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。     

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases

IntroductionIntra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures.Presentation of casesFour patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed.DiscussionIn the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective.ConclusionsThese preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions.     

肝素联合低分子肝素预防动静脉内瘘术后早期血栓形成

摘 要 目的： 研究肝素联合低分子肝素对预防动静脉内瘘（AVF）术后早期血栓形成的影响。方法: 采用前瞻性研究方法,将299例行AVF术的患者随机分为两组,对照组患者术后给予低分子肝素5 000 IU皮下注射qd×7 d;观察组术中在游离动脉端与静脉端分别推注1 500 u肝素钠,术后给予低分子肝素5 000 IU皮下注射qd×7 d。观察两组患者术后1周和4周AVF血栓形成率及药品不良反应（ADR）发生情况。结果: 术后1周,对照组和观察组的AVF血栓形成率分别为3.4%和0;术后4周分别为4.8%和0.67%,观察组均明显低于对照组（P<0.05）。两组ADR发生率差异无统计学意义（P>0.05）,未发生严重不良反应。结论: 肝素联合低分子肝素可降低AVF术后早期血栓形成率,提高手术成功率,安全性较好。     

抗凝剂在连续性肾脏替代疗法中的应用进展

连续性肾脏替代疗法(CRRT)被越来越多地应用于临床。但在CRRT过程中最大的不利是需要延长抗凝来防止体外回路中血液凝固。本文通过对CRRT治疗方法和抗凝剂的历史回顾,对各种抗凝机制进行详细论述并对各种抗凝方法优缺点进行比较,使我们对CRRT过程中使用的抗凝剂有更深入的了解,掌握CRRT过程中使用抗凝剂的最新研究进展,从而指导我们根据患者实际情况选择最佳的抗凝方法。既能保证活动性出血及高危出血患者的安全问题,避免损失血液及加重出血,又能保证透析质量及降低透析成本。     

Rapid determination of anti-heparin/platelet factor 4 antibody titers in the diagnosis of heparin-induced thrombocytopenia

PURPOSE: Heparin-induced thrombocytopenia is mediated by antibodies directed against the heparin-platelet factor 4 (heparin/PF4) complex. Our aim was to investigate whether rapid measurement of anti-heparin/PF4 antibodies could improve the diagnostic workup of patients with suspected heparin-induced thrombocytopenia. METHODS: We examined 148 consecutive patients in our laboratory between January 1995 and June 2001 for suspected heparin-induced thrombocytopenia. Clinical data allowed retrospective assessment of the likelihood of heparin-induced thrombocytopenia. Antibodies against the heparin/PF4 complex were detected by a rapid particle gel immunoassay. RESULTS: Anti-heparin/PF4 antibodies were detected in 69 (47%) of the 148 patients, at dilution titers from 1 to 256. Clinically "likely" or "very likely" heparin-induced thrombocytopenia was significantly more common in patients with titers >or=4 (95% [39/41]) than in those with undetectable antibodies (13% [9/70]; P <0.0001), a titer of 1 (18% [4/22]; P <0.0001), or a titer of 2 (33% [2/6]; P = 0.001). All 19 samples with a positive platelet aggregation test had anti-heparin/PF4 antibody titers of at least 4, including 15 samples with titers >or=32. Thromboembolic complications in heparin-treated patients were significantly more prevalent in patients with titers >or=4 (63% [26/41]) than in those with undetectable antibodies (8% [6/79]; P <0.0001) or a titer of 1 (9% [2/22]; P <0.0001). Of the 11 patients with a titer of 1 who were maintained on heparin, none developed worse thrombocytopenia or thromboembolic complications. CONCLUSION: Anti-heparin/PF4 antibody titers, which can be measured rapidly and reproducibly using a particle gel immunoassay, can be used as a confirmatory test to complement a clinical likelihood score among patients with suspected heparin-induced thrombocytopenia.     

复方丹参注射液抗脂多糖诱导的兔弥漫性血管内凝血

目的: 研究复方丹参注射液对脂多糖(LPS)诱导的兔弥漫性血管内凝血(DIC)的作用。方法: 用LPS诱导兔DIC模型。凝固法测定纤维蛋白原含量,全自动凝血分析仪检测活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和纤维蛋白原含量;全自动血细胞分析仪进行血小板计数;全自动血浆分析仪测定谷丙转氨酶(ALT)以及血尿素氮(BUN);发色底物法测定蛋白C及抗凝血酶Ⅲ的活性。观察复方丹参注射液对LPS诱导的兔DIC的拮抗作用。结果: 兔耳缘静脉持续滴注LPS,观察到:APTT和PT显著延长;血小板计数和纤维蛋白原含量明显减少;ALT和BUN显著升高;蛋白C和抗凝血酶Ⅲ的活性明显降低。给予复方丹参注射液后,APTT和PT的延长明显缩短;血小板计数和纤维蛋白原的含量均明显恢复;ALT和BUN显著下降;蛋白C及抗凝血酶Ⅲ的活性显著改善。结论: 复方丹参注射液对LPS诱导的兔DIC有良好的拮抗作用。     

Effect of sustained heparin release from PCL/chitosan hybrid small-diameter vascular grafts on anti-thrombogenic property and endothelialization

Thrombus formation and subsequent occlusion are the main reasons for the failure of small-diameter vascular grafts. In this study, a hybrid small-diameter vascular graft was developed from synthetic polymer poly(ε-caprolactone) (PCL) and natural polymer chitosan (CS) by the co-electrospinning technique. Heparin was immobilized on the grafts through ionic bonding between heparin and CS fibers. The immobilization was relatively stable, and heparin could continuously release from the grafts for more than 1 month. Heparin functionalization evidently improved the hemocompatibility of the PCL/CS vascular grafts, which was illustrated by the reduced platelet adhesion and prolonged coagulation time (activated partial thromboplastin time, prothrombin time and thromboplastin time) as shown in the human plasma assay, and was further confirmed by the ex vivo arteriovenous shunt experiment. In vitro cell proliferation assay showed that heparin can promote the growth of human umbilical vein endothelial cells, while moderately inhibiting the proliferation of vascular smooth muscle cells, a main factor for neointimal hyperplasia. Implantation in rat abdominal aorta was performed for 1 month. Results indicate that sustained release of heparin provided optimal anti-thrombogenic effect by reducing thrombus formation and maintaining the patency. Furthermore, heparin functionalization also enhanced in situ endothelialization, thereby preventing the occurrence of restenosis. In conclusion, it provides a facile and useful technique for the development of heparinized medical devices, including vascular grafts.     

阻抑eIF-4E对大肠腺癌LS-174T细胞乙酰肝素酶mRNA及其翻译表达水平的影响

目的:确定阻抑结肠癌LS-174T细胞中过量表达的真核细胞起始因子-4E(eukaryoticinitiationfactor-4E,eIF-4E)是否促进乙酰肝素酶(heparanase)mRNA的降解,并改变其翻译表达水平。方法:应用脂质体包裹与eIF-4EmRNA翻泽起始点互补的asODN,转染处理人大肠腺癌细胞LS-174T。使用Westernblot和RT-PCR方法分别检测eIF-4E被阻抑后其转录和翻译水平的改变。乙酰肝素酶mRNA在细胞内水平采用Northernblot定量检测,其蛋白表达水平改变采用Westernblot检测。结果:asODN经脂质体转染LS-174T细胞后,eIF-4E基因表达明显受到抑制,其蛋白表达产物也显著下降。伴随eIF-4E被阻抑表达,Northernblot结果显示乙酰肝素酶mRNA水平下降,且其蛋白翻译表达量也降低。结论:阻抑eIF-4E影响LS-174T细胞乙酰肝素酶mRNA稳定、促使其降解,并降低乙酰肝素酶表达。     

低分子肝素皮下注射操作的最佳证据总结

目的 检索、评价和整合低分子肝素皮下注射操作的相关证据。方法 计算机检索国内外数据库、相关专业网站中关于低分子肝素皮下注射操作的临床决策、推荐实践、证据总结、技术报告、指南、专家共识、系统评价,文献检索时限为建库至2021年11月,由2名研究者独立进行文献质量评价后,根据主题对证据进行提取与汇总。结果 根据纳入标准,共筛选出9篇文献,包括2篇证据总结、2篇专家共识、5篇系统评价。通过文献阅读、证据提取和归类,从注射前准备、注射中规范、注射后处置3个方面总结出12条证据。结论 该研究总结了低分子肝素皮下注射操作的最佳证据,可为护理人员开展临床实践提供参考。护理人员应结合临床情境、患者意愿,审慎地选择并应用证据,从而保障注射安全,降低相关并发症的发生率。     

Engineering strategies to control vascular endothelial growth factor stability and levels in a collagen matrix for angiogenesis: The role of heparin sodium salt and the PLGA-based microsphere approach

New vessel formation is the result of the complex orchestration of various elements, such as cells, signalling molecules and extracellular matrix (ECM). In order to establish the suitable conditions for an effective cell response, the influence of vascular endothelial growth factor (VEGF) complexation with heparin sodium salt (Hp) on its pro-angiogenic activity has been evaluated by an in vitro capillary-like tube formation assay. VEGF with or without Hp was embedded into collagen gels, and the activated matrices were characterized in terms of VEGF activity and release kinetics. Taking into account the crucial role of Hp in VEGF stability and activity, VEGF/Hp complex was then encapsulated into microspheres based on poly(lactide-co-glycolide) (PLGA), and microsphere properties, VEGF/Hp release kinetics and VEGF in vitro activity over time were evaluated. Integrated microsphere/collagen matrices were developed in order to provide a continuous release of active VEGF/Hp inside the matrix but also a VEGF gradient at the boundary, which is an essential condition for endothelial cell attraction and scaffold invasion. The results confirmed a strong influence of Hp on VEGF configuration and, consequently, on its activity, while the encapsulation of VEGF/Hp complex in PLGA-microspheres guaranteed a sustained release of active VEGF for more than 30 days. This paper confirms the importance of VEGF stability and signal presentation to cells for an effective proangiogenic activity and highlights how the combination of two stabilizing approaches, namely VEGF/Hp complexation and entrapment within PLGA-based microspheres, may be a very effective strategy to achieve this goal.