Erythropoietin in aplastic anemia

Pavlović-Kentera, V; Milenković, P; Ruvidic, R; Jovanović, Vesna; Biljanović-Paunović, L

doi:10.1007/bf01014197

Cited by 26 publications

(11 citation statements)

References 12 publications

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“…This difference was probably not due to variations in iron availability since plasma iron concentrations were in the normal range in the two strains that received I00 IU/kg, even though they were highly variable from rat to rat (data not shown). Erythroid hyperactivity in SHR was partly expected since three reports demonstrated increased plasma EPO levels in SHR relative to normotensive con trols [23][24][25]. This anomaly was thought to be the proximal cause of increased red blood cell count, elevated hemato crit, bone marrow erythroid hyperplasia, and increased iron incorporation into red cells, all described in the SHR [25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…Erythroid hyperactivity in SHR was partly expected since three reports demonstrated increased plasma EPO levels in SHR relative to normotensive con trols [23][24][25]. This anomaly was thought to be the proximal cause of increased red blood cell count, elevated hemato crit, bone marrow erythroid hyperplasia, and increased iron incorporation into red cells, all described in the SHR [25][26][27]. Elevated hematocrit in SHR increases blood vis cosity [24], and this has been suggested to contribute to the development of hypertension [23,24], The present findings extend these earlier reports by demonstrating increased erythroid responsiveness to rHuEPO in SHR.…”

Section: Discussionmentioning

confidence: 99%

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Erythropoietin Increases Blood Pressure in Normotensive and Hypertensive Rats

Muntzel

Hannedouche

Lacour

et al. 1993

Nephron

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Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses anemia in uremic patients. Of major concern, however, are blood pressure increases during rHuEPO therapy, observed particularly in patients with a history of hypertension. The present study was designed to determine whether high-dose rHuEPO elevates blood pressure in nonuremic rats, and if so, whether preexisting hypertension enhances this response. We examined blood pressure responses to high (100 IU/kg) and very high (200 IU/kg) doses of rHuEPO or placebo, given subcutaneously every other day for 3 weeks to male spontaneously hypertensive rats (SHR) and their normotensive genetic controls (Wistar-Kyoto rats, WKY). The high and very high doses of rHuEPO stimulated equivalent increases in hematocrit, and this increase was always larger in SHR than in WKY. In contrast to the pattern of hematocrit changes, blood pressure did not change following high-dose rHuEPO but was elevated in both strains after the very high dose of the drug. Although the rise in blood pressure tended to be greater in SHR than in WKY, this difference was not significant. The data indicate that very high-dose rHuEPO raises blood pressure comparably in normotensive and hypertensive rats and this increase is relatively independent of the increase in hematocrit.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Erythropoietin Increases Blood Pressure in Normotensive and Hypertensive Rats

Muntzel

Hannedouche

Lacour

et al. 1993

Nephron

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“…His conclusion was that EPO levels were significantly "influenced by the functional state of the erythroid tissue of the marrow". Subsequently, other investigators documented that following bone marrow ablation, 12,23,24 or in patients with aplastic anemia, 25 plasma EPO levels were disproportionately increased relative to slightly decreased Hb levels. Conversely, individuals with hyperactive marrow owing to hemolytic anemia had disproportionately low plasma EPO levels [26][27][28] and rapid EPO plasma disappearance.…”

Section: Discussionmentioning

confidence: 99%

Change in Erythropoietin Pharmacokinetics Following Hematopoietic Transplantation

Widness

Schmidt

Hohl

et al. 2007

Clin Pharmacol Ther

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Pre-clinical studies have demonstrated that bone marrow ablation has a profound effect in decreasing erythropoietin (EPO) elimination. The study's objective was to determine in humans if EPO pharmacokinetics (PKs) are perturbed following bone marrow ablation. EPO PK studies were performed in eight subjects, aged 4 to 61 years, undergoing fully myeloablative hematopoietic stem cell transplantation. Serial PK studies using intravenous injection of recombinant human EPO (92 ±2.0 U/kg) (mean±SEM) were carried out during four periods of altered marrow integrity: baseline pre-ablation, post-ablation pre-transplant, early post-transplant pre-engraftment, and late posttransplant full engraftment. Compared with baseline, post-ablation pre-transplant and early posttransplant EPO PKs demonstrated declines in clearance increases in terminal elimination half-life of 36 and 95%, respectively. Clearance and half-life returned to baseline following full engraftment. The association of EPO elimination with decreased bone marrow activity in patients undergoing transplantation conclusively establishes the bone marrow as a key determinant of EPO elimination in humans.Erythropoietin (EPO), a 34-kDa glycoprotein hormone, has a dominant action in the regulation of erythrocyte production. 1 EPO exerts its biological effect in stimulating the proliferation and differentiation of erythroid progenitors by binding to specific cell-surface receptors (EPO-Rs) that are in greatest abundance on erythroid progenitors located primarily in the bone marrow. 2 EPO-Rs are also located on virtually all non-hematopoietic tissues and have diverse additional biologic effects. 3 There is a paucity of information regarding which organ(s) and tissue(s) are important in EPO metabolism and elimination. Previous in vivo studies demonstrated that the kidney and liver exert no measurable effect on EPO in vivo elimination. [4][5][6] Erythropoietic tissues in rats, e.g., bone marrow and spleen, have also been shown to rapidly metabolize EPO with tissue uptake and clearance directly correlated with the number of erythroid colony-forming units. 7 These pre-clinical in vivo studies are supported by in vitro studies demonstrating that EPO is rapidly degraded by ligand-specific EPO-R erythroid progenitors, 8,9 and by clinical studies in anemic patients with hypoplastic marrows manifesting high serum EPO levels relative to their hemoglobin (Hb) levels. [10][11][12] Correspondence: JA Widness (john-widness@uiowa.edu). CONFLICT OF INTERESTThe authors declared no conflict of interest. In adults, EPO has demonstrated nonlinear pharmacokinetic (PK) behavior, with EPO clearance decreasing as the administered EPO dose increases. [12][13][14] The half-life of EPO ranges from 4 to 8 h in healthy adults given therapeutic doses of EPO. 13 In very-low-birth-weight premature infants, EPO also manifests nonlinear PK behavior, with clearances approximately threefold greater than adults. 15 Notably premature and term infants also manifest proportionally greater red marrow spac...

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“…In AA, it has been found that the abnormally high levels of EPO at diagnosis [13][14][15][16] decline along with hemopoietic recovery. However, EPO levels in remission AA patients remain increased with respect to their hematocrit [17].…”

Section: Introductionmentioning

confidence: 99%

Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes

1998

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Immunoreactive serum erythropoietin (EPO) was measured in anemic and non-anemic patients with acquired non-severe aplastic anemia (AA; n = 22) and myelodysplastic syndromes (MDS; n = 31) receiving or not androgens to examine the effect of androgen therapy and anemia on EPO levels in these disorders. Soluble transferrin receptor (TfR) and absolute reticulocyte count (ARC) were also assayed in order to evaluate erythropoietic activity. AA and MDS patients were stratified for anemia and androgen treatment as follows: 12 untreated anemic patients; 17 anemic patients during androgen therapy; 14 non-anemic patients without any treatment (>1 year); and 10 non-anemic patients on androgen therapy. Although EPO levels in non-anemic patients were significantly higher than in healthy controls (n = 29) no statistically significant differences in Hb and EPO values were found between non-anemic patients receiving or not androgen therapy. In the linear regression analysis between Hb and log EPO concentration, no statistically significant differences in the slopes between untreated and androgen-treated anemic groups nor between both groups and patients with iron deficiency anemia (n = 23) were observed. However, the y intercept (log EPO) of regression line was significantly higher in androgen-treated anemic patients than in the androgen therapy-free anemic group. Serum TfR levels were higher in treated than in untreated anemic patients, whereas ARC was not different between both groups. These data seemingly indicate that (1) androgens at pharmacological doses do not increase serum EPO levels in non-anemic AA and MDS patients, and (2) in patients with AA and MDS, androgen-driven EPO stimulation is appreciably enhanced by anemia. Am.

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Erythropoietin in aplastic anemia

Cited by 26 publications

References 12 publications

Erythropoietin Increases Blood Pressure in Normotensive and Hypertensive Rats

Erythropoietin Increases Blood Pressure in Normotensive and Hypertensive Rats

Change in Erythropoietin Pharmacokinetics Following Hematopoietic Transplantation

Effect of androgen therapy and anemia on serum erythropoietin levels in patients with aplastic anemia and myelodysplastic syndromes

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