阿加曲班与肝素在维持性血液透析患者抗凝治疗中的比较

目的 比较两种不同的抗凝方法在维持性血液透析(hemodialysis,HD)患者中的抗凝效果以及对患者凝血功能的影响.方法 选取40例维持性血液透析患者,先后采用不同的抗凝剂,一次使用肝素抗凝(肝素组),一次使用阿加曲班抗凝(阿加曲班组).监测患者治疗前血路管动脉端、治疗中2h血路管动、静脉端、治疗结束后1h活化部分凝血活酶时间(activated partial thromboplastin time,APTT),治疗过程中管路和透析器凝血情况,治疗后穿刺点压迫止血平均时间及组织器官24h内有无出血情况(包括鼻出血、牙龈出血、结膜出血、皮下出血点和黑便等).结果 阿加曲班组HD治疗中APTT明显延长,达到HD抗凝治疗要求,与HD治疗前相比,差异有统计学意义(P＜0.01);阿加曲班组与肝素组相比,治疗中2h及治疗后1h的APTT差异有统计学意义(P＜0.01);阿加曲班组与肝素组治疗中管路和透析器凝血情况比较差别不大,两组差异无统计学意义(P＞0.05);阿加曲班组与肝素组治疗后穿刺点压迫止血平均时间比较差异有统计学意义(P＜0.01);阿加曲班组治疗后组织器官出血较肝素组明显减少,两组比较差异有统计学意义(P＜0.05).结论 阿加曲班在HD抗凝治疗中抗凝效果确切,出血风险较普通肝素少,安全性高,尤其适用于有出血倾向的HD患者.     

阿加曲班对儿童血液透析抗凝疗效和安全性的观察

目的：以肝素为对照组,探讨阿加曲班在儿童血液透析中的抗凝疗效及安全性。方法：选取79例血液透析儿童随机应用阿加曲班和普通肝素作为血液透析抗凝剂。阿加曲班首次给药剂量为0.05～0.08mg/kg,透析前1h静脉给入,维持剂量为0.05～0.08mg·kg-1·h-1,透析结束前0.5h停用;普通肝素首次给药剂量为0.35～0.5mg/kg,维持剂量为0.05～0.15mg·kg-1·h-1,透析结束前0.5h停用。采用评分方法评价透析器及管道凝血、股静脉置管处出血和血肿情况,并比较透析前后凝血酶原时间（PT-S）、部分凝血活酶时间（APTT）。结果：与普通肝素组比较,阿加曲班组透析器和管路凝血情况差异无统计学意义,但是,股静脉置管处出血情况阿加曲班组显著降低（P〈0.05）,在相同透析器凝血情况下,透析3h后阿加曲班组APTT和PT-S值显著降低（P〈0.01）。阿加曲班组无出血事件发生,且使用剂量远低于血液净化标准操作规程（2010版）推荐剂量。结论：与普通肝素相比较,阿加曲班用于儿童血液透析疗效好且更安全。因此,阿加曲班可能成为儿童血液透析抗凝的首选药物。     

枸橼酸钠与阿加曲班在血液透析患者抗凝治疗中的效果比较

目的 比较枸橼酸钠与阿加曲班在血液透析患者抗凝治疗中的疗效及安全性.方法 12例存在出血倾向的血液透析患者采用数字表法随机分为2组,每组6例.阿加曲班组予2.5mg/h阿加曲班泵入,提前半小时停泵;枸橼酸钠组予4％枸橼酸钠200 ml/h动脉端泵入,维持至透析结束.透析过程中观察患者有无不适症状(包括发热、头痛、恶心、口唇发麻、手足抽搐、心室颤动或停搏)、心率、血压;监测透析中静脉压、动脉压变化.透析前、后检测患者外周血凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、离子(钾、钠、钙、磷)浓度、血气分析(pH值)情况.透析结束后观察透析器、动静脉壶凝血及患者出血情况,透析器凝血分为3度,Ⅰ°为透析器＜ 1/3出现凝血;Ⅱ°为透析器1/3 ～ 2/3出现凝血;Ⅲ°为透析器＞2/3出现凝血、动静脉壶根据有无血凝块监测.结果 (1)阿加曲班组1例出现头痛症状,其他无明显不适症状出现;透析中心率、血压、透析中动脉压及静脉压两组比较差异无统计学意义.(2)两组透析前PT、APT、PH、BE及离子钾、钠、钙、磷无明显差异;透析后阿加曲班组PT及APTT较透析前及枸橼酸组均明显延长,差异有统计学意义(P＜0.05).与透析前相比,透析后两组pH值及离子钙显著增高,离子钾、磷均显著下降,差异有统计学意义(P＜0.05);透析后枸橼酸钠组与阿加曲班组pH值及离子钾、钠、钙、磷无明显变化,差异无统计学意义.(3)透析结束后,枸橼酸钠组有1例出现透析器Ⅰ°凝血,无动静脉血凝块;阿加曲班组透析器有3例出现Ⅰ°凝血、1例出现Ⅱ°凝血、2例出现动静脉血凝块,两组比较差异无统计学意义.枸橼酸钠组患者透析后无出血倾向,阿加曲班组4例出现出血倾向,其中2例为伤口渗血、2例为原有出血加重,两组比较差异有统计学意义(P＜0.05).结论 阿加曲班与枸橼酸抗凝均是安全、可行的方法,且易于掌握,两者相比,枸橼酸不增加透析后的出血风险,是更为理想的血液透析抗凝方法.     

简化法局部枸橼酸与阿加曲班抗凝在高危出血风险血液透析患者中的对比观察

目的观察简化法局部枸橼酸抗凝(simplified-regional citrate anticoagulation,S-RCA)与小剂量阿加曲班(Argatroban)抗凝在高危出血风险维持性血液透析(maintenance hemodialysis,MHD)患者中的抗凝效果。方法选取空军特色医学中心血液净化中心2017年2月至2019年5月具有活动性出血或出血倾向的32例血液透析患者,随机分为S-RCA组(A组),阿加曲班组(B组)。A组在体外循环管路起始端持续泵入4%枸橼酸至透析结束,静脉壶不追加枸橼酸,静脉回路不补钙,B组在滤器前持续泵入小剂量阿加曲班(0.69μg·kg~(-1)·min~(-1))至透析结束,两组均使用含钙(1.5 mmol/L)透析液。观察透析充分性、滤器和静脉壶抗凝有效率、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)及滤器前后游离钙(iCa~(2+))变化,记录不良反应及出血事件。结果 (1)两组患者均顺利完成4 h血液透析治疗,两组透析充分性Kt/v无明显差异(1.33±0.16 vs 1.26±0.06,P=0.129)。(2)A组与B组滤器抗凝有效率无统计学差异(P=0.600),静脉壶抗凝有效率A组优于B组(93.75%vs 56.25%,P=0.037)。(3)B组透析后APTT较A组明显延长(40.4±8.2 vs 28.8±1.6,P0.001),B组透析2h滤器前、后及透析后APTT较同组透析前均延长(40.0±4.8 vs 39.8±7.2,40.4±8.2 vs 30.7±1.8,P均为0.01),B组透析后1 h APTT较透析前仍延长(38.8±7.4 vs 30.7±1.8,P=0.003)。(4)A组透析后iCa~(2+)略高于HD前(1.13±0.06 vs 1.06±0.10,P=0.012),虽略升高,但仍处于正常范围内。(5)A组出现1例口唇麻木,经调整枸橼酸流速和补钙治疗后好转,B组出现1例皮下瘀斑,后自行好转,无明显新发出血或原有出血加重。结论对于高危出血风险MHD患者,S-RCA优于小剂量阿加曲班法,较常用的两段法局部枸橼酸抗凝更具优势。     

阿加曲班治疗肺动脉栓塞的临床观察(附4例报告)

目的观察阿加曲班对肺动脉栓塞(PE)患者抗凝疗效及安全性。方法 4例PE合并下肢深静脉血栓形成(DVT)患者,均经CT肺动脉造影(CTPA)及下肢深静脉加压彩超(CUS)检查确诊,给予阿加曲班治疗20 mg/d,治疗8~12天。后续给予低分子肝素钙4100IU,2~6天,再改为口服抗凝药利伐沙班或华法林,共3个月。结果 4例患者使用阿加曲班后,行CTPA检查提示肺动脉血栓大部分溶解吸收,CUS检查下肢DVT的血管完全和部分再通。临床症状明显缓解,无出血、血小板减少并发症。随访3~6个月,无PE及DVT复发症状。结论阿加曲班可作为临床治疗PE安全有效的抗凝手段。     

阿加曲班治疗下肢深静脉血栓的疗效评价

目的比较常规使用肝素和阿加曲班治疗下肢深静脉血栓（DVT）患者的临床疗效。方法将188例下肢DVT患者按照随机数字表分成阿加曲班组（n=94）和对照组（低分子肝素钙＋尿激酶,n=94）,比较2组患者治疗前、后双侧肢体周径差和疗效的差异,并在治疗过程中监测凝血指标（PT、APTT及PLT）变化。结果阿加曲班组治疗10d后,双侧肢体周径差较治疗前明显减小（P〈0.05）,总有效率（97.87%）优于对照组（89.37%）,P〈0.05。阿加曲班组无血小板减少症（HIT）发生,对照组发生2例HIT;阿加曲班组PT、APTT和PLT变化均处于正常范围,与对照组比较差异无统计学意义（P〉0.05）。结论阿加曲班治疗下肢DVT安全、有效。     

阿加曲班在中心静脉置管诱导血液透析中的应用

目的：探讨阿加曲班在中心静脉置管诱导血液透析中的抗凝效果和出血事件。方法：将104例患者随机分为普通肝素组和阿加曲班组。所有患者在置入右侧颈内静脉置管后接受连续2d的2次诱导血液透析,阿加曲班抗凝剂量按1.5μg·kg^-1·min^-1续由动脉端给予。测定透析前后患者的血常规、肝肾功能、电解质和凝血功能并采用评分方法评价透析器凝血和置管处出血和血肿情况。结果：普通肝素组和阿加曲班组透析器凝血情况无明显差异,但是颈内静脉置管处出血情况,阿加曲班组较普通肝素组显著降低（P〈0.05）,在相同透析器凝血情况下,阿加曲班组APTT和ACT值较肝素组低（P〈0.01）。在透析1h时同时检测阿加曲班组动脉端和静脉端APTT值,两者有统计学差异（P〈0.05）。结论：在达到同样抗凝效果时,阿加曲班较普通肝素所需的APTT和ACT值更低,而且阿加曲班体外的抗凝作用强于体内,因此阿加曲班可能成为血液透析一种新型的替代抗凝药物。     

不同抗凝剂对血液透析过程凝血状态的影响

目的 探讨血液透析（HD）中不同抗凝剂的特点和合理选择。 方法 选取HD患者21例,分为普通肝素（UFH）组,10例,首剂 3000 U,追加1000 U/h,下机前1 h停止追加;达肝素钠组,11例,达肝素钠5000 U透前30 min静脉注射。另选取伴有出血倾向的HD患者10例,作为阿加曲班组,首剂8 mg,追加6～8 mg/h,总剂量1.5 μg&#8226;kg-1&#8226;min-1,下机前20 min停止追加。同时选取8例健康人为对照。在上机前管路动脉端、HD 2 h管路动、静脉端及下机前管路动脉端采血。应用Sonoclot 分析仪测定前玻璃珠激活的凝血时间（gbACT）、凝血速率（CR）及血小板功能（PF）;酶联免疫法测定前凝血酶原片段1+2（PF1+2）及血小板表面α颗粒膜蛋白（GMP-140）。健康对照组采血1次测定上述指标。 结果 （1）与健康对照组比较,全部患者上机前CR、PF1+2和PF、GMP-140均显著增高（P < 0.05）。（2）UFH组：与透析前比较,HD 管路2 h动、静脉端及下机前的gbACT显著延长（P < 0.05）,CR、PF和PF1+2均显著减少（P < 0.05）;与健康对照组比较,下机前gbACT显著延长（P < 0.05）,CR显著减少（P < 0.05）。（3）达肝素钠组：与透析前比较,HD 管路2 h动脉端的gbACT显著延长（P < 0.05）,HD管路2 h的动、静脉端的CR和PF1+2均显著减少（P < 0.05）,下机前CR仍减少（P < 0.05）,但PF1+2差异无统计学意义。2 h管路动脉端gbACT延长与CR减少值大于静脉端;与健康对照组比较,下机前gbACT延长（P < 0.05）,但CR差异无统计学意义。（4）阿加曲班组：与透析前比较,上机后的gbACT均无明显变化;管路2 h的动、静脉端的CR均显著减少（P < 0.05）,而以静脉端更明显;2 h管路动脉端的CR与健康对照组相比,差异无统计学意义;下机前的CR大于对照组（P < 0.05）;在监测过程中PF1+2呈上升趋势。 结论 UFH具有较强的抗凝血作用,HD过程中和结束后均有较大出血风险。达肝素钠具有良好的抗凝作用,但HD过程中有出血风险。阿加曲班适用于有出血或出血倾向的HD患者。     

阿加曲班联合尿激酶治疗下肢深静脉血栓形成的临床研究

目的 探讨阿加曲班合尿激酶治疗下肢深静脉血栓（DVT)的临床应用价值。方法 选择我科2006年1月～2010年12月收治的160例下肢DVT患者,随机分为阿加曲班组和对照组,各组80例。阿加曲班组患者给予阿加曲班注射液和尿激酶治疗,对照组患者予低分子肝素钙合尿激酶治疗,共治疗2周。比较两组患者临床疗效的差异。结果 阿加曲班组临床疗效优于对照组（P＜0.05）,两组患者凝血指标(PT、TT和APTT) 及PLT变化均处于正常范围。结论 阿加曲班合尿激酶治疗下肢DVT疗效肯定,副作用小,安全性大,值得临床推广。     

阿加曲班联合置管溶栓治疗肝素诱导的血小板减少症及继发血栓

目的探讨阿加曲班抗凝联合阿替普酶溶栓治疗急性下肢深静脉血栓(DVT)合并肝素诱导血小板减少症(HIT)患者的临床疗效。方法回顾性分析6例急性DVT合并HIT患者的临床资料,均为使用肝素治疗DVT期间出现血小板减少合并血栓范围扩大,立即停用肝素,给予阿加曲班抗凝治疗,同时给予阿替普酶置管溶栓治疗。结果对6例HIT患者行阿加曲班联合阿替普酶溶栓综合介入治疗均有效,4例下肢肿胀完全消失,2例症状明显缓解。随访6~24个月,6例患者DVT均无复发。结论对于急性DVT接受肝素治疗后高度怀疑HIT者,应立即停用肝素,改用阿加曲班等替代抗凝药物,对于血栓范围扩大而尿激酶溶栓治疗无效者,可考虑改用阿替普酶溶栓治疗。     

Prediction of Anticoagulation During Hemodialysis by Population Kinetics and an Artificial Neural Network

All systems currently used for routine hemodialysis require heparin administration to prevent blood clotting in the extracorporeal circuit. We tested the hypothesis that population-based statistical techniques can be used to predict heparin concentrations during routine hemodialysis. Two predictive models were developed, one based on nonlinear mixed effects modeling (NONMEM) and the other on a multilayer perceptron neural network. Serial clotting time data were obtained from forty-nine patients and used to develop the models. The models were used to predict the clotting times of 70 patients in a prospective test. We determined that the neural network provided greater precision, had fewer outliers in its predictions, and did not have the model misspecification in bolus administration that the NONMEM predictions demonstrated. A final NONMEM model was developed using all data from 119 patients to identify important covariates for predicting the heparin pharmacodynamic parameters, volume of distribution, and clearance. Both the volume of distribution and clearance increased following the initiation of dialysis and as the patient's baseline clotting time increased. The volume of distribution also increased as the patient's weight increased but was decreased by smoking and diabetes. Population-based statistical techniques may provide a useful alternative to existing methods for prescribing heparin.     

Filling Hemodialysis Catheters in the Interdialytic Period: Heparin Versus Citrate Versus Polygeline: A Prospective Randomized Study

Heparin and saline are commonly used to fill hemodialysis central venous catheters to prevent their thrombosis during the interdialytic period. The purpose of this prospective clinical study was to evaluate whether replacing heparin with citrate or polygeline could ensure satisfactory catheter function without exposing patients to the risk of systemic heparinization. Thirty end-stage renal disease (ESRD) patients with subclavian or jugular single lumen catheters as temporary vascular access for hemodialysis were enrolled. After the insertion of the catheters, the patients were randomly assigned to one of the following three filling groups: Group A, heparin; Group B, citrate; Group C, polygeline. Before each dialysis, the filling solution was aspirated and clot volume, if present, was measured. The catheter usage time and the clot volume were 23 ± 24 days and 0.052 ± 0.035 ml in Group A, 51 ± 36 days and 0.059 ± 0.032 ml in Group B, and 32 ± 10 days and 0.056 ± 0.038 ml in Group C, respectively. Our results indicate that citrate or polygeline can replace heparin effectively as a filling solution for single lumen temporary hemodialysis catheters.     

Hemodialysis in infants and small children

Hemodialysis in infants and small children requires specialized nursing staff, equipment and adequate access. The techniques, requirements and available equipment for this population are discussed.     

Loss of Anticoagulant Effect of Heparin During Circulation of Human Blood In Vitro

Device-induced thrombogenesis was studied in an in vitro model using human blood circulated through an artificial ventricle. A new constant pressure filtration technique was used to detect circulating microemboli, the activated partial thromboplastin time (APTT) test was used to monitor the blood for the presence of anticoagulant activity of heparin, and hemolysis was quantified by measuring the plasma free hemoglobin level. Circulation of blood through a 20-ml stroke volume pneumatically driven ventricle for 6-9 h resulted in a significant reduction of APTT, indicating the loss of the anticoagulant effect of heparin. Microemboli concentration was minimal until the APTT decreased below 125 s, at which time the microemboli concentration increased rapidly. This was presumed to be due to the formation of thrombi following a decrease in heparin activity. A significant increase in hemolysis was also noted when blood was pumped. None of these changes was noted in the nonpumped control blood. Spontaneous loss of heparin activity in blood circulated by a pneumatically driven pump may have clinical implications and may help understanding of the problems associated with device-induced thrombogenesis.     

Dialysis Treatment Using an Ethylene Vinyl Alcohol Membrane and No Anticoagulation for Chronic Uremic Patients

Abstract: Anticoagulation used in hemodialysis treatment brings with it the risk of hemorrhagic complications and the possible consequences associated with chronic heparin administration. These problems have not been satisfactorily addressed to date. This study examined a new dialysis method that does not require the administration of anticoagulants. Dialysis is performed for 3 h with a continuous infusion of 750 ml of physiological saline solution in predilution mode and using filters made of ethylene vinyl alcohol copolymer membranes. Eleven patients with chronic uremia underwent more than 2,000 dialysis treatments performed with 9 episodes of coagulation of the dialyzer or blood tubings (0.43%). An evaluation of individual treatments revealed a high degree of biocompatibility and only a scanty activation of coagulation. Blood depuration efficacy was very good as evaluated from pretreatment and posttreatment routine blood chemistries. The technique described here represents a simple and effective method for performing regular dialysis treatment and does not require anticoagulant therapy.