Use of recombinant human erythropoietin to enhance autologous blood donation in a patient with multiple red cell allo-antibodies and the anemia of chronic disease.

We treated a patient with alcohol-induced cirrhosis, intractable pain from a defective hip prosthesis, and multiple red cell allo-antibodies with recombinant human erythropoietin (EPO) in order to facilitate collection of blood for autologous transfusion during an elective total hip revision. This patient had experienced a delayed transfusion reaction 4 months earlier after receiving least incompatible packed red cells for gastrointestinal bleeding. His blood could not be crossmatched because of the development of multiple antibodies to homologous blood given during previous surgery and several episodes of gastrointestinal hemorrhage. Following initiation of EPO therapy, there was a prompt and persistent increase in the reticulocyte count from a baseline of 1.6% to a maximum of 8.6%. This was accompanied by maintenance of the hematocrit between 32% and 38.5% despite withdrawal of seven units of autologous blood over the 45-day treatment period. Poor venous access and availability of blood bank personnel, not hematocrit level, were the limiting factors that determined how frequently blood could be collected. We conclude that EPO stimulated erythropoiesis in this patient with underlying anemia of chronic disease and facilitated harvest of autologous blood for elective surgery.

Erythropoietin: biology and clinical use.

Red cell production in vertebrates is controlled by a glycoprotein hormone known as erythropoietin (Ep), which is produced by the kidney in response to hypoxia and acts on the marrow to selectively stimulate erythropoiesis. The gene for Ep has recently been cloned, and highly pure recombinant human Ep (rHuEp) is now available in considerable quantity. This has led to a better understanding of many aspects of Ep biology and to clinical trials in humans. The amino acid sequence of Ep is now completely known, and the protein portion of the natural hormone and the recombinant product are identical. Both the natural hormone and rHuEp produced in Chinese hamster ovary cells are heavily glycosylated in a very similar manner. This glycosylation is not necessary for in vitro activity but is required for activity in vivo. Radioimmunoassays (RIAs), which use labeled rHuEp, have been developed and are sufficiently sensitive to measure normal plasma levels. However, since Ep exists in plasma in several forms that vary in their immunologic and biologic activities, the ability of a RIA to provide information on the pathogenesis of clinical disease may be limited and should be referenced to the polycythemic mouse assay. The kidney's role in the production of Ep has been greatly clarified. Studies using probes to Ep mRNA have shown that Ep is primarily made in the kidney and secreted as the intact hormone. Moreover, renal secretion appears to be regulated by the rate of synthesis of the hormone, which in turn is dependent on the rate of synthesis of Ep mRNA. The cells that produce Ep have been identified as peritubular interstitial cells that may be endothelial in origin. The initiating mechanism for hormone production appears primarily to involve recruitment of additional cells rather than increased production by individual cells. Ep primarily acts on the marrow to stimulate the growth and maturation of early cells in the erythroid lineage that are known as the burst-forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E). The BFU-E is a very early cell closely related to the pluripotent stem cell, while the CFU-E is a later cell close to the first recognizable erythroblast.(ABSTRACT TRUNCATED AT 400 WORDS)