.) was administered. Analytical determinations were performed basally and 48 h, 7 days and 14 days after a DFO test. Hb increased from a basal value of 10 +/- 0.28 to 10.7 +/- 0.33 (p < 0.05), 10.4 +/- 0.33 (p < 0.05) and 10.1 +/- 0.31 g/dl (NS), respectively, and similar increases were seen with the hematocrit. Serum iron increased from 52 +/- 7.62 to 89.2 +/- 14.48 (p < 0.01), 94 +/- 18.73 (p < 0.01) and 85 +/- 14.01 micrograms/dl (p < 0.01), respectively. TIBC and ferritin did not change but the transferrin saturation index increased significantly. DFO produces an immediate improvement of the anemia in HD patients treated with rHuEPO and who have minimal aluminium accumulation: it should be related to an increased iron availability to erythroid precursors either releasing stored iron or decreasing aluminum-bound transferrin.

Topics: Aged; Aluminum; Anemia, Hypochromic; Deferoxamine; Erythropoietin; Ferritins; Hematocrit; Hemoglobins; Humans; Iron; Middle Aged; Recombinant Proteins; Renal Dialysis; Transferrin

Serum erythropoietin levels (s-Epo) were measured by radioimmunoassay in 61 consecutive anaemic patients (Hb < 12 g/dl) with myelofibrosis with myeloid metaplasia (MMM). S-Epo was inversely correlated with Hb (r = -0.48, P < 0.0001). When observed s-Epo values were compared with predicted levels based on the relationship between s-Epo and Hb in control subjects, all but eight patients (87%) had s-Epo levels appropriate for the degree of anaemia. The observed/predicted (O/P) s-Epo ratio was significantly lower in patients with signs of active disease, and a significant inverse correlation was found between the O/P ratio and erythrokinetic measurement of the extent of erythropoiesis (r = 0.31; P = 0.02). Circulating Epo levels were appropriate for the variations in Hb during the postsplenectomy period in three patients. In conclusion, this study does not support the idea that therapy with erythropoietin should be extensively used in anaemic patients with MMM, but rather that it should be considered only in selected cases.

Topics: Adult; Aged; Anemia; Anemia, Hypochromic; Blood Component Transfusion; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Primary Myelofibrosis; Splenectomy; Thalassemia

In patients with chronic renal failure, renal transplantation improves anemia and the production of erythropoietin. In patients undergoing hemodialysis the administration of recombinant human erythropoietin improves anemia with a decrease in bodily iron stores. Therefore, one would expect a similar decrease after kidney transplantation. We followed the ferric parameters to determine the incidence of iron deficiency anemia in 24 consecutive renal transplant patients for an interval long enough to achieve steady state values of hemoglobin (5.1 +/- 0.8 months). Hematological parameters and serum levels of iron, ferritin and erythropoietin were measured. The patients were divided into 2 groups according to the decrease in serum ferritin: group 1--16 with a decrease in respect to basal values (114 +/- 56 ng./ml.) and group 2--those without modifications (720 +/- 320 ng./ml.). Except for the similar values, group 1 showed greater improvement in anemia (red blood cells 4.3 x 10(6) +/- 1.1 x 10(6) versus 3.7 x 10(6) +/- 1.5 x 10(6)/ml., p < 0.01) and hematocrit index (38.5 +/- 5.2 versus 33.0 +/- 5.1%, p < 0.05). Four patients had microcythemia (mean corpuscular volume 76.6 +/- 1.4 fluid) with lower hemoglobin values than the other patients in group 1 (10.77 +/- 0.42 versus 12.79 +/- 0.42 gm./dl., p < 0.05). Among the 16 patients in group 1, 7 of 8 whose basal serum ferritin was less than 150 ng./ml. achieved ferritin levels of less than 30 ng./ml. In conclusion, our data support that renal transplantation produces a rapid decrease in iron stores and in some cases induces iron deficiency anemia. This fact should be evaluated and treated properly.

Topics: Adult; Anemia; Anemia, Hypochromic; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Incidence; Iron; Kidney Failure, Chronic; Kidney Transplantation; Male

Serum erythropoietin (EP) concentration was measured by the recombinant EP-based radioimmunoassay and was examined to standardize the hemoglobin (Hb) related level of 144 normal control and 56 patients with iron deficiency anemia and hemolytic anemia excluding paroxysmal nocturnal hemoglobinuria. The standardization was achieved by logarithmic regression of the EP titier on Hb either by the two-phase linear form or by the third degree sigmoid form at a 95% confidence limit for each regression. The third degree regression was found to be preferable from the view point of both statistics and the negative feedback mechanism. The average and scattering of the deviation from the standard level thus determined of the disease groups indicated that the EP level is: (1) 12 fold higher than the standard level in 42 aplastic anemias (the most in excess and a few in standard). (2) three fold higher than that in 27 myelodysplastic syndromes (relatively higher dispersed state). (3) 29% of the standard level in 33 anemias associated with chronic renal failure (deficient state). (4) 105% of the extrapolated standard level in 22 polycythemia veras (standard state). The standardization of Hb-related Ep titer may provide new pathophysiological approaches in a variety of hematopoietic disorders.

Topics: Anemia, Hemolytic; Anemia, Hypochromic; Erythropoietin; Hemoglobins; Humans; Myelodysplastic Syndromes; Polycythemia Vera; Radioimmunoassay; Reference Standards

Absolute or functional iron deficiency decreases the effectiveness of erythropoietin in patients undergoing hemodialysis. We describe a patient who developed pica associated to a ferritin level of 800 ng/ml during recombinant human erythropoietin treatment. The symptom subsided after supplementation with iron dextran. Therefore we recommend iron supplementation during the initial phase of treatment with erythropoietin until serum ferritin levels raise above 1000 ng/ml.

Topics: Adult; Anemia, Hypochromic; Erythropoietin; Ferritins; Glomerulonephritis, IGA; Humans; Immunologic Factors; Iron; Iron Deficiencies; Male; Pica; Protoporphyrins; Recombinant Proteins; Renal Dialysis; Transferrin; Uremia

The mechanisms responsible for anaemia in leprosy were studied prior to the institution of therapy in 56 patients with active disease. Haematological indices, iron-related measurements, inflammatory markers and erythropoietin levels were assessed, with bone-marrow studies being performed on anaemic patients. Anaemia was more common in the patients with lepromatous leprosy (85.7%) than it was in the rest of the group (19%). The lepromatous group exhibited the disordered iron transport of the anaemia of chronic disorders in that they had a significantly lower mean serum iron level (P less than 0.05), and a mildly raised serum ferritin concentration. Anaemic lepromatous patients also showed a blunted erythropoietin response compared with controls with non-inflammatory anaemia. A subgroup of five anaemic subjects displayed apparently adequate transport of iron to the erythroid marrow (normal percentage transferrin saturations and appropriate sideroblast counts) and the blunted erythropoietin response appeared to be the dominant factor in the pathogenesis of their anaemia. Analysis of inflammatory markers revealed that while the erythrocyte sedimentation rate was very high in the lepromatous subjects, there was no concomitant rise in C-reactive protein concentration. This suggests the presence of a disordered cytokine-mediated acute phase response in the condition.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analysis of Variance; Anemia, Hypochromic; Biomarkers; Chi-Square Distribution; Erythropoietin; Female; Hematologic Tests; Humans; Iron; Leprosy; Leprosy, Lepromatous; Male; Middle Aged

Topics: Anemia, Hypochromic; Dose-Response Relationship, Drug; Erythropoiesis; Erythropoietin; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Kidney Failure, Chronic; Recombination, Genetic; Renal Dialysis

This study attempts to evaluate the adequacy of the erythropoietin (EPO) response in 42 anaemic patients with advanced human immunodeficiency virus (HIV) infection [30 with acquired immunodeficiency syndrome (AIDS) and 12 with AIDS-related conditions] by comparing their serum EPO levels with those found in a non-HIV reference population consisting of 36 patients with anaemia of chronic disorders (ACD) and 57 with iron deficiency anaemia (IDA). Although the average Hb concentration was similar in the three groups, the EPO level for HIV patients (mean +/- SEM, 64.3 +/- 7.7 mU/ml) did not differ significantly from that in ACD patients (45.3 +/- 8.3 mU/ml, P > 0.1), and both groups had a lower mean EPO level (P < 0.05 and P < 0.01 respectively) than IDA subjects (133.5 +/- 18.7 mU/ml). Thirteen HIV patients on zidovudine therapy showed similar mean Hb and EPO levels to those in the untreated patients. A significant inverse correlation between the log of serum EPO and the Hb values was observed in the three groups. However, this relationship was found to be stronger in IDA patients than in either HIV or ACD subjects (P < 0.001), with no difference between the two latter groups (P > 0.2). These data suggest that the EPO response is blunted in the anaemia associated with advanced HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Acute-Phase Reaction; Adolescent; Adult; Aged; Anemia; Anemia, Hypochromic; Child; Chronic Disease; Erythropoietin; Female; Hemoglobins; HIV Infections; Humans; Male; Middle Aged

Erythrocyte ferritin may be a better estimator of iron bioavailability than the conventional markers of iron stores (serum ferritin and transferrin saturation). To investigate the accuracy of these conventional markers in uremic patients compared with erythrocyte ferritin, we studied 29 chronic hemodialysis patients on erythropoietin (EPO) therapy, 18 without EPO therapy, and 22 healthy control subjects. Apart from the red blood cell indices, serum ferritin, transferrin saturation, and erythrocyte ferritin, the analytical study included red blood cell protoporphyrin and plasma aluminum levels. The control group showed erythrocyte ferritin concentrations between 8.3 and 12.5 attograms/cell (95% confidence interval). In the EPO group, red blood cell protoporphyrin correlated negatively with erythrocyte ferritin, but not with serum ferritin or transferrin saturation. In the non-EPO group, serum ferritin, erythrocyte ferritin, and transferrin saturation did not correlate with red blood cell protoporphyrin. Even though erythrocyte ferritin correlated well with serum ferritin in the EPO group (r = 0.61, P = 0.0003), the sensitivity of normal serum ferritin levels (30 to 300 ng/mL) to discard a low erythrocyte ferritin concentration (erythrocyte ferritin less than 7 ag/cell) was 0.53, while the sensitivity of serum ferritin at levels less than 30 ng/mL to indicate an absolute iron deficiency expressed as a low erythrocyte ferritin concentration was 0.28. Only values of serum ferritin and transferrin saturation greater than 300 ng/mL and 35%, respectively, could rule out a relative iron deficiency expressed as a low erythrocyte ferritin and high red blood cell protoporphyrin concentration. Plasma aluminum levels did not correlate with red blood cell protoporphyrin or erythrocyte ferritin levels in either uremic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anemia, Hypochromic; Erythrocytes; Erythropoietin; Female; Ferritins; Humans; Iron; Male; Middle Aged; Protoporphyrins; Renal Dialysis; Sensitivity and Specificity; Transferrin; Uremia

We studied the relationship between serum erythropoietin (EPO) concentration and iron status in 67 patients undergoing chronic hemodialysis. Serum concentrations of EPO were measured by RIA with recombinant human EPO. The geometric mean of the serum EPO concentration was 10.9 int. units/L (mean +/- SD range = 7.8 - 15.3 int. units/L) in hemodialysis patients, considerably lower than that in normal subjects (12.9 int. units/L). We found no significant correlation between concentrations of serum EPO and hemoglobin in hemodialysis patients, but found a significant negative correlation between serum concentrations of EPO and iron in hemodialysis patients. Moreover, we also found a significant positive correlation between the EPO concentration and the unsaturated iron-binding capacity (UIBC) in serum, and a significant negative correlation between the serum concentrations of EPO and ferritin in hemodialysis patients. Several patients who had relatively high EPO concentrations for hemodialysis patients also had low iron concentrations, high UIBC values, and low ferritin concentrations. These findings suggest that iron was utilized even at these EPO concentrations, which were very low for the degree of anemia observed in the hemodialysis patients.

Topics: Adult; Aged; Anemia, Hypochromic; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Iron; Male; Middle Aged; Reference Values; Renal Dialysis

To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease.. Three year retrospective study.. Subregional nephrology service serving a mixed urban and rural population of 800,000.. 60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants).. Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin.. All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures.. Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.

Topics: Adult; Aged; Anemia, Hypochromic; Blood Transfusion; Cost-Benefit Analysis; Drug Costs; England; Erythropoietin; Female; Hemoglobins; Hospitalization; Humans; Injections, Subcutaneous; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

To assess the effects of decreased erythrocyte production on the levels of serum erythropoietin in children, we measured simultaneous hemoglobin concentrations and erythropoietin in 18 children with iron deficiency anemia, 17 children with transient erythroblastopenia of childhood (TEC), and 7 children with aplastic anemia. In all but two patients (one with TEC; one with aplastic anemia), erythropoietin was measured at diagnosis, before institution of specific therapy for the anemia. There was a statistically significant inverse linear correlation between log10 erythropoietin and hemoglobin values for all patient groups (r = 0.904 to 0.912; p less than 0.005). A comparison of the slopes of the regressions for each patient group by analysis of covariance revealed a significantly steeper slope for the iron deficiency group (-0.553) versus the TEC (-0.287) and aplastic anemia (-0.256) groups (p = 0.0001). The difference in erythropoietin levels appeared greatest in patients whose presenting hemoglobin level was greater than 5 gm/dl. Decline in serum erythropoietin levels was more precipitous in the less severely anemic patients with iron deficiency anemia than in the patients with TEC or aplastic anemia. These data reveal quantitative and qualitative differences in the relationship between serum erythropoietin and hemoglobin levels when children with severe iron deficiency anemia versus those with TEC or aplastic anemia are considered, even though all three conditions are characterized by hypoproliferation of erythrocytes.

Topics: Analysis of Variance; Anemia, Aplastic; Anemia, Hypochromic; Child; Child, Preschool; Erythropoietin; Hemoglobins; Humans; Infant; Red-Cell Aplasia, Pure

Anemia in patients with grade IV pressure sores is usually refractory to therapy with iron salts, and red cell transfusions are commonly required when reconstructive surgery is performed. The anemia is characterized by hypoferremia, reticulocytopenia, and normal-to-increased serum ferritin. Five patients with this anemia were treated with recombinant human erythropoietin (rHuEPO) in doses of 50 to 100 U/kg, given subcutaneously three times per week. The hemoglobin increased in every patient; the mean (+/- SD) value at the initiation of treatment was 8.8 +/- 1.0 g/dL, and after a median of 4 weeks of therapy, it was 12.4 +/- 1.6 g/dL (p less than .001). No adverse effects of treatment were observed. It is concluded that rHuEPO is a promising new agent for pressure sore anemia, but randomized, controlled clinical trials will be required to firmly establish its place in the management of patients with this type of anemia.

Topics: Adult; Aged; Anemia, Hypochromic; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Pressure Ulcer; Recombinant Proteins

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Intestinal Absorption; Iron; Recombinant Proteins; Renal Dialysis; Uremia

1. The ATP production rate in isolated skeletal muscle mitochondria was measured with a bioluminescence method, before and during erythropoietin treatment, in 21 anaemic haemodialysis patients. In addition, the concentrations of ATP, phosphocreatine and total creatine and the ratio of alkali-soluble protein to DNA were determined in skeletal muscle. Maximal oxygen uptake and maximal exercise capacity were determined on a bicycle ergometer. 2. The results unexpectedly showed a 35% higher mitochondrial ATP production rate in the patients before erythropoietin treatment than in sedentary control subjects. On the other hand, mitochondrial density, as measured by the activity of the matrix enzyme glutamate dehydrogenase, was the same in the patients as in the sedentary control group. After 1 year on maintenance erythropoietin treatment, the ATP production rate per kg of muscle decreased in five out of seven patients and reached the same level as in the sedentary control subjects. The ratio between ATP production rate and glutamate dehydrogenase activity was on average 40% higher in the patients at the start and decreased towards the control level in six out of seven patients after 1 year on maintenance erythropoietin treatment. When related to the mitochondrial protein content, a significant reduction in the ATP production rate was observed. 3. The ratio of alkali-soluble protein to DNA in skeletal muscle and the concentrations of ATP, phosphocreatine and total creatine in skeletal muscle at rest were normal in the patients and did not change during the study. The maximal aerobic power improved by 25% after the correction of anaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Adult; Anemia, Hypochromic; Creatine; Erythropoietin; Female; Glutamate Dehydrogenase; Humans; Male; Middle Aged; Mitochondria, Muscle; Phosphocreatine; Recombinant Proteins; Renal Dialysis

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Hyperkalemia; Hypertension; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis; Thrombosis

Pathophysiological and therapeutic properties of anemia in rats with adjuvant-induced arthritis (AA) were investigated. Both anemia and chronic inflammation were induced in rats by a single injection of Freund's complete adjuvant. This study confirmed other earlier data that these anemic rats with AA had reduced serum iron levels and that the anemia was characterized as mild, non-progressive, hypochromic, microcytic. In addition, our studies showed that these anemic rats had slightly but significantly enhanced erythropoietin titers, but not renal failure; there was no significant difference in blood urea nitrogen and creatinine levels in anemic and normal groups. The anemia in rats with AA was improved by recombinant human erythropoietin (r-HuEPO) at 30 and 100 U/kg/day, given i.v. for 5 days. In contrast, iron-chondroitin-sulfate colloid (10 mg/kg/day, i.v. for 5 days) failed to improve the anemia and to enhance the effects of r-HuEPO. These data suggest that anemia in rats with adjuvant-induced arthritis is distinguished, pathophysiologically and therapeutically, from iron deficiency anemia, hemolytic anemia, and renal anemia.

Topics: Anemia, Hypochromic; Animals; Arthritis, Experimental; Body Weight; Chondroitin Sulfates; Colloids; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Iron; Rats; Rats, Inbred Lew; Recombinant Proteins

Hematological disorders are commonly complicated by anemia, and the symptoms of red cell deficiency adversely affect the quality of life. Erythropoietin is a glycoprotein which controls red blood cell production. Recombinant human erythropoietin, 50 U/kg/day, was given subcutaneously to 16 patients with myelodysplastic syndrome and anemia. All but one patient was transfusion dependent. Diverse pretreatment endogenous serum erythropoietin levels were noted and ranged from 17 to 3616 IU/l. Two patients (12.5%) demonstrated an improvement in hemoglobin levels obviating the need for transfusions. Their responses lasted 5+ and 7 months with maintenance erythropoietin treatment. The responders had endogenous serum erythropoietin levels of 44 and 170, respectively. Treatment was generally tolerated without constitutional side-effects. However, three patients developed thrombocytopenia and one developed joint pain and leukocytosis on treatment. Overall, six patients showed changes in non-erythroid cells: two patients had an increase in platelet counts; three patients, a decrease in platelet counts; and one patient, an increase in white blood cell counts. Most of these changes reversed rapidly once erythropoietin was stopped. It is concluded that (a) serum erythropoietin levels are extremely variable in anemia patients with myelodysplastic syndrome, (b) only a minority of patients benefit from treatment with recombinant human erythropoietin, and (c) erythropoietin can affect cells of the myeloid and megakaryocytic lineage in a small proportion of patients.

Topics: Aged; Aged, 80 and over; Anemia, Hypochromic; Erythropoiesis; Erythropoietin; Female; Humans; Leukocyte Count; Male; Middle Aged; Myelodysplastic Syndromes; Platelet Count; Recombinant Proteins

Serum erythropoietin (S-EPO) levels were measured in 50 patients with anaemia of chronic disorders (ACD), classified into three groups according to their aetiology: inflammatory (n = 20), infectious (n = 15) and neoplastic (n = 15). The inflammatory group showed a higher mean S-EPO level (mean value +/- SEM, 69 +/- 11 mU ml-1) than the neoplastic (43 +/- 5 mU ml-1; P less than 0.05) and infectious groups (27 +/- 4 mU ml-1; P less than 0.01). The S-EPO level in the inflammatory group also differed from that of 32 healthy controls (36 +/- 3 mU ml-1; P less than 0.05). Fourteen patients with added iron deficiency (12 subjects from the inflammatory group) showed the highest S-EPO concentration (72 +/- 17 mU ml-1). Conversely, S-EPO levels were lower in febrile subjects (12 patients with infection and five with malignancy) than in non-febrile patients (28 +/- 4 mU ml-1 vs. 55 +/- 7 mU ml-1; P less than 0.01). In the infectious group, the logarithm of S-EPO correlated directly with the haemoglobin and haematocrit values. We conclude that differences in S-EPO concentration in ACD may be further related to the patient's iron stores and temperature. A decrease in EPO production may contribute to the pathogenesis of ACD secondary to infection.

Topics: Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Bacterial Infections; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Humans; Male; Middle Aged; Neoplasms

Eighteen patients on chronic hemodialysis with renal anemia were treated with recombinant human erythropoietin (r-HuEPO). Hemodynamic parameters in the resting state were determined before and after successful treatment. Posttreatment cardiac index was decreased (3.3 v 2.8 L/min/m2), whereas diastolic blood pressure (72 v 79 mm Hg) and calculated peripheral resistance (2,230 v 2,860 dyne.cm.s-5) were increased significantly when compared with the pretreatment period. We conclude from our study that the increase of blood pressure as seen in patients on dialysis, who are effectively treated with r-HuEPO, is due to an increase in peripheral resistance. This increase overrules the decrease of cardiac index and might well be a result of peripheral vasoconstriction due to improved oxygen availability.

Topics: Adult; Anemia, Hypochromic; Chronic Disease; Erythropoietin; Female; Hemodynamics; Humans; Hypotension; Male; Recombinant Proteins; Renal Dialysis

Defective iron metabolism, mild haemolysis and impaired erythropoiesis contribute to the anaemia of chronic disorders (ACD), but evidence for a deficiency of circulating erythropoietin (Epo) is equivocal. We have examined serum Epo in moderately anaemic patients with Hb less than 10 g/dl--41 patients with ACD (23 associated with rheumatoid disease and 18 with malignancy), 17 with uncomplicated iron-deficiency anaemia and 33 with chronic renal failure (CRF). In ACD the serum Epo (mean (confidence limits] results of 41 (31, 54) mU/ml for the rheumatoid group and 63 (49, 80) mU/ml for the malignancy group, were significantly lower than the Epo of 104 (78, 136) mU/ml for the iron-deficiency group. The CRF group with more severe anaemia had serum Epo of 27 (19, 35) mU/ml. Thus, recombinant human erythropoietin (rHu Epo) should be considered for the treatment of ACD associated with rheumatoid disease and malignancy.

Topics: Adult; Anemia; Anemia, Hypochromic; Chronic Disease; Erythropoietin; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Neoplasms; Rheumatic Diseases

Effects of erythropoietin treatment on haem synthesis in peripheral blood were evaluated in 11 patients on haemodialysis. After 2 weeks of erythropoietin, mean (SEM) uroporphyrinogen-l synthase activity increased significantly from 88 (10) to 116 (9) pmol/h per mg protein. Haem synthase activity, thought to be the rate-limiting step in erythroid haem synthesis, also showed a significant increase from 4.5 (0.8) to 8.4 (1.8) pmol/h per 10(6) reticulocytes. 4 patients, who showed only a partial response to erythropoietin, had significantly higher serum aluminium concentrations than the 7 who responded fully (225 [44] vs 55 [23] micrograms/l); erythrocyte protoporphyrin concentrations in partial responders were also much higher than in responders (973 [120] vs 388 [29] nmol/l). Aluminium intoxication may cause resistance to erythropoietin by interference with haem synthesis, with accumulation of protoporphyrin.

Topics: Adult; Aluminum; Anemia, Hypochromic; Deferoxamine; Drug Evaluation; Drug Resistance; Drug Therapy, Combination; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Ferrochelatase; Humans; Hydroxymethylbilane Synthase; Lyases; Male; Middle Aged; Protoporphyrins; Recombinant Proteins; Renal Dialysis

Topics: Adult; Aged; Aluminum; Anemia, Hypochromic; Erythrocytes; Erythropoietin; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Porphyrins; Protoporphyrins; Renal Dialysis

Topics: Aluminum; Anemia, Hypochromic; Drug Administration Schedule; Erythropoietin; Humans; Protoporphyrins; Renal Dialysis

Topics: Adult; Aluminum; Anemia; Anemia, Hypochromic; Erythropoiesis; Erythropoietin; Humans; Hyperparathyroidism; Infections; Iron Deficiencies; Kidney Failure, Chronic; Middle Aged; Occult Blood; Recombinant Proteins; Renal Dialysis

Topics: Adult; Anemia; Anemia, Hypochromic; Blood Cell Count; Colony-Stimulating Factors; Erythroid Precursor Cells; Erythropoietin; Fetal Blood; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Hematocrit; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature; Interleukin-3; Reticulocytes

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

Patients with solid tumors are often anemic even before they undergo cytotoxic therapy. Since the cause of the anemia of cancer is unknown, we examined the possible role of erythropoietin. Using a sensitive radioimmunoassay, we determined serum immunoreactive erythropoietin levels in 81 anemic patients with solid tumors. For any given degree of anemia, the serum concentration of immunoreactive erythropoietin was lower in this group of patients than in a group of control patients with iron-deficiency anemia (P = 0.0001). Furthermore, the expected inverse linear relation between serum levels of immunoreactive erythropoietin and of hemoglobin was absent in the group with cancer. The erythropoietin response was further decreased in patients receiving chemotherapy; it was not influenced by the presence or absence of cisplatin in the treatment regimen. The inability of the patients with cancer to produce erythropoietin was not absolute; if they had hypoxemia, adequate erythropoietin production was restored. We conclude that erythropoietin levels are inappropriately low in anemia associated with cancer, and that erythropoietin deficiency may contribute to the development of this form of anemia. Treatment of the anemia of cancer with erythropoietin may be of value.

Topics: Anemia; Anemia, Hypochromic; Antineoplastic Agents; Erythropoietin; Female; Hemoglobins; Humans; Hypoxia; Male; Neoplasms; Radioimmunoassay

The emergence of the Epoetin alfa as an effective therapy in the treatment of the anemia of chronic renal failure has reemphasized the importance of nursing monitoring and intervention in the treatment of these patients. This article examines the role of nurses in monitoring and managing patients receiving Epoetin alfa and the development of medications, such as Epoetin alfa, with recombinant DNA technology.

Topics: Anemia, Hypochromic; DNA, Recombinant; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins; Renal Dialysis

Epoetin alfa (EPOGEN, recombinant human erythropoietin) has proven to be a major therapeutic advance in treating the chronic refractory anemia associated with end-stage renal disease (ESRD). As with many medications, the dose of Epoetin alfa must be individualized for each patient. In order to elicit a consistent production of red cells from the bone marrow, it is desirable that dose modifications be made as infrequently as possible. Gotch and Uehlinger have developed a kinetic model that can limit dose modifications by predicting the optimal dose of Epoetin alfa for each patient. Termed the Erythrokinetic Model, it compares individual patient response to Epoetin alfa to the life cycle of a red blood cell. This article describes the Gotch/Uehlinger Erythrokinetic Model and uses it to gauge the clinical response of 2 patients to Epoetin alfa.

Topics: Aged; Aged, 80 and over; Anemia, Hypochromic; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis

A sensitive radioimmunoassay (RIA) for the detection of erythropoietin (EPO) was developed using anti-recombinant EPO antibody with high affinity. The sensitivity was 100 amol/tube (5 mIU/ml) and it was possible to detect a serum EPO level between 5 and 200 mIU/ml. This method enabled us to measure native EPO as well as recombinant EPO. With this method we determined serum EPO levels in healthy individuals and patients with chronic renal disease, rheumatoid arthritis and iron deficiency anemia. Values in patients with chronic renal disease were lower than those in healthy individuals, while values in patients with rheumatoid arthritis, or iron deficiency anemia were significantly higher than those in healthy individuals.

Topics: Anemia, Hypochromic; Arthritis, Rheumatoid; Erythropoietin; Evaluation Studies as Topic; Female; Humans; Kidney Failure, Chronic; Male; Radioimmunoassay; Recombinant Proteins; Reference Values

We measured serum erythropoietin levels serially in 31 renal-transplant recipients treated with cyclosporine, using the recently developed recombinant human erythropoietin-based radioimmunoassay. The mean (+/- SEM) serum erythropoietin concentration in these patients before transplantation (14 +/- 2 U per liter) was similar to that in normal subjects who did not have anemia. A transient postoperative 9-fold increase (range, 0- to 74-fold) in the serum erythropoietin levels was followed by a smaller (3-fold) and sustained (28 +/- 3 days) second elevation. The initial increase occurred in the absence of graft function and was not accompanied by an erythropoietic response, whereas the second increase was associated with graft recovery and the complete resolution of the anemia. Serum erythropoietin levels returned to normal as the hematocrit rose above 0.32. Thereafter, the hematocrit continued to rise toward normal, while the serum erythropoietin levels remained normal. The patients in whom erythrocytosis or iron-deficiency anemia developed had persistently elevated serum erythropoietin levels. We conclude that in patients who have undergone renal transplantation, slight increases in endogenous erythropoietin levels induce erythropoiesis to the same extent as do large doses of exogenous erythropoietin in patients with uremia. Moreover, once initiated, erythropoiesis in renal-transplant recipients may be sustained by normal serum erythropoietin levels. These results suggest that the restoration of renal function improves the erythropoietic response to erythropoietin.

Topics: Adult; Anemia, Hypochromic; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Kidney Transplantation; Male; Middle Aged; Radioimmunoassay

18 anemic patients undergoing maintenance hemodialysis were treated with recombinant human erythropoietin (EPO) 1-3 times per week for 10.7 +/- 3 months. 4 patients underwent renal transplantation whereas 14 patients could be followed up during 12 months of EPO treatment. Hemoglobin concentration rose (from 7.0 +/- 0.7 to 11.0 +/- 1.1 g/dl, p less than 0.001) with an EPO maintenance dose of 298 units/kg/week. Blood transfusions were totally eliminated. 12 patients without iron overload required iron supplements. In the course of an infectious episode and notwithstanding an increase in EPO dosage, 2 patients exhibited a fall in hemoglobin which rose again after successful treatment of the infection. The few complications observed in connection with the rise in hemoglobin were: 1. deterioration of arterial hypertension in 7/18 with hypertensive encephalopathy in 3 patients, 2. thrombotic occlusion of the vascular hemodialysis access (a-v fistula) in 3/18, 3. periarticular inflammation with calcified deposits due to an elevated calcium-phosphorus product of 6.8 mmol/l in 4/18, 4. occurrence of hyperkalemia (6.9 +/- 0.3 mmol/l) in 7/18. These complications were more frequent during the first 3 months. They were corrected with close monitoring, drug therapy for hypertension, and intensification of dialysis and of treatment with phosphate binding substances, with the result that no differences were found in 14 patients before and after 12 months of treatment with EPO (blood pressure 133 +/- 25/77 +/- 9 vs 139 +/- 26/79 +/- 13 mm Hg [ns], potassium 5.4 +/- 0.4 vs 5.6 +/- 1.0 mmol/l [ns] and calcium-phosphorus product 4.3 +/- 1.0 vs 4.6 +/- 1.3 [ns]).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anemia, Hypochromic; Calcium; Erythropoietin; Female; Hemoglobins; Humans; Hyperkalemia; Hypertension; Infections; Male; Middle Aged; Phosphorus; Recombinant Proteins; Renal Dialysis

The quality of life was assessed in 37 maintenance hemodialysis patients during treatment with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) for correction of anemia. All patients experienced an increase in hematocrit level. The mean hematocrit level in the study population was 19.8% before therapy and 31.5% after therapy. Eighty-four percent of patients reported an increase in their sense of well-being. Better appetite was subjectively noted by 81% of patients. Improvements in sexual function (62%), socializing (70%), sleep (68%), and skin color (51%) were also noted. An increase in exercise capacity was reported by 78% of patients; objective measurements showed that the mean value of VO2max in a subgroup of 11 patients increased by 50% after treatment. The Karnofsky score calculated in 29 patients showed improvement in all patients except those aged greater than 70 years. The group mean Karnofsky score increased from 76 before to 86.6 after therapy, indicating that with r-HuEPO treatment subjects were able to exert themselves to perform ordinary activities. Before therapy 14 of the patients were unemployed; after therapy only two did not work. Those side effects that occurred, predominantly iron deficiencies, hypertension, and hyperkalemia, were controlled by appropriate clinical management. Treatment with r-HuEPO does improve the quality of life and ability to work of uremic patients and does not adversely affect their transplant potential.

Topics: Adult; Anemia; Anemia, Hypochromic; Erythropoietin; Female; Hematocrit; Humans; Kidney Failure, Chronic; Male; Quality of Life; Recombinant Proteins; Renal Dialysis

Treatment with recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) rapidly corrects the anemia associated with end-stage renal disease during the acute phase of therapy and supports hematocrit levels throughout the maintenance phase. However, during the acute phase of therapy, iron deficiency will develop in most patients; it is therefore initially essential to monitor body iron stores monthly. A plasma ferritin level of less than 30 ng/mL or a transferrin saturation level of less than 20% confirms the diagnosis of iron deficiency. Microcytic, hypochromic red cell morphology appears only after prolonged iron deficiency due to inadequate monitoring and insufficient iron supplementation; alternatively, microcytosis in the presence of adequate iron stores suggests aluminum toxicity. In all patients except those with transfusional iron overload, prophylactic supplementation with ferrous sulfate (325 mg up to three times daily) is recommended. When oral supplements, which are poorly tolerated at high doses, are insufficient to meet the extraordinary needs resulting from r-HuEPO-induced erythropoiesis, intravenous iron dextran (500 to 1,000 mg administered in five to ten doses) may be required. During the maintenance phase of therapy, it may be necessary to continue iron supplementation to counteract ongoing loss of iron associated with blood loss through dialyzers and gastrointestinal bleeding. At the other extreme of iron balance, iron overload in transfusion-dependent patients, recent studies suggest that the ability of r-HuEPO to mobilize iron stores can be harnessed with therapeutic phlebotomy to reverse transfusional iron overload.

Topics: Adult; Anemia; Anemia, Hypochromic; Delayed-Action Preparations; Erythropoietin; Ferrous Compounds; Hematocrit; Humans; Iron-Dextran Complex; Kidney Failure, Chronic; Male; Recombinant Proteins

The accurate radioimmunological measurement of serum erythropoietin (EPO) levels has only been possible since the development of highly specific antibodies directed against recombinant human EPO. In the present study, we determined the serum EPO levels in 100 healthy volunteers and in over 300 patients with anemias and hyperglobulinemia of various causes. In the healthy group, the females had levels of 11.3 +/- 3.4 mU/ml, while the males had levels of 8 +/- 3.2 mU/ml. The serum EPO concentrations were inversely related to the degree of anemia in patients with nonrenal anemias, while predialysis patients with renal anemias showed only partially such a tendency. Hemodialysis patients exhibited EPO-levels that were inadequately low relative to the degree of anemia. Patients with hyperglobulinemia had significantly higher serum EPO-levels than healthy individuals and polycythemia vera patients, the latter having particularly low serum EPO levels. Our results show that the determination of serum EPO levels can be of value in the differential diagnosis of hyperglobulinemia. Finally, sequential measurements document fluctuating serum EPO-levels after gastrointestinal hemorrhages and in patients with iron deficiency anemias receiving iron substitution. The probable reason for this phenomenon seems to be the intermittent utilisation of the hormone by EPO-sensitive erythropoietic precursor cells.

Topics: Acquired Immunodeficiency Syndrome; Anemia; Anemia, Hypochromic; Erythropoietin; Female; Gastrointestinal Diseases; Hemoglobins; Humans; Hypergammaglobulinemia; Kidney Diseases; Male; Myelodysplastic Syndromes; Polycythemia Vera; Renal Dialysis

To clarify the control mechanism of production of erythropoietic growth factors in anemic states, we compared erythropoietin (Epo) and burst-promoting activity (BPA) in patients with aplastic anemia and iron deficiency anemia, using in vitro erythroid progenitor assays. Although serum levels of Epo activity increased in the presence of anemia, the rise was more marked in patients with aplastic anemia. BPA was high only in the sera of aplastic anemia patients. Serum levels of BPA of patients with aplastic anemia negatively correlated with hemoglobin concentrations, while those of patients with iron deficiency anemia did not correlate. In 2 patients with aplastic anemia who responded well to androgen therapy, serum levels of Epo activity and BPA decreased after the hemopoiesis had recovered. These results suggest that serum levels of BPA do not rise in response to anemia only. The elevated BPA levels in sera in cases of aplastic anemia are probably related to a reduction in the number of hemopoietic stem cells. Moreover, we observed that BPA in bone-marrow-conditioned medium (BMCM) from patients with severe aplastic anemia increased more than in the BMCM from patients with severe iron deficiency anemia. Therefore, our findings suggest that the enhanced BPA production depends on a decrease in hemopoietic precursors rather than the anemic state.

Topics: Adolescent; Adult; Aged; Anemia, Aplastic; Anemia, Hypochromic; Bone Marrow; Culture Media; Erythropoietin; Female; Hematopoiesis; Humans; Lymphokines; Male; Middle Aged; Tissue Inhibitor of Metalloproteinases

Effects of cadmium (Cd) on in vitro and in vivo erythropoiesis in rats were studied by methylcellulose colony assay. Cd suppressed the in vitro growth of late erythroid progenitors (CFU-E) in a dose-dependent fashion and did not lose its inhibitory potency with increasing doses of erythropoietin (EPO). In addition, in marrow suspension cultures, Cd did not significantly influence 59Fe incorporation into both the cells and heme, and the Cd dose-responsive inhibition curve of the number of living cells was similar to that of CFU-E. These results suggest that the suppression of CFU-E colony formation by Cd is not due to the blocking of either EPO action to stimulate the growth of CFU-E or the iron incorporation into the cells ahd heme, but due to its direct cytotoxic effect. The colony suppression by Cd could be prevented by adding metallothionein to the cultures. On the other hand, oral administration of Cd to animals (100 mg/liter in drinking water) induced an iron deficiency anemia characterized by microcytic hypochromic red cells, decreased plasma iron, and increased total iron binding capacity. Marrow CFU-E density steadily increased as plasma iron decreased due to Cd administration and reached a plateau after 50 days. Plasma EPO titers were also found to be elevated in such a Cd-induced anemia. Parenteral iron administration during the Cd drinking period could completely prevent the development of iron deficiency anemia and the increase of both CFU-E and plasma EPO. There was a hyperbolic correlation between CFU-E and plasma iron or transferrin saturation. These results demonstrate that oral CD administration produces bone marrow hyperplasia at the CFU-E level due to iron deficiency.

Topics: Anemia, Hypochromic; Animals; Cadmium; Cell Survival; Colony-Forming Units Assay; Erythropoiesis; Erythropoietin; Hematopoietic Stem Cells; Iron; Iron Deficiencies; Male; Metallothionein; Rats; Rats, Inbred Strains

Stimulating the production of fetal hemoglobin may benefit patients with sickle cell anemia by inhibiting sickling. We gave pulsed treatments with high doses of recombinant human erythropoietin to baboons in order to test the hypothesis that the resultant rapid erythroid regeneration would stimulate F cells--i.e., cells that contain fetal hemoglobin. In normal animals, this treatment caused sharp increments in F-reticulocyte levels, which rose from 1 to 2 percent before treatment to 40 to 50 percent afterward. In two animals with chronic anemia and high levels of endogenous erythropoietin, recombinant human erythropoietin induced further increments in F-reticulocyte levels, which rose in one animal from 6 to 8 percent before treatment to 23 percent after treatment, and in the other from 20 percent before to 50 percent afterward. The time course of F-reticulocyte stimulation suggested that these cells were the products of mobilized early erythroid progenitors. These results raise the possibility that pulses of erythropoietin could be used to stimulate F-cell formation in patients with sickle cell disease.

Topics: Anemia, Hypochromic; Anemia, Sickle Cell; Animals; Erythrocyte Count; Erythropoietin; Fetal Hemoglobin; Humans; Papio; Recombinant Proteins; Reticulocytes; Stimulation, Chemical

Topics: Anemia, Hypochromic; Erythropoietin; Humans; Kidney Failure, Chronic; Recombinant Proteins

Erythropoietin (Epo) titers in various hematological states were determined by a radioimmunoassay. Epo titers in patients with uremic anemia and iron deficiency anemia were inversely correlated with their respective hemoglobin concentrations. Epo titers in patients with uremic anemia were significantly lower than those in patients with iron deficiency anemia with comparable hemoglobin concentrations.

Topics: Anemia; Anemia, Aplastic; Anemia, Hypochromic; Erythropoietin; Humans; Kidney Failure, Chronic; Polycythemia Vera; Renal Dialysis; Uremia

The relationship of serum immunoreactive erythropoietin to haemoglobin concentration was defined for 54 patients with rheumatoid arthritis (RA) and 41 patients with anaemia of varying aetiology (excluding pregnancy and renal insufficiency), not associated with RA. Significant inverse correlations between the logarithm of serum immunoreactive erythropoietin and the haemoglobin concentration were noted for the anaemic patients in both groups. The regression line for the RA patients had a similar slope, but a significantly lower y-intercept as compared to that for the non-RA patients. Erythropoietin levels were also significantly lower for the group of RA patients than for the group of non-RA patients when matched for comparable haemoglobin concentrations. These studies suggest that the erythropoietin response to anaemia in RA is intact but blunted relative to that for anaemia of other aetiologies. Lower levels of serum erythropoietin in anaemic RA patients may contribute to the pathogenesis of their anaemia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Child; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged

The concentration of plasma erythropoietin was determined by radioimmunoassay during the progression of and subsequent recovery from iron-deficiency anemia in the rat. During the development of anemia, the plasma erythropoietin level rose as the hemoglobin (Hgb) concentration declined, reaching maximal levels when the Hgb was lowest. During the recovery from iron-deficiency anemia after institution of the control diet, the plasma erythropoietin concentration rapidly declined to baseline or below baseline levels even before the Hgb had completely returned to control values. This early fall in the erythropoietin level was associated with a sustained decrease in blood oxygen affinity (increase in P50). The rise in P50 was associated with an increase in the number of circulating reticulocytes in addition to and independently of an increase in the concentration of 2,3-diphosphoglycerate (DPG) in red cells. Therefore, reticulocytosis may play a part in the recovery from anemia, not only by replenishing the red cell pool but also by temporarily facilitating oxygen delivery to the tissues.

Topics: Anemia, Hypochromic; Animals; Diet; Diphosphoglyceric Acids; Erythropoietin; Hemoglobins; Male; Rats; Rats, Inbred Strains

Topics: Anemia, Aplastic; Anemia, Hypochromic; Animals; Erythropoietin; Humans; Kidney Failure, Chronic; Male; Mice; Polycythemia; Rats; Renal Dialysis

Based on extensive own investigations of a great number of pediatric patients with chronic renal failure at the University Children's Hospital of Heidelberg, renal anemia is reviewed. After the demonstration of its clinical importance, its intensity depending on the mode of treatment (conservative therapy, regular dialysis, renal transplantation), and its diagnostic characteristics, an analysis of the three most important pathomechanisms is given: bone marrow hypoplasia, increased hemolysis and chronic blood loss. These pathomechanisms influence each other, are the result of multifactorially acting uremic toxins and can additionally be potentiated by iron-, folate-, and vitamin B12-deficiency. The hematologic mechanisms to compensate renal anemia are insufficient: first the indirect way, because the increase in erythrocyte organic phosphates is insufficient and the shift of the hemoglobin oxygen dissociation curve to the right is inadequate, second the direct way because erythropoietin is secreted inadequately. After description of the diagnostic paramenters for long-term care of renal anemia therapeutic recommendations are given with respect to each stage of treatment.

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Blood Transfusion; Bone Marrow; Child; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Ferritins; Hemoglobinometry; Humans; Iron; Kidney Failure, Chronic; Kidney Transplantation; Renal Dialysis

Topics: Anemia, Hypochromic; Bone Marrow; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Iron; Kidney Failure, Chronic; Kinetics; Nephrectomy; Renal Dialysis; Transferrin; Uremia

A mesenteric mass, histologically characterized as giant lymph node hyperplasia was found in an 18-yr-old man with at least 11 yr of growth retardation and anemia. The anemia was characterized by iron deficiency from selective malabsorption of iron, and by features of the anemia of chronic disorders. In contrast with a previous report, no inhibitor of erythropoietin was found and there was no abnormality of erythropoietin secretion. Resection of the mass was followed by rapid correction of the anemia and catch-up growth. The mass had histologic features of the hyaline vascular and plasma cell types of Castleman's disease with multinucleate giant cells probably of macrophage origin. Immunologic studies of the mass showed that the B lymphocytes were polyclonal and the T lymphocyte helper/suppressor cell ratio was normal, suggesting that giant lymph node hyperplasia is a local inflammatory reaction.

Topics: Adolescent; Anemia, Hypochromic; Child; Erythropoietin; Humans; Hyperplasia; Intestinal Absorption; Iron; Lymph Nodes; Male; Mesentery

Studies of red cell metabolism, erythropoeitin concentration, iron and folate status were made in 48 children with protein-energy malnutrition in Johannesburg (altitude 1800 m). Biochemical evidence of iron deficiency was presented in 26% cases on admission and developed in 90% during recovery. Biochemical evidence of folate deficiency was present in 14% of cases on admission and resolved on dietary therapy alone. Serum erythropoeitin was increased on admission and remained elevated during recovery. There was no relationship between serum erythropoeitin and Hb concentrations. Key enzymes in the red cell glycolytic and hexose monophosphate pathways and red cell membrane showed increased activity. Red cell adenosine triphosphate concentration was increased and unstable. Red cell potassium was decreased and, in the fatal cases, red cell sodium was increased. The possible significance and practical implications of these findings are discussed.

Topics: Adenosine Triphosphatases; Anemia, Hypochromic; Child, Preschool; Erythrocytes; Erythropoietin; Folic Acid; Hemolysis; Humans; Infant; Iron; Potassium; Protein-Energy Malnutrition; Sodium; South Africa

Erythropoietin (ESF) titers were determined in sera from patients with different types of anemia using the fetal mouse liver cell bioassay. An inverse relationship was found between hemoglobin concentration and ESF titer. However, ESF titers differed markedly between patients at comparable degrees of anemia. Several groups of patients were distinguished on the basis of the activity of their erythroid bone marrow. In each of these groups, a significant negative correlation was found between the hemoglobin concentration and the logarithm of the ESF titer. ESF titers in patients with pure red cell aplasia were fourfold higher than those in patients with iron-deficiency anemia and tenfold higher than those in patients with megaloblastic anemia and homozygous sickle cell anemia at comparable hemoglobin concentrations. Following the initiation of specific therapy in patients with pernicious anemia and patients wit iron-deficiency anemia, serum ESF titers were found to decrease prior to any substantial rise in hemoglobin concentrations. In the patients with pernicious anemia, the lowest ESF levels were found 1 day after administration of vitamin B12, whereas in the patients with iron-deficiency anemia, the lowest ESF levels were reached in the second week of oral iron therapy. ON the basis of these data it was concluded that serum ESF titers in anemic patients are not only inversely related to the hemoglobin concentration but also to the activity of the erythroid bone marrow.

Topics: Anemia; Anemia, Hypochromic; Anemia, Pernicious; Animals; Bone Marrow Cells; Erythrocyte Count; Erythropoietin; Female; Hemoglobins; Humans; Iron; Mice; Mice, Inbred Strains; Pregnancy; Reticulocytes; Vitamin B 12

Urinary proteins from patients with iron deficiency anemia and acquired aplastic anemia were fractionated by chromatography on QAE-Sephadex A-50 and Sephadex G-25. Fractions containing erythroid burst promoting activity (code named regulatory protein RP) were separated from erythropoietin. Mouse bone marrow cells were preincubated for one day in suspension culture, in the presence or absence of RP, transferred to a methylcellulose based system and incubated for six more days with erythropoietin (EPO). It was found that the presence of RP in the preincubation medium had a 2 to 4 fold enhancing effect on subsequent erythroid burst colony formation. However, when RP was added to methylcellulose based cultures simultaneously with EPO, the erythroid burst response was reduced or abolished. Addition of RP to marrow cell suspension cultures increased the number of self replicating, pluripotent (erythroid/granuloid, E/G ratio = 3) spleen colony forming units (CFU-S) found at the end of 2 days incubation 3-5 fold over their number in control cultures incubated without the factor. In marked contrast to this, addition of EPO to the cultures caused an increased persistence of CFU-S with a predominantly erythroid commitment (E/G ratio = 19) and a low self replicating ability, as measured by retransplantation of spleen cells into secondary recipients. These observations are compatible with the presence in RP of a factor, or factors, capable of maintaining the size of certain early precursor cell compartments.

Topics: Anemia, Aplastic; Anemia, Hypochromic; Animals; Cells, Cultured; Colony-Forming Units Assay; Erythropoiesis; Erythropoietin; Humans; Male; Mice; Mice, Inbred C3H; Mice, Inbred DBA; Proteinuria; Spleen

The level of erythropoietin (Ep) was measured in sera and urine from aplastic anemia patients. Increased levels of Ep were demonstrated in sera from all 25 patients studied. An elevated level of Ep was found in the urine of 17 of 23 patients in whom the urine was tested. No correlation between blood hemoglobin and Ep level was observed. A higher serum Ep level was noted in patients with aplastic anemia than in patients with sideropenic anemia of the same severity. To explain the discrepancy diminished Ep consumption in bone marrow of aplastic anemia patients is discussed.

Topics: Anemia, Aplastic; Anemia, Hypochromic; Animals; Erythropoietin; Female; Hemoglobins; Humans; Mice

Human urinary erythropoietic-active crude protein was isotachophoretic fractionated in a LKB Uniphor apparatus equipped with a plastic column using polyacrylamide as a stabilizing medium, phosphat ions as leading and glycinat ions as terminating electrolytes and Ampholine carrier ampholytes (pH: 5--7) as spacers. The exhypoxic polycythemic mouse method to assay erythropoietic activity showed that the majority of the hormon was sharply resolved. Under these conditions preparative isotachophoresis demonstrated a higher purification factor compared to other biochemical preparation-methods.

Topics: Anemia, Aplastic; Anemia, Hypochromic; Electrophoresis; Erythropoietin; Humans

Topics: Anemia, Hypochromic; Animals; Bacterial Infections; Cell Division; Erythroblasts; Erythrocyte Aging; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Neoplasms

The erythropoietic activity in the sera of 18 patients with sideropenic anemia was investigated. The ex-hypoxic mouse bioassay was used and the 48 hour incorporation of radioiron into the peripheral blood was measured. The level of erythropoietin found was compared to the hemoglobin concentration and the PCV values in those patients. The statistically significant correlation was found between erythropoietin in the patients sera and the degree of anemia. Higher erythropoietin values were found in men as compared to women with the same severity of anemia. It was concluded that the results obtained in this study can be used as control values when erythropoietic activity in the sera of patients with different hematological disorders is measured.

Topics: Adult; Aged; Anemia, Hypochromic; Erythrocyte Count; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Male; Middle Aged

The serum levels of granulocyte colony-stimulating factor (CSF) and erythropoietin (Ep) were measured in 16 patients with iron-deficiency anemia and 15 patients with the anemia of chronic disease. Levels of both CSF and Ep in the serum of patients with iron-deficiency anemia had an inverse linear relationship to the level of the packed cell volume (PCV). There was no correlation between PCV and the levels of CSF or Ep in the serum of patients with the anemia of chronic disease. The similarity in the behavior of CSF and Ep in iron-deficiency anemia suggests that they may be influenced by similar control mechanisms or have a common cellular or molecular source.

Topics: Anemia; Anemia, Hypochromic; Bone Marrow Examination; Chronic Disease; Colony-Stimulating Factors; Erythropoietin; Female; Glycoproteins; Granulocytes; Hematocrit; Humans; Iron; Male

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

Erythropoiesis in spleens of lethally irradiated Lewis rats grafted with 4-35 X 10(6) syngeneic marrow cells was inhibited or delayed during the test period of 5 days; this was in marked contrast to observation in irradiated mice. The mechanism of this inhibition was the subject of this study. Pretreatment of recipients 9 days prior to irradiation with the cytotoxic drugs cyclophosphamide (CY), busulfan (BUS), or dimethylmyleran (DMM), or the induction of iron deficiency with anemia in recipients reversed this delayed erythropoiesis. However, neither iron-deficiency anemia nor pretreatment with BUS or DMM affected the ability of irradiated recipients to reject 20 to 50 X 10(6) allogeneic marrow cells. The administration of commercial preparations of erythropoietin to hosts stimulated erythropoiesis moderately. However, proliferation of syngeneic marrow cells was not enhanced when infused into lethally irradiated Spontaneous Hypertensive (SH) inbred-strain rats which have high levels of endogenous erythropoietin. Finally, plasma from irradiated rats treated with phenylhydrazine to produce severe anemia was rich in erythropoietin but failed to stimulate erythropoiesis in the cell transfer system. Two hypotheses are considered: (1) Irradiation inhibits the secretion of a factor (not erythropoietin) responsible for initiating early stages in differentiation of transplanted stem cells; iron-deficiency anemia and cytotoxic drugs stimulate the secretion of this factor. (2) Normal rats secrete a factor which suppresses erythropoiesis; iron-deficiency anemia and cytotoxic drugs inhibit the production or function of this factor. Cellular rather than humoral factors may by involved.

Topics: Anemia, Hypochromic; Animals; Bone Marrow Cells; Bone Marrow Transplantation; Busulfan; Cyclophosphamide; Deferoxamine; Erythropoiesis; Erythropoietin; Graft Rejection; Immunosuppression Therapy; Male; Radiation Chimera; Rats; Rats, Inbred Lew; Spleen; Time Factors; Transplantation, Isogeneic

The diminished erythropoiesis in the anemia of chronic renal disease has been attributed to three possible factors: (1) decreased erythropoietin production, (2) inhibition of erythropoietin activity, and (3) decreased bone marrow response to erythropoietin. In this report we isolated and evaluated these parameters in 19 patients with chronic renal disease, nine patients with iron-deficiency anemia, and seven control subjects. The results in patients with chronic renal failure were as follows: (1) erythropoietin enhanced heme synthesis in bone marrow cell cultures by 88 +/- 12 per cent in renal failure, as compared to 65 +/- 7 per cent in the control group; (2) plasma erythropoietin activity did not increase appropriately for the degree of anemia; and (3) erythropoietin inhibitor activity in renal failure was not greater than in a control group. In conclusion, the relative failure of erythropoiesis in chronic renal disease appears to be due primarily to decreased production of erythropoietin and not to diminished marrow response to erythropoietin.

Topics: Adult; Anemia; Anemia, Hypochromic; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Erythropoiesis; Erythropoietin; Heme; Humans; Kidney Failure, Chronic; Male

In vitro culture technique of bone marrow cells has been applied to study the cause of anemia in uraemic patients on maintenance haemodialysis. Incorporation of 59Fe into haem in bone marrow cells of the patients in the presence of erythropoietin, as well as the inhibitory effect of their plasma on the response of normal bone marrow cells to erythropoietin, was examined. Increase in haem synthesis rate by erythropoietin in the bone marrow cells of uraemic patients (n 14; 7.9 +/- 1.4) wasnot significantly different from that in normal bone marrow cells (n 9; 5.9 +/- 1.4,p greater than 0.05), thus indicating the presence of erythroid precursor cells with normal responsiveness to erythropoetin in uraemic patients. All the plasma from uraemic patients inhibited, in dose-dependent way, the response of normal bone marrow cells to erythropoietin. Levels of erythropoietin in the plasma samples of uraemic patients were much lower than those of the patients with iron deficiency anaemia with comparable Hb concentrations. On the basis of these results, the humoral inhibitory factor appears to play a significant role in the pathogenesis of renal anaemia, in addition to the low level of circulating erythropoietin.

Topics: Adolescent; Adult; Anemia, Hypochromic; Bone Marrow; Bone Marrow Cells; Dose-Response Relationship, Drug; Erythropoietin; Female; Hematopoiesis; Heme; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Uremia

An 11-year-old girl presented with a refractory hypochromic microcytic anemia, hypoferremia, normoblastic hyperplastic bone marrow, hypergammaglobulinemia, and growth retardation. Many varied treatments failed to produce any improvement. Ferrokinetic studies revealed rapid plasma clearance and increased plasma iron turnover, but impaired incorporation of 59Fe. Excretion of 57Co after an oral dose indicated an increased iron absorption. A (99M)Tc-sulfur colloid scintigram of the abdomen failed to demonstrate abnormal uptake. A nodal mass showing the plasma-cell variant of angiofollicular hyperplasia was removed from the gastrolienal ligament. Follow-up studies at 3 and 6 months revealed complete correction of the anemia, a 4.8-cm increase in height, and normal serum gamma-globulin levels. Serum obtained before operation inhibited the incorporation of 59Fe that was induced by a standard dose of erthyropoietin in the exhypoxic mouse system, and this inhibition persisted in serum obtained 3 days after surgery but disappeared by 6 days. The data suggest that the hyperplastic angiofollicular lymph node (plasma-cell variant) secreted a substance the inhibited erythropoiesis.

Topics: Anemia, Hypochromic; Body Height; Child; Depression, Chemical; Erythropoiesis; Erythropoietin; gamma-Globulins; Humans; Hyperplasia; Immunoglobulin G; Iron; Lymph Nodes; Male

Topics: Adult; Anemia; Anemia, Hypochromic; Bone Marrow; Endotoxins; Erythropoiesis; Erythropoietin; Female; Humans; Immunosuppression Therapy; Iron; Kidney; Kidney Diseases, Cystic; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Nephrectomy; Renal Dialysis; Time Factors; Transplantation, Homologous

Topics: Anemia, Hypochromic; Arthritis, Rheumatoid; Erythropoietin; Female; Humans; Male; Polycythemia; Polycythemia Vera; Uremia

Topics: Anemia, Aplastic; Anemia, Hypochromic; Erythropoietin; Humans; Polycythemia Vera

Topics: Administration, Oral; Anemia, Hypochromic; Animals; Ascorbic Acid; Biological Transport; Body Weight; Diet; Erythropoietin; Female; Genetic Linkage; Hematocrit; Hemorrhage; Hypoxia; Injections, Intraperitoneal; Intestinal Absorption; Iron; Iron Radioisotopes; Male; Mice; Mice, Inbred Strains; Phenobarbital; Sex Chromosomes; Statistics as Topic

Topics: Anemia, Hypochromic; Animals; Erythropoiesis; Erythropoietin; Female; Humans; Iron; Kidney; Mice; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic

Topics: Anemia, Hypochromic; Bone Marrow; Erythropoietin; Humans; Iron; Kidney Failure, Chronic

Topics: Adult; Anemia, Hypochromic; Erythropoiesis; Erythropoietin; Female; Humans; Male; Middle Aged; Serum Albumin; Serum Globulins

Topics: Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Macrocytic; Bilirubin; Erythropoietin; Humans; Iron; Neoplasms

The serum level of erythropoietin was measured in 31 patients with anemia secondary to chronic infection or malignancy and compared with erythropoietin levels in 23 patients with iron-deficiency anemia and 14 patients with primary hematopoietic diseases. Erythropoietin levels varied directly with the degree of anemia in patients with iron deficiency or primary hematopoietic disorders. There was no correlation of erythropoietin and the degree of anemia in patients with chronic infection or malignancy and the erythropoietin levels were significantly lower than in patients with iron deficiency or primary hematopoietic disease and the same degree of anemia. A major factor in the anemia of chronic disorders is a decrease in levels of erythropoietin.

Topics: Anemia; Anemia, Hypochromic; Animals; Biological Assay; Bone Marrow Diseases; Carcinoma; Chronic Disease; Erythropoietin; Hodgkin Disease; Humans; Infections; Lymphoma, Non-Hodgkin; Male; Mice; Middle Aged; Neoplasms; Neutralization Tests

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

Topics: Adult; Aged; Anemia; Anemia, Aplastic; Anemia, Hypochromic; Anemia, Macrocytic; Animals; Bone Marrow; Bone Marrow Diseases; Daunorubicin; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Phenylhydrazines; Rabbits; Radiation Effects

Topics: Anemia, Hypochromic; Animals; Autoradiography; Blood Cell Count; Blood Proteins; Erythropoiesis; Erythropoietin; Hematocrit; Hemoglobins; Histocytochemistry; Iron; Iron Isotopes; Kinetics; Male; Rats; Reticulocytes; Transferrin

Topics: Anemia, Hypochromic; Animals; Biological Assay; Bone Marrow; Erythropoietin; Female; Humans; Iron; Iron Isotopes; Liver; Mice; Polycythemia; Pregnancy; Pregnancy Complications, Hematologic; Spleen; Time Factors

Topics: Anemia; Anemia, Hypochromic; Arthritis, Rheumatoid; Erythropoietin; Hematocrit; Humans; Neutralization Tests

Topics: Adolescent; Anemia; Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Sickle Cell; Animals; Biological Assay; Blood Cell Count; Bone Marrow Examination; Child; Child, Preschool; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hemoglobinometry; Humans; Iron; Iron Isotopes; Male; Rats; Reticulocytes; Thalassemia

Topics: Aged; Anemia, Hypochromic; Bone Marrow; Cell Differentiation; Erythropoiesis; Erythropoietin; Female; Heme; Humans; In Vitro Techniques; Male; Middle Aged; Polycythemia Vera

Topics: Adult; Anemia, Hypochromic; Animals; Biological Assay; Blood Cell Count; Blood Platelets; Child; Erythropoietin; Humans; Iron Isotopes; Male; Purpura, Thrombocytopenic; Rats; Thrombopoietin

Topics: Adult; Aged; Anemia, Hypochromic; Erythropoietin; Female; Hookworm Infections; Humans; Iron; Male; Middle Aged

Topics: Anemia, Hypochromic; Erythrocytes; Erythropoietin; Neoplasms; RNA, Messenger

Topics: Anemia, Aplastic; Anemia, Hemolytic; Anemia, Hypochromic; Animals; Erythropoietin; Hodgkin Disease; Humans; Infant; Infant, Newborn; Leukemia; Lymphatic System; Mice; Mononuclear Phagocyte System; Polycythemia; Umbilical Cord

Topics: Adolescent; Anemia, Aplastic; Anemia, Hemolytic, Autoimmune; Anemia, Hypochromic; Child; Child, Preschool; Erythroblastosis, Fetal; Erythropoietin; Female; Humans; Infant; Infant, Newborn; Kidney Diseases; Male; Pregnancy; Wilms Tumor

Topics: Absorption; Anemia, Hypochromic; Erythropoietin; Glomerulonephritis; Humans; Iron; Uremia

Topics: Adolescent; Anemia, Hypochromic; Anemia, Macrocytic; Animals; Blood; Blood Cell Count; Blood Chemical Analysis; Erythropoietin; Female; Humans; Hypothyroidism; Iodine Isotopes; Male; Middle Aged; Rabbits; Rats; Thyroid Hormones; Thyroidectomy

Topics: Anemia; Anemia, Hemolytic; Anemia, Hypochromic; Anemia, Pernicious; Blood Coagulation; Blood Proteins; Chloramphenicol; Epidemiology; Epoetin Alfa; Erythropoietin; Haptoglobins; Hematologic Diseases; Hematology; Hemochromatosis; Humans; Iron-Dextran Complex; Leukemia; Polycythemia; Thromboplastin; Vitamin B 12

Topics: Anemia; Anemia, Hypochromic; Anemia, Iron-Deficiency; Anemia, Macrocytic; Blood Platelets; Bone Marrow Cells; Drug Therapy; Epoetin Alfa; Erythropoietin; FIGLU Test; Folic Acid; Folic Acid Deficiency; Glutamates; Hemoglobins; Humans; Infant; Infusions, Parenteral; Injections, Intravenous; Iron; Iron-Dextran Complex; Megakaryocytes; Reticulocytes; Thrombocytopenia; Thrombocytosis; Vitamin B 12

Topics: Anemia; Anemia, Hypochromic; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematologic Diseases; Humans