Patient blood management (PBM) is an evidence-based, patient-focused approach to optimize the management of patient and blood transfusion. While PBM is relatively well established in perioperative care, it is not as well established in the medical field. Since anemia in medical patients is heterogeneous and complex in its pathogenesis, the evidence for the threshold of hemoglobin for red blood cell (RBC) transfusion and the use of erythropoiesis-stimulating agents (ESAs) is not strong. While anemia seems to be an adverse risk factor for mortality, it is uncertain if rapid correction of anemia through RBC transfusion can reverse the negative impact of anemia on clinical outcomes. The introduction of ESA is a breakthrough in reducing RBC transfusion and managing anemic patients with renal disease and cancer. Despite promising results from early trials, the United States Food and Drug Administration issued a black box warning for ESAs in 2007 because of concerns about higher mortality, serious cardiovascular and thromboembolic events, and tumor progression. Therefore, the individualized approach to each patient with anemia is recommended in various medical conditions such as acute coronary syndrome, heart failure, chronic kidney disease, and malignancies.
Acute Coronary Syndrome ; Anemia ; Blood Transfusion ; Drug Labeling ; Erythrocytes ; Erythropoietin ; Heart Failure ; Humans ; Iron ; Mortality ; Perioperative Care ; Renal Insufficiency, Chronic ; Risk Factors ; United States Food and Drug Administration

OBJECTIVETo evaluate preoperative application of recombinant human erythropoietin (rHuEPO) in reducing transfusion requirements in elderly patients undergoing elective surgery for femoral intertrochanteric fractures.

METHODSFrom January 2011 to December 2013,442 cases of elderly patients with femoral intertrochanteric fracture were retrospectively reviewed. According to inclusion and exclusion criteria, 119 cases were eventually included and divided into the treatment group and the control group. There were 12 males and 40 females, with a mean age (71.4 ± 12.8) years old, and the patients received preoperative administration of rHuEPO 10,000 U qod combined with iron dextran 200 mg (3 times each day). While 16 males and 51 females in control group, with a mean age (70.9 ± 16.2) years old, and the patients only received preoperative administration of iron dextran 200 mg (3 times each day). All the patients received closed reduction and PFNA-II or Internal fixation surgeries. The perioperative blood transfusion rate, average amount of blood transfusion, postoperative complications, the length of hospital stay and mortality within 30 days were compared between the two groups.

RESULTSThere were no statistical differences between two groups in the baseline indexes (P > 0.05). Overall,71 of 119 patients (59.7%) received at least one unit allogeneic blood transfusion (ABT). However,there were significant differences in perioperative ABT rates (48.1% vs 68.7%, χ2 = 4.77, P < 0.05) and the average amount of blood transfusion between treatment group and control group, which were (1.8 ± 0.4) U/pte vs (3.6 ± 1.1) U/pte (t = 2.244, P < 0.05). Postoperative hemoglobin (Hb) on postoperative days 7 and 30 was higher in treatment group than that in control group. In addition, in treatment group, Hb levels were higher on postoperative day 30 than those on admission, which were (128.2 ± 20.6) g/L vs (118.2 ± 18.9) g/L (t = 2.133, P < 0.05). There were no statistical differences in postoperative complications, the length of hospital stay and mortality within 30 days.

CONCLUSIONFor elderly patients with femoral intertrochanteric fractures undergoing elective surgery, preoperative application of rHuEPO can significantly reduce perioperative transfusion requirements, and is likely to reduce ABT-related infection, but its long-term safety remains to be evaluated.

Aged ; Aged, 80 and over ; Blood Transfusion ; Case-Control Studies ; Erythropoietin ; administration & dosage ; Female ; Femoral Fractures ; blood ; surgery ; therapy ; Fracture Fixation, Internal ; Hemoglobins ; analysis ; Hip Fractures ; blood ; surgery ; therapy ; Humans ; Male ; Preoperative Care ; Retrospective Studies

OBJECTIVETo investigate the efficacy and impact factors in lower-risk [International prognostic scoring system (IPSS) low or intermediate-1 risk] myelodysplastic syndrome (MDS) patients treated with recombinant human erythropoietin (rhEPO) alone or in combination with recombinant human granulocyte colony- stimulating factor (rhG-CSF).

METHODSA total of 52 consecutive lower-risk MDS patients received subcutaneous injection of rhEPO alone or in combination with rhG-CSF at least 8 weeks, the rhEPO dose would be reduced slowly to stop or kept at minimum to maintain the response when the best efficacy achieved and maintained for 4 weeks. Their clinical features, efficacy, survival and the predictors of efficacy were analyzed retrospectively.

RESULTSThe overall response rate was 51.9% (27/52) with 33.3%(9/27) achieving complete remission (CR) and 66.7%(18/27) achieving erythroid response (HI-E). In multivariate analysis, sEPO level (less than 500 U/L), BFU-E count (more than 25/10⁵ BMMNC), intermediate and high doses rhEPO±rhG-CSF therapy were independent predictors of better response. The median therapy period was 8(2-45) months and the median efficacy duration was 37(6-94) months (38 months for CR, 36 months for HI-E). Ten of the 27 responsive patients relapsed and 40% of them had disease progressions. Hemoglobin levels and karyotype affect response duration. Median overall survival was 47(6-114) months on a 37(6-114) months median follow-up. In multivariate analysis, ages (less than 60 years old), karyotype (good or intermediate) and response to rhEPO±rhG-CSF therapy may have a favorable survival impact on MDS.

CONCLUSIONrhEPO, alone or in combination with rhG-CSF, is a useful drug for the treatment of anemia in lower-risk MDS patients and has favorable impact on life expectancy.

Adult ; Aged ; Aged, 80 and over ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; therapy ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult

This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections prevents acute mountain sickness (AMS). This open-label, randomized, controlled trial involved 39 healthy volunteers with hemoglobin < or =15.5 g/dL who were divided randomly into erythropoietin (n=20) and control (n=19) groups. Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks. On day 1, and 7 days after the last injection (day 29), oxygen saturation (SaO2), and hemoglobin were measured. The subjects departed Seoul on day 30 and arrived at Annapurna base camp (ABC, 4,130 m) on day 34. AMS was diagnosed when headache and Lake Louise score (LLS) of > or =3 were present. Immediate descent criteria followed US Army recommendations. Two groups differ in hemoglobin levels on day 29 (15.4+/-1.1 vs 14.2+/-1.0 g/dL, P=0.001). At ABC, erythropoietin group had a significantly lower mean LLS, AMS incidence, and number of subjects who met immediate descent criteria. Multiple logistic regression analysis showed that SaO2<87% and control group, but not hemoglobin<15.0 g/dL, independently predicted satisfaction of immediate descent criteria. Erythropoietin-related adverse effects were not observed. In conclusion, erythropoietin may be an effective prophylaxis for AMS.(Clinical Trial Registry Number; NCT 01665781).
Acute Disease ; Adult ; Altitude Sickness/diagnosis/epidemiology/*prevention & control ; Blood Pressure/physiology ; Drug Administration Schedule ; Erythropoietin/*therapeutic use ; Female ; Headache/physiopathology ; Hemoglobins/analysis ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Oxygen/blood ; Questionnaires ; Recombinant Proteins/therapeutic use

The protective effect of erythropoietin (EPO) on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing endotoxin-induced organ damage. Rat model of multiple organ failure (MOF) was established by tail vein injection of 10 mg/kg lipopolysaccharide (LPS). Recombinant human EPO treatment (5000 U/kg) was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN) and creatinine (Cr), were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α) were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ultrastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein expression levels were detected by using Western blotting. EPO treatment showed a modest effect in preventing LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-α levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase (AKT) and increased nuclear factor-κB (NF-κB) activation in the lung, liver, and kidney (P<0.05 vs. control). However, EPO treatment significantly decreased the LPS-induced pAKT up-regulation in these tissues (P<0.05 vs. LPS treatment alone). The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Blotting, Western ; Creatinine ; blood ; Endotoxins ; Erythropoietin ; administration & dosage ; genetics ; pharmacology ; Injections, Intravenous ; Kidney ; drug effects ; metabolism ; ultrastructure ; Lipopolysaccharides ; Liver ; drug effects ; metabolism ; ultrastructure ; Lung ; drug effects ; metabolism ; ultrastructure ; Male ; Microscopy, Electron, Transmission ; Multiple Organ Failure ; blood ; chemically induced ; prevention & control ; NF-kappa B ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Recombinant Proteins ; administration & dosage ; pharmacology ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVEOxygen toxicity is thought to be a major contributing factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Animal experiments reveal that erythropoietin (EPO) may have protective effects against hyperoxic lung injury, but the mechanisms remain unknown. The aim of this study was to evaluate effects of hyperoxia on erythropoietin receptor expression in lung development of neonatal rats.

METHODSSeveral litters of Wistar pups were pooled together within 12 hours after birth and randomly divided into two groups (n = 24 in each): air-exposed control group and hyperoxia-exposed group. In hyperoxia-exposed group, the rats were exposed to 85% oxygen. Pups (n = 8) from each group were sacrificed on postnatal days 3, 7, and 14. The pulmonary histological and morphometric changes were observed after hematoxylin-eosin (HE) staining under light microscope. Radical alveolar counts (RAC) were compared between the two groups to evaluate the differences of alveolarization. Expressions of platelet endothelial cell adhesion molecule-1 (PECAM-1) and erythropoietin receptor (EPOR) in lung tissue were measured by immunohistochemistry. Expressions of EPOR mRNA and EPOR protein were measured by RT-PCR and Western blotting.

RESULTSIn hyperoxia-exposed group, there were a few inflammatory cells infiltration in interstitium on day 3 and inflammatory response worsened on day 7. Alveolar and capillary hypoplasia and interstitial fibrosis were evident on day 14. RAC increased in air-exposed control group along with the age in days. RAC decreased from day 7 in hyperoxia-exposed group compared with air-exposed control group [(6.85 ± 1.04) vs. (7.33 ± 1.0), P < 0.01], which was more evident on day 14 [(6.20 ± 1.58) vs. (9.07 ± 0.69), P < 0.001]. Expression of PECAM-1 protein increased in air-exposed control group along with the age in days. But in hyperoxia-exposed group, it decreased on day 7 and 14 [(15.14 ± 1.51) vs. (31.47 ± 2.43), (11.04 ± 1.76) vs. (41.41 ± 3.83), P < 0.001] compared with air-exposed control group. Expression of EPOR on day 3 in air-exposed control group was the strongest and weakened gradually with the increase of postnatal days. Expression of EPOR in hyperoxia-exposed group decreased on day 3 and became more evident on day 7 and day 14 compared with air-exposed control group [(1.62 ± 0.04) vs. (1.82 ± 0.06), P < 0.05; (0.48 ± 0.01) vs. (1.10 ± 0.07), (0.39 ± 0.04) vs. (0.87 ± 0.03), P < 0.001]. Expression of EPOR mRNA on day 3 in air-exposed control group was the strongest and was decreased significantly in hyperoxia-exposed group compared with air-exposed control group at all time points [(0.87 ± 0.07) vs. (1.1 ± 0.17), (0.18 ± 0.07) vs. (0.36 ± 0.08), P < 0.01;(0.14 ± 0.05) vs. (0.36 ± 0.09), P < 0.001].

CONCLUSIONSEPOR may participate in the modulation of normal lung development. Depressed expression of EPOR and PECAM-1 may be involved in the pathogenesis of alveolar and capillary hypoplasia induced by hyperoxia.

Animals ; Animals, Newborn ; Disease Models, Animal ; Female ; Lung Injury ; etiology ; metabolism ; Male ; Oxygen ; administration & dosage ; adverse effects ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Pulmonary Alveoli ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Receptors, Erythropoietin ; metabolism

Erythropoietin combined with parenteral iron sucrose therapy is an alternative to blood transfusion in anemic patients. It was shown to be effective in surgical patients in several previous studies when used in conjunction with other methods. However, there are no guidelines about safety limits in dosage amounts or intervals. In this study, we report a case of significant postoperative hemorrhage managed with high dose parenteral iron sucrose, low dose erythropoietin, vitamin B12, vitamin C, and folic acid. An 80-year-old female patient presented for severe anemia after a total hip arthroplasty and refused an allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2 g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of intravenous iron sucrose was given postoperatively for 6 consecutive days. Erythropoietin was also administered at 2,000 IU every other day for a total of 12,000 IU. The patient was discharged in good condition on the twelfth postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL on the twentieth postoperative day.
Aged ; Aged, 80 and over ; Anemia/*drug therapy ; Arthroplasty, Replacement, Hip/*adverse effects ; Blood Transfusion ; Drug Therapy, Combination ; Erythropoietin/*administration & dosage ; Female ; Ferric Compounds/*administration & dosage ; Humans

OBJECTIVETo compare the effect on erythropoietin (Epo) resistance between acupoint injection and subcutaneous injection of rHuEpo in patients with chronic renal failure (CRF).

METHODSThirty-eight cases were randomly divided into two groups, 19 cases in each one. In subcutaneous injection group (control group), subcutaneous injection of rHuEpo was administered, 3 times a week, lasting 2 months. In acupoint group (observation group), rHuEpo was injected on unilateral Shenshu (BL 23) and Zusanli (ST 36), one point was chosen each time, the bilateral acupoints were injected alternatively, 3 times a week, for 2 months. Meanwhile, a normal control group of 19 healthy persons was set up. The levels of CRP, IL-6, TNF-alpha, Scr, BUN, Hb, Hct and SF were observed.

RESULTSBefore treatment, the values of CRP, IL-6 and TNF-alpha in two groups were all higher than those in normal control group (all P < 0.01). After treatment for 2 months, the values of CRP, IL-6,TNF-alpha, Scr and BUN in two groups decreased apparently and those of Hb, Hct and SF increased obviously, indicating statistic significant differences as compared with the values before treatment separately (P < 0.05, P < 0.01). In comparison between two groups after treatment, every index above in observation group was improved much significantly (P < 0.05, P < 0.01).

CONCLUSIONAcupoint injection of rHuEpo at Zusanli (ST 36) and Shenshu (BL 23) increases significantly the values of Hb, Hct and SF, and decreases apparently the values of BUN, Scr and inflammatory factors, such as CRP, IL-6 and TNF-alpha as compared with subcutaneous injection. Acupoint injection improves Epo resistance and enhances Epo efficacy via alleviating micro-inflammatory state of the body.

Acupuncture Points ; Adult ; Aged ; Drug Resistance ; Erythropoietin ; administration & dosage ; Female ; Humans ; Inflammation Mediators ; blood ; immunology ; Injections, Subcutaneous ; Interleukin-6 ; blood ; immunology ; Kidney Failure, Chronic ; blood ; drug therapy ; immunology ; Male ; Middle Aged ; Recombinant Proteins ; Tumor Necrosis Factor-alpha ; blood ; immunology

OBJECTIVETo investigate the effect of intranasal administration of low dosage recombinant human erythropoietin (r-HuEPO) on seizure in rats.

METHODSAfter intranasal or intraperitoneal administration of r-HuEPO, the behavioral and electroencephalographic changes were observed in pentylenetetrazol (PTZ) and maximal electroshock (MES) induced seizure or electrical amygdaloid-kindled seizure of rats.

RESULTIntranasal administration of low dosage r-HuEPO increased the seizure latency, and decreased the seizure grade and duration, and the number of convulsive episodes in PTZ induced seizure, with the most potential dosage of 2.4 IU. Intraperitoneal administration of r-HuEPO (3 000, 4 000 IU/kg) only decreased the seizure duration and number of convulsive episodes. The seizure grade, forelimb or hindlimb extension duration were decreased in MES-induced seizure by intranasal administration of 2.4 IU r-HuEPO. In addition, intranasal administration of 2.4 IU r-HuEPO decreased the seizure grade, generalized seizure duration and afterdischarge in electrical amygdaloid-kindled rats stimulated with generalized seizure threshold.

CONCLUSIONIntranasal administration of low dosage r-HuEPO can inhibit the seizure in rats.

Administration, Intranasal ; Animals ; Anticonvulsants ; administration & dosage ; Epilepsy ; chemically induced ; drug therapy ; Erythropoietin ; administration & dosage ; Humans ; Male ; Pentylenetetrazole ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins

5-Lipoxygenase inhibitor and human recombinant erythropoietin might accelerate renal recovery in cisplatin-induced acute renal failure rats. Male Sprague-Dawley rats were randomized into four groups: 1) normal controls; 2) Cisplatin group-cisplatin induced acute renal failure (ARF) plus vehicle treatment; 3) Cisplatin+nordihydroguaiaretic acid (NDGA) group-cisplatin induced ARF plus 5-lipoxygenase inhibitor treatment; 4) Cisplatin+erythropoietin (EPO) group-cisplatin induced ARF plus erythropoietin treatment. On day 10 (after 7 daily injections of NDGA or EPO), urea nitrogen and serum Cr concentrations were significantly lower in the Cisplatin+NDGA and Cisplatin+EPO groups than in the Cisplatin group, and 24 hr urine Cr clearances were significantly higher in the Cisplatin+EPO group than in the Cisplatin group. Semiquantitative assessments of histological lesions did not produce any significant differences between the three treatment groups. Numbers of PCNA(+) cells were significantly higher in Cisplatin, Cisplatin+NDGA, and Cisplatin+EPO groups than in normal controls. Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration.
Animals ; Arachidonate 5-Lipoxygenase/administration & dosage ; Blood Urea Nitrogen ; Cisplatin/*toxicity ; Creatinine/urine ; Epithelial Cells/drug effects ; Erythropoietin/administration & dosage/*therapeutic use ; Kidney/metabolism ; Kidney Failure, Acute/*chemically induced/*drug therapy ; Kidney Tubules/drug effects ; Male ; Nordihydroguaiaretic Acid/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Regeneration