PubMed · 13043521
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1953. SICKLE-CELL anaemia.. https://pubmed.ncbi.nlm.nih.gov/13043521/
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In vivo selection may provide a means to increase the relative number of cells of donor origin in recipients with hemopoietic chimerism. We have tested whether in vivo selection using chemical inducers of dimerization (CIDs) can direct the expansion of transduced normal donor erythrocytes in recipients with chimerism using a mouse model of pyruvate kinase deficiency. Marrow cells from normal CBA/N mice were transduced with a vector (F36Vmpl(GFP)) that promotes cell growth in the presence of CIDs. Transduced cells were then transplanted into minimally conditioned, pyruvate kinase-deficient recipients (CBA-Pk-1(slc)/Pk-1(slc)) to establish stable chimerism. CID administration resulted in expansion of normal donor erythrocytes and improvement of the anemia. The preferential expansion of normal erythrocytes also resulted in a decrease in erythropoietin levels, reducing the drive for production of pyruvate kinase-deficient red blood cells. CID-mediated expansion of genetically modified erythrocytes could prove a useful adjunct to transplantation methods that achieve erythroid chimerism.
OBJECTIVE: To discuss the controversies regarding the use of epoetin alfa (EPO) for reducing red blood cell (RBC) transfusions in critically ill patients with anemia. DATA SOURCES: A MEDLINE search (1966-July 2003) was conducted using the search terms anemia; critical illness; erythropoietin; epoetin alfa; and erythropoietin, recombinant. References of selected articles were reviewed for studies that may have been missed by the computerized search. STUDY SELECTION AND DATA EXTRACTION: Studies pertaining to the use of EPO for anemia of critical illness with an emphasis on data obtained from controlled trials. DATA SYNTHESIS: Anemia is a common complication in patients admitted to the intensive care unit (ICU). Two prospective, randomized studies have demonstrated decreased transfusion requirements associated with EPO administration in medical/surgical patients who were in the ICU for at least 3 days and had hematocrit concentrations <38%. No differences were found in length of stay or mortality. A multicenter trial found that a restrictive strategy of RBC transfusion (hemoglobin goal 7-9 g/dL) was associated with in-hospital mortality lower than that with a more liberal approach, which calls into question the 38% hematocrit goal in the EPO trials. Furthermore, preliminary results from an economic analysis of EPO use in the ICU setting have demonstrated that EPO is not cost-effective. CONCLUSIONS: Given the controversies surrounding EPO administration in critically ill patients, institutions are encouraged to develop EPO guidelines to help ensure the most appropriate use of this expensive product. Additional studies regarding patients most likely to benefit from EPO therapy, the most effective dosing regimen, and use of adjunctive therapies are needed.
A 42-year-old man with human immunodeficiency virus (HIV) infection and a history of complex partial seizures developed severe anemia after the addition of valproic acid to his stable antiretroviral regimen of zidovudine, lamivudine, and abacavir. The inhibition of zidovudine glucuronidation by valproic acid and the resultant zidovudine hematologic toxicity is the proposed mechanism of the interaction.