Erythropoiesis and erythrocyte age distribution in hemodialysis patients undergoing erythropoietin therapy

Renal anemia is caused in part by a reduced life span of red blood cells (RBCs) and by reduced erythropoietin biosynthesis in the damaged kidney. The RBC age can be determined by density gradient centrifugation and estimation of cell-age-dependent enzyme activities, as aspartate aminotransferase. The RBC age distribution influences the median density (D50) of RBCs and the blood rheology in coherence with the hematocrit. In our study, the median density was determined by Percoll density gradient centrifugation in 18 healthy subjects (D50 = 1.0674 +/- 0.0016 g/ml) and in 14 hemodialysis patients (D50 = 1.0674 +/- 0.0016 g/ml in the course of recombinant human erythropoietin (rhEPO) therapy. During the first 4 weeks of therapy, a strong rejuvenation of RBCs was observed whereby the D50 reached a minimum after 2 weeks (D50 = 1.0655 +/- 0.0022 g/ml; p less than 0.05 vs. value before therapy) and a steady state after 4 weeks (D50 = 1.0658 +/- 0.0013 g/ml; p less than 0.1 vs. value before therapy). In 5 of the patients with elevated plasma parathyroid hormone (i-PTH) concentrations greater than 10 pmol/l, a significantly (p less than 0.05) reduced amount of younger RBCs (D50 = 1.0675 +/- 0.0016 g/ml) was observed in the first 2 weeks of rhEPO therapy as compared to patients with i-PTH less than 10 pmol/l (D50 = 1.0677 +/- 0.0019 g/ml). Thus, erythropoiesis in the early phase of rhEPO therapy is strongly influenced by elevated plasma i-PTH concentrations. Therefore, a gradual increase in rhEPO doses is preferable before therapy at elevated doses with an uncontrolled increase in RBC amount.     

Serum erythropoietin levels in the elderly.

We evaluated the relationship between erythropoietin (EPO) and hemoglobin (Hb) concentrations in 156 normal subjects ranging from 60 to 98 years old. EPO was determined by a radioimmunoassay. The serum EPO concentration in subjects with Hb concentrations greater than 12.0 g/dl (26.9 +/- 15.2 mU/ml), was significantly higher than that in younger controls (15.8 +/- 5.0 mU/ml, p less than 0.001). No sex difference in serum EPO level was detected. In addition, there was an inverse semilogarithmic relationship between EPO and Hb concentrations in subjects with Hb concentrations less than 12.0 g/dl (r = -0.559, p less than 0.001). EPO concentrations in the elderly were lower than those in young subjects with iron deficiency anemia with the same Hb level. Thus, in the elderly, a high EPO concentration may be preventing a decrease in the Hb concentration. However, a decreased EPO response to low Hb concentrations may be a contributing factor in anemia in the elderly.     

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.     

Efficacy of erythropoietin on dialysis in patients with beta thalassemia minor

BACKGROUND: It is unknown whether chronic erythropoietin (EPO) treatment is able to normalize hemoglobin (Hb) levels and ameliorate cardiac remodeling avoiding blood transfusions in uremic blood transfusion-dependent patients with beta-thalassemia minor (beta-thal). METHODS: In 12 hemodialysis (HD) patients with beta-thal, requiring blood transfusions despite EPO therapy, we planned to increase Hb levels up to the target levels (11-12 g/dl) within a one-year period by administering progressively higher doses of EPO (correction phase). We also planned to maintain the Hb target for an additional year (maintenance phase). RESULTS: In the year before the study, patients required 3.3 +/- 0.9 units of packed red blood cells. At baseline, the Hb level obtained with an EPO dose of 212 +/- 73 U/kg/week i.v. was 8.2 +/- 0.8 g/dl. The EPO dose was gradually increased within the first year up to 458 +/- 78 U/kg/week at month 12 (correction phase) and then significantly tapered down during the maintenance phase (390 +/- 54 U/kg/week at month 24). During the correction phase, the Hb levels markedly increased (11.1 +/- 0.3 g/dl at month 12) and did not change in the maintenance phase. No blood transfusion was required throughout the 2 years of follow-up. Left ventricular (LV) mass index progressively decreased from the basal value of 144 +/- 12 to 124 +/- 11 g/m2 in the first year and normalized in all patients at month 24 (109 +/- 12 g/m2, p < 0.001); this occurred in the absence of any change of LV cavity volume index (<90 ml/m2). CONCLUSIONS: In HD transfusion-dependent patients with beta-thal, the administration of high EPO dose for 2 years permits the attainment and the maintenance of Hb targets without blood transfusions. This therapeutic approach permits a complete remission of concentric LV hypertrophy without any adverse effects on the vascular system.     

Erythropoietin depletion and anaemia in diabetes mellitus.

AIMS: To discover whether Type 1 diabetic patients with autonomic neuropathy might be anaemic and erythropoietin (EPO)-depleted. METHODS: Fifteen Type 1 diabetic patients with serious complications (DM-COMP) were selected because of severe symptomatic autonomic neuropathy, including significant postural hypotension. All had proteinuria from nephropathy (three microalbuminuria and 12 macroalbuminuria), but a normal serum creatinine (< 122 micromol/l). They were compared to age and duration matched Type 1 diabetic controls without autonomic neuropathy (DM-controls) and non-diabetic patients with and without hypochromic, microcytic anaemia. RESULTS: The DM-COMP patients were anaemic (mean haemoglobin (Hb) 11.1+/-1.2 g/dl), sometimes severely (minimum Hb 9.2 g/dl), compared to non-neuropathic DM-controls (Hb 13.7+/-0.7 g/dl; P < 0.001). Furthermore, EPO failed to increase in association with anaemia in the DM-COMP group compared to the progressive increase in the non-diabetic, anaemic patients (difference of regression lines P < 0.001), indicating EPO depletion in the anaemic, diabetic patients. There was no other demonstrable cause for the anaemia. Treatment with EPO in 5 DM-COMP patients led to a rapid increase in haemoglobin (range 1.7-5.0 g/dl) with improvement in wellbeing. CONCLUSION: Some Type 1 diabetic patients with autonomic neuropathy present with an EPO-depleted anaemia, which responds to treatment with EPO. This observation supports the concept of autonomic neuropathy as a cause of anaemia with EPO depletion, although the role of established renal damage cannot be excluded.     

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.     

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.     

Erythropoietin response to hypoxia in patients with diabetic autonomic neuropathy and non-diabetic chronic renal failure.

AIMS: An erythropoietin (EPO)-deficient anaemia is recognized in Type 1 diabetic patients with early nephropathy and symptomatic autonomic neuropathy (DN). The aim of this study was to determine whether the EPO response to hypoxia was deficient in order to clarify the mechanisms involved in this process. METHODS: Five Type 1 diabetic patients DN (age 39 (28-48) years (mean (range))) with EPO-deficient anaemia (haemoglobin, Hb 10.6 (9.5-12.0) g/dl, EPO 5.0 (3.2-6.5) IU/l) and early diabetic nephropathy (persistent proteinuria 1161.6 (130-2835) mg/day, serum creatinine 97.6 (63-123) micromol/l)) were compared with nine normal subjects (age 31 (24-39) years, Hb 13.4 (11.8-15.7) g/dl, EPO 7.6 (5.6-10.3) IU/l) and four patients with non-diabetic advanced chronic renal failure RF (proteinuria 2157.5 (571-4578) mg/day, serum creatinine 490.2 (406-659) micromol/l, Hb 10.3 (9.0-11.3) g/dl, EPO 4.6 (2.9-8.5) IU/l). The subjects were exposed to 6 h of hypoxia (inspired oxygen 11.6-12.6%) by breathing a gas mixture via a hood. Hourly serum EPO levels were measured. RESULTS: All groups showed a rise in EPO production after 2 h. The diabetic DN group achieved a similar maximal response to the normal subjects at 6 h (EPO 17.3 +/-5.4 vs. 17.8 +/-7.9 IU/l). The renal failure patients mounted an EPO response to hypoxia but at lower EPO levels. CONCLUSIONS: Although the DN patients have inappropriately low EPO levels for the severity of their anaemia, they can mount an appropriate EPO response to moderate hypoxia. The mechanism underlying the EPO-deficient anaemia present in some diabetic patients remains unclear.     

Which patients are more likely to benefit from postoperative shed blood salvage after unilateral total knee replacement? An analysis of 581 consecutive procedures

INTRODUCTION: Requirements for allogeneic blood transfusion (ABT) after total knee replacement (TKR) are still high (30-50%), and salvage of unwashed filtered postoperative shed blood (USB) may represent an alternative to ABT. We evaluated that patients are more likely to benefit of USB reinfusion after TKR. PATIENTS AND METHODS: Data from 581 consecutive primary TKR, managed with (reinfusion group, n = 382) or without (control group, n= 199) reinfusion of USB, were retrospectively reviewed. RESULTS: Patients from reinfusion group received 119 +/- 88 ml of red blood cells from USB, without clinically relevant incidents, and showed a lower ABT rate (30.6% vs. 8.4%, for control and reinfusion groups, respectively; P = 0.001) (transfusion trigger, haemoglobin [Hb] < 9 g/dl). Differences in ABT rate between groups were significant for all preoperative Hb levels, except for Hb < or = 12 g/dl. A lower transfusion threshold (Hb < 8 g/dl) might have further decreased ABT rate (14.6% vs. 5.2%, respectively; P < 0.001), with differences being significant for preoperative Hb between 12 and 15 g/dl. There were no differences with respect to postoperative infection rate, but patients from reinfusion group had a shorter length of hospital stay (11 +/- 4 vs. 13 +/- 4 days, respectively; P= 0.001). CONCLUSIONS: Return of USB after TKR seems to reduce the need for ABT, especially in patients with preoperative Hb between 12 and 15 g/dl. There is little benefit of USB reinfusion for patients with preoperative Hb > 15 g/dl, whereas patients with preoperative Hb < 12 g/dl would probably benefit from the combination of USB with some other blood-saving method.     

Venous hum and innominate vein flow velocity in chronic anemia: a pulsed Doppler echocardiographic study

To assess the hemodynamic correlates of the cervical venous hum in patients with chronic anemia, 14 patients (mean age; 49 years, mean hemoglobin (Hb); 7.3 g/dl) and 14 control subjects (mean age; 50 years, mean Hb; 14 g/dl) without cardiac disease were studied by auscultation, phonocardiography and Doppler echocardiography in two positions (supine and sitting). Venous hum was detected in the sitting position in 11 of the 14 anemic patients whose Hb was less than 9 g/dl, and in six anemic patients in the supine position, while venous hum was absent in the control subjects in both positions. Pulsed Doppler echocardiography with the transducer in the supraclavicular fossa revealed significantly (p less than 0.01) higher peak velocity in the innominate vein in the 11 anemic patients with venous hum (supine; 71 +/- 12, sitting; 111 +/- 24 cm/sec, mean +/- SD) than in the control subjects (supine; 46 +/- 15 sitting; 76 +/- 27 cm/sec) in both positions. Intensity of venous hum increased concomitantly with increased innominate vein flow velocity when the body position was changed from supine to sitting. Peak velocity in the innominate vein correlated significantly with Hb in all study subjects (r = 0.65, p less than 0.01). In conclusion, the cervical venous hum in patients with chronic anemia is related to the hemoglobin concentration and flow velocity in the innominate vein.     

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.     

Effect of long-term treatment with recombinant human growth hormone on erythropoietin secretion in an anemic patient with panhypopituitarism

We studied the effect of treatment with recombinant human GH in an anemic patient with panhypopituitarism in which hemoglobin (Hb) concentration remained as low as 11.0 g/dl in spite of appropriate replacement with thyroid and adrenocortical hormones. Recombinant human GH was subcutaneously and constantly infused for 12 months using a portable syringe pump at a rate of 0.25 U/kg/week. After the treatment with human GH plasma erythropoietin (EPO) levels increased from 12.2 to 25.1 mIU/ml, with a concomitant increase of Hb concentration to 13.6 g/dl. When the administration of human GH was interrupted, both plasma EPO levels and Hb concentrations decreased. There was a close correlation between plasma GH and EPO levels before and during the human GH administration (y=2.444x+1 3.423, r=0.641, p<0.05). Plasma GH levels were well correlated with Hb concentrations before and during human GH administration (y=0.529x+11.313, r=0.690, p<0.01). Plasma IGF4 levels were also correlated with Hb concentrations (y=0.007x+10.874, r=0.832, p<0.001), but not with plasma EPO levels. These findings suggest that GH treatment may be useful in anemic patients with panhypopituitarism.     

Pretreatment prediction of anemia progression by pegylated interferon alpha-2b plus ribavirin combination therapy in chronic hepatitis C infection: decision-tree analysis

Background

This study aimed to develop a model to predict the development of severe anemia during pegylated interferon alpha-2b plus ribavirin combination therapy.

Methods

Data were collected from 1081 genotype 1b chronic hepatitis C patients who were treated at 6 hospitals in Japan. These patients were randomly assigned to a model-building group (n?=?691) or an internal validation group (n?=?390). Factors predictive of severe anemia (hemoglobin, Hb?Results Hb values at baseline, creatinine clearance (Ccr), and an Hb concentration decline by 2?g/dl at week 2 were used to build a decision-tree model, in which the patients were divided into 5 subgroups based on variable rates of severe anemia ranging from 0.4 to 11.8%. The reproducibility of the model was confirmed by the internal validation group (r ²?=?0.96). The probability of severe anemia was high in patients whose Hb value was <14?g/dl before treatment (6.5%), especially (a) in those whose Ccr was <80?ml/min (11.8%) and (b) those whose Ccr was ??80?ml/min but whose Hb concentration decline at week 2 was ??2?g/dl (11.5%). The probability of severe anemia was low in the other patients (0.4?C2.5%).

Conclusions

The decision-tree model that included Hb values at baseline, Ccr, and an Hb concentration decline by 2?g/dl at week 2 was useful for predicting the probability of severe anemia, and has the potential to support clinical decisions regarding early dose reduction of ribavirin.     

Variable efficacy of recombinant human erythropoietin in anemic pregnant women with different forms of heterozygous hemoglobinopathy

OBJECTIVE: The aim of this study was to determine the response to recombinant human erythropoietin (rhEPO) in anemic pregnant women with heterozygous hemoglobinopathies. METHODS: A prospective study including 19 consecutive pregnant women with anemia and heterozygous hemoglobinopathy was performed. Treatment was divided into two phases: the initial low-dose phase and the subsequent high-rhEPO phase. In the initial phase, 3 x 10,000 U of rhEPO was administered with intravenous iron sucrose. In patients showing a poor response (Hb increase <1 g/dl) to low-dose rhEPO, the rhEPO dose was increased to 20,000 U per treatment in the subsequent phase. RESULTS: All patients showed stimulation of erythropoiesis as evidenced by an increase in hemoglobin. In 13 patients, a good response to therapy was observed (mean Hb increase 1.6 +/- 0.5 g/dl). In 6 patients, resistance to rhEPO was noted (mean Hb increase 0.5 +/- 0.5 g/dl). The mean gestational age at the start of therapy was 28 weeks of gestation and at the end 32 weeks. The mean duration of a complete therapy was 3.5 weeks (range 2-4.5 weeks). If calculated for body weight, the initial low- rhEPO dose of 160.4 +/- 30.6 U/kg body weight/treatment was increased to 320.9 +/- 61.2 U/kg body weight/treatment in the subsequent phase. CONCLUSION: Response to rhEPO treatment differs widely in anemic pregnant patients with heterozygous hemoglobinopathy. Resistance was observed in anemic pregnant patients with the beta-thalassemia trait originally from the Mediterranean region.     

Sustained long-term complete remission in an elderly aplastic anemia patient after cessation of combined therapy consisting of granulocyte-colony stimulating factor and erythropoietin

An 83-year-old woman received a diagnosis of moderate aplastic anemia in November 1990. Immunosuppressive therapy consisting of anti-lymphocyte globulin combined with high-dose corticosteroids was effective until pancytopenia developed in August 1993. The patient was hospitalized again and recurrence of aplastic anemia was diagnosed on the basis of hematologic findings, including RBC 129 x 10(4)/microliter, Hb 5.5 g/dl, Ret 23,200/microliter, WBC 2,200/microliter with 27% neutrophils, platelets 2.2 x 10(4)/microliter, and hypoplastic bone marrow. Recombinant human granulocyte-colony stimulating factor (G-CSF) of 125 micrograms/day combined with recombinant human erythropoietin (EPO) of 6,000 U/day were started in November 1993. The doses of G-CSF and EPO were increased to 250 micrograms/day and 12,000 U/day, respectively. We stopped combination therapy in March 1995, after trilineage hematopoietic cell recovery had been achieved. Complete recovery in peripheral blood was sustained for more than 2 years despite the termination of G-CSF and EPO therapy. Combination therapy with G-CSF and EPO may be safe and effective for elderly patients with aplastic anemia when the choice of therapy is limited.     

Lipid peroxidation and antioxidant enzyme levels in type 2 diabetics with microvascular complications

Serum levels of total cholesterol, triglycerides, lipoproteins, lipid peroxides (TBARS) and erythrocyte antioxidant enzyme activities were measured in 105 non insulin dependent diabetic patients, among whom 38 had microvascular complications (MVC) of diabetes. All the diabetic patients had higher concentrations of glycated hemoglobin (HbA1) compared to controls (10.51 +/- 2.42% vs 6.31 +/- 0.85% P <0.001). Significant increase of serum triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) and a significant decrease of high density lipoprotein cholesterol (HDL-C) were observed in the diabetic patients compared to controls (TG: 2.31 +/- 0.9 mmol/l vs 1.53 +/- 0.48 mmol/l P <0. 001; TC: 5.94 +/- 1.4 mmol/l vs 4.3 +/- 0.85 mmol/l P <0.001; LDL-C: 3.96 +/- 1.33 mmol/l vs 2.39 +/- 0.8 mmol/l P <0.001; VLDL-C: 0.46 +/- 0.2 mmol/l vs 0.3 +/- 0.09 mmol/l P <0.001; HDL-C: 0.81 +/- 0.24 mmol/l vs 1.04 +/- 0.18 mmol/l P <0.001). Significantly increased levels of serum TBARS were observed in diabetic patients compared to those in controls (TBARS: 6.7 +/- 1.5 mmol/l vs 5.14 +/- 0.61 mmol/l P <0.001). Erythrocyte catalase (CAT) activity was increased and Glutathione peroxidase (GPx) activity was decreased in diabetic patients compared to controls, but no significant change in Superoxide dismutase (SOD) activity was observed in diabetic patients (CAT: 104.94 +/- 37.1 KU/g Hb vs 85.8 +/- 23.6 KU/g Hb, P <0.01; GPx: 30 +/- 9.7 U/g Hb/min vs 40.84 +/- 12.3 U/g Hb/min, P <0. 001; SOD: 2.4 +/- 1.2 U/mg Hb/min vs 2.55 +/- 0.84 U/mg Hb/min, P=NS). In comparison with the diabetic group without MVC, the diabetic group with MVC had decreased GPx and SOD activities, while no difference was observed between these two groups regarding CAT activity (GPx: 25.32 +/- 8.4 U/g Hb/min vs 34.5 +/- 8.8 U/g Hb/min, P <0.001; SOD: 1.83 +/- 0.53 U/mg Hb/min vs 2.84 +/- 1.4 U/mg Hb/min, P<0.001; CAT: 106.3 +/- 39.9 KU/g Hb vs 103 +/- 34.9 KU/g Hb, P =NS). TBARS concentrations were significantly increased in the group with MVC compared to the group without these complications, indicating a positive relationship between TBARS and MVC of diabetes (7.05 +/- 1.23 mmol/l vs 6.3 +/- 1.02 mmol/l, P <0.001). Serum triglycerides, LDL and VLDL cholesterol concentration were significantly higher in diabetics with MVC than in diabetics without the complications (TG: 2.7 +/- 0.98 mmol/l vs 2.13 +/- 0.82 mmol/l, P<0.01; LDL - C: 4.45 +/- 1.3 mmol/l vs 3.67 +/- 1.3 mmol/l, P <0. 02; VLDL-C: 0.53 +/- 0.19 mmol/l vs 0.43 +/- 0.16 mmol/l, P <0.01), and the serum levels of TC in the group with MVC showed a positive correlation with their lipid peroxide levels (r =0.368, P <0.001). The increase in TBARS and the decreased GPx and SOD activities in diabetics with MVC in this study indicate that these factors may contribute to the occurrence of micro vascular complications in NIDDM patients.     

Prevalence of anemia in patients admitted to hospital with a primary diagnosis of congestive heart failure

OBJECTIVES: To find the prevalence of anemia in patients hospitalized with the primary diagnosis of congestive heart failure (CHF). BACKGROUND: There is growing evidence that anemia is common in CHF and may contribute to the high morbidity and mortality associated with this condition. However, there is considerable disagreement about the prevalence of anemia in this condition. METHODS: In 338 consecutive patients who were admitted to the medical wards with a primary diagnosis of CHF we extracted from the charts the hemoglobin (Hb), serum creatinine, age, sex, New York Heart Association (NYHA) functional class, presence of smoking, diabetes, hypertension, hyperlipidemia and the primary cardiac etiology of the CHF. Anemia was considered to be present when the Hb on admission was <12 g/dl. RESULTS: All the patients were NYHA functional class III-IV. One hundred seventy seven (52.4%) of the 338 patients had a Hb on admission that was <12 g/dl. The mean Hb for the entire group was 12.0+/-1.8 g/dl. One hundred three (51.0%) of the 202 males were anemic compared to 74 (54.4%) of the 136 women. The mean serum creatinine was 1.7+/-1.1 mg/dl. The prevalence of renal insufficiency (serum creatinine >1.5 mg%) was 47.6%. There was a negative correlation between the level of serum creatinine and Hb (r=-0.294) P<0.00001. Of the 177 patients who were anemic, most of 114 (64.4%) had a serum creatinine >1.5 mg/dl. CONCLUSIONS: Anemia is a common finding in patients hospitalized with CHF and most anemic CHF patients have some degree of renal insufficiency. In view of the negative effect of anemia on cardiac function, it may be a common and important contributor to the mortality and morbidity of CHF in these patients.     

Serum erythropoietin levels in anaemic patients with advanced human immunodeficiency virus infection

This study attempts to evaluate the adequacy of the erythropoietin (EPO) response in 42 anaemic patients with advanced human immunodeficiency virus (HIV) infection [30 with acquired immunodeficiency syndrome (AIDS) and 12 with AIDS-related conditions] by comparing their serum EPO levels with those found in a non-HIV reference population consisting of 36 patients with anaemia of chronic disorders (ACD) and 57 with iron deficiency anaemia (IDA). Although the average Hb concentration was similar in the three groups, the EPO level for HIV patients (mean +/- SEM, 64.3 +/- 7.7 mU/ml) did not differ significantly from that in ACD patients (45.3 +/- 8.3 mU/ml, P > 0.1), and both groups had a lower mean EPO level (P < 0.05 and P < 0.01 respectively) than IDA subjects (133.5 +/- 18.7 mU/ml). Thirteen HIV patients on zidovudine therapy showed similar mean Hb and EPO levels to those in the untreated patients. A significant inverse correlation between the log of serum EPO and the Hb values was observed in the three groups. However, this relationship was found to be stronger in IDA patients than in either HIV or ACD subjects (P < 0.001), with no difference between the two latter groups (P > 0.2). These data suggest that the EPO response is blunted in the anaemia associated with advanced HIV infection.     

Relationship between resistance to erythropoietin and high anomalous hemoglobin levels in hemodialysis patients with beta-thalassemia minor

In dialysis patients beta-thalassemia is a cause of resistance to erythropoietin (EPO). The aim of the present study is to evaluate the relationship between the amount of circulating anomalous hemoglobin chain and EPO resistance in hemodialysis. Ten hemodialyzed patients with beta-thalassemia minor were studied. The mean hemoglobin level was 9.22 +/- 0.91 g/dl, the HbA2 ranging between 5.6 and 6.8%; the weekly EPO dose was 13,500 +/- 7,185 IU/week and significantly correlated with HbA2 (r = 0.965; p = 0.0001). When stratifying patients in two groups according to HbA2 level (LOW <6%, n = 4; HIGH >6%, n = 6; HbA2 levels, respectively, 5.7 +/- 0.1 and 6.4 +/- 0.3 g/dl, p = 0.002), it was evidenced that the need of EPO was 13,200 +/- 3,033 IU/week in LOW and 36,167 +/- 13,060 IU/week in HIGH (p < 0.001). The EPO Resistance Index in the two groups was 13.4 +/- 4.1 IU/kg BW/week/g Hb in LOW and 21.9 +/- 10.0 in HIGH (p < 0.05). No differences were evidenced between the two groups regarding age, dialysis, body weight, serum levels of urea nitrogen, creatinine, albumin, C-reactive protein, aluminum, ferritin, transferrin and parathyroid hormone. In conclusion, in patients with beta-thalassemia minor on chronic hemodialysis, the amount of anomalous hemoglobin chain directly correlate with EPO dose, strongly indicating the magnitude of resistance to erythropoietin.