epoetin-alfa and Anemia--Hemolytic

In the United States, about 2.7 million people are chronically infected with the hepatitis C virus, accounting for nearly 1.8% of the population. The current standard of therapy is a combination of pegylated interferon products and ribavirin. A common adverse effect associated with this therapy is anemia, which is frequently referred to as mixed anemia because of the synergistic contribution of the interferons and ribavirin. The effect of ribavirin on the development of anemia is considered greater than that of interferon. The current standard of practice for treating this adverse effect is reduction of the dosages of both drugs, at prespecified hemoglobin levels. However, recent findings underscore the importance of maintaining adequate dosages of interferon and ribavirin, which may be crucial in achieving an early virologic response and a sustained virologic response in treating patients with hepatitis C infection. Treatment with epoetin alfa for this mixed anemia significantly improved hemoglobin levels and quality of life, and enabled adequate dosages of ribavirin to be maintained. Future studies should address several issues: when to start epoetin alfa treatment, the duration of treatment, the drug's optimal dosage, its effects on end-of-treatment and sustained virologic response rates, and a cost analyses.

Topics: Anemia, Hemolytic; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Health Care Costs; Hepatitis C; Humans; Interferon-alpha; Recombinant Proteins; Ribavirin; Risk Factors

Infection with the hepatitis C virus (HCV) remains chronic in 75% of infected individuals, in whom it can cause liver inflammation and progressive fibrosis leading to cirrhosis in 20% of patients. A sustained viral response (SVR) to HCV therapy, i.e. undetectable plasma HCV RNA 6 months after the end of treatment, leads to permanent eradication of the virus in 98.3% of patients. The current treatment of choice is combination therapy with pegylated interferon alfa (PEG-IFN alfa), 2a or 2b, and ribavirin (RBV), which achieves an SVR in 54-56% of patients. In patients with HCV genotype 1, RBV doses of 1000-1200 mg/day are associated with a higher SVR than 800 mg/day (51 vs 40%). However, RBV also causes dose-dependent reversible haemolytic anaemia that, in combination with the myelosuppressive effects of PEG-IFN, results in a mean drop in haemoglobin (Hb) level of 3.7 g/dL within 4 weeks. Conventionally, this acute anaemia has been managed with RBV dose reductions. However, this may result in a decreased SVR rate. Alternatively, this anaemia can be managed with administration of epoetin alfa at 40 000 IU once weekly. In a randomized placebo-controlled trial, treatment with epoetin alfa has been shown to raise Hb levels and maintain RBV doses. Furthermore, the increase in Hb level was associated with improved quality of life. Anaemia in patients treated with interferon plus RBV combination therapy can be managed effectively and safely with once weekly epoetin alfa without sacrificing optimal dosing of RBV.

Topics: Anemia, Hemolytic; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Polyethylene Glycols; Recombinant Proteins; Ribavirin

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa).

Topics: Anemia, Hemolytic; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Recombinant Proteins; Ribavirin

Chronic hepatitis C affects one-third of HIV(+) patients worldwide. High ribavirin (RBV) exposure is crucial to maximize the response to hepatitis C therapy in this population, although it may increase the risk for hemolytic anemia. PERICO is a prospective multicenter trial in which HIV/HCV-coinfected patients are randomized to receive peginterferon (pegIFN) alfa-2a 180 microg/week plus either weight-based RBV (1000-1200 mg/day) or RBV 2000 mg/day, the latest along with erythropoietin alfa (EPO) 30,000 IU/week from the first day until week 4. A total of 149 patients were assessed in a planned interim analysis at week 4. In both arms, 22% of patients achieved negative HCV-RNA (rapid virological response, RVR). Multivariate analysis [OR (IC 95%), p] showed that factors associated with RVR were HCV genotypes 2/3 vs. 1/4 [20 (5-100), <0.01] and baseline HCV-RNA [0.16 (0.07-0.37) per log IU/ml, <0.01]. The occurrence of severe anemia (hemoglobin <10 g/dl) did not differ when comparing RBV vs. high RBV + EPO (7% vs. 3%; p = 0.4). Moreover, RBV plasma trough levels were comparable at week 4 (1.9 vs. 2.4 microg/ml; p = 0.2). Use of high RBV doses with preemptive EPO during the first 4 weeks of hepatitis C therapy is safe, but fails to enhance significantly RBV plasma exposure and RVR rates. Extensive intraerythrocyte accumulation of RBV following boosted production of red blood cells by EPO could explain these findings.

Topics: Adult; Anemia, Hemolytic; Antiviral Agents; Epoetin Alfa; Erythrocytes; Erythropoietin; Female; Hematinics; Hepacivirus; Hepatitis C, Chronic; HIV; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Male; Polyethylene Glycols; Prospective Studies; Recombinant Proteins; Ribavirin; RNA, Viral; Treatment Outcome

BACKGROUND Drug-induced immune hemolytic anemia (DIIHA) is a rare condition that may result from the administration of an antibiotic, most notably the cephalosporin class, commonly used in both the adult and pediatric populations. A delay in recognition by a provider may lead to continuation of the offending agent and possibly result in fatal outcomes. CASE REPORT We report the case of a 65-year-old woman on ceftriaxone infusions after being diagnosed with acute mitral valve endocarditis 3 weeks prior, which presented with severe anemia and bilateral transient vision loss. Being a Jehovah's Witness, the patient refused blood product transfusions and was managed with alternative therapies. The etiology of the symptoms was suspected to be a hemolytic anemia directly related to her ceftriaxone infusions. CONCLUSIONS This report demonstrates the importance of close vigilance while prescribing drugs known to cause hemolytic anemia. Although rare, drug-induced immune hemolytic anemia caused by ceftriaxone may be a potentially fatal condition, but with early recognition and withdrawal of the offending agent, successful treatment may ensue. Serological tests should be utilized to obtain a definitive diagnosis.

Topics: Aged; Anemia, Hemolytic; Anti-Bacterial Agents; Ceftriaxone; Endocarditis, Bacterial; Epoetin Alfa; Female; Ferrous Compounds; Folic Acid; Hematinics; Humans; Jehovah's Witnesses; Vitamin B 12

Treating anemia associated with chemotherapy and many cancers is often necessary. However, patient satisfaction with anemia treatment is limited by the lack of validated instruments. We developed and validated a new treatment-specific patient satisfaction instrument: the Patient Satisfaction Questionnaire for Anemia Treatment (PSQ-An). Treatment burden and overall satisfaction scales were designed for ease of use in clinical practice.. 312 cancer patients (141 breast, 69 gynecological, and 102 non-small cell lung) were targeted to complete the PSQ-An at 4 week intervals. Data from weeks 5 and 9 were analyzed. Patients also completed the MOS SF-36 Global Health assessment and questions concerning resources devoted to anemia treatment. Item reduction used endorsement rates, floor/ceiling effects, and item-item correlations. Factor analysis identified meaningful subscales. Test-retest reliability was assessed. Construct validity was tested, using Pearson's correlations, by comparing subscale scores to Global Health, hemoglobin levels, and resources devoted to anemia treatment.. The overall response rate was 92.9% (264/284) at week 5. Most (84.2%) of the patients were female, and the mean (SD) age was 60.2 (+/- 11.8) years. Two distinct subscales were identified measuring treatment burden (7 items) and overall satisfaction (2 items). Test-retest reliability was examined (ICC: 0.45-0.67); both were internally consistent (alpha = 0.83). Both subscales exhibited convergent and divergent validity with independent measures of health. ANOVA results indicated that the PSQ-An Satisfaction subscale discriminated between 5 levels of MOS SF-36 Global Health (P = 0.006).. The PSQ-An is a validated, treatment-specific instrument for measuring satisfaction with anemia treatment for cancer patients. PSQ-An subscales reflect the burden of injection anemia treatment on cancer patients and their assessment of the overall treatment value.

Topics: Aged; Anemia, Hemolytic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Factor Analysis, Statistical; Female; Genital Neoplasms, Female; Hematinics; Humans; Karnofsky Performance Status; Male; Middle Aged; Multicenter Studies as Topic; Outcome Assessment, Health Care; Patient Satisfaction; Psychometrics; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Surveys and Questionnaires

Few observational studies have evaluated the use of epoetin alfa (EPO) and darbepoetin alfa (DARB) in chronic kidney disease (CKD) patients with anemia. The objective of this study was to investigate dosing patterns, hematologic outcomes, and intervention costs with EPO and DARB in anemic CKD patients treated in an ambulatory care setting.. This was a multicenter, retrospective, chart review of predialysis CKD patients with anemia treated with EPO or DARB. Charts were sequentially selected from 435 EPO and 432 DARB patients naive to erythropoietic therapy and treated for > or = 24 weeks. Hemoglobin (Hb) levels, dates, and EPO/DARB doses were recorded. Drug costs using 2005 wholesale acquisition costs (WAC) and Federal Supply Schedule (FSS) pricing were based on the mean cumulative drug dose over the 24-week study period.. A total of 393 EPO and 396 DARB charts met all criteria with predominantly male subjects (EPO: 94%; DARB: 96%). Mean baseline GFR and Hb levels were similar. Once-weekly and extended dosing (> or = Q2W) was common in both groups. At Weeks 4, 8, and 12 following initiation of therapy, a greater proportion of EPO than DARB patients reached target Hb levels (> or = 11 g/dL) (p < 0.0001); at Week 24, all patients reached target Hb levels. Mean 24-week cumulative doses were EPO 279 336 +/- 68 302 units and DARB 1084 +/- 246 microg. Drug cost was higher for DARB independent of pricing utilized (WAC: EPO = 3400 US dollars, DARB = 4726 US dollars; FSS: EPO = 1528 US dollars, DARB = 2379 US dollars).. Extended dosing (Q2W) was common in EPO- and DARB-treated patients with CKD-related anemia, with EPO-treated patients experiencing a significantly greater hematologic response (at Weeks 4, 8, and 12). In addition, drug cost was 39-56% higher in the DARB group. The male predominance may limit generalizability, warranting further research in other populations.

Topics: Anemia, Hemolytic; Darbepoetin alfa; Disease Progression; Dose-Response Relationship, Drug; Drug Costs; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Renal Dialysis; Retrospective Studies; Time Factors; Treatment Outcome

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, Hemolytic; Cell Division; DNA; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hemoglobins; Metabolism; Proteins; Reticulocytes; RNA; RNA, Messenger

Topics: Anemia; Anemia, Hemolytic; Animals; Biomedical Research; Bone and Bones; Bone Marrow; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hematocrit; Hemoglobinometry; Hemorrhage; Humans; Iron Isotopes; Liver; Male; Pharmacology; Phenylhydrazines; Physiology, Comparative; Rabbits; Rats; Research; Spleen

Topics: Acetylcholinesterase; Alkaline Phosphatase; Anemia; Anemia, Hemolytic; Anticoagulants; Australia; Blood Transfusion; Chromium Isotopes; Coombs Test; Dextrans; Diagnosis, Differential; Drug Therapy; Epoetin Alfa; Erythrocyte Count; Erythrocytes; Erythropoietin; Hematologic Tests; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Hemosiderin; Humans; Iron; Iron Isotopes; Phenindione; Prednisone; Splenectomy; Waldenstrom Macroglobulinemia

Topics: Anemia; Anemia, Hemolytic; Antineoplastic Agents; Cytostatic Agents; Epoetin Alfa; Erythropoiesis; Erythropoietin; Pharmacology; Rats; Research; Triaziquone

Topics: Anemia; Anemia, Hemolytic; Animals; Biomedical Research; Bone Marrow; Bone Marrow Examination; Epoetin Alfa; Erythropoiesis; Erythropoietin; Humans; Iron Isotopes; Male; Phenylhydrazines; Rabbits; Radiography; Radioisotopes; Radionuclide Imaging; Rats; Research; Skeleton

Topics: Anemia; Anemia, Hemolytic; Bone Marrow Examination; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematology; Humans; Infant; Infant, Newborn; Metabolism; Physiology

Topics: Anemia; Anemia, Hemolytic; Anemia, Sickle Cell; Epoetin Alfa; Erythroblastosis, Fetal; Erythrocytes; Erythropoietin; Humans; Infant, Newborn