epoetin-alfa and Hemolysis

There are different approaches for treating recurrent hepatitis C viral infection after a liver transplant. However, sustained virologic response is achieved in < 40% of infected allografts. We examined sustained virologic response improvement using a prolonged course of peginterferon and aggressive use of ribavirin.. From October 1998 to May 2008, 24 patients (13 male, 11 female; mean age at transplant, 49.4 +/- 7.7 years) received a prolonged course of peginterferon and ribavirin (range, 48-180 weeks). The mean interval from liver transplant to hepatitis C antiviral therapy was 26.6 +/- 27.8 months. Patients began weight-based standard dosages of peginterferon and ribavirin. In case of hemolysis, patients were treated with Epogen, with and without blood transfusions.. Fourteen patients (58.3%) had an end of treatment response, and 8 patients (33.3%) maintained sustained virologic response after the first course of therapy. Of 10 patients who did not respond to the first course, 6 received an extended course of antiviral therapy after a mean of 15 +/- 4.6 weeks from completion of first course. Five of these 6 patients achieved end of treatment response and maintained a sustained virologic response, resulting in an overall end of treatment response in 17 patients and a sustained virologic response in 13 patients. Twenty-two patients experienced hemolysis and were treated with Epogen. Fifteen patients received blood transfusions. Ribavirin dosage was reduced in 12 patients, and peginterferon dosage was reduced in 2 patients.. Aggressive use of ribavirin and prolonged course of peginterferon provided sustained virologic response in 54.1% of liver transplant recipients with recurrent hepatitis C virus-infection. More prospective studies are warranted to evaluate the benefit of this approach fully.

Topics: Adult; Antiviral Agents; Blood Transfusion; Drug Administration Schedule; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Genotype; Hematinics; Hemolysis; Hepacivirus; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Liver Transplantation; Male; Middle Aged; Pennsylvania; Polyethylene Glycols; Recombinant Proteins; Recurrence; Retrospective Studies; Ribavirin; RNA, Viral; Time Factors; Treatment Outcome; Viral Load

We have described the rapid destruction of young red blood cells (neocytolysis) in astronauts adapting to microgravity, in polycythemic high altitude dwellers who descend to sea level, and in patients with kidney disorders. This destruction results from a decrease in erythropoietin (EPO) production. We hypothesized that such EPO withdrawal could trigger physiological changes in cells other than red cell precursors and possibly lead to the uptake and destruction of young red cells by altering endothelial cell-macrophage interactions, most likely occurring in the spleen.. We identified EPO receptors on human splenic endothelial cells (HSEC) and investigated the responses of these cells to EPO withdrawal.. A monolayer of HSEC, unlike human endothelial cells from aorta, glomerulus, or umbilical vein, demonstrated an increase in permeability upon EPO withdrawal that was accompanied by unique morphological changes. When HSEC were cultured with monocyte-derived macrophages (but not when either cell type was cultured alone), EPO withdrawal induced an increased ingestion of young red cells by macrophages when compared with the constant presence or absence of EPO.. HSEC may represent a unique cell type that is able to respond to EPO withdrawal by increasing permeability and interacting with phagocytic macrophages, which leads to neocytolysis.

Topics: Adaptation, Physiological; Cells, Cultured; Endothelium, Vascular; Epoetin Alfa; Erythrocyte Aging; Erythrocytes; Erythropoietin; Hemolysis; Humans; In Vitro Techniques; Macrophages; Microscopy, Electron; Models, Biological; Receptors, Erythropoietin; Recombinant Proteins; Spleen; Weightlessness

Topics: Anemia; Animals; Epoetin Alfa; Erythrocyte Count; Erythropoietin; Hemoglobinometry; Hemolysis; Mice; Phenylhydrazines; Physiology; Polycythemia; Rabbits; Research; Toxicology

Topics: Anemia; Blood Chemical Analysis; Bone Marrow; Dietary Proteins; Epoetin Alfa; Erythrocytes; Erythropoietin; Hemoglobins; Hemolysis; Iron; Iron Isotopes; Liver; Phenylhydrazines; Protein Deficiency; Rats; Research; Reticulocytes