Increased Erythropoietin Levels Research Articles

Polycythemia and increased erythropoietin in a patient with chronic kidney disease

A 16-year-old white male with a history of obstructive uropathy presented to a pediatric outpatient clinic with a first syncope. At presentation, he had a hemoglobin level of 220 g/l, a serum erythropoietin level of 27.4 U/l and a serum creatinine level of 200.7 micromol/l (2.27 mg/dl). Physical examination, serum laboratory analysis, renal ultrasound, MRI, and 99mTc-MAG3 scintigraphy of the kidneys. Chronic renal insufficiency caused by obstructive hydronephrosis and accompanied by increased erythropoietin levels of renal origin and polycythemia. Serial phlebotomies and laparoscopic removal of the right hydronephrotic kidney.

Protection Against Radiation Induced Hematopoietic Damage in Bone Marrow of Swiss Albino Mice by Mentha piperita (Linn)

The protective effects of Mentha piperita (Linn) extract against radiation induced hematopoietic damage in bone marrow of Swiss albino mice have been studied. Mice were given either double distilled water or leaf extract of M. piperita orally (1 g/kg b.wt./day) once a day for three consecutive days, and after 30 min of treatments on the third day were exposed to 8 Gy gamma radiation. Mice were autopsied at 12, 24, 48 hrs and 5, 10 and 20 days post-irradiation to evaluate the percentage of bone marrow cells, frequency of micronuclei and erythropoietin level in serum. An exposure to gamma radiation resulted in a significant decline in the number of bone marrow cells such as leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes. Pretreatment with leaf extract of M. piperita followed by radiation exposure resulted in significant increases in the numbers of leucoblasts, myelocytes, metamyelocytes, band/stab forms, polymorphs, pronormoblasts and normoblasts, lymphocytes, and megakaryocytes in bone marrow as compared to the control group. Pretreatment with leaf extract of M. piperita followed by radiation exposure also resulted in significant decreases in micronucleus frequencies in bone marrow of Swiss albino mice. A significant increase in erythropoietin level was observed at all the studied intervals in leaf extract of M. piperita pretreated irradiated animals as compared to control animals (radiation alone). The results of the present investigation suggest the protective effects of leaf extract of M. piperita against radiation induced hematopoietic damage in bone marrow may be attributed to the maintenance of EPO level in Swiss albino mice.

Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: Results of a randomized, double-blind, placebo-controlled trial*

To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. Randomized, double-blind, placebo-controlled study. Medical, surgical, or mixed medical/surgical intensive care units. A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.

ACE Gene Polymorphism and Erythropoietin in Endurance Athletes at Moderate Altitude

To determine the role of the ACE (I/D) gene polymorphism on erythropoietic response in endurance athletes after natural exposure to moderate altitude. Erythropoietic activity was measured in 63 male endurance athletes following natural exposure to moderate altitude (2200 m) during 48 h. Erythropoietin (EPO) levels and hemoglobin (Hb) concentrations were measured at baseline and 12, 24, and 48 h after reaching the set altitude. Reticulocyte counts were determined at baseline and 48 h thereafter. Subjects were grouped into two groups (responders and nonresponders) based on significant increase in EPO levels (median: > 16.5 ng x m(-1)) after 24 h at altitude. ACE gene polymorphism was ascertained by polymerase chain reaction (DD, 31 (49%); ID, 24 (38%); II, 8 (13%)). Overall, EPO levels significantly increased at 12 (70%; P = 0.0001) and 24 h (72%; P = 0.0001) above baseline concentration following exposure to 2200 m. Thereafter, EPO concentration decreased at 48 h, but a significant increase in Hb levels (4.6 +/- 4%; P = 0.0001) and reticulocyte count (50.5 +/- 79%; P = 0.0001) was observed at the end of the experiment, suggesting negative feedback. There were no significant differences in EPO and Hb concentration profiles between subjects with DD genotype and those with other genotypes (ID/II). Moreover, responders (N = 42; DD, 50%; ID/II, 50%) and nonresponders (N = 21; DD, 48%; ID/II, 52%) showed a similar erythropoietic profile during the experiment and the ACE gene polymorphism did not influence the time course of the erythropoietic response. The ACE gene polymorphism does not influence erythropoietic activity in endurance athletes after short-term exposure to moderate altitude.

Renal Cyst Development in Mice with Conditional Inactivation of the von Hippel-Lindau Tumor Suppressor

Inactivation of the von Hippel-Lindau tumor suppressor, pVHL, is associated with both hereditary and sporadic renal cysts and renal cell carcinoma, which are commonly thought to arise from the renal proximal tubule. pVHL regulates the protein stability of hypoxia-inducible factor (HIF)-alpha subunits and loss of pVHL function leads to HIF stabilization. The role of HIF in the development of VHL-associated renal lesions remains to be determined. To investigate the functional consequences of pVHL inactivation and the role of HIF signaling in renal epithelial cells, we used the phosphoenolpyruvate carboxykinase (PEPCK) promoter to generate transgenic mice in which Cre-recombinase is expressed in the renal proximal tubule and in hepatocytes. We found that conditional inactivation of VHL in PEPCK-Cre mutants resulted in renal cyst development that was associated with increased erythropoietin levels and polycythemia. Increased expression of the HIF target gene erythropoietin was limited to the liver, whereas expression of carbonic anhydrase 9 and multidrug resistance gene 1 was up-regulated in the renal cortex of mutant mice. Inactivation of the HIF-alpha binding partner, arylhydrocarbon receptor nuclear translocator (Arnt), but not Hif-1alpha, suppressed the development of renal cysts. Here, we present the first mouse model of VHL-associated renal disease that will provide a basis for further genetic studies to define the molecular events that are required for the progression of VHL-associated renal cysts to clear cell renal cell carcinoma.

357 Is Hypoxia Induced Erythropoietin (EPO) Release a Mediator of Preconditioning in the Nervous System?

Background: Erythropoietin has been implicated in the mechanisms of ischemic tolerance or preconditioning. It has been shown, experimentally, that the EPO/EPO receptor system might serve as an endogenous system to protect brain cells from damage caused by intermittent episodes of hypoxia. In addition, it is known, that after perinatal asphyxia, EPO levels are increased. Our hypothesis was that increased EPO levels at birth, as a result of a perinatal hypoxia insult, might activate endogenous protective mechanisms and potentially lessen the impact of subsequent, more severe insults. Objective: The aim of this study was to assess if there was any association between EPO levels at birth and early neurological outcome. Moreover, to see if exogenous EPO administration has an additional effect on this issue compared to controls. Methods: This study is a part of a controlled randomized study of EPO administration in premature neonates, early after birth, for the anemia (AOP). In 75 neonates, EPO levels have been measured in the first day of life. Cranial ultrasonograms and neurological examinations were recorded through the whole hospitalization period. Results: The neonates according to EPO values were divided in 2 groups: EPO levels>50mU/ml (n=12, 135,7±75,78) and EPO levels<50mU/ml(n=63, 10,74±9,32 ). Cranial ultrasound lesions, (stage III IVH, and parenchymal involvement), detected early in life, were significantly fewer (p=0,04) in neonates with high EPO values compared to neonates with low EPO values. Although all neonates in the former group had a perinatal history of PROM either chorioamnionitis or IUGR, the difference was not significant compared to the perinatal history of the neonates with low EPO levels. Of the 75 neonates 47 were EPO treated and 28 controls. There was not any difference in early neurological outcome between them. Conclusion: It seems that high EPO levels at birth, probably, as a result of a perinatal insult may have an association with early neurological outcome. rHuEPO treatment in doses for (AOP) has not any effect in early neurological outcome. Imitation of brain endogenous mechanisms may be the key to future successful approaches to neuroprotection.

Increased erythropoietin level and reticulocyte count during arsenic trioxide therapy

Increased erythropoietin level and reticulocyte count during arsenic trioxide therapy

Perioperative use of erythropoietin.

Erythropoietin (EPO) is the primary regulator of red blood cell (RBC) production, and hypoxia is the main stimulus for EPO secretion. Increases in circulating levels of EPO are proportionate to the levels of tissue hypoxia, which are influenced by hematocrit (HCT). Small decreases in HCT as would be typical after presurgical autologous blood donation often do not result in increased EPO levels or in compensatory erythropoiesis. Erythropoiesis may also be limited by deficiencies of vitamin B(12), folate, and, most commonly, iron. The preoperative administration of EPO is effective in increasing erythrocyte mass and autologous donation volumes while maintaining higher HCT levels. In some surgical populations, particularly those individuals who experience surgical blood losses in excess of 2 L, EPO treatment also reduces allogeneic blood exposure. This effect is prominent in patients with a low initial HCT. Current assessments of the cost-effectiveness of EPO suggest that it achieves little overall improvement in patient health and that what improvement it does offer, it does at enormous cost.

Novel approaches to anemia associated with cancer and chemotherapy.

Novel approaches to anemia associated with cancer and chemotherapy are reviewed. Anemia in cancer patients is usually related to treatment with antineoplastic agents or to the disease itself. The normal concentration of endogenous erythropoietin ranges from 0.1 to 0.2 microU/mL and may increase to 2-10 microU/mL in patients with severe anemia. Many cancer patients with anemia do not have an increase in erythropoietin levels, however. Recombinant human erythropoietin (epoetin alfa), the standard for treating anemia caused by chronic renal failure, is also used to treat cancer chemotherapy-related anemia. It resolves anemia, decreases the need for transfusions, and may improve a patient's quality of life. A newer erythropoiesis-stimulating protein, darbepoetin alfa, was initially evaluated in patients with chronic renal disease. In patients who had never taken epoetin alfa, darbepoetin alfa was able to achieve a hemoglobin concentration of 11 g/dL by four weeks in most patients, and 97% of patients maintained on epoetin alfa were successfully switched to the other drug. Similar positive results were achieved in patients with solid tumors receiving chemotherapy, patients with anemia of chronic disease associated with cancer, and patients with lymphoproliferative malignancies. Darbepoetin alfa has a longer half-life than epoetin alfa, enabling less frequent administration. No difference in toxicity between the two agents has been reported. Epoetin alfa and darbepoetin alfa are effective in the treatment of anemia in patients with cancer.

Increased erythropoietin levels in reactive thrombocytosis.

Erythropoietin, the major humoral regulator of red cell production, was reported to stimulate various levels of megakaryocytopoiesis. We investigated levels of thrombopoietin (TPO) and erythropoietin (EPO) in patients with reactive thrombocytosis (RT) and clonal thrombocytosis (CT). 17 patients with RT and 18 patients with CT and 15 healthy subjects were enrolled into the study. TPO levels were higher in both patient groups than the controls. EPO levels were significantly higher than these in reactive thrombocytosis and in controls (p < 0.05). We suggest that besides TPO, EPO may play an important role in the pathogenesis of RT.

Oral isobutyramide reduces transfusion requirements in some patients with homozygous β-thalassemia

AbstractThe butyrate derivative isobutyramide (IBT) increases fetal hemoglobin (HbF) in patients with β-hemoglobinopathies, but little is known about its usefulness for prolonged therapeutic use. We treated 8 patients with transfusion-dependent β-thalassemia with 350 mg/kg of body weight per day of oral IBT for 126 to 384 days. During the trial period, the hemoglobin level was maintained between 85 g/L (range 82-87 g/L) (pretransfusion) and 115 g/L (range 110-119 g/L) (post-transfusion) (median, interquartile range), corresponding to 4-week transfusion intervals in all patients during the pretreatment phase. Adverse effects (bitter taste, epigastric discomfort) did not cause discontinuation of IBT. HbF increased in all patients from 3.1% (range 1.9%-4.8%) to 6.0% (range 3.3%-8.7) (P = .0017), while free Hb dropped from 0.48 g/L (range 0.39-0.81 g/L) to 0.19 g/L (range 0.16-0.24 g/L) (P < .0001). Transfusion intervals were consistently extended to 8 or 9 weeks in 1 patient, resulting in a decrease of daily iron load from 455 μg/kg per day (range 451-459 μg/kg per day) before therapy to 211μg/kg per day (range 203-286 μg/kg per day) during the 12-month treatment period. Prolongation of transfusion intervals achieved by IBT was less consistent in another patient, whose parenteral iron load nevertheless decreased from 683 μg/kg per day (range 618-748 μg/kg per day) to 542 μg/kg per day (340-596 μg/kg per day). In the other 6 patients, no prolongation of transfusion intervals was achieved. Response to treatment was associated with high pretreatment HbF (> 4.5%), high parental HbF, and increased erythropoietin levels (> 150 IU/L). We conclude that IBT prolongs transfusion intervals and reduces parenteral iron burden in some patients with transfusion-dependent β-thalassemia.

Oral isobutyramide reduces transfusion requirements in some patients with homozygous β-thalassemia

The butyrate derivative isobutyramide (IBT) increases fetal hemoglobin (HbF) in patients with β-hemoglobinopathies, but little is known about its usefulness for prolonged therapeutic use. We treated 8 patients with transfusion-dependent β-thalassemia with 350 mg/kg of body weight per day of oral IBT for 126 to 384 days. During the trial period, the hemoglobin level was maintained between 85 g/L (range 82-87 g/L) (pretransfusion) and 115 g/L (range 110-119 g/L) (post-transfusion) (median, interquartile range), corresponding to 4-week transfusion intervals in all patients during the pretreatment phase. Adverse effects (bitter taste, epigastric discomfort) did not cause discontinuation of IBT. HbF increased in all patients from 3.1% (range 1.9%-4.8%) to 6.0% (range 3.3%-8.7) (P = .0017), while free Hb dropped from 0.48 g/L (range 0.39-0.81 g/L) to 0.19 g/L (range 0.16-0.24 g/L) (P &lt; .0001). Transfusion intervals were consistently extended to 8 or 9 weeks in 1 patient, resulting in a decrease of daily iron load from 455 μg/kg per day (range 451-459 μg/kg per day) before therapy to 211μg/kg per day (range 203-286 μg/kg per day) during the 12-month treatment period. Prolongation of transfusion intervals achieved by IBT was less consistent in another patient, whose parenteral iron load nevertheless decreased from 683 μg/kg per day (range 618-748 μg/kg per day) to 542 μg/kg per day (340-596 μg/kg per day). In the other 6 patients, no prolongation of transfusion intervals was achieved. Response to treatment was associated with high pretreatment HbF (&gt; 4.5%), high parental HbF, and increased erythropoietin levels (&gt; 150 IU/L). We conclude that IBT prolongs transfusion intervals and reduces parenteral iron burden in some patients with transfusion-dependent β-thalassemia.

ACE Inhibitors and Anemia in Congestive Heart Failure

The use of angiotensin-converting enzyme inhibitors can be accompanied by a number of adverse events, including cough, angioedema, and hyperkalemia, as well as a peculiar form of functional renal insufficiency. Other, less obvious side effects accompany ACE inhibitor use, such as a reduction in red blood cell production. This feature of ACE inhibitor use may be employed to good effect, as in the management of post-transplant erythrocytosis. Alternatively, the suppressive effect of ACE inhibitors on red blood cell production may intensify the anemia of chronic renal failure and/or congestive heart failure. The untreated congestive heart failure patient typically has an increased red blood cell mass as a consequence of increased erythropoietin levels, with the latter governed by congestive heart failure-related renal hypoxia. This is not expressed as an increase in hemoglobin concentration because of the increase in plasma volume that marks advanced congestive heart failure. ACE inhibitor therapy can be expected to both reduce plasma volume and decrease red blood cell production. As a result, the hemoglobin concentration changes very little in the ACE inhibitor-treated congestive heart failure patient and usually falls in the low normal range. Recently, erythropoietin has been employed to good effect in congestive heart failure patients with borderline anemia. (c)2000 by CHF, Inc.

Increased erythropoietin level induced by hydroxyurea treatment of sickle cell patients.

Administration of hydroxyurea in sickle cell disease is associated with a dramatic increase of HbF along with a significant clinical improvement and, occasionally, increased total hemoglobin levels. The underlying mechanisms are not yet fully elucidated. We report the response of three patients with homozygous sickle cell disease and 10 patients with compound HbS/beta-thalassemia (four with beta(o)thal/HbS and six with beta(+)thal/HbS respectively) to hydroxyurea treatment with regards to their serum erythropoietin levels (sEpo). Baseline sEpo levels varied from 33.0 to 284.0 IU/L and showed a significant negative correlation with the respective Hb values (P<0.007). Two to three weeks after initiation of treatment, the sEpo values started to increase and reached levels three to 31 times higher than the baseline two to three weeks later. Thereafter, in most cases the Epo values decreased and remained at intermediate levels throughout the rest of hydroxyurea administration, while in a few cases, they returned to baseline. An inappropriate increase of sEpo following treatment with various cytostatic drugs, independently of anemia induced by cytostatic agents, has already been reported in the literature. The cytostatics included cyclophosphamide, anthracyclines, cytosine arabinoside etc., but not hydroxyurea. The results described here with hydroxyurea are virtually similar, ie, they show a significant sEpo increase five to ten days post therapy with no apparent cause. Pulses of high dose Epo have been reported to promote proliferation of erythroid precursors with HbF synthesizing capacity. Our hypothesis is that a similar phenomenon may occur here also, in the sense that peaks of endogenous Epo may promote proliferation of erythroid precursors which maintain the capacity to synthesize HbF.

Serum erythropoietin levels in kidney donors after renal transplantation.

Renal transplantation is the treatment of choice for many patients with end-stage renal disease. In the donor, renal excretory function is not affected after nephrectomy; however, little is known about other functions such as erythropoietin production. We studied the erythropoietin production in renal donors after nephrectomy. We included healthy individuals fulfilling the criteria for kidney donation. Blood samples were collected before and monthly from 1 to 6 months after nephrectomy. Complete blood cell counts and erythropoietin were assayed. Eight kidney donors were studied. A significant increase in erythropoietin levels was observed during the first 3 months, but no difference was observed by the 4th month as compared with basal values. Erythropoietin production rose during the first 3 months after nephrectomy. However, erythropoietin was normal by the 4th month. Unchanged hemoglobin levels may suggest that the compensatory production of erythropoietin could participate in the preservation of an adequate physiological status of the donor after nephrectomy.

Why Are Hemoglobin F Levels Increased in HbE/β Thalassemia?

AbstractTo try to further define the mechanisms that increase the levels of hemoglobin F (HbF) in the blood of patients with severe forms of β thalassemia, we have studied two comparable populations of hemoglobin E (HbE)/β thalassemics, one regularly transfused and one receiving only occasional blood transfusions. Regular transfusion was associated with a significant decrease in soluble transferrin receptor and erythropoietin levels. Globin chain synthesis studies also show a highly significant decrease in HbF synthesis relative to HbE in the transfused patients. This effect was confirmed by sequential data on one patient, studied before and after the commencement of regular blood transfusion; blood transfusion was followed by a marked increase in the ∝/γ, βE/γ, and HbE/HbF ratios. These data suggest that the high HbF levels in HbE/β thalassemia, and other β thalassemia syndromes, result from increased erythropoietin levels leading to bone marrow expansion, and possibly increased F-cell production, combined with ineffective erythropoiesis giving a survival advantage to F cells. This study also suggests that alteration in blood transfusion regimes must be taken into account when interpreting changes in HbF levels seen in trials of HbF-promoting drugs.

Why Are Hemoglobin F Levels Increased in HbE/β Thalassemia?

To try to further define the mechanisms that increase the levels of hemoglobin F (HbF) in the blood of patients with severe forms of β thalassemia, we have studied two comparable populations of hemoglobin E (HbE)/β thalassemics, one regularly transfused and one receiving only occasional blood transfusions. Regular transfusion was associated with a significant decrease in soluble transferrin receptor and erythropoietin levels. Globin chain synthesis studies also show a highly significant decrease in HbF synthesis relative to HbE in the transfused patients. This effect was confirmed by sequential data on one patient, studied before and after the commencement of regular blood transfusion; blood transfusion was followed by a marked increase in the /γ, βE/γ, and HbE/HbF ratios. These data suggest that the high HbF levels in HbE/β thalassemia, and other β thalassemia syndromes, result from increased erythropoietin levels leading to bone marrow expansion, and possibly increased F-cell production, combined with ineffective erythropoiesis giving a survival advantage to F cells. This study also suggests that alteration in blood transfusion regimes must be taken into account when interpreting changes in HbF levels seen in trials of HbF-promoting drugs.

The influence of automated plateletpheresis on systemic levels of hematopoietic growth factors.

Megakaryocytopoiesis and platelet production are regulated by several hematopoietic growth factors. The present study focuses on the effects of automated plateletpheresis on systemic levels of different hematopoietic growth factors. Platelet count, mean platelet volume, and serum levels of thrombopoietin, erythropoietin, interleukin-1beta, interleukin-6, and stem cell factor in 21 healthy donors were measured before platelet collection, after the first half of the apheresis procedure, at the end of apheresis, and on Days 1, 2, and 7 thereafter. Thrombopoietin levels (initial level: 49.5 +/- 25.5 pg/mL) showed a significant increase between measurements taken at the end of apheresis and Day 1 (56.9 +/- 26.7 pg/mL; p = 0.01). There was a highly significant decrease in stem cell factor levels during apheresis (p<0.0005), reaching preapheresis values (1679 +/- 210 pg/mL) on Day 1. A highly significant increase in erythropoietin levels (initial level: 7.5 +/- 4.0 U/L) was seen after apheresis (p<0.0005 on Days 1 and 2). The level remained significantly elevated until Day 7 (p = 0.004). Interleukin-1beta and interleukin-6 levels (before donation: 1.4 +/- 1.8 pg/mL and 1.1 +/- 0.7 pg/mL, respectively) did not change during the observation period. Thrombopoietin levels correlated consistently and inversely with stem cell factor levels after apheresis (Day 1, r = -0.46, p = 0.035; Day 2, r = -0.50, p = 0.02; Day 7, r = -0.50, p = 0.02). The data show a coordinated response of the hematopoietic system to platelet loss. It is suggested that the decrease in serum stem cell factor levels during apheresis reflects the consumption of stem cell factor by early hematopoietic progenitors that expand to initiate early megakaryocytopoiesis. The temporary increase in thrombopoietin is the result of platelet loss and serves as a stimulus for subsequent thrombopoiesis. The pronounced elevation of erythropoietin after apheresis suggests a role for this primarily erythropoietic cytokine in thrombopoiesis, too.

Erythropoietin production in anemia associated with experimental cancer

Serum erythropoietin (EPO) concentrations reportedly are depressed in patients with chronic disorders such as cancer, rheumatoid arthritis, and acquired immunodeficiency syndrome. We evaluated serum EPO levels in mice with tumors and found that the EPO response was appropriate for the associated anemia during the major part of the disease process. The levels of the hormone increased as the anemia worsened in association with progression of the disease. The increased EPO levels were comparable to those of controls with a similar degree of experimentally induced anemia. Only during the terminal stages of cancer, when the animals were severely cachectic, were serum EPO concentrations lower than in controls with a similar degree of anemia. These findings suggest that a blunted EPO response in experimental cancer occurs only in association with advanced disease.

Erythropoietin concentration and arterial haemoglobin saturation with supramaximal exercise

The aim of this study was to determine if the hypoxaemic stimulus generated by intense exercise results in the physiological response of increased erythropoietin production. Twenty athletes exercised for 3 min at 109+/- 2.8% (mean+/-s) maximal oxygen consumption. Estimated oxyhaemoglobin saturation was measured by reflective probe pulse oximetry (Nellcor N200) and was validated against arterial oxyhaemoglobin saturation by CO-oximetry in eight athletes. Serum erythropoietin concentrations – as measured using the INCSTAR Epo-Trac radioimmunoassay – increased significantly by 28+/- 9% at 24h post-exercise in 11 participants, who also had an arterial oxyhaemoglobin saturation 91% (P < 0.05). Decreased ferritin levels and increased reticulocyte counts were observed at 96h post-exercise. However, no significant changes in erythropoietin levels were observed in nine non-desaturating athletes and eight non-exercise controls. Good agreement was shown between arterial oxyhaemoglobin saturation and percent estimated oxyhaemoglobin saturation (limits of agreement = -3.9 to 3.7%). In conclusion, short supramaximal exercise can induce both hypoxaemia and increased erythropoietin levels in well-trained individuals. The decline of arterial hypoxaemia levels below 91% during exercise appears to be necessary for the exercise-induced elevation of serum erythropoietin levels. Furthermore, reflective probe pulse oximetry was found to be a valid predictor of percent arterial oxyhaemoglobin saturation during supramaximal exercise when percent estimated oxyhaemoglobin saturation >86%.