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。     

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.     

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.     

阿加曲班与肝素在血液透析抗凝治疗中作用的比较分析

目的：探讨阿加曲班（argatroban）在血液透析（hemodialysis,HD）抗凝治疗中作用的疗效及安全性.方法：将90例次HD患者随机分成实验组和对照组,实验组45例次,使用阿加曲班抗凝,对照组45例次,使用肝素抗凝,监测HD患者治疗前血路管动脉端、治疗中2 h、治疗结束前血路管动、静脉端及治疗后1 h活化部分凝血活酶时间（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24 h内出血情况（包括牙龈出血、鼻衄、结膜出血、皮下出血点、血尿、黑便及便血等）.结果：实验组HD治疗中APTT明显延长,达到HD抗凝治疗要求,与HD治疗前比较差异有统计学意义（P＜0.01）;实验组与对照组治疗中APTT比较差异有统计学意义（P＜0.01）;实验组治疗后1 h APTT恢复基本正常,而对照组仍然很高,两组比较差异有统计学意义（P＜0.01）;实验组与对照组治疗中管路和透析器凝血情况比较差别不大,两组比较差异无统计学意义（P＞0.05）;实验组与对照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＜0.05）;实验组治疗后组织器官出血较对照组明显减少,两组比较差异有统计学意义（P ＜0.01）.结论：阿加曲班在HD抗凝治疗中与普通肝素效果相当,但出血风险少,安全性高,适用于有出血倾向的HD患者.     

血液透析中心静脉置管出血性并发症的分析

目的回顾性分析血液透析患者临时中心静脉置管出血并发症发生的原因。方法回顾性分析471例接受临时中心静脉置管的血液透析患者资料，分析置管位置（颈内、锁骨下、股静脉）、置管后透析时机（即刻或隔日）、透析中抗凝方式（普通肝素、低分子量肝素和无肝素）与出血并发症的关系。结果①置管后即刻透析患者发生出血并发症的风险较隔日透析高（16．4％ vs 4．2％，P〈0．01）；②低分子量肝素抗凝较普通肝素抗凝出血少（5．2％ vs 13．8％，P〈0．01）。结论恰当的安排透析时机、选用合适的抗凝技术以可有效减少中心静脉置管患者出血并发症的发生。     

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。     

不同剂量的首剂肝素在维持性血液透析患者中的抗凝效果

目的探讨不同剂量的首剂肝素在维持性血液透析患者中的抗凝效果。方法 62例维持性血液透析患者随机分为A、B两组,A组30例,B组32例。肝素抗凝方法:A组每次透析开始时从静脉端给予首次剂量肝素28~32 mg(约0.5 mg/kg),维持期用肝素泵每小时追加肝素6~10mg;B组每次透析开始时从静脉端给予首次剂量肝素14~20 mg(约0.3 mg/kg),维持期用肝素泵每小时追加肝素8~12 mg;同时监测2组患者0、0.5、2、3.5及4 h活化凝血时间(activated clotting time,ACT)及变化曲线,观察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、组织器官24 h内出血情况以及在线KT/V情况。结果 2组患者首剂肝素量及维持期肝素用量存在显著性差异,而肝素总量无差异。2组均能顺利完成血液透析,A组透析充分性更好。A组血液透析治疗0.5及2 h ACI较B组明显延长,而在透析3.5及4 h时ACT明显缩短,2组比较均有显著性差异(P0.01);2组ACT 0.5与3.5 h自身比较,A组有明显下降趋势(P0.05),B组无明显差异。2组患者透析器凝血情况、穿刺点压迫时间、透析治疗后24 h内组织器官出血情况比较A组优于B组,差异有统计学意义(P0.01)。结论选择合适剂量的首剂肝素及维持期肝素用量是血液透析顺利进行的关键,首剂肝素用量为28~32 mg(约0.5 ng/kg)时抗凝效果好、透析充分性好,透析后患者出血机会少。     

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。     

不同浓度肝素封管对颈内静脉半永久双腔导管置管的影响

目的:探讨不同浓度肝素封管对维持性血透患者颈内静脉半永久双腔导管置管术后出血、血栓形成和第一次透析时血流量的影响。方法:按半永久性颈内静脉留置导管置管术后肝素封管浓度分为三组,观察颈内静脉留置管置管前、后凝血功能;置管后伤口出血情况及透析时导管内血栓形成及透析中血流量情况。结果:三组置管前凝血功能正常,B、C组置管后PT、APTT较置管前,较A组置管后显著升高;C组置管后PT、APTT较置管前,较B组置管后显著升高。三组穿刺点及隧道口出血程度随着肝素封管浓度的增加而显著增加,A组第一次透析时11例患者导管内有不同程度的血栓形成,栓塞率达到35.5%,B组和C组栓塞率明显低于A组,血流量欠佳率明显高于A组,两组间无显著差异。结论:用比导管内容量多0.1～0.2ml的50mg肝素盐水封管,既能减少手术后伤口出血,又能防止导管内血栓形成、保证透析时血流量,不时为一种术后较好的封管方法。     

高浓度枸橼酸钠抗凝法对围手术期血液透析患者的疗效和安全性

目的观察高浓度枸橼酸钠溶液抗凝法在围手术期血液透析患者中的临床应用价值及安全性。方法选择围手术期血液透析患者90例,随机分成2组：枸橼酸钠组（45例,169例次）采用30％的枸橼酸钠溶液抗凝,无抗凝剂组（45例,157例次）采用无抗凝剂法透析,观察透析器及管路凝血情况、检测透析前后部分凝血活酶时间（APTT）、观察出血情况、测定尿素清除率（Kt／V）。结果枸橼酸钠组中,I级凝血12例次（占7．1％）;未发生Ⅱ级或Ⅲ级凝血。无抗凝剂组中,I级凝血18例次（占11．5％）,Ⅱ级凝血15例次（占9．6％）,Ⅲ级凝血15例次（占9．6％）。无抗凝剂组体外循环管路凝血率高于枸橼酸钠组（P〈0．05）。无抗凝剂组透析器前APTT低于枸橼酸钠组（P〈O．05）。枸橼酸钠组Kt／V为（1．35±0．15）,高于无抗凝剂组的（0．96±0．18）（P〈0．05）。透析后,2组血肌酐、尿素氮均较透析前降低（P〈O．05）。透析后枸橼酸钠组较无抗凝剂组血HCO3^-明显升高（P〈0．05）但仍在正常值内。枸橼酸钠组透析后血钙较透析前降低（P〉0．05）。结论作为围手术期血液透析患者抗凝方式,局部枸橼酸钠溶液抗凝较之无抗凝剂法抗凝效果肯定,安全性好。     

Usefulness of Thrombelastography for Dosage Monitoring of Low Molecular Weight Heparin and Unfractionated Heparin During Hemodialysis

Low molecular weight heparin (LMH) acts as an anticoagulation agent mainly through its anti-activated coagulation factor X (Xa) activity. Thrombelastography (TEG) is expected to be useful to monitor the dosage of LMH during hemodialysis because reaction time on TEG (TEG-r) is considered to reflect blood thromboplastin formation time, which depends on the formation of Xa. To test this possibility, we compared the usefulness of TEG, activated coagulation time (ACT), activated partial thromboplastin time (APTT), and anti-Xa activity in 28 hemodialysis patients using both conventional unfractionated heparin (UFH) and LMH on separate dialysis procedures. Anti-Xa activity of LMH was comparable to that of UFH when it was measured using both LMH and UFH as standards. Anti-Xa activity, which theoretically depended on the heparin concentration in blood samples, did not correlate with the degree of dialyzer clotting. The APTT correlated well with anti-Xa activity in patients using LMH (r = 0.686, p less than 0.01) and UFH (r = 0.906, p less than 0.01), but not with the degree of dialyzer clotting. The TEG-r correlated well with the degree of dialyzer clotting both in patients using LMH and those using UFH (measurements of samples obtained from the venous side of the extracorporeal circuit) and weakly correlated with anti-Xa activity in patients using LMH (r = 0.402, p less than 0.05). The ACT did not correlate with the degree of dialyzer clotting or anti-Xa activity. These results suggest that TEG-r reflects the efficacy of heparin in the extra-corporeal blood circuit, whereas APTT mainly reflects heparin concentration of the blood samples.(ABSTRACT TRUNCATED AT 250 WORDS)     

The safety of heparins in end-stage renal disease

In patients on chronic dialysis, unfractionated heparin (UFH) is the most commonly used agent for anticoagulation of the hemodialysis extracorporeal circuit, for hemodialysis catheter "locking" between dialysis treatments, and for nondialysis indications such as venous thromboembolic disease, peripheral vascular disease, and acute coronary artery disease. Potentially serious complications of UFH, such as hemorrhage, osteoporosis, and thrombocytopenia, have led to consideration of other options for anticoagulation, including low molecular weight heparin (LMWH) and direct thrombin inhibitors (DTIs). LMWH can be used for anticoagulation of the hemodialysis circuit, but whether this has significant benefit compared to UFH remains to be proven. Because of the somewhat unpredictable risk of severe bleeding complications when LMWH is used for other indications in dialysis patients, UFH rather than LMWH is preferred for treatment of thromboembolic disease in these patients. DTIs have been used for anticoagulation in dialysis patients with heparin-induced thrombocytopenia (HIT), with argatroban being the preferred agent if heparin-free hemodialysis cannot be performed. UFH still remains the preferred anticoagulant in the vast majority of dialysis patients requiring systemic anticoagulation and for anticoagulation of the extracorporeal hemodialysis circuit.     

Depolymerized holothurian glycosaminoglycan (DHG), a novel alternative anticoagulant for hemodialysis,is safe and effective in a dog renal failure model

BACKGROUND: Depolymerized holothurian glycosaminoglycan (DHG) is a new agent with anticoagulant properties quite different from those of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in terms of antithrombin III-dependency, and exerts an antithrombotic effect with less bleeding than UFH and LMWH in vivo. In this study, the anticoagulant and hemorrhagic effects of DHG were investigated on hemodialysis in a dog model of renal failure and compared with those of UFH, LMWH, and nafamostat mesilate (FUT). METHODS: The dog renal failure model was prepared by 7/8 renal artery ligation. Effectiveness was based on completion of 3-hour hemodialysis, no marked clot deposition in the extracorporeal circuit, and permeability of blood urea nitrogen (BUN) and creatinine. Template bleeding was measured by determining the hemoglobin content of the blood from the wound. RESULTS: DHG induced no major bleeding or clot formation during 3-hour hemodialysis, in contrast to UFH and LMWH, each of which induced marked bleeding. These glycosaminoglycans (GAGs) were equally effective in decreasing plasma levels of BUN and creatinine. On the other hand, dogs treated with FUT failed to complete 3-hour hemodialysis. These anticoagulants prolonged activated partial thromboplastin time (APTT) to different extents and GAGs prolonged thrombin clotting time markedly but FUT did not. CONCLUSION: Our findings suggest that thrombin clotting time prolongation can contribute to prevention of clot formation in extracorporeal circuits, and the non-antithrombin III-dependent activities of DHG may be related to its low risk of hemorrhage for hemodialysis. DHG appears to be promising as an alternative anticoagulant with low risk of hemorrhage for hemodialysis.     

Anesthesia for a hemodialysis patient with HIT undergoing CABG using argatroban

Anesthetic Management of CABG in a Hemodialysis patient complicated by heparin-induced thrombocytopenia (HIT) type II is one of the different procedures in hemodialysis patients using heparin. An 81-year-old man receiving hemodialysis complicated by HIT type II was scheduled for coronary artery bypass grafting (CABG). Anesthesia was induced and maintained with propofol, remifentanil and rocuronium. During artificial cardiopulmonary bypass, activated clotting time (ACT) was maintained above 300 sec by in initial 0.1 mg x kg(-1) and subsequent 2.0-7.0 microg x kg(-1) x min(-1) doses of argatroban; a direct thrombin inhibitor. Immediately after the completion of the external cardiopulmonary circulation, continuous infusion of argatroban was discontinued. Seven hours later ACT was restored to the preoperative level. Both intra and postoperative courses were uneventful.     

Failure of argatroban anticoagulation during off-pump coronary artery bypass surgery

Heparin-induced antibodies create vexing problems during cardiac surgery. Although alternative medications have been used for intraoperative anticoagulation, the results have been sufficiently variable that no one medication is recommended. In our case, due to the poor reversibility of the antithrombin agents, argatroban was chosen as a heparin substitute due to its short half-life and its anticoagulation assessment using the activated clotting time (ACT). Unfortunately, our experience was that argatroban does not provide adequate anticoagulation during off-pump coronary bypass surgery, even when the ACT is maintained at more than 380 sec.     

Anticoagulation for cardiac surgery in patients receiving preoperative heparin: use of the high-dose thrombin time

Patients receiving heparin infusions have an attenuated activated clotting time (ACT) response to heparin given for cardiopulmonary bypass (CPB). We compared patients receiving preoperative heparin (Group H) to those not receiving heparin (REF group) with respect to ACT, high-dose thrombin time (HiTT), and markers of thrombin generation during CPB. Sixty-five consecutive patients (33 Group H, 32 REF group) undergoing elective CPB were evaluated. ACT and HiTT were measured at multiple time points. Plasma levels of thrombin-antithrombin III complex and fibrin monomer were determined at baseline, during CPB, and after protamine administration. Transfusion requirements and postoperative blood loss were measured and compared. ACT values after heparinization increased less in Group H and were significantly lower than those in the REF group (P < 0.01). HiTT values did not differ significantly between the two groups. Blood loss and transfusion requirements were not significantly different between the two groups. Plasma levels of thrombin-antithrombin III complexes and fibrin monomer also did not differ between groups at any time, despite a lower ACT in Group H after heparinization and during CPB. Our data suggest that thrombin formation and activity are not enhanced in patients receiving heparin therapy, despite a diminished ACT response to heparin. The utility of ACT and the threshold values indicative of adequate anticoagulation for CPB are relatively undefined in patients receiving preoperative heparin. HiTT should be investigated as a safe and accurate monitor of anticoagulation for CPB in patients receiving preoperative heparin therapy. Implications: The diminished activated clotting time response to heparin, in patients receiving preoperative heparin therapy, poses difficulties when attempting to provide adequate anticoagulation for cardiopulmonary bypass. Current data suggest that heparin resistance is not observed when high-dose thrombin time is used to monitor anticoagulation and that a lower activated clotting time value in these patients may be safe.