间歇性充气加压疗法对下肢深静脉血栓患者血液流变学的影响

目的：观察间歇性充气加压疗法（intermittent pneumatic compression,IPC）对下肢深静脉血栓形成（deep vein thrombosis oflower limbs,DVT）患者的治疗效果,并从血液流变学方面探讨间歇性充气加压的作用机理。方法：2003年3月-2010年9月我科收治的243例下肢深静脉血栓患者,将其中42例IPC治疗病例定为B组实验组,145例单纯药物治疗病例中选取60例定为A组对照组。观察两组患者血液流变学指标和小腿肿胀消退情况的对比。结果：两组患者全血粘度、红细胞聚集指数、红细胞电泳时间、红细胞变形性,在治疗第1天较入院时无差异,组间无差异（P〉0.05）,第3天较入院时有差异（P〈0.05）,组间第3天有差异（P〈0.05）,两组患者下肢肿胀度均明显消退,但B组肿胀消退速度明显快于对照组（P〈0.05）。结论：间歇性充气加压治疗仪可有效改变血液流变学状态,改善血液高凝状态,有效缓解肢体肿胀症状,缩短住院时间。且不增加治疗难度,使用简单,治疗依从性好。     

两种介入途径治疗急性、亚急性门静脉及肠系膜上静脉血栓的临床疗效分析

目的：评价介入技术治疗急性和亚急性门静脉（portal vein,PV）及肠系膜上静脉（superior mesenterie vein, SMV）血栓形成的临床疗效。方法：对28例治疗急性和亚急性（发病一周至一月）的PV及SMV血栓患者进行介入治疗。按介入治疗途径不同分为下述两组：选择经颈静脉穿刺门静脉（transjugular intrahepatic portosystemic shunt , TIPS途径）置管溶栓（19例）和经皮穿肝内门脉（percutaneous transhepatic）置管溶栓治疗（9例）。结果：所有患者随访一周至三个月,其中治疗成功24例,临床症状明显改善,无严重并发症。经TIPS途径治疗的患者组中,16例随访显示大部分血栓被清除,门静脉系统有血流通过,临床症状缓解。3例SMV及PV恢复部分血流,但临床症状无明显改善。经皮穿肝内门脉直接置管溶栓治疗组中,6例患者的PV及SMV内血栓大部分清除,血流基本改善,2例患者PV及SMV血流部分好转,临床症状无明显改善,严重并发症1例（术后两天死于腹腔出血）。结论：经TIPS途径介入技术和经皮穿肝内门脉直接置管溶栓治疗是治疗急性和亚急性PV及SMV血栓形成的有效方法,前者的疗效及安全性均好于后者。     

术前血浆D二聚体水平对全膝关节置换术后下肢深静脉血栓形成的预测

目的:探讨术前三天血浆D-二聚体水平是否与人工全膝关节置换术(TKA)术后病人下肢深静脉血栓(DVT)的发生相关。方法:89名拟行TKA的病人在术前三天时行血浆D二聚体检测。在术后并未接受预防性抗凝措施。在术后6-10天左右予以双下肢血管彩超,如果在术后更早期出现临床症状,则立即予以双下肢血管彩超检查。结果:89名行TKA手术病人均在术前行血浆D二聚体检测。术后在46名(52%)的病人的血管彩超中发现DVT。以500ng/ml为临界值,D二聚体对DVT发生预测的敏感性,特异性,阳性和阴性值分别为59%,47%,56%,和51%。结论:此研究结果表明术前血浆D二聚体无法对TKA术后DVT进行预测。     

Iodine-131-lipiodol therapy in hepatic tumours

The incidence of hepatocellular carcinoma (HCC) is worldwide sharply on the rise and patients with advanced disease carry a poor prognosis. HCC is the sixth most common cancer and the third leading cause of cancer associated deaths in the world. Intra-arterially administered ¹³¹I-Lipiodol is selectively retained by hepatocellular carcinomas, and has been used as a vehicle for delivery of therapeutic agents to these tumours. In this review we focus on the therapeutic indications, usefulness and methods of treatment with 131-Iodine Lipiodol.The effectiveness of ¹³¹I-Lipiodol treatment is proven both in the treatment of HCC with portal thrombosis and also as an adjuvant to surgery after the resection of HCCs. It is at least as effective as chemoembolization and is tolerated much better. Severe liver dysfunction represents theoretic contraindication for radioembolization as well as for TACE. In such cases ¹³¹I-Lipiodol is an alternative therapy option especially in tumours smaller than 6 cm.     

The clinical and laboratory manifestations profile of antiphospholipid syndrome among Saudi Arabia population: Examining the applicability of Sapporo criteria

Antiphospholipid syndrome is a organized autoimmune disease presented with vascular thrombosis and pregnancy morbidity. The Sapporo classification criteria of APS were revised in 2006 and are used as the main diagnosis guideline, which validity as standard measurements is still in debate. This study observe the clinical and laboratory indices of APS among Saudi patients. This is a retrospective study hospital-based population. The clinical and Laboratory manifestations of diagnosed APS patients from electronical medical records identifies by ICD-9 code 795.79 in the King Saud University Medical City, Riyadh, Saudi Arabia, between 1990 and 2012. We selected patients with ICD-9 code 795.79 as. Sapporo criteria applied to all patients, then divided into cases fulfilled criteria and cases failed the criteria. To notice the difference in clinical and laboratory indices and comorbidities between the two groups, the T-test was performed and Logistic regression for the fulfilled criteria and clinical indices of vascular thrombosis, DVT/PE, recurrent, and pregnancy morbidity. A total of 72 (90%) females and 8 (10%) males, with the female-to-male ratio 9:1. The mean (±SD) age at diagnosis was 28.1 (±8.7) years (range 11–63 years). There were 22 patients (27.5%) attained the revised criteria (APS confirmed) and no significant difference between the two groups was observed (p > 0.2). However, we found Sapporo confirmed APS cases had significantly higher percentage of serological manifestation presence than clinically diagnosed APS cases. Though there is no statistically significance, Sapporo confirmed APS cases had advanced odds of undergoing vascular thrombosis (OR = 1.61, 95%CI) and DVT/PE (OR = 1.53, 95%CI) and lesser odds of undergoing recurrent DVT/PE (OR = 0.67, 95%CI) and pregnancy morbidity (OR = 0.63, 95%CI) than the clinically diagnosed APS cases. Over 70% of the study population with diagnosed APS did not accomplish the revised Sapporo criteria due to negative laboratory manifestations, which reflects heterogeneous but not degreed disease severity profiles.     

Oxidation-induced destabilization of the fibrinogen αC-domain dimer investigated by molecular dynamics simulations

Upon activation, fibrinogen is converted to insoluble fibrin, which assembles into long strings called protofibrils. These aggregate laterally to form a fibrin matrix that stabilizes a blood clot. Lateral aggregation of protofibrils is mediated by the αC domain, a partially structured fragment located in a disordered region of fibrinogen. Polymerization of αC domains links multiple fibrin molecules with each other enabling the formation of thick fibrin fibers and a fibrin matrix that is stable but can also be digested by enzymes. However, oxidizing agents produced during the inflammatory response have been shown to cause thinner fibrin fibers resulting in denser clots, which are harder to proteolyze and pose the risk of deep vein thrombosis and lung embolism. Oxidation of Met⁴⁷⁶ located within the αC domain is thought to hinder its ability to polymerize disrupting the lateral aggregation of protofibrils and leading to the observed thinner fibers. How αC domains assemble into polymers is still unclear and yet this knowledge would shed light on the mechanism through which oxidation weakens the lateral aggregation of protofibrils. This study used temperature replica exchange molecular dynamics simulations to investigate the αC-domain dimer and how this is affected by oxidation of Met⁴⁷⁶. Analysis of the trajectories revealed that multiple stable binding modes were sampled between two αC domains while oxidation decreased the likelihood of dimer formation. Furthermore, the side chain of Met⁴⁷⁶ was observed to act as a docking spot for the binding and this function was impaired by its conversion to methionine sulfoxide.     

Molecular docking‐assisted screening reveals tannic acid as a natural protein disulphide isomerase inhibitor with antiplatelet and antithrombotic activities

Protein disulphide isomerase (PDI) promotes platelet activation and constitutes a novel antithrombotic target. In this study, we reported that a PDI‐binding plant polyphenol, tannic acid (TA), inhibits PDI activity, platelet activation and thrombus formation. Molecular docking using plant polyphenols from dietary sources with cardiovascular benefits revealed TA as the most potent binding molecule with PDI active centre. Surface plasmon resonance demonstrated that TA bound PDI with high affinity. Using Di‐eosin‐glutathione disulphide fluorescence assay and PDI assay kit, we showed that TA inhibited PDI activity. In isolated platelets, TA inhibited platelet aggregation stimulated by either GPVI or ITAM pathway agonists. Flow cytometry showed that TA inhibited thrombin‐ or CRP‐stimulated platelet activation, as reflected by reduced granule secretion and integrin activation. TA also reduced platelet spreading on immobilized fibrinogen and platelet adhesion under flow conditions. In a laser‐induced vascular injury mouse model, intraperitoneal injection of TA significantly decreased the size of cremaster arteriole thrombi. No prolongation of mouse jugular vein and tail‐bleeding time was observed after TA administration. Therefore, we identified TA from natural polyphenols as a novel inhibitor of PDI function. TA inhibits platelet activation and thrombus formation, suggesting it as a potential antithrombotic agent.     

人vWF-A1多肽的融合表达及生物学活性鉴定

血管性血友病因子 (vWF)通过与血小板膜糖蛋白结合介导血小板的粘附和聚集 ,在血栓形成过程中发挥重要作用 .通过阻断血小板与vWF的结合可抑制血栓形成 .应用RT PCR方法从人脐带内皮细胞中克隆vWF A1区基因并在原核细胞内进行表达 ,经过纯化、复性 ,获得重组蛋白(rvWF A1) .用流式细胞术检测rvWF A1与转染了糖蛋白Ib(GPⅠb)的CHO K1细胞和血小板GPⅠb的结合能力 ,血小板聚集仪测定rvWF A1对瑞斯托霉素 (ristocetin)诱导的血小板聚集作用的影响 .重组表达载体pET 2 0b(+ ) vWF A1在大肠杆菌BL2 1(DE3)plus中得到有效表达 ,表达的重组蛋白量占菌体总蛋白 30 % .次氮基三乙酸镍琼脂糖 (Ni NTAagarose)柱纯化后 ,其纯度为 95 % .经复性的rvWF A1蛋白具有良好的生物学活性 ,它可与转染了GPⅠb的CHO K1细胞和血小板结合 ,阳性率分别为 96 90 %与 78 6 0 % ,且可以抑制ristocetin诱导的血小板聚集 ,其抑制效应呈剂量依赖性 .IC50 的rvWF A1浓度为 0 5 6 μmol L ,当浓度为 1 4 μmol L时抑制率最高达 84 70 % .结果表明 ,在原核细胞中表达人rvWF A1区蛋白可抑制血浆中野生型vWF与血小板的结合 ,具有抗血栓形成的潜在应用前景     

天麻醒脑胶囊对家兔血小板聚集和花生四烯酸诱导大鼠脑血栓形成的影响

采用比浊方法测定天麻醒脑胶囊在体内和体外对腺苷二磷酸（ADP）、花生四烯酸（arachidonic acid,AA）和血小板活化因子（platelet activating factor,PAF）诱导家兔血小板活化聚集的影响。采用从经大鼠颈内动脉注射诱发同侧大脑半球脑血栓形成方法评价天麻醒脑胶囊的抗脑血栓形成作用。天麻醒脑胶囊在体外呈浓度依赖性明显抑制从和ADP引起的血小板聚集,其半数抑制浓度（50％of inhibitory concentration,IC50）分别为1．83和3．25g/L。0．5和1g/kg的天麻醒脑胶囊于灌胃后明显抑制从诱导的家兔血小板聚集,本品1g/kg时显著阻抑ADP引起的血小板聚集。天麻醒脑胶囊在体内外对PAF诱导的血小板聚集均无明显影响。1、2g/kg天麻醒脑胶囊组的右侧与左侧脑重差值均显著减小,显著降低右脑伊文思蓝吸光度与右脑重的比值。结果提示,天麻醒脑胶囊具有较强的抗血小板和减轻脑血栓形成作用,有利于血小板聚集性增高的血栓栓塞性疾病的防治。     

Supra-annular Valve-in-Valve implantation reduces blood stasis on the transcatheter aortic valve leaflets

Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) and Valve-in-Valve (ViV) procedures has been increasingly recognized. This study aimed to investigate the effect of positioning of the transcatheter aortic valve (TAV) in ViV setting on the flow dynamics aspect of post-ViV thrombosis by quantifying the blood stasis in the intra-annular and supra-annular settings. To that end, two idealized computational models, representing ViV intra-annular and supra-annular positioning of a TAV were developed in a patient-specific geometry. Three-dimensional flow fields were then obtained via fluid-solid interaction modeling to study the difference in blood residence time (BRT) on the TAV leaflets in the two settings. At the end of diastole, a strip of high BRT ($⩾1.2s$) region was observed on the TAV leaflets in the ViV intra-annular positioning at the fixed boundary where the leaflets are attached to the frame. Such a high BRT region was absent on the TAV leaflets in the supra-annular positioning. The maximum value of BRT on the surface of non-, right, and left coronary leaflets of the TAV in the supra-annular positioning were 53%, 11%, and 27% smaller compared to the intra-annular positioning, respectively. It was concluded that the geometric confinement of TAV by the leaflets of the failed bioprosthetic valve in ViV intra-annular positioning increases the BRT on the leaflets and may act as a permissive factor in valvular thrombosis. The absence of such a geometric confinement in the ViV supra-annular positioning leads to smaller BRT and subsequently less likelihood of leaflet thrombosis.