急性心肌梗死患者贫血与促红细胞生成素水平和肾功能的关系

目的研究急性心肌梗死(AMI)患者贫血的患病情况及贫血与促红细胞生成素(EPO)和肾功能的关系。方法对72例AMI患者和44例健康对照者进行血红蛋白(Hb)、血EPO和尿白蛋白与尿肌酐比值(ACR)测定。采用简化MDRD公式计算肾小球滤过率(GFR)。结果AMI患者中贫血(女性Hb<110 g/L;男性Hb<120 g/L)患病率为44.4%,显著高于对照组(P<0.001)。AMI患者中,贫血多见于女性、低体质指数、合并高血压、糖尿病和心、肾功能不全的患者。贫血组EPO水平较非贫血组显著升高[(25.12±2.19)U/Lvs.(15.84±1.91)U/L,P<0.05],但实测与预计lgEPO(O/P)比值两组差异无统计学意义。对于AMI患者,Hb水平还与Killip评分(r=-0.447,P<0.001)、血Cr(r=-0.448,P<0.01)、GFR(r=0.603,P<0.001)和lgACR(r=-0.502,P<0.01)相关。结论AMI患者常伴有贫血,血红蛋白可作为反映AMI患者病情严重程度的指标。肾功能受损可加重贫血的发生,而EPO降低不是AMI患者贫血发病的主要原因。     

Low dose erythropoietin‐beta improves anemia and maintains ribavirin dose in chronic hepatitis C patients receiving combination therapy with ribavirin plus pegylated interferon Alfa‐2b

Aim: Anemia during combination therapy with pegylated interferon alfa‐2b plus ribavirin (RBV) for chronic hepatitis C virus (HCV) patients usually leads to RBV dose reduction or discontinuation. This study evaluated the effect of erythropoietin‐beta (EPO‐β) to maintain RBV dose and hemoglobin (Hb) level in chronic HCV patients treated with antiviral combination therapy. Methods: Eighty‐eight chronic HCV patients who developed anemia during therapy were enrolled into this retrospective study: 55 in the EPO‐β group and 33 in the untreated group. The study endpoints were to assess the RBV maintenance and the changes in Hb. Results: A higher percentage of patients with RBV maintenance was observed in the EPO‐β group compared with the untreated group (nadir Hb level <10.5 g/dL; 70% vs. 38%, P = 0.020; nadir Hb < 10 g/dL; 62% vs. 27%, P = 0.046). The mean Hb change from week 12 to week 20 was higher in the EPO‐β group when compared with the untreated group, especially for patients receiving a total EPO‐β dose of more than 16 000 U (+0.70 g/dL vs. ?0.32 g/dL, P = 0.023) and of 10 000 U‐14 000 U (+0.60 g/dL vs. ?0.32 g/dL, P = 0.023). Conclusions: Low‐dose EPO‐β can maintain RBV dose and increase Hb levels in anemic chronic HCV patients receiving combination therapy.     

The Advia 120 red blood cells and reticulocyte indices are useful in diagnosis of iron-deficiency anemia

We have investigated the red blood cell (RBC) and reticulocyte indices of the Advia 120 hematology system in assessment of body iron stores as well as in diagnostics of iron-deficiency anemia in two separate study populations. The first study population consisted of a total of 34 apparently healthy females who were found to be anemic (Hb<125gL1) in a screening test. The anemic subjects were classified on the basis of plasma transferrin receptor (TfR) concentration into an iron-deficiency anemia group (TfR concentration 2.4mgL1, n=14) and an adequate iron stores group (TfR concentration <2.4mgL1, n=20). Another study population consisted of 95 hospital patients of whom 31 had depleted iron stores according to TfR concentration. The same population was classified further on the basis of hemoglobin value (Hb<125gL1 for females, Hb<135gL1 for males) into patients with iron-deficiency anemia (n=21) and those with anemia together with adequate iron stores (n=44). In the population of young anemic female students the percentage of hypochromic RBC (%HYPOm) had a remarkably high ROC AUC of 0.98 when evaluating the diagnostic accuracy for the distinction between the patients with iron-deficiency anemia and those with anemia and adequate iron stores. Also, among the hospitalized patients %HYPOm had the highest ROC AUC of 0.77. The diagnostic efficiency provided by the red blood cell and reticulocyte indices was considerably lower in the heterogeneous group of hospitalized patients than in the group of female students. Nevertheless, the advanced RBC and reticulocyte indices may prove to be useful tools in the evaluation of iron status and diagnosis of iron-deficiency anemia.     

Recombinant human erythropoietin for the treatment of anemia in the myelodysplastic syndromes: A clinical and erythrokinetic assessment

Summary The clinical and ferrokinetic effects of escalating doses of subcutaneously administered recombinant human erythropoietin (rh-EPO) were studied in ten patients with myelodysplastic syndromes and severe transfusion-dependent anemia. Red blood cell transfusion requirements diminished in four patients, and one of the patients eventually became transfusion independent with an EPO-induced rise of Hb from 7.7 g/dl to 12.3 g/dl. Endogenous serum levels of EPO were significantly increased in all patients (100–5700 mU/ml), but three of four responders had a relatively low baseline level. The effective red cell iron turnover (RCIT) improved in two responding patients and even normalized in one patient. This increase in RCIT was accompanied with a decline in the ineffective red cell iron turnover (IIT). The other responding patients had a relatively preserved RCIT before EPO treatment. EPO therapy further increased the fraction of IIT in the latter patients. Red cell survival time did not increase during EPO therapy, even in the responding patients. One transient and one maintained increase in platelet count were observed. Disease progression with a sustained increase in blast cells in one patient and a transient elevation of blasts in another patient was seen. No other side effects of EPO therapy were observed. These results suggest that anemic MDS patients with low serum EPO levels and relatively spared effective erythropoiesis as measured by ferrokinetic studies may be the best candidates for treatment with recombinant human EPO.     

Soluble transferrin receptor and its ratio to erythroblasts in bone marrow may be a new diagnostic tool to distinguish between aplastic and refractory anemia

Myelodysplastic syndromes (MDS), especially refractory anemia (RA) are very heterogeneous diseases regarding their morphological, biological and clinical features. One important clinical problem is the difficulty of diagnosis. Soluble transferrin receptors (sTfRs) reflect the erythropoietic activity in the bone marrow (BM). To establish whether determination of serum sTfR could be useful for the differential diagnosis between RA and aplastic anemia (AA), we measured the serum sTfR concentrations, BM cellularity and BM erythroblast percentages in 14 untreated AA and 7 untreated RA patients. The serum sTfR levels of the RA patients (820.1 +/- 402.8 ng/ml) were significantly higher than those of the AA patients (491.1 +/- 195.2 ng/ml; p = 0.0207). However, the serum sTfR values of RA and AA patients also overlapped. A new index, the 'sTfR-E index' [the ratio of serum sTfR level (ng/ml) to BM cellularity (%) x BM erythroblasts (%)] is proposed, which is expected to reflect the number of transferrin receptors (TfR) on the cell membrane per BM erythroblast. The sTfR-E index values of the 7 RA patients (0.395 +/- 0.234) were significantly lower than those of the 14 AA patients (2.669 +/- 1.633; p = 0.0003). The sTfR-E index values of AA and RA patients overlapped only marginally. In conclusion, the sTfR-E index may be a useful new diagnostic tool to distinguish between AA and RA patients.     

Effect of maternal anemia at high altitude on infant hematocrit and oxygenation

Hematocrit levels were determined in 36 mothers living at high altitudes (3,750 meters) and their infant cord bloods to determine the effect of maternal anemia on the infant. The arterial oxygen saturation (SaO(2)) and respiratory rate of the infants were also followed during the first four months of life. There was a negative correlation between maternal hematocrit and infant hematocrit (r(s) = - 0.57). Nineteen babies born to anemic women (hematocrit < 41%) had a significantly higher mean hematocrit (59.9%) than those born to non-anemic mothers (55.8%; P = 0.003). The SaO(2) levels and respiratory rates of infants were not different between infants born to non-anemic and anemic mothers. At high altitudes, infants from mothers with anemia have higher hematocrits than those born to non-anemic mothers.     

Reduced erythropoietin secretion in senile anemia.

To investigate the etiology of the age-related decrease in hemoglobin (Hb) concentration, we measured serum erythropoietin (EPO), serum iron, total iron binding capacity, and serum ferritin levels in 247 elderly subjects aged 60-99 years. EPO levels were determined by radioimmunoassay. An age-related increase in the serum EPO concentration (r = 0.220; P < 0.01) and a significant inverse relationship between EPO and Hb concentrations were found in normal elderly subjects without anemia (r = -0.302; P < 0.001), but not in 111 younger controls. Serum EPO levels were slightly higher in elderly subjects with pre-anemic iron deficiency than in the normal elderly subjects (P < 0.05). These results suggest that the EPO secretion is accelerated in the elderly even though the Hb remains above 12.0 g/dl, probably as a compensatory mechanism for peripheral tissue hypoxia. An inverse relationship between the EPO and Hb concentrations was found in the elderly subjects with iron deficiency anemia, but not in those with unexplained senile anemia. The changes of EPO levels were also assessed in 20 elderly subjects who had developed anemia when reviewed after 12 months. Serum EPO levels increased in relation to the decrease in Hb concentration in those with iron deficiency anemia, but not in those with unexplained senile anemia. Reduced EPO secretion thus seems to play a role in the progression of unexplained senile anemia, and recombinant human EPO may possibly be effective for treating this type of anemia by mobilizing excess iron.     

Suppressed serum erythropoietin response to anemia and the efficacy of recombinant erythropoietin in the anemia of rheumatoid arthritis

Serum erythropoietin (EPO) was measured by radioimmunoassay in 67 patients with rheumatoid arthritis (RA). Twenty of these patients judged to have iron deficiency anemia, based on reduced serum ferritin levels, had higher serum EPO levels than did the 24 other anemic patients with normal or elevated serum ferritin levels. A significant negative correlation between serum EPO and hemoglobin concentrations was noted in the former group, but not in the latter. Human recombinant erythropoietin (r-EPO) was administered to 6 anemic patients with RA, resulting in improvement of anemia in 4 patients, 2 of whom showed no change in RA activity. These findings suggest a suppressed serum EPO response ot anemia and the effectiveness of r-EPO in treating anemia associated with RA.     

老年人肾功能、贫血和促红细胞生成素的相关性

目的 通过分析老年人肾小球滤过率（ GFR）和血清促红细胞生成素（EPO）水平对老年贫血患病率的影响,探讨老年贫血发生的相关因素及其与老年人肾功能水平的关系.方法 选取200例年龄≥60岁的老年患者作为观察对象,既往无慢性疾病的健康体检者30人作为正常对照组.采用Cockcroft-Gault方程计算eGFR;根据eGFR分为A组[eGFR＞ 50ml/（ min·1.73m2）,62例]、B组[30ml/（ min· 1.73m2）≤eGFR≤50ml/（ min·1.73m2）,114例]和C组[eGFR＜ 30ml/（ min· 1.73m2）,24例];66例老年贫血患者再根据GFR估算值（eGFR）分为AA组、AB组和AC组（分组标准同上）.测定血红蛋白（Hb）、血肌酐（Scr）、EPO水平.结果 伴随着肾功能水平的降低,老年人贫血患病率呈升高趋势,并且A,B,C3组之间比较均有显著性差异（P＜0.05）;正常对照组Log EPO与Hb呈负相关（r2=0.219,P=0.009）;A组Log EPO与Hb成负相关（r2=0.065,P=0.045）,B组Log EPO与Hb之间无相关关系,C组Log EPO与Hb为正相关（r2=0.294,P=0.006）;老年贫血患者随着肾功能水平的降低,EPO呈现下降趋势,AA组和AC组比较有显著性差异（P=0.042）.结论 老年人肾功能水平中度减退时贫血患病率即显著增加;随着年龄的增长,老年人EPO的分泌代偿性增加,但随着eGFR的不断下降,这种代偿机制逐渐减弱;当肾功能水平严重降低时,EPO分泌的减少是老年贫血发生的主要原因.     

Intravenous iron alone for the treatment of anemia in patients with chronic heart failure.

OBJECTIVES: This study was undertaken to assess the hematologic, clinical, and biochemical response to intravenous iron in patients with chronic heart failure (CHF) and anemia. BACKGROUND: Anemia is common in patients with CHF and is associated with higher morbidity and mortality. The combination of erythropoietin (EPO) and iron increases hemoglobin (Hb) and improves symptoms and exercise capacity in anemic CHF patients. It is not known whether intravenous iron alone is an effective treatment for anemia associated with CHF. METHODS: Sixteen anemic patients (Hb < or =12 g/dl) with stable CHF (age 68.3 +/- 11.5 years, 12 men, 9 participants New York Heart Association [NYHA] functional class II and the remainder class III, left ventricular ejection fraction 26 +/- 13%) received a maximum of 1 g of iron sucrose by bolus intravenous injections over a 12-day treatment phase in an outpatient setting. Mean follow-up was 92 +/- 6 days. RESULTS: Hemoglobin rose from 11.2 +/- 0.7 to 12.6 +/- 1.2 g/dl (p = 0.0007), Minnesota Living with Heart Failure (MLHF) score fell (denoting improvement) from 33 +/- 19 to 19 +/- 14 (p = 0.02), 6-min walk distance increased from 242 +/- 78 m to 286 +/- 72 m (p = 0.01), and all patients recorded NYHA class II at study end (p < 0.02). Changes in MLHF score and 6-min walk distance related closely to changes in Hb (r = 0.76, p = 0.002; r = 0.56, p = 0.03, respectively). Of all baseline measurements, only iron and transferrin saturation correlated with increases in Hb (r = 0.60, p = 0.02; r = 0.60, p = 0.01, respectively). There were no adverse events relating to drug administration or during follow-up. CONCLUSIONS: Intravenous iron sucrose, when used without concomitant EPO, is a simple and safe therapy that increases Hb, reduces symptoms, and improves exercise capacity in anemic patients with CHF. Further assessment of its efficacy should be made in a multicenter, randomized, placebo-controlled trial.     

Comparison of the serum erythropoietin levels in chemotherapy-naive and cisplatin-treated cancer patients

There are conflicting data about the effects of cisplatin on erythropoietin (EPO) response to anemia. Aim of our study was to investigate whether endogenous EPO response to anemia in cisplatin treated patients was insufficient in comparison to the anemic chemotherapy-naive cancer patients and non cancer patients with iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110 g/l were included in the study. Fifteen chemotherapy- naive cancer patients were enrolled in Group A. Group B consisted of 15 patients who had been treated with three cycles of cisplatin chemotherapy and then became anemic and in Group C were included 15 patients who had iron deficiency anemia, without any malignancy. The mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/-2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively). However, EPO levels were found to be significantly lower in Group A and Group B than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml, respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No significant difference was found between Group A and B (p=0.917). Opposite the iron deficiency anemia, cancer anemia is associated with an inadequate EPO response to anemia and administration of cisplatin does not lead to it further deterioration.     

Mechanisms of unexplained anemia in the nursing home

OBJECTIVES: To characterize anemia in elderly nursing home residents. DESIGN: Prospective multiinstitutional cohort study. SETTING: Five nursing homes. PARTICIPANTS: From retrospective analysis, residents found to be anemic using chart review were prospectively randomized. Of the 81 residents enrolled, 60 were anemic. MEASUREMENTS: Chart review for medical history and factors related to treatment or history of anemia, extensive laboratory evaluation for causes of anemia, and classification of anemia by two hematologists. RESULTS: Among the 60 anemic residents, the causes of anemia were idiopathic (n=27), iron-deficiency (n=14), anemia associated with chronic disease (n=8), anemia of renal insufficiency (n=6), and other (n=5). The eryrthropoietin (EPO) response to anemia was lower in residents with idiopathic anemia (IA) than in those with iron-deficiency anemia, and this correlated with renal function as estimated using calculated creatinine clearance. In this elderly population, advancing age was not correlated with lower EPO response. CONCLUSION: IA is common in nursing home residents. A lower EPO response contributes to the high prevalence of anemia in this setting and may be due, in part, to occult renal dysfunction.     

Clinical and basal aspects of anemia during antiviral therapy for hepatitis C

Background and Rationale. Anemia is a major side effect of combination therapy for chronic hepatitis C. In this study, severity, potential risk factors for and potential underlying mechanisms of anemia were evaluated.Patients and methods. 44 chronic hepatitis C patients on interferon-ribavirin treatment were included. Anemia-related parameters were measured before and during treatment. Potential changes in membrane phospholipids composition of erythrocytes of patients on anti-viral treatment and potentially increased erythrocyte susceptibility to osmotic or bile salt induced stress were explored.Results. Anemia was almost universal during treatment, with evidence of hemolysis. Decrease of Hb after six months of therapy was 2.1 ± O.I mmol/L (range -0.6-4.1). Higher pre-treatment Hb, highest ribavirin dose (1S-17.S mg/kg) and lower pre-treatment platelet level were independent risk factors for decrease of Hb. Serum erythropoietin levels increased during treatment with negative correlation to Hb levels at week 12 (r = -0.70, p = 0.002) and 24 (r = -0.72, p = 0.002). Erythrocyte membrane phospholipid composition did not differ between anemic patients and healthy controls. Also, resistance to osmotic or bile salt induced stress was normal in anemic patients. Phosphatidylserine exposure at the outer membrane leaflet did not change upon 24 hrs ex vivo incubation with pharmacological ribavirin concentration.Conclusions. Anemia is almost universal during anti-HCV treatment. The extent of anemia correlates with pre-treatment levels of thrombocytes and Hb and with high ribavirin dosing. Although we found hemolysis as contributing factor, our data do not indicate that altered membrane phospholipids composition is an important factor in pathogenesis of anemia.     

内源性促红细胞生成素对慢性心力衰竭患者预后的影响

目的了解内源性促红细胞生成素(EPO)对慢性心力衰竭(CHF)患者预后的判定价值。方法选择住院的CHF患者115例,以患者是否存活分为死亡组55例,存活组60例。另选同期住院的年龄、性别相匹配的非CHF患者67例为对照组,以便建立logEPO和血红蛋白(Hb)的回归方程。对CHF患者进行全因死亡和因心力衰竭再次入院的随访观察,测定血EPO,并进行分析。结果与存活组比较,死亡组高龄患者多、心功能(NYHA)Ⅱ级比例低、Hb降低和B型钠尿肽(BNP)水平升高(P<0.01)。Kaplan-Meier生存曲线显示,贫血的CHF患者病死率增高(RR=2.50,95%CI:1.38～4.54,P=0.002)。ROC曲线评估EPO和BNP预测CHF患者死亡的最佳界值分别为44.4 U/L和752 ug/L(P=0.036,=0.000)。年龄、Hb、BNP和NYHA对CHF患者全因死亡有独立预测价值;而男性、BNP和Hb水平对因心力衰竭再次入院有独立预测价值。贫血的CHF患者EPO是独立于Hb的全因死亡的强预测指标(RR=2.86,95%CI:1.18～6.94,P=0.020)。结论贫血是CHF患者不良预后的独立预测因素。EPO是贫血CHF患者全因死亡的独立预测指标。     

Low serum levels of prohepcidin, but not hepcidin-25, are related to anemia in familial amyloidosis TTR V30M

Familial amyloidosis TTR V30M (FAP-I) usually presents as a sensorimotor and autonomic neuropathy. Anemia was first described in this disease more than 20 years ago and classified as an anemia of chronic disease. However, so far no studies have addressed the role of inflammatory proteins in this disease. The anemia affects 24.8% of symptomatic FAP-I Portuguese patients, and is associated with low serum erythropoietin levels, independently of the presence of clinical nephropathy. In this study we evaluate the role of systemic inflammation on the erythropoietin production and anemia genesis in FAP-I. Data from 24 FAP-I patients (50% with anemia) and 33 healthy controls were analysed. Laboratory data included hemoglobin, hematocrit, ferritin, transferrin saturation, soluble transferrin receptors (sTR), prohepcidin, hepcidin-25, C-reactive protein (CRP), interleukin-6 and erythropoietin levels. In general, FAP-I patients presented significantly lower hemoglobin, hematocrit and observed/expected erythropoietin levels. Mean sTR was lower in FAP-I patients than in controls (2.36+/-1.3 vs 2.96+/-0.8 mg/l, P=0.055) correlating with hemoglobin and hematocrit. As expected, sTR were positively correlated with erythropoietin both in controls and in FAP-I patients. No significant differences on CRP, interleukin-6, transferrin saturation, ferritin and hepcidin-25 were found between anemic and non-anemic FAP-I patients and between non-anemic FAP-I patients and healthy controls. In all groups, a positive correlation was observed between hepcidin-25 and ferritin. Surprisingly, significantly lower prohepcidin levels were found in FAP-I patients, with or without anemia, not correlated with serum hepcidin-25 levels. In general, the decreased observed/expected EPO levels in FAP-I correlated with the prohepcidin levels, therefore raising the possibility that a common defect in these two hormones may be somehow involved in the genesis of the disease.     

Effects of the chemokine MIP-1alpha on anemia and inflammation in rheumatoid arthritis

Macrophage inflammatory protein-1alpha (MIP-1alpha) is an interesting chemokine because in addition to its variety proinflammatory activities including chemotaxis and immunomodulation, it is a potent inhibitor of hematopoetic stem cell proliferation. Inhibition of erythroid progenitor cells due to MIP-1alpha or other cytokines can play a role in the pathogenesis of anemia which is one of the most common extra-articular features of active rheumatoid arthritis (RA). In 84 patients with RA, serological and immunological parameters were assessed to detect inflammatory mechanisms and anemia in relation to the serum concentrations of MIP-1alpha. All patients fulfilled the ACR criteria for the diagnosis of a definite or classic RA. We used a quantitative enzyme immuno assay for the detection of MIP-1alpha as well as for the measurement of the acute phase protein serum amyloid A (SAA), the erythropoiesis inducer erythropoietin (EPO) and the transferrin receptor (TfR). The immune activation marker neopterin was measured radioimmunologically. Half of the patients with RA were anemic with hemoglobin values below 12 g/dl. MIP-1alpha was found to be elevated significantly in serum of patients with active rheumatoid arthritis and in patients with anemia. Most of the anemic patients with markedly elevated acute phase reactions had an anemia with chronic diseases and not a functional iron deficiency alone. TfR correlated with EPO. The results show that enhanced expression of MIP-1alpha is indicative of systemic inflammation in RA. Moreover, besides the regulation of inflammatory processes, this chemokine may influence the pathogenesis of anemia in RA patients.     

The relationship between iron deficiency anemia and lipid metabolism in premenopausal women

BACKGROUND/AIM: Iron deficiency and lipid metabolism disorders are common health problems. We investigated the relationship between iron deficiency anemia and lipid metabolism in premenopausal women, in whom iron deficiency anemia is not uncommon. METHODS: This prospective cohort study was carried out in 64 premenopausal women (median age of 40 years, ranging from 15 to 52) with iron deficiency anemia and 21 non-anemic control women (median age of 38 years, ranging from 28 to 50). Serum ferritin values less than 11 ng/mL and transferrin saturation below 15% were accepted as indicators of iron deficiency. All anemic patients were treated with oral iron replacement. RESULTS: The mean levels of total and low density lipoprotein cholesterol of anemic women were lower than those of non-anemic control patients (173.6 +/- 39.3 vs 205.7 +/- 36.0, P = 0.001, 105.3 +/- 32.7 vs 135.6 +/- 31.3 mg/dL, P < 0.001, respectively). Despite increasing significantly after treatment of anemia (from 173.6 +/- 39.3 to 181.6 +/- 35.2, P = 0.018, from 105.3 +/- 32.7 to 111.3 +/- 29.4 mg/dL, P = 0.029, respectively), their levels were still lower than in the control subjects (181.6 +/- 35.2 vs 205.7 +/- 36.0 mg/dL, P = 0.008, 111.3 +/- 29.4 vs 135.6 +/- 31.3 mg/dL, P = 0.002, respectively). In anemic patients, statistically significant positive correlations were found between the pre-treatment total cholesterol levels and hemoglobin (r = 0.336, P = 0.007), hematocrit (r = 0.326, P = 0.009), serum iron (r = 0.404, P = 0.001), serum ferritin (r = 280, P = 0.026), and transferrin saturation (r = 0.314, P = 0.012). The only significant factor affecting pre-treatment total cholesterol levels was serum iron. CONCLUSIONS: We hypothesize that low iron states in premenopausal women may exert an additional protective effect against atherosclerotic heart disease via lipid metabolism.     

Distribution of serum erythropoietin levels in lower risk myelodysplastic syndrome cases with anemia

International guidelines for myelodysplastic syndrome (MDS) state that the standard therapy for lower risk MDS patients with symptomatic anemia of serum erythropoietin (EPO) <500 IU/L is erythroid-stimulating agents (ESAs). The objective of this study is to examine the distribution of EPO levels in lower risk MDS patients, and to inquire into the relationship of EPO distribution to hemoglobin levels and transfusions. Twenty cases of lower risk MDS (low or intermediate-1 by the International Prognostic Scoring System) with hemoglobin level <90 g/L at our institution were enrolled. Eight received more than two units of transfusions per month. Median hemoglobin level was 78 g/L. EPO levels ranged between 26.4 and 11300 IU/L (median 645 IU/L), including 10 cases (50 %) with >500 IU/L. EPO levels were inversely correlated to hemoglobin levels, especially in the cases without transfusion support (p < 0.001, R = 0.92). The rate of the cases with EPO <500 IU/L was significantly higher in the group without transfusion than the others (p = 0.020). Considering that, in Japan, the indication for transfusion is around 70 g/L of hemoglobin for chronic diseases, it may be possible to improve anemia in a subset of lower risk MDS cases by administration of ESAs before transfusions are required.     

Recombinant human erythropoietin in cancer-related anemia: an evidence-based review

Anemia is a common complication of cancer or anticancer therapy, with a significant negative impact on the functional status of patients and their quality of life (QOL). Recombinant human erythropoietin (EPO) was developed in the 1980's and was initially developed for the treatment of anemia associated with chronic renal failure. Subsequently, randomized, placebo-controlled clinical trials in the oncology setting were performed in the early 1990's. These studies demonstrated in cancer patients that EPO could increase the levels of hemoglobin (Hb), decrease the need for red blood cell transfusions, and also suggested that these outcomes were associated with improved QOL metrics as reported by the patients themselves. Based on the results of these studies, EPO was granted regulatory approval to be used for the treatment of anemia in patients with non-myeloid malignancies where anemia was due to the effect of concomitantly administered chemotherapy. To further expand the findings of the registration studies, and to develop more complete QOL data, three similarly designed open-label community-based studies were performed, enrolling a total of approximately 7000 patients. These studies consistently demonstrated in the supportive care of cancer patients receiving chemotherapy that the use of EPO could induce increases in the levels of Hb and that these correlated with patient-reported improvements in QOL metrics. The correlation between an improvement in Hb and QOL has also been confirmed in a larger randomized, placebo-controlled trial. Careful analyses of data from this study also helped support earlier findings that EPO could be effective for patients with varying degrees of anemia, and that increasing and maintaining Hb levels close to the physiologically normal levels resulted in the optimal improvements in QOL. While further investigations of EPO as a mechanism to improve the antineoplastic efficacy of chemoradiotherapy have not yet been positive, the overall experience with this agent remains very favorable after extensive studies and long-term clinical use in oncology.