非瓣膜性房颤并急性缺血性卒中抗凝治疗时机

抗凝治疗是非瓣膜性房颤合并急性缺血性卒中的脑卒中二级预防重要策略,但其最佳启动时机尚无一致性意见。近年的循证医学证据发现急性缺血性卒中后早期启动抗凝治疗较延期抗凝治疗更具优势。本文拟对非瓣膜性房颤合并急性缺血性卒中患者抗凝治疗的启动时机进行综述,以期在平衡减少脑卒中复发与降低出血性转化风险的基础上,为此类患者选择更合理的抗凝治疗启动时机提供参考。     

近年国外采用肝素治疗急性缺血性脑血管病的新动向

肝素抗凝治疗急性缺血性脑血管病(AICVD),目前国外应用较广,研究较多,国内则少。肝素抗凝治疗主要应用于:(1)进展性卒中;(2)急性部分性卒中;(3)新发作的TIA,特别是反复发作的TIA;(4)心源性脑栓塞。其确切疗效仍没有肯定,对其应用治疗AICVD一直存在很大分歧和争     

心源性栓塞性卒中后的急性抗凝治疗

心源性栓塞性卒中可能再发脑及全身栓塞。再发栓塞多发生在原发卒中的最初数周内。为降低早期再发栓塞的发生率,有人提倡急性抗凝治疗,但亦有人提出该治疗能导致脑出血。本文进一步评价了心源性栓塞性卒中后急性抗凝治疗的安全性和功效。本文评价了124名病人,均符合心源性栓塞性卒中心脏异常及临床表现的诊断标准。本组排除感染性或消耗性心内膜炎及心脏内肿瘤。除去3名细菌性心内膜炎患者,将121名患者回顾性地分为3组。第一组比较了以往未接受抗凝治疗,卒中后96小时内接受肝素抗凝治疗的患者,第2组为卒中时和卒     

嘉兴地区急性缺血性卒中合并心房颤动患者抗凝治疗现状分析

目的 调查嘉兴地区急性缺血性卒中合并心房颤动患者的抗凝治疗现状。 方法 回顾性分析2016年1月-2020年12月基于CT临床数据采集系统对卒中医疗质量改进的研究登 记库-Ⅱ（computer analysing system to improve stroke management quality evaluation-Ⅱ,CASE-Ⅱ）中的 嘉兴地区卒中中心登记的急性缺血性卒中合并心房颤动住院患者的信息。根据患者出院是否带有抗 凝药物分为出院抗凝组与出院未抗凝组,比较两组患者的基本特征,采用logistic回归分析出院抗凝 药物使用的影响因素;并进一步在既往诊断心房颤动且卒中高危（CHA2DS2-VASc≥2分）患者亚群中分 析抗凝药物使用的影响因素。 结果 共纳入患者2005例,平均年龄77±8岁,男性979例（48.8%）,NIHSS中位评分5（2～13）分。 无抗血栓治疗禁忌证患者1817例,出院时带抗血栓药物比例为83.9%（1525/1817）,其中抗凝药 物比例为41.3%（750/1817）。年龄（OR 0.964,95%CI 0.952～0.976）,基线NIHSS评分（OR 0.935, 95%CI 0.920～0.951）,住院时间（OR 1.045,95%CI 1.025～1.066）,深静脉血栓（OR 2.797, 95%CI 1.472～5.311）,住院期间是否发生任意的颅内出血（OR 0.085,95%CI 0.038～0.188）、消化 道出血（OR 0.503,95%CI 0.257～0.985）、肺炎（OR 0.646,95%CI 0.488～0.856）是急性缺血性卒中 合并心房颤动患者出院接受抗凝治疗与否的独立影响因素。既往诊断心房颤动且卒中高危患者接受 抗凝治疗比例仅为16.0%（153/954）,低龄（OR 0.957,95%CI 0.938～0.975）、低收缩压（OR 0.985, 95%CI 0.977～0.993）、卒中/TIA病史（OR 2.773,95%CI 1.954～3.936）是其接受抗凝治疗的独立保护 因素。 结论 嘉兴地区急性缺血性卒中合并心房颤动患者的抗凝治疗率较低,低龄、低基线NIHSS评分、 长住院时间、合并深静脉血栓的患者更多接受抗凝治疗,住院期间发生颅内出血、消化道出血和肺炎 的患者更少接受抗凝治疗。     

急性脑梗死合并慢性阻塞性肺疾病急性加重期抗凝治疗的意义

目的 探讨急性脑梗死合并慢性阻塞性肺疾病加重期(AECOPD)抗凝治疗的意义.方法 将65例急性脑梗死合并AECOPD患者随机分2组,对照组31例,常规治疗;治疗组34例,常规治疗基础上加低分子肝素钙抗凝治疗10 d.2组治疗前及第28天均行欧洲脑卒中量表(ESS)评分、生活能力量表(ADL)评分,抗凝治疗10 d后评价2组AECOPD治疗效果.结果 第28天,治疗组ESS评分较对照组改善更明显(P＜0.05);治疗组ADL水平较对照组提高更明显(P＜0.05);抗凝治疗10 d后治疗组AECOPD治疗总有效率较对照组高(P＜0.05).结论 急性脑梗死合并AECOPD给予低分子肝素钙抗凝治疗不但能够提高AECOPD治疗效果,而且能改善神经功能缺损、提高生活能力.     

心房颤动相关性缺血性卒中临床研究现状

心房颤动是急性缺血性卒中的独立危险因素,由其引起的缺血性卒中约占全部缺血性卒中的20%;与心房颤动相关的危险因素包括高龄(≥75岁)、高血压、糖尿病、近期心力衰竭、缺血性卒中或短暂性脑缺血发作病史,风险评价体系包括CHADS2和CHA2DS2-VASC评分系统。风险评价体系的建立有利于评价脑卒中风险、决定采取何种治疗措施。预防性治疗原则为高度和中度风险行抗凝治疗、低度风险行抗血小板治疗或不治疗。华法林目前仍是主要抗凝药物,新型口服抗凝药虽具有脑卒中发生率和出血率低、无需监测等优点,但缺乏多中心大样本随机对照试验的验证。     

基因指导下的抗凝治疗

抗凝治疗是急性冠状动脉综合征、心房颤动、静脉血栓形成、肺栓塞等栓塞类疾病非常 有效的治疗手段。抗凝药物包括肝素、华法林、达比加群、利伐沙班、阿哌沙班等。抗凝药物剂量个 体差异大、出血风险高。如何提高抗凝治疗的有效性和安全性作为目前的研究热点。基因多态性在 抗凝药物的剂量效应关系方面起了非常重要的作用。本文旨在探讨影响华法林、达比加群等抗凝药 物的遗传因素,为个体化治疗提供依据     

比伐卢定联合低分子肝素在急性脑梗死机械取栓术后抗凝治疗中的应用

目的观察比伐卢定联合低分子肝素在急性脑梗死机械取栓术后抗凝治疗中的应用效果。方法采用前瞻性巢式病例研究法,以血管内机械取栓术后接受低分子肝素抗凝治疗的急性脑梗死病例作为单纯肝素组(60例),接受比伐卢定联合低分子肝素抗凝治疗作为比伐肝素组(60例)。比较两组凝血功能、康复性评估指标及不良事件发生率。结果在停药即刻、停药1、8、24及48 h两组活化凝血时间、活化部分凝血活酶时间均高于用药前(P0.05),两组间比较,差异无统计学意义(P0.05)。术后6及12个月,比伐肝素组的Barthel评分、Fugl-Meyer评分高于单纯肝素组,改良Rankin量表(MRS)评分低于单纯肝素组(P0.05)。比伐肝素组不良事件发生率(11.67%)与单纯肝素组(16.67%)比较,差异无统计学意义(P0.05)。结论比伐卢定联合低分子肝素应用于急性脑梗死机械取栓术后抗凝效果好,且更利于术后康复。[国际神经病学神经外科学杂志, 2021, 48(2):167-170]     

急性脑梗死合并慢性阻塞性肺疾病急性加重期抗凝治疗的意义

目的 探讨急性脑梗死合并慢性阻塞性肺疾病加重期(AECOPD)抗凝治疗的意义.方法 将65例急性脑梗死合并AECOPD患者随机分2组,对照组31例,常规治疗;治疗组34例,常规治疗基础上加低分子肝素钙抗凝治疗10 d.2组治疗前及第28天均行欧洲脑卒中量表(ESS)评分、生活能力量表(ADL)评分,抗凝治疗10 d后评...     

普通肝素联合低分子肝素钙治疗症状轻微急性缺血性卒中临床分析

目的 探讨症状轻微的进展性急性缺血性卒中的治疗方案.方法 对我院2009-01-2013-01符合症状轻微的进展性缺血性卒中患者120例,入院后随机分为2组,治疗组60例患者采用常规治疗加普通肝素联合低分子肝素钙抗凝治疗,另外60例作为对照组,常规治疗;观察治疗前和治疗后14 d的神经功能缺损（NIHSS）评分比较.结果 治疗组第14天临床神经功能缺损评分（NIHSS）与对照组比较差异有统计学意义（P＆lt;0.05）.结论 对于症状轻微的进展性急性缺血性卒中的治疗,选择普通肝素联合低分子肝素钙为主的治疗方案疗效肯定,安全性高.     

The anti-inflammatory effects of heparin and related compounds

Heparin is a glycosaminoglycan well known for its anticoagulant properties. In addition, heparin possesses anti-inflammatory effects. Although the mechanisms responsible for the anticoagulant effects of heparin are well understood, those underlying its anti-inflammatory effects are not. This review presents some of the evidence from clinical and animal studies supporting an anti-inflammatory role for heparin and heparin-related derivatives. Potential mechanisms by which heparin can exert its anti-inflammatory effects are discussed. The clinical use of heparin as an anti-inflammatory agent has been held back by the fear of bleeding. Development of nonanticoagulant heparins or heparin derivatives should mitigate this concern.     

Activity of antithrombin III and effect of heparin on coagulation in shock

In 16 patients admitted for DIC and shock,series of coagulation tests were carried out prior to and during heparin therapy. Plasma heparin concentrations measured were corresponding to expected levels. In some cases however,considerably higher or lower levels were found. This could be partly explained by release of PF 4 from platelets and by a decreased turnover of heparin because of a malfunction of the kidneys or of the liver. A relation between the effect of heparin on coagulation and the activity of antithrombin III could be established. A diminution of this activity resulted in a diminished or even missing effect of heparin. In some instances,the PTTand the thrombin clotting time were considerably prolonged when FDP were present or when procoagulant factors were diminished. These tests therefore,did not reflect true heparin concentrations in shock. For this reason,regular assays of antithrombin III and of heparin are proposed.     

The heparin-mobilisable pool of platelet factor 4: a comparison of intravenous and subcutaneous heparin and Kabi heparin fragment 2165

Some clinical advantages are claimed for low molecular weight heparin so the mobilisation of platelet factor 4 (PF 4) from the endothelial pool by the heparins may be relevant. Unfractionated (UF) heparin has been compared with Kabi heparin fragment 2165. A single intravenous (i.v.) injection of 60 iu/kg heparin was compared with 5000 anti-Xa units of Kabi-2165. Less PF 4 was mobilised by Kabi-2165 and some apparently remained in the pool and was released when the pool was subsequently challenged by giving i.v. heparin. Subcutaneous (s.c.) injections of 5000 iu heparin twice daily were compared with 5000 anti-Xa units of Kabi-2165 once daily, each given for a week. The plasma PF 4 was never raised yet when finally challenged with i.v. heparin the pool was "empty" or refractory after the s.c. heparin but some PF 4 remained after the s.c. Kabi-2165. The two glycosaminoglycans (GAGs) had widely differing half-lives but the t/2 of the PF 4 mobilised by the two GAGs was similar even though the PF 4 is apparently bound to the GAG.     

Characterization of platelet binding of heparins and other glycosaminoglycans

The binding of glycosaminoglycans to intact washed human platelets was studied. The platelet binding of a ³H-labeled unfractionated heparin was saturable and reached equilibrium in 10–15 minutes. Heparin binding was specific: a 50-fold molar excess of an equivalent unlabeled heparin displaced up to 90% of labeled heparin, while chondroitin sulfate A and hyaluronic acid minimally displaced the binding of labeled heparin. Low molecular weight heparin fragments showed intermediate efficacy in displacing the binding of unfractionated [³h]heparin. Dextran sulfate (M 8,000, sulfation 17%) was as potent as unfractionated heparin in displacing binding, while neutral dextrans were ineffective. We observed that platelet activation by the calcium ionophore A23187 increased heparin binding by 2 to 3-fold, principally by enhancement of binding capacity not binding affinity. This process of heparin binding to the platelet surface may mediate some of the reported effects of heparin on platelet behavior.     

For the initial treatment of venous thromboembolism: are all low-molecular-weight heparin compounds the same?

Low-molecular-weight heparin compounds have been used in the treatment of patients with venous thromboembolism for approximately 15 years. Ever since their introduction, there has been discussion about whether low-molecular-weight heparin compounds differ in their efficacy and safety. The best answer would be provided by direct comparison of different low-molecular-weight heparin preparations; however, these trials have not been conducted. Classical meta-analysis has its limitations for such a comparison since only a very small number of trials with the respective low-molecular-weight heparin compounds are available. The objective of the present analysis has been the use of meta-regression to compare the efficacy and safety of different low-molecular-weight heparin compounds in the initial treatment of patients with venous thromboembolism. We used computerized literature searches to identify studies that compared dose-adjusted unfractionated heparin treatment with fixed dose subcutaneous low-molecular-weight heparin treatment in patients with established venous thromboembolism. The individual odds ratios of the studies were plotted against the absolute percentage of the major outcomes in the unfractionated heparin control group. Linear regression was used to find differences between different low-molecular-weight heparin compounds. There appears to be some variation in efficacy and safety among the currently available low-molecular-weight heparin preparations.     

Pasteurisation induced changes in an antithrombin III concentrate

The changes that take place when a therapeutic antithrombin III (AT III) concentrate is heated in the presence of citrate ion have been assessed. There is some loss of heparin cofactor antithrombin activity and of heparin binding ability. Protein aggregates are also formed during heating. These aggregates are not AT III but impurities in the concentrate.     

Binding, internalization and degradation of heparin and heparin fragments by cultured endothelial cells

We have studied the binding to bovine adrenal capillary endothelial cells cultured in vitro of heparin from different sources (porcine heparin Ep. 152 P, Av.M.W. 15.9 Kd and bovine heparin Ep. 756 P, Av.M.W. 12.9 Kd) and heparin fractions of various molecular weights (low molecular weight heparin, LMW 2123 OP, Av.M.W. 4.5 Kd and very low molecular weight heparin, VLMW 1027/45 OP Av.M.W. 2.1 Kd). The binding was specific for heparin; heparan sulphate showed some competition whereas dextran sulphate and glycosaminoglycans did not. We determined the affinity of heparin and heparin fragments for endothelial cells by means of displacement of bound 3H-labeled heparin in response to increasing concentration of unlabeled compounds. The binding of the different heparin fractions depends on their molecular weights. VLMW 1027/45 OP was unable to bind to the cells, whereas LMW 2123 OP showed an affinity 10 times lower then porcine heparin. Bovine adrenal capillary endothelial cells incubated with unfractionated 3H-labeled heparin selectively bound internalized and degraded high molecular weight heparin fractions, as shown by gel filtration of the 3H-labeled heparin both after binding to the cells and after internalization.     

Selective PF4 release in vitro induced by heparin and related glycosaminoglycans (GAGs)--correlation with beta-TG release and platelet aggregation

We studied human platelet aggregation and beta-TG/PF4 release induced by heparin and related GAGs in vitro both in normal PRP and in PRP after aspirin. In our experimental conditions, heparin and related GAGs always caused PF4 release in vitro from normal platelets, whether or not there was measurable platelet aggregation in the aggregometer. Significant beta-TG release was induced only by the mucosal heparin preparation (which also induced platelet aggregation in some citrated PRP). Therefore, while beta-TG release in vitro seems to correlate with platelet aggregating activity of heparin, the selective PF4 release, caused by heparin and related GAGs also in conditions in which neither platelet aggregation nor beta-TG are measurable, is probably associated with the high affinity of PF4 for heparin. The degree of affinity of GAGs for PF4 (heparin greater than DeS greater than HS) seems to correlate with PF4 release. Moreover, the significant reduction in PF4 release in vitro after aspirin suggests that GAGs-induced PF4 release is related to a cyclooxygenase-dependent activation process.     

CXCL4-platelet factor 4, heparin-induced thrombocytopenia and cancer

Platelet factor 4 (CXCL4-PF4) is a chemokine that binds to and neutralizes heparin and other negatively charged proteoglycans, but is also involved in angiogenesis and cancer development. In some patients exposed to heparin, antibodies are generated against the CXCL-PF4/heparin complex that may activate platelets and coagulation and lead to thrombocytopenia and arterial or venous thrombosis, a condition commonly named heparin induced thrombocytopenia (HIT). HIT has been investigated in numerous clinical settings, but there is limited data on the epidemiology and phenotype of HIT in cancer patients. The present review describes the role of CXCL4-PF4 in cancer, the immunobiology, clinical presentation and diagnosis of HIT, and the specific problems faced in cancer patients.     

Antithrombotic properties of heparin in a neonatal piglet model of thrombin-induced thrombosis

The relative deficiency of antithrombin III (AT III) in neonatal plasma results in lower recovery of heparin in some assay systems. It is uncertain whether low AT III levels also limit the antithrombotic effects of heparin in this age group. We therefore compared the antithrombotic properties of heparin in mature pigs and newborn piglets, whose coagulation and inhibitor system closely resembles that of the human neonate. Animals were pretreated with saline, 10 or 25 U/kg heparin (n greater than or equal to 16 per age group and dose). Following an injection of 100 U/kg thrombin, systemic 125I-fibrinogen consumption and local 125I-fibrinogen incorporation into jugular venous stasis thrombi were measured. Significantly more 125I-fibrinogen was consumed in piglets than in pigs systemically (p less than 0.0001), as well as within the occluded vein segment (p = 0.0112), largely because heparin was less effective in piglets than in pigs. This neonatal resistance to heparin could not be explained by lower heparin levels in the newborn animals. However, pretreatment with AT III concentrate significantly improved the antithrombotic properties of heparin in this age group (p less than 0.0001). We conclude that physiologically low AT III levels reduce the efficacy of heparin in neutralizing thrombin activity in newborn piglets. We speculate that AT III deficiency may also limit the antithrombotic properties of heparin in newborn infants with thrombotic disease.