血液系统疾病（20051559-20051610）

20051559血清促红细胞生成素水平和可溶性转铁蛋白受体水平测定的意义；20051560 1-苏糖酸亚铁治疗缺铁性贫血的疗效；20051561 重组人红细胞生成素6000U每周1次治疗非透析患者肾性贫血的临床观察；2001562 rhG-CSF穴位注射治疗化疗后粒细胞减少的临床研究；20051556 血透患者深静脉导管行血液透析的临床比较；     

丙酸睾丸酮与小剂量促红细胞生成素治疗慢性肾性贫血

目的：观察丙酸睾丸酮与小剂量的重组人促红细胞生成素（rHuEPO)治疗慢性肾性贫血的临床疗效及其不良反应。方法：联用组16例患者同时使用丙酸睾丸酮（300mg/周，分3次肌肉注射）与小剂量的rHuE-PO(3000U／周，分3次皮下注射），共用6－8周；对照组16例患者采用常规剂量的rHuEPO皮下注射治疗（3000U／次，每周3次），共6－8周。治疗期间停用输知及透析等治疗措施。结果：治疗后两组患者的血红蛋白含量均升高，与治疗前比较，差异均有显著性意义（P＜0.05），两组的临床疗效差异无显著性意义（P＞0.05）；但联用组高血压的发生率明显低于对照组（P＜0.05）。结论：与常规剂量的rHuEPO相比，丙酸睾丸酮与小剂量的rHuEPO联合治疗慢性肾性贫血具有疗效肯定、副作用少等优点，是一种安全、有效的治疗方法。     

重组促红细胞生成素治疗慢性肾功能不全患者营养不良的临床价值

重组促红细胞生成素 (r Hu EPO)已广泛用于治疗肾性贫血 ,本文观察了 2 0例慢性肾衰患者使用r Hu EPO治疗后的营养状态变化 ,现报告如下。1　资料与方法1 .1　临床资料　本文 40例慢性肾功能不全合并肾性贫血患者 (男 2 4例 ,女 1 6例 ) ,年龄 2 5～ 69(48.7± 1 9.5)岁 ,均接受血液透析治疗超过 6个月 ,每周行碳酸盐透析 8～ 1 2小时。原发病为慢性肾小球肾炎 2 7例 ,高血压性肾病 9例 ,糖尿病肾病 4例。两组贫血程度、残余肾功能水平及透析治疗均无显著性差异。随机分为治疗组和对照组各 2 0例 ,治疗组给予国产重组促红细胞生成素 (益…     

促红细胞生成素治疗慢性肾功能衰竭性贫血

慢性肾功能衰竭(CRF)性贫血的原因,主要是肾萎缩所致的促红细胞生成素(EPO)的生成不足。近来我们用 EPO 治疗15例因 CRF 接受腹膜透析或血液透析患者,报告如下。材料与方法15例 CRF 患者中,男11例,女4例,接受 HD12例,CAPD3例。年龄27～63岁,平均43.5岁。除一例注射 EPO 二周后接受肾移植外,余治疗>4周,其中>14周有9例。除1例给予 EPO2000U,每周三次外,其14例用3000U,每周三次。HD 患者于透视结束时从静脉     

依倍注射液治疗肾性贫血23例疗效分析

目的 观察依倍注射液(重组人红细胞生成素)对肾性贫血患者的临床疗效及安全性。方法 23例肾性贫血患者给予依倍100IUkg周，分2—3次皮下注射，用药期间观察红细胞压积(HCT)上升到33％以上或血红蛋白(HB)超过110gL时，剂量减少14—13，维持用药，共观察12周。结果 显效14例(60．9％)；有效7例(30．4％)；无效2例(8．7％)；总有效率91．3％。依倍主要不良反应为血压升高，头痛等，未发现严重不良反应。结论：依倍治疗肾性贫血安全、有效。     

大剂量重组人促红细胞生成素治疗血透患者肾性贫血的临床疗效观察

贫血是慢性肾衰竭（CRF）患者最常见的并发症之一，其原因是体内红细胞生成素（EPO）的绝对或相对不足，补充外源性EPO可有效治疗肾性贫血，明显改善CRF患者的生活质量。目前公认的方案是NKF-K／DOQI推荐的治疗方法，但对大剂量每周一次用药尚缺乏经验。顾勇等采用大剂量EPO每周一次用药治疗肾性贫血能使患者较高的Hb水平维持于理想范围，同时具有较高的安全性。我院用大剂量rHuEPO治疗肾性贫血，以期了解其对肾性贫血的疗效及安全性。     

在线血液透析滤过联合血液透析对肾陛贫血的治疗作用

目的观察血液透析（HD）与HD联合在线血液透析滤过（online—HDF）治疗肾性贫血的临床疗效。方法将32例维持性血液透析患者随机分为HD组15例,HD＋online-HDF组17例。HD组采取维持性HD治疗,每周透析3次,每次透析4h。HD＋online—HDF组每周行online-HDF1次,HD治疗2次,时间均4h。观察6个月后两组在使用红细胞生成素（EPO）并常规补充铁剂、叶酸,维生素B12的情况下血红蛋白（Hb）、血清白蛋白（ALB）、血清铁蛋白（FER）、血清甲状旁腺激素（fyrH）、二氧化碳结合力（TCO2）及透析充分性指标（KT／V及URR）的变化。结果两组治疗后KT／V、URR、ALB、FER、PTH、TCO2比较无统计学差异（P均〉0．05）;治疗后HD＋online—HDF组Hb明显升高,与HD组比较有统计学差异（P〈0．05）。结论online-HDF联合HD治疗肾性贫血效果良好。     

左旋肉碱与促红细胞生成素联合治疗维持性血液透析患者肾性贫血的临床观察

目的观察左旋肉碱和促红细胞生成素治疗维持性血液透析患者肾性贫血的疗效，及左旋肉碱对促红细胞生成素用量的影响。方法将维持性血液透析肾性贫血患者40例随机分成两组，均于血液透析后皮下注射促红细胞生成素，剂量每周100—150U／kg，分2—3次进行，当血红蛋白（Hb）≥100g／L，红细胞压积（Hct）≥30％后逐渐减量。治疗组于每次血液透析后加用静脉注射左旋肉碱1．0g，疗程8周。结果两组患者的Hb、Hct较治疗前均有所提高（P〈0．01），治疗组提高比对照组更显著（P〈0．01），且治疗组促红细胞生成素的维持用量更少（P〈0．05）。结论左旋肉碱能显著提高促红细胞生成素治疗肾性贫血的疗效，减少促红细胞生成素的用量。     

结肠透析配合中药保留灌肠治疗慢性肾衰竭疗效观察

目的观察结肠透析配合中药保留灌肠治疗慢性肾功能衰竭的临床疗效。方法将57例慢性肾功能衰竭（CKD）患者随机分成两组,观察组32例,对照组25例。观察组应用结肠透析加中药保留灌肠治疗,每周2～3次;对照组应用传统中药保留灌肠,每周2～3次。疗程均为14 d。结果观察组显效12例,有效17例,无效3例,总有效率为90.6%;对照组显效5例,有效11例,无效9例,总有效率为64.0%,两组疗效比较差异有统计学意义（u=2.264,P=0.024）。结论结肠透析加中药灌肠治疗慢性肾衰疗效显著。     

左卡尼汀联合EPO治疗尿毒症性贫血疗效观察

目的观察左卡尼汀联合红细胞生成素（EPO）治疗尿毒症性贫血的临床效果。方法将维持性血液透析的肾性贫血患者随机分成两组,治疗组在应用EPO的同时口服左卡尼汀,对照组单用EPO。治疗12周,两组红细胞生成素初始用量均为每周150U／kg,当血红蛋白（Hb）≥100g／L,红细胞压积（Hct）≥30％时,EPO逐渐减量至维持量。结果两组Hb、Hct较治疗前均有所提高（P〈0．05）,治疗组提高比对照组更显著（P〈0．05）,且治疗组EPO的维持用量更少。结论左卡尼汀能显著提高EPO治疗尿毒症性贫血的疗效,减少EPO用量。     

Low-dose subcutaneous erythropoietin in continuous ambulatory peritoneal dialysis

We evaluated changes in hematocrit in patients on continuous ambulatory peritoneal dialysis (CAPD) before and after the administration of erythropoietin (EPO). Thirty-five patients were evaluated at the beginning of treatment with CAPD and after an average of 3.5 years on CAPD; mean hematocrit (Hct) rose from 25.4 +/- 5.4% to 28.1 +/- 6.7% (P less than 0.001). In the period before EPO administration 11 patients required a total of 44 transfusions (one patient needed 23 transfusions). Fifteen patients were started on subcutaneous erythropoietin 3,000 units 3 times a week and were followed for a mean period of 6.3 months. Hct rose from 23.8 +/- 1.8% to 25.2 +/- 2.4% (P less than 0.01) within the first 2 weeks and up to 27.5 +/- 3.7% (P less than 0.01) in the fourth week. By the eighth week the target Hct (30 to 35%) was reached. During the next 5 months the EPO doses were adjusted to each patient's needs ranging between 2,000 U per week to 4,000 U 3 times per week. Mild hypertension was the only side effect seen in some of the patients. In conclusion low dose subcutaneous EPO is effective in managing the anemia of patients on CAPD with only minor side effects.     

Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial.

We have used recombinant human erythropoietin (rHuEPO) in a phase I/II clinical trial to evaluate its ability to reverse refractory anemia in hematologic disorders. rHuEPO was administered subcutaneously 5 days per week at escalating doses (50 to 150 U/kg per day). The aim of treatment was a hemoglobin (Hb) level greater than or equal to 10 g/dL without blood transfusion. Of 25 patients treated, 17 were evaluable, most of them with a regular need for transfusion. Eight of these had lymphoproliferative disorders (three cases of malignant lymphoma and five of monoclonal gammopathy) and were exposed to cytotoxic therapy. The other nine patients had hematopoietic stem cell disorders (four cases of myelodysplastic syndrome, three of idiopathic myelofibrosis, and two of chronic myelogenous leukemia). All patients with lymphoproliferative disorder had serum EPO levels inappropriately low for the degree of anemia, while patients with stem cell disorder showed variable values. Erythroid marrow activity was inadequate in all cases. Seven of eight patients with lymphoproliferative disorder responded to treatment maintaining Hb above 10 g/dL without transfusion. The median dose of rHuEPO required for correction of anemia was 75 U/kg. In four cases response was maintained with 50 U/kg, three times per week. There was no complete response among patients with hematopoietic stem cell disorder, although transfusion requirement was eliminated or reduced in four cases. Four patients developed functional iron deficiency during rHuEPO treatment and required iron supplementation to obtain response. Aggravation of splenomegaly was observed in two cases of myeloproliferative disorder. We conclude that: (1) subcutaneous administration of rHuEPO can be effective and safe in patients with lymphoproliferative disorder exposed to chemotherapy and showing inappropriate EPO response to anemia; (2) this is less likely in hematopoietic stem cell disorders, although favorable responses may be observed in occasional patients; and (3) functional iron deficiency as a cause of nonresponse to rHuEPO is frequent also in nonrenal anemia.     

Development of a long-acting erythropoietin by fusing the carboxyl-terminal peptide of human chorionic gonadotropin beta-subunit to the coding sequence of human erythropoietin

Human erythropoietin (EPO) is a glycoprotein hormone secreted from the kidney and controls red blood cell production. EPO has a wide clinical use in the treatment of anemia associated with renal disease, certain chronic diseases, and anemia related to chemotherapy and radiotherapy. One major issue regarding the clinical use of EPO is its relatively short half-life due to its clearance by glomerular filtration. Thus, the therapeutic protocol used in the treatment of patient-required frequent injections of EPO. To address this issue, we constructed a chimeric gene that contains the sequence of the carboxyl-terminal peptide (CTP) of human chorionic gonadotropin-beta subunit bearing four O-linked oligosaccharide recognition sites and the coding sequence of human EPO cDNA. Fusing the CTP to the carboxyl-terminal of EPO did not affect secretion, receptor binding affinity, or in vitro bioactivity. However, both in vivo potency and half-life of EPO-CTP were significantly enhanced. A single injection dose (660 IU/kg) of EPO wild-type administered once a week had no significant effect on haematocrit levels. However, EPO-CTP administered as 660 IU/kg once a week was effective as well as the same total dose of EPO wild-type administered as 220 IU/kg three times a week. This may emphasize the importance of sustained blood levels rather than total dose of administration for in vivo bioactivity. These data established the rationale for using this chimera as a long-acting EPO analog. The therapeutic efficacy of EPO-CTP analog needs to be established in higher animals and human clinical trials.     

Erythropoietin can obviate the need for repeated heart valve replacement in high-risk patients with severe mechanical hemolytic anemia: case reports and literature review

BACKGROUND AND AIM OF THE STUDY: Brisk hemolysis due to perivalvular leak is usually an indication for valve re-replacement. Repeated surgery after multiple previous valve operations is associated with high mortality, morbidity and failure rates. The present study evaluated the role of erythropoietin (EPO) administration in deferring or obviating the need for repeated surgery. METHODS: Three patients (two men, one woman; age range 62-76 years) with two mechanical valves each and two to four previous heart valve operations, who suffered from severe mechanical hemolytic anemia, were given subcutaneous EPO for 15-17 months. RESULTS: A marked reduction in red blood cell consumption was achieved with a weekly EPO dose of 18,000 U in two patients, both of whom also had mild or moderate kidney malfunction. A third patient with normal renal function and extreme hemolysis showed a transient, partial response to 30,000 U of EPO per week, and eventually needed a fifth operation. CONCLUSION: EPO may defer or even obviate the need for repeated valve surgery in patients with severe hemolysis due to perivalvular leak, especially those with inadequate EPO response, such as those with renal malfunction.     

不同剂量低分子肝素治疗慢性肺源性心脏病疗效观察

目的观察不同剂量低分子肝素(LMWH)治疗慢性肺源性心脏病(慢性肺心病)的疗效及副作用。方法选取2007-04～2011-04救治的107例慢性肺心病急性加重期患者,并随机分为治疗一组(53例)和治疗二组(54例),两组患者均给予持续氧疗、抗感染、止咳、祛痰、平喘、扩血管、强心、利尿、维持水电解质平衡等综合治疗,治疗一组在此基础上加用LMWH 4250 U,皮下注射,1次/d,治疗二组加用LMWH 4250 U,皮下注射,2次/d(1次/12 h),两组均治疗7 d。比较两组治疗后的疗效和总有效率,并观察出血情况。结果 LMWH治疗后,两组的疗效和总有效率相近(P0.05),均未发生全身出血情况,但治疗二组有4例出现注射部位出血。结论在慢性肺心病急性加重期患者的治疗中,在治疗剂量固定情况下,采取1次/d给药与2次/d给药的疗效相同,且注射部位出血比例明显减少。     

红细胞生成素的临床应用

红细胞生成素（EPO）是一种调节红系造血的糖蛋白激素，EPO只有结合到红系祖细胞表面有活性的EPO受体（EPO-R）才能发挥生物效应，自1989年人类基因重组EPO（rHuEPO)成功治疗肾脏病晚期贫血后，近年来已应用于其他类型贫血的治疗，本文对EPO治疗某些贫血（癌症，自身免疫性疾病，再生障碍性贫血及骨髓增生异常综合征等）的临床应用和进展作一综述。     

The metabolism of erythropoietin in liver cirrhosis patients compared with healthy volunteers.

The purpose of the investigation was to study the metabolism of erythropoietin (EPO) in patients with liver disease. Twelve patients with liver cirrhosis and 10 healthy volunteers were studied. The patients were moderately anemic with a hematocrit of 33 vs 42% (medians) in the volunteers. The pharmacokinetic parameters were calculated after an intravenous (i.v.) injection of 100 U/kg of recombinant human EPO. The serum EPO was measured by radioimmunoassay at regular intervals until 48 h. The median terminal elimination half life in the cirrhosis patients was 5.15 h vs 5.37 h in the control subjects. The clearance was 7.78 vs 7.52 ml/min/1.73 m² (ns). The steady-state volume of distribution was 3.69 vs 3.09 1/1.73 m² (ns). The estimated endogenous EPO production was significantly higher in liver cirrhosis (486 vs 290 U/d/1.73m², p<0.01). The basal serum EPO was significantly higher in the cirrhosis patients (43.5 vs 26.3 U/***l, p<0.01). The hematocrit correlated inversely with the basal serum EPO level in the cirrhosis patients (r= -0.63, p<0.04). The EPO-clearance was not related to the presence of ascites, esophageal varices, or to abnormal blood chemistry. It was concluded that normal metabolism of EPO was maintained in liver cirrhosis and that the cirrhotic patients had a moderate compensatory increase of EPO production in response to anemia     

促红细胞生成素联用参附注射液治疗慢性心力衰竭合并贫血的临床观察

目的观察促红细胞生成素（EPO）联合参附注射液治疗合并贫血的慢性心力衰竭（CHF）的临床疗效。方法将160例合并贫血的CHF患者随机分成4组：对照组（常规治疗组）、EPO组、参附注射液组和EPO加参附注射液组,每组各40例。记录治疗前、后各组患者的心功能分级（NYHA）、明尼苏达心衰生活质量评分、左心室射血分数（LVEF）、左心室舒张末期内径（LVEDD）、血浆N末端B型利钠肽原（NT-pro-BNP）水平及血红蛋白（Hb）浓度,统计再住院率,观察不良反应。结果治疗后各组患者的心功能分级和生活质量评分均明显下降,LVEF提高,LVEDD缩小,NT-pro-BNP水平降低,Hb浓度升高,而EPO组、参附注射液组和EPO加参附注射液组的疗效较对照组又有显著提高,再住院率显著低于对照组（尸〈0．05）。各组治疗后未见明显不良反应。结论EPO联合参附注射液治疗慢性心力衰竭合并贫血能显著提高临床疗效。     

Prediction of response to erythropoietin treatment in chronic anemia of cancer [see comments]

Chronic anemia of cancer can be corrected in approximately 50% of the cases by treatment with recombinant human erythropoietin (rHuEPO). Early prediction of responsiveness would avoid the emotional and financial burden of ineffective medical intervention. Eighty patients with chronic anemia of cancer undergoing treatment with rHuEPO (150 U/kg, 3 times per week by subcutaneous injection; after 6 weeks without response, 300 U/kg) participated in this study. Response was defined as a gain of at least 2 g/dL hemoglobin (Hb) within 12 weeks. Multivariate discriminant analysis and logistic regression analysis of response were performed on routine blood tests; serum levels of EPO, iron, ferritin, transferrin, and its receptor; World Health Organization (WHO) performance status; various cytokines; neopterin; stem cell factor; C- reactive protein; and alpha 1-antitrypsin. At baseline, none of these factors showed sufficient prognostic power. The following predictive algorithm was developed: (1) If after 2 weeks of therapy both the serum EPO level is > or = 100 mU/mL and Hb concentration has not increased by at least 0.5 g/dL, unresponsiveness of the patient is very likely (predictive power, 93%); otherwise, response may be predicted with an accuracy of 80%. (2) If both the serum level of EPO is less than 100 mU/mL and Hb concentration has increased by > or = 0.5 g/dL, response is highly probable (predictive power, 95%). (3) Alternatively, a serum ferritin level of > or = 400 ng/mL after 2 weeks of rHuEPO therapy strongly indicates unresponsiveness (predictive power, 88%), whereas a level less than 400 ng/mL suggests response in 3 of 4 patients.     

Two years experience of daily self-administered subcutaneous erythropoietin

Recombinant human erythropoietin (EPO) has been used for 4 years in end-stage renal disease patients, administered intravenously 3 times a week. A study was undertaken to determine the optimal way of administration comparing 3 times weekly intravenous EPO to self-administered daily subcutaneous EPO (SADSCEPO). In a first group of 4 patients, we demonstrated that the change from 3 times weekly intravenous EPO to SADSCEPO permitted a dose reduction of 70%. In a second group of 20 patients who started the EPO therapy with the daily subcutaneous route at a median dose of 12 U/kg/day, the hematocrit increased from 20 to 30% in 4 months and remained over 30% in spite of a median dose reduction to 9 U/kg/day. The patients' acceptance of SADSCEPO was good. The mechanism allowing such a dose reduction is unknown. However, the significant reduction in median dosage requirement with the subcutaneous route should allow a greater number of patients to be treated more cost-effectively.