阿加曲班在肝素诱发血小板减少症的应用

目的探讨肝素引起的血小板减少症伴血栓形成（HIT）及其治疗。方法对我院2008年6月至2011年7月175例行介入治疗后接受肝素抗凝治疗的患者进行临床分析,定期监测其血常规。结果其中有5例患者发生肝素诱导的血小板减少症,在应用肝素第3～11 d出现血小板数下降,发生率为2.86%,其下降率为58.4%～80.2%。对5例患者停用肝素后改为阿加曲班继续治疗,第2～5 d血小板数回升至抗凝治疗前时水平。结论在使用肝素进行抗凝治疗期间,应常规监测血小板数变化,如发现血小板数进行性下降〉50%,应及时停用肝素,需继续抗凝的患者可改用阿加曲班治疗。     

阿加曲班防治肝素致血小板减少症诱发的血栓综合征4例临床观察

目的 观察阿加曲班对4例肝素致血小板减少症的抗凝疗效。方法 对临床确诊并以肝素进行抗凝治疗的202例静脉血栓栓塞症患者进行临床分析,定期监测血常规及凝血指标,以确定是否发生血小板减少症的不良反应。对其中4例肝素致血小板减少症患者,停用肝素,给以阿加曲班治疗,20 mg/d,治疗3～7 d。结果 4例肝素致血小板减少症患者换用阿加曲班后,血小板水平恢复至入院时水平,没有发生血栓综合征,同时患者下肢肿痛症状缓解速度快、疗效好。结论 阿加曲班可替代肝素,有效预防肝素致血小板减少症继发的血栓综合征。     

阿加曲班治疗肺血栓栓塞症——3例临床观察并文献复习

目的 探讨阿加曲班对中-低危肺血栓栓塞症抗凝治疗疗效.方法 回顾性分析3例阿加曲班治疗中-低危肺栓塞患者的临床资料并复习文献.结果 3例肺栓塞患者经阿加曲班治疗后,临床症状明显缓解,下肢血管超声、肺动脉CT提示血栓溶解吸收.3例患者无出血、血小板减少并发症.结论 阿加曲班用于治疗肺栓塞安全性高,起效快,是肺栓塞抗凝治疗的有效治疗手段之一.     

低分子肝素诱导的血小板减少症 1 例临床用药分析

1例74岁的男性患者,因“双下肢动脉粥样硬化闭塞症”行“左髂动脉、左胭动脉支架成形术”后出现急性肾功能衰竭,行连续性肾脏替代治疗（CRRT）过程中血小板计数从93×10^9／L降至8×10^9／L,并伴有下肢发绀,临床药师果断判定患者的血小板减少伴血栓形成与CRRT过程中所用的抗凝剂低分子肝素高度相关,建议将低分子肝素更换为阿加曲班继续抗凝治疗。3d后患者血小板回升至正常,下肢发绀症状明显改善。此病例提醒医务工作者虽然低分子肝素较之肝素较少引起肝素诱导的血小板减少症,但在低分子肝素的临床使用中,尤其用于CRRT体外抗凝时,不要忽视其诱导血小板减少症的不良反应。     

4 例复杂先天性心脏病术后并发肝素诱导的血小板减少症患者的监测

2013年7月至2015年2月中南大学湘雅医院心脏大血管外科收治的复杂先心病接受心脏直视手术的患者中有 4例先后出现肝素诱导的血小板减少症(heparin-induced thrombocytopenia,HIT),通过严密动态监测血小板计数,观察 HIT所致的栓塞性皮肤损伤情况,监测阿加曲班用药效果等综合治疗,3例痊愈,1例死亡。HIT是接受肝素治疗出现 的罕见的严重并发症,栓塞发生率和病死率较高。早期识别、早期诊断高风险人群可以有效改善预后。     

肝素诱导的血小板减少症6例临床分析

目的探讨应用普通肝素(UFH)和低分子肝素(LMWH)抗凝治疗时所致肝素诱导的血小板减少症(HIT)的临床诊断和治疗。方法回顾性分析应用UFH和LMWH抗凝治疗所致HIT患者6例的临床表现、治疗及预后。结果221例患者应用UFH和LMWH后发生HIT6例(2.7%)。男5例,女1例,年龄49~73(63±12)岁,应用UFH息者5例,应用LMWH患者1例。血小板降低时间为应用UFH和LMWH后5~12 d,中位时间7.4 d;最低降至(36~87)×10~9/L,下降幅度均>30%。其中3例患者发生血栓栓塞症状。所有患者均停用UFH和LMWH,改为阿加曲班或利伐沙班抗凝。血小板恢复正常时间3~14 d,中位数6.7 d,患者症状逐渐缓解或消失。随访4~17个月,中位数9.5个月,6例患者均未再出现血栓栓塞及出血并发症。结论HIT可导致血栓栓塞等严重后果,应用UFH和LMWH时需常规监测血小板计数,早期诊断和正确治疗可降低致死率和致残率。     

临床药师参与1例化疗后血小板减少症患者的药学监护赵子龙 刘小艳 宁佳

目的 探讨肿瘤化疗后血小板减少症患者的药学服务要点,为临床药师参与此类患者临床治疗提供参考。方法 临床药师参与1例化疗后血小板减少合并静脉血栓患者的抗凝过程,从抗凝药物的选择、剂量的调整,协助医师优化个体治疗方案。结果 选择阿加曲班替代抗凝治疗, 患者血小板逐步恢复,顺利出院。结论：临床药师通过提供个体化用药服务,提高肿瘤相关静脉血栓患者抗凝治疗的效果及用药安全性。     

阿加曲班与普通肝素在连续性血液滤过抗凝中的作用比较

目的:探讨阿加曲班与普通肝素在连续性静脉-静脉血液滤过(CVVH)治疗中抗凝作用和安全性比较。方法:将40例肾功能不全需行CVVH治疗的患者随机分成阿加曲班组和普通肝素组各20例,分别使用阿加曲班和普通肝素抗凝。检查患者CVVH治疗前后血小板和肾功能,第1、4、8 h、治疗结束前以及治疗结束后1 h的活化部分凝血活酶时间(APTT)。观察治疗过程中管路和滤器凝血情况,监测患者治疗结束后24 h内有无出血事件的发生。结果:CVVH治疗后,普通肝素组血小板数量较治疗前明显下降(PP>0.05);阿加曲班组和普通肝素组APTT在CVVH治疗后1 h和治疗结束前延长时间差异均有统计学意义(PP>0.05),而普通肝素组仍高于治疗前(PPP>0.05)。结论:阿加曲班在CVVH治疗中的抗凝作用与普通肝素效果相当,停药后APTT恢复较快,且对血小板影响较小,安全性高,可能是CVVH治疗中比较理想的抗凝剂。     

小分子直接凝血酶抑制剂阿加曲班在急性冠脉综合征中的应用

目的:观察小分子商接凝血酶抑制剂阿加曲班在急性冠脉综合征疗效及副作用方法:将64例急性冠脉综合征患者随机分为阿加曲班治疗组(A组)和普通肝素治疗组(H组).阿加曲班治疗组给予生理盐水加阿加曲班20mg静脉滴注,普通肝素治疗组给予生理盐水加普通肝素loomg静脉滴注,分别比较两组患者治疗前和治疗后2小时、4小时,12小时、24小时、48小时的血小板计数、部分凝斑酶活动时间变化情况并观察两组病例疼痛、心梗发生情况及出血等不良反应发生情况.结果:阿加曲班治疗组和普通肝素治疗组治疗前和治疗后2小时、4小时、12小时、24小时、48小时部分凝血酶活动时间出现不同程度,变化,对疼痛改善、心梗发生情况两组比较无差异.阿加曲班治疗组对血小板影响小,存少量不良反应,普通肝素治疗组对血小板右一定影响,存在出血等不良反应.结论:小分子直接凝血酶抑制剂阿加曲班在急性冠脉综合征中应用安全有效,尤其适用于肝索诱发的血小板减少患者和不能对凝血功能严格监测患者.     

肝素诱导血小板减少症1例的治疗体会

肝素是临床上常用的抗凝剂,肝素诱导的血小板减少症（HIT）是肝素治疗的严重并发症,表现为由免疫介导所致的血小板大量丢失。血小板减少一般发生在应用肝素后的第5-14d内,血小板较基础值下降50%或绝对值降至50×109/L-80×109/L,而停用肝素后血小板计数一般可在1周内恢复正常,临床表现为无症状的血小板减少或广泛的致死性的血栓栓塞症。国外资料报道接受肝素抗凝治疗的患者中HIT发生率为1％-5％。现将本院1例HIT病例及治疗体会报道如下。     

低分子肝素与普通肝素治疗急性肺血栓栓塞症疗效和安全性比较的Meta分析

目的根据现有随机对照临床研究,综合评价低分子肝素(LMWH)和普通肝素(UFH)作为初始治疗方案对非大面积肺血栓栓塞症(PTE)的有效性和安全性.方法从1966年1月～2003年8月MEDLINE光盘数据库和1978年1月～2003年8月中国生物医学文献光盘数据库(CBM-Disk)中,检索以非大面积PTE为研究对象,比较LMWH和UFH作为初始抗凝药物治疗效果和安全性的随机对照试验(RCT)文献,并对RCT结果进行Meta分析.结果共5项RCT 999例患者入选.与UFH抗凝治疗比较,LMWH治疗PTE的合并比数比(OR)结果如下:(1)病死率比较:合并OR为0.81,95%可信区间为0.36～1.81,OR合并假设检验,χ2合并=0.52,P＞0.05;(2)静脉血栓栓塞症(VTE)复发率比较:1项研究显示LMWH组TE复发率差异低于UFH组,合并OR为0.37,95%可信区间为0.14～1.00,OR合并假设检验,χ2合并=1.95,P=0.05;(3)严重出血率比较:合并OR为0.47,95%可信区间为0.16～1.39,OR合并假设检验,χ2合并=1.37,P＞0.05;(4)肝素诱导的血小板减少症(HIT)发生率比较:1项研究显示LMWH组HIT发生率显著低于UFH组,合并OR为0.66,95%可信区间为0.06～6.92,OR合并假设检验,χ2合并=0.35,P＞0.05.结论与UFH抗凝治疗比较,LMWH治疗非大面积PTE病死率无差异;部分研究提示UFH组(VTE)复发率显著高于LMWH组,但合并效应量显示无差异;LMWH的严重出血率与UFH亦无显著差异;部分研究提示HIT的发生率UFH组显著高于LMWH组,但合并效应量显示无差异.就总体而言,LMWH治疗非大面积PTE的疗效与安全性至少与UFH相当.     

Cost-effectiveness of low-molecular-weight heparin and unfractionated heparin in treatment of deep vein thrombosis

BACKGROUND: Acute deep vein thrombosis has traditionally been treated with unfractionated heparin (UFH), administered intravenously, but low-molecular-weight heparins (LMWH), administered subcutaneously, have recently become available. The authors sought to determine which therapy was more cost-effective for inpatient and outpatient treatment of deep vein thrombosis. METHODS: An incremental cost-effectiveness analysis based on a decision tree was performed for 4 treatment strategies for deep vein thrombosis. Rate of major hemorrhage while receiving heparin, rate of recurrence of venous thromboembolism 3 months after treatment and mortality rate 3 months after treatment were determined by meta-analysis. Costs for the UFH therapy were prospectively collected by a case-costing accounting system for 105 patients with deep vein thrombosis treated in fiscal year 1995/96. The costs for LMWH therapy were modelled, and cost-effectiveness was determined by decision analysis. RESULTS: Meta-analysis revealed a mean difference in risk of hemorrhage of -1.1% (95% confidence interval [CI] -2.4% to 0.3%), a mean difference in risk of recurrence of venous thromboembolism of -2.6% (95% CI -4.5% to -0.7%) and a mean difference in risk of death of -1.9% (95% CI -3.6% to -0.4%), all in favour of subcutaneous unmonitored administration of LMWH. The cost to treat one inpatient was $2993 for LMWH and $3048 for UFH. Even more would be saved if LMWH was delivered on an outpatient basis (cost of $1641 per patient). The cost-effectiveness analysis showed that LMWH in any treatment setting is more cost effective than UFH. A sensitivity analysis demonstrated the robustness of this conclusion. INTERPRETATION: Treatment of deep vein thrombosis with LMWH is more cost effective than treatment with UFH in both inpatient and outpatient settings.     

血液透析患者普通肝素与低分子肝素抗凝血小板参数变化

目的探讨维持血液透析患者应用不同分子量肝素抗凝血小板参数变化。方法测定26例应用普通肝素(UFH)及38例应用低分子量肝素(LMWH)抗凝的血液透析患者血小板数量(PLT)及血小板平均体积(MPV),并进行对比,分别与30例健康体检者PLT及MPV进行比较。测定并比较18例患者自UFH改为LMWH抗凝3个月PLT及MPV的变化。结果UFH组PLT及MPV低于对照组(P<0.01);LMWH组PLT及MPV低于对照组,差异有显著意义(P<0.05);在UFH组及LMWH组间,后者PLT及MPV高于前者,(P<0.05);自UFH改为LMWH抗凝后,PLT及MPV有升高,但差异无显著意义(P>0.05)。结论肝素抗凝可致PLT及MPV下降,UFH尤其显著;UFH抗凝致PLT及MPV下降后改用LMWH抗凝并不能使PLT及MPV有明显上升。     

Thromboprophylaxis and early antithrombotic therapy in patients with acute ischemic stroke and cerebral venous and sinus thrombosis

So far, neither treatment with standard unfractionated heparin (UFH) nor with low-molecular-weight heparin (LMWH) has been shown to reduce mortality or to improve neurological outcome in patients with acute ischemic stroke. Although a reduction of early recurrent stroke has been demonstrated for the use of subcutaneous UFH, this benefit was offset by a similar-sized increase in hemorrhagic stroke. Double-blinded studies of LMWH have demonstrated no difference between active treatment and placebo suggesting that LMWH is not effective for the early secondary prevention of ischemic stroke. Although UFH and LMWH may be beneficial in certain subgroups of stroke who are at high risk for early stroke recurrence, these subgroups are still to be defined. Currently, low-dose UFH and LMWH can only be recommended for prophylaxis of deep vein thrombosis in patients with acute ischemic stroke with impaired mobility or other factors determining a particular high risk of venous thromboembolism. Available treatment data from controlled trials favor the use of anticoagulation as the first-line therapy for patients with cerebral venous and sinus thrombosis because it may reduce the risk of a fatal outcome and severe disability and does not promote intracranial hemorrhage.     

全髋关节置换患者注射低相对分子质量肝素与口服利伐沙班对深静脉血栓形成的预防效果比较

目的比较全髋关节置换患者注射低相对分子质量肝素(LMWH)与口服利伐沙班对深静脉血栓形成(DVT)的预防效果差异。方法选取我院2010年3月至2015年3月行全髋关节置换术患者90例,抽签随机分为两组,每组45例,一组患者注射LMWH(置LMWH组),另一组患者口服利伐沙班(利伐沙班组)。比较两组患者术后出血量、伤口引流量、血红蛋白下降水平以及不同时间段血小板计数(PLT)、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(a PTT)水平变化情况,比较两组患者术后DVT及不良反应发生率。结果术后出血量、伤口引流量、血红蛋白下降水平差异无统计学意义(P0.05)LMWH组患者术后DVT发生率为13.33%与利伐沙班组15.56%比较无统计学意义(P0.05);两组术后不良反应发生率无统计学意义(P0.05)。结论应用LMWH素和利伐沙班均能有效预防全髋关节置换术后静脉血栓栓塞的发生,且均具有较高的安全性。     

阿加曲班或低分子肝素联合阿司匹林对于早期进展性缺血性卒中的疗效和安全性

目的：观察和比较阿加曲班或低分子肝素（LMWH）联合阿司匹林对于早期进展性缺血性卒中（PIS的疗效和安全性。方法：将95例符合标准的PIS患者随机分为两组,阿加曲班联合阿司匹林组48例（AA组）,LMWH联合阿司匹林组47例（LA组）。比较两组治疗前后的美国国立卫生研究院卒中量表（NIHSS）、日常生活能力评定量表（Barthel指数）、改良Rankin量表（mRS）。同时监测血红蛋白（Hb）浓度、血小板（PLT）计数、活化部分凝血酶原时间（APTT）、超敏C反应蛋白（hs-CRP）浓度、药物不良反应发生情况。结果：治疗7 d后,两组与治疗前相比均有一定疗效,AA组总有效率显著高于LA组（P<0.05）。治疗后AA组NIHSS评分低于LA组（P<0.05）,Barthel指数明显高于LA组（P<0.01）。AA组治疗3个月后mRS评分明显低于LA组（P<0.01）。同时,治疗3个月时的mRS0-1评分占比相比,AA组优于LA组（P<0.05）。此外,AA组治疗后APTT长于LA组（P<0.01）,LA组PLT较AA组降低（P<0.01）。两组治...     

Low-molecular-weight heparin (LMWH) in the treatment of thrombosis

Thromboembolic complications are a common and costly medical problem, associated with significant morbidity and mortality, especially in postoperative patients. There have been reports of death due to thromboembolic complications even after short procedures, e.g. arthroscopy. Low-molecular-weight heparins (LMWHs) (e.g., certoparin, dalteparin, enoxaparin, nadroparin, reviparin, tinzaparin) have been tested for treatment of deep vein thrombosis in comparison to unfractionated heparin (UFH) in many patients being effective and safe alternative for treatment of deep vein thrombosis (DVT) and venous thromboembolism (VTE). Fixed-dose subcutaneous LMWH once daily is in most cases of equivalent efficacy and safety compared to conventional UFH therapy. There may be less risk for bleeding, less platelet activation together with a control of markers of haemostatic system activation, and either no progression or regression of thrombus size in patients treated with LMWH. The handling of LMWH is more comfortable for patients and less time consuming for nurses and laboratories compared to UFH. The cost-effectiveness analysis showed that LMWH are more cost effective than UFH. It has been calculated that outpatient treatment with LMWH may save 1641 dollars per patient in comparison to hospital treatment. This economic benefit of outpatient treatment of DVT seems to be realized in different health systems. Women with antiphospholipid antibodies and a history of either prior thrombotic events or pregnancy loss are at high risk during pregnancy for either another fetal death or thrombosis and may benefit from treatment with LMWH. In patients with malignant tumors secondary prophylaxis or long-term treatment with LMWH is successful. Patients with a contraindication for oral anticoagulants may benefit from treatment with LMWH as do patients on chronic anticoagulation treatment scheduled for an operative intervention. In most instances LMWH (dalteparin, enoxaparin, nadroparin) treatment for DVT may be given once daily at a fixed dose without any harm, based on a prolonged antithrombin activity. Effectiveness and safety of LMWH (dalteparin, enoxaparin, nadroparin, tinzaparin) in comparison to UFH treatment on outpatient basis has been demonstrated in several studies. In summary, LMWHs have an established role in the treatment of DVT and pulmonary embolism (PE), on an in- and outpatient basis and could realize substantial savings. Most studies were performed with dalteparin, enoxaparin and nadroparin. There is evidence that LMWHs may help to prolong survival in cancer patients and to avoid complications of the acute coronary syndrome.     

低分子肝素联合间歇充气加压预防髋、膝关节手术后静脉血栓栓塞症

目的探讨低分子肝素（low-molecular-weight heparin,LMWH）联合间歇充气加压（intermittent pneumatic compression,IPC）预防髋、膝关节手术后静脉血栓栓塞症（venous thromboembolism,VTE）的疗效和安全性。方法对53例髋、膝关节手术患者术后使用LMWH联合IPC预防VTE。其中人工全髋关节置换术18例,人工全膝关节表面置换术7例,动力髋螺钉（DHS）内固定术17例,髋臼骨折重建钢板内固定术11例。术后8h给予常规剂量LMWH,以后每24h重复使用一次,直至术后10d。同时术后当天持续使用IPC 8h,第2天起每天分2次使用,每次1h时,疗程10～14d。术后5～7d进行VTE症状评估和下肢静脉的彩超检查,并监测血小板计数及血凝,可疑肺动脉栓塞患者行CT肺动脉造影。术后1～3个月的随访中,对可疑DVT患者行第二次彩超检查。结果 53例髋、膝关节手术患者有4例出现深静脉血栓（deep venous thrombosis,DVT）,发生率为7.54%,均在出院后的3个月术后随访期内发生,伴有不同程度的下肢肿胀症状,所有患者均未出现肺栓塞（pulmonary embolism,PE）症状及严重出血并发症。国际标准化比值（international normalizedration,INR）在2.5以内,未引起血小板计数减少。结论联合使用LMWH和IPC可以显著降低髋、膝关节手术后VTE的发生率,并且具有良好的安全性。