亚低温对脑弥漫性轴索损伤后凝血功能和血液流变性改变的影响

目的探讨脑弥漫性轴索损伤(DAI)后凝血功能和血液流变学指标改变以及亚低温治疗的影响。方法对47例DAI患者伤后凝血功能和血液流变学指标进行分析,并将其分为亚低温治疗组22例和常温治疗组25例,同时设正常对照组40例。结果DAI患者伤后血小板计数、纤维蛋白原含量、血浆D-二聚体含量、血浆粘度、全血高切还原粘度和红细胞刚性指数均显著升高;常温治疗组血小板计数和血浆D-二聚体含量仍持续增高,纤维蛋白原含量则明显下降,血液流变学指标也均有不同程度升高;亚低温治疗组则使血小板计数、纤维蛋白原含量、血浆粘度及红细胞刚性指数接近于正常对照组水平,D-二聚体含量也明显降低。未见亚低温对预后的显著影响。结论DAI患者伤后即表现为高凝血状态,血液粘滞性升高,随后表现为纤溶亢进。亚低温治疗对伤后的凝血与纤溶系统以及血液流变性具有明显的调节和改善作用,但对患者预后未见明显影响。     

脑梗死患者血清纤维蛋白原和D-二聚体含量的变化及其意义

目的　探讨脑梗死患者急性期、亚急性期和恢复期血清纤维蛋白原、D-二聚体含量的变化及其意义。方法　对 6 0例脑梗死患者急性期、亚急性期和恢复期纤维蛋白原、D-二聚体的含量进行测定 ,并与 30名健康对照者进行比较。结果　纤维蛋白原和 D-二聚体的含量在 3个阶段均较对照组显著升高 (P<0 .0 1) ,升高的程度与梗死体积密切相关 ;纤维蛋白原的含量在 3个阶段之间比较无显著性差异 (P>0 .0 5 ) ,而 D-二聚体的含量在亚急性期显著升高 (P<0 .0 5 ) ,恢复期开始下降。结论　缺血性脑血管疾病的发生和发展与凝血 -纤溶系统的异常有密切关系     

急性脑梗死患者血清纤维蛋白原、D-二聚体与颈动脉粥样硬化斑块的相关性研究

目的 探讨急性脑梗死患者血清纤维蛋白原、D-二聚体与颈动脉粥样硬化斑块的关系. 方法 选择解放军第三医院神经内科自2009年4月至2011年4月收治的120例急性脑梗死患者(脑梗死组)、同期单纯颈动脉粥样硬化而无脑梗死患者60例(颈动脉粥样硬化组)和健康体检者80例(正常对照组)作为研究对象,采用双抗体夹心法测定血清D-二聚体含量,全自动血凝仪测定纤维蛋白原含量,颈动脉彩色多普勒超声检测患者颈动脉粥样硬化斑块和颈动脉内一中膜厚度(IMT)值. 结果 脑梗死组、颈动脉粥样硬化组及正常对照组血清纤维蛋白原、D-二聚体水平及颈动脉IMT值依次降低,差异有统计学意义(P＜0.05);进展性卒中患者血清纤维蛋白原、D-二聚体水平高于非进展性卒中患者,差异有统计学意义(P＜0.05);随着动脉粥样硬化严重程度的升高,脑梗死患者血清纤维蛋白原及D-二聚体水平逐渐升高,差异有统计学意义(P＜0.05);脑梗死患者血清纤维蛋白原、D-二聚体水平均与颈动脉粥样硬化严重程度呈正相关关系(r=0.426,P=0.006; r=0.535,P=0.001). 结论 纤维蛋白原及D-二聚体参与了急性脑梗死的发生发展,与病情进展密切相关.二者做为急时相反应物参与动脉粥样硬化的发生机制提示,相对于高凝状态,动脉粥样硬化的形成与慢性炎症反应关系更为密切.     

再发脑梗死患者血浆D-二聚体与纤维蛋白原变化的临床意义

目的探讨脑再梗死患者与初次脑梗死患者的血浆D-二聚体、纤维蛋白原的改变。方法分别对68例初次脑梗死患者及68例脑再梗死患者的血浆D-二聚体、纤维蛋白原进行测定并对不同脑再梗死体积患者血浆D-二聚体、纤维蛋白原含量进行对比。结果再次脑梗死组血浆D-二聚体、纤维蛋白原均高于初次脑梗死组(P<0.05);在再次脑梗死组大面积梗死灶患者血浆D-二聚体、纤维蛋白原含量明显高于中、小面积梗死灶者(P<0.05)。结论血浆D-二聚体、纤维蛋白原的变化与脑再梗死的发生及预后有一定的关系,是再发脑梗死事件的重要危险因素。     

血浆B型脑钠肽前体和D-二聚体水平对急性脑梗死预后的影响

目的探讨急性脑梗死患者血浆B型脑钠肽前体(NT-proBNP)和D-二聚体水平对预后的影响。方法采用前瞻性对照研究。急性脑梗死组50例,为发病24h内住院的脑梗死患者;对照组20例,为本院同期的非脑血管疾病患者。观察指标:入院时血浆NT-proBNP和D-二聚体水平;患者一般情况;脑梗死面积;NIHSS评分;随访3个月时的预后。结果脑梗死组入院时血浆NT-proBNP和D-二聚体水平显著高于对照组(P<0.05);大面积脑梗死组NT-proBNP和D-二聚体水平显著高于非大面积脑梗死组(P<0.0 5)。有意识障碍者和高血压组血浆NT-proBNP和D-二聚体水平明显高于无意识障碍和正常血压组。随访3个月时,10例死亡,死亡组血浆NT-proB-NP和D-二聚体水平高于存活组。结论急性脑梗死后血浆NT-proBNP和D-二聚体水平增高。梗死面积越大,血浆NT-proBNP和D-二聚体水平越高,脑梗死预后越差。因此,血浆NT-proBNP和D-二聚体水平有可能成为监测脑梗死患者病情变化和预测预后的重要及快捷的指标之一。     

原发性肾病综合征合并脑梗死患者的临床特征及发病机制研究

目的观察原发性肾病综合征合并脑梗死患者的临床特征,并对其发病机制进行研究。方法选择我院收治的31例PNS合并脑梗死患者为研究组,并选择我院同期收治的31例排除脑梗死表现的PNS患者为对照组,对2组血小板计数(PLA)、血浆白蛋白(SALB)、总胆固醇(CHOL)、24h尿蛋白、三酰甘油(TG)、D-二聚体及血纤维蛋白原(FIB)水平进行实验室检测并比较。同时,对2组临床症状(高血压、水肿、蛋白尿、低蛋白血症、高脂血症、血小板增高及纤维蛋白原增高)发生率进行比较。结果研究组PLA、CHOL、TG、D-二聚体及FIB水平均显著高于对照组(P0.05),而SALB水平显著低于对照组(P0.05),研究组水肿、蛋白尿、低蛋白血症、高脂血症、血小板增高及纤维蛋白原增高发生率显著高于对照组(P0.05)。结论蛋白及脂类代谢紊乱和血液高凝状态是原发性肾病综合征合并脑梗死的重要发生机制。同时,肾病综合征引起的水肿、蛋白尿、低蛋白血症、高脂血症、血小板增高及纤维蛋白原增高是引起原发性肾病综合征合并脑梗死的重要因素。     

依达拉奉辅助亚低温对重型颅脑创伤的血清细胞因子及凝血功能的影响

目的探讨依达拉奉辅助亚低温治疗对重型颅脑创伤（TBI）患者的凝血功能及神经生长因子（NGF）、降钙素基因相关肽（CGRP）的影响。 方法选取沧州市中心医院神经外三科自2018年8月至2019年8月收治的62例重型TBI患者,按随机数字表法分为观察组（31例）和对照组（31例）。对照组患者给予亚低温治疗,观察组患者在亚低温治疗基础上给予依达拉奉辅助治疗14 d。比较2组患者的神经功能缺损评分和疗效,观察治疗前后患者的脑内凝血功能以及血清内NGF、CGRP含量的变化。 结果观察组患者的临床治疗有效率显著高于对照组（P<0.05）。观察组患者采用依达拉奉辅助亚低温治疗后颅内水肿面积显著降低,大脑中动脉平均血流速度明显升高,美国国立卫生研究院卒中量表评分水平显著下降,巴塞尔指数评定量表评分和GCS评分显著增高,差异有统计学意义（P<0.05）。观察组患者采用依达拉奉辅助亚低温治疗后NGF、CGRP水平明显升高,血浆D-二聚体、纤维蛋白原、凝血酶原时间、凝血酶原时间国际标准比值、活化部分凝血活酶时间、凝血酶时间显著下降,抗凝血酶显著上升,差异均有统计学意义（P<0.05）。 结论依达拉奉辅助亚低温治疗重型TBI的临床治疗效果较好,安全性较高,可有效恢复患者的凝血功能,促进NGF、CGRP表达。     

丹参酮ⅡA磺酸钠注射液治疗急性脑梗死临床疗效及对血清D-二聚体的影响

目的观察丹参酮ⅡA磺酸钠注射液对急性脑梗死患者的疗效及血清D-二聚体的影响。方法采用丹参酮ⅡA磺酸钠注射液静滴治疗急性脑梗死80例(治疗组),维脑路通静滴治疗急性脑梗死80例(对照组)。比较2组的临床疗效和治疗前后患者血清中D-二聚体的含量变化。结果治疗组及对照组总有效率分别为92.5%和80.0%,2组疗效比较差异有统计学意义(P<0.05)。2组患者血浆D-二聚体含量均明显下降;治疗组较对照组血浆D-二聚体含量下降更明显(P<0.05)。结论丹参酮ⅡA磺酸钠注射液治疗急性脑梗死有利于早期恢复脑血供,改善微循环,降低D-二聚体含量,调节体内凝血一纤溶系统功能平衡,促进患者康复,安全性好。     

急性脑梗死静脉溶栓治疗中凝血相关指标变化

目的:探讨纤维蛋白原、纤维蛋白降解产物、D-二聚体等凝血相关指标在急性缺血性脑卒中(AIS)静脉溶栓前后的改变。方法:选择80例发病后7h静脉内溶栓的急性大脑中动脉供血区AIS病例,观察溶栓前、溶栓后2h、溶栓后24h的凝血相关指标变化。结果:在AIS溶栓治疗中,纤维蛋白原在溶栓后2h较溶栓前降低(P<0.01),溶栓24h后上升(P<0.01),但仍低于溶栓前水平(P<0.05);纤维蛋白溶解产物在溶栓后2h较溶栓前升高(P<0.01),溶栓24h后下降(P<0.01);D-二聚体在溶栓后2h较溶栓前升高(P<0.01),溶栓24h后降低(P<0.01),但仍高于溶栓前(P<0.01);ⅩⅢ因子水平在溶栓24h后明显下降(P<0.01);α2-抗纤溶酶水平在溶栓后2h较溶栓前下降(P<0.01),溶栓24h后上升(P<0.01),但仍低于溶栓前水平(P<0.01);纤溶酶原水平在溶栓后2h较溶栓前下降(P<0.01),溶栓24h后上升(P<0.01),但仍低于溶栓前水平(P<0.01);血小板在溶栓治疗后低于溶栓前,尤其是溶栓24h后(P<0.05)。结论:在AIS溶栓治疗中,纤维蛋白原、ⅩⅢ因子、α2-抗纤溶酶、纤维蛋白溶解酶原、D-二聚体、纤维蛋白降解产物及血小板都发生明显变化,与纤溶作用机制相符。     

急性缺血性脑卒中TOAST分型与血浆D-二聚体的相关研究

目的探讨不同亚型急性缺血性脑卒中患者血浆D-二聚体含量的变化及其意义。方法 107例急性缺血性脑卒中患者按照TOAST标准进行病因学分型,大动脉粥样硬化性脑卒中(large-artery athero-sclerosis,LAA),小动脉闭塞性脑卒中或腔隙性脑卒中(small artery occlusion,SAO),心源性脑栓塞(cardio-embolism,CE),其他确定原因引起的缺血性脑卒中(stroke of other demonstrated etiology,SOE)和不明原因的缺血性脑卒中(stroke of undemomtrated etiology,SUE)。用酶联免疫吸附试验检测急性缺血性脑卒中患者发病后1、7和14d时血浆D-二聚体含量,并与65例对照者进行比较。结果在急性缺血性脑卒中亚型组血浆D-二聚体含量显著高于对照组(P0.05);在急性期(第1d)增高,在高峰期(第7d)较急性期明显增高,在恢复期(第14d)下降至急性期水平,仍明显高于正常值;在急性缺血性脑卒中组中CE组血浆D-二聚体含量最高,显著高于其他各亚型组(P0.05);LAA组血浆D-二聚体含量也显著高于SAO组、SUE组和SOE组(P0.05).结论在急性缺血性脑卒中血浆D-二聚体含量升高明显,不同亚型的升高程度不同,这对于临床早期分型诊断并及时给予相应治疗具有重要意义。     

亚低温治疗重型颅脑损伤病人纤维蛋白原和D-二聚体的变化及其临床意义

目的观察重型颅脑损伤病人在亚低温和常温治疗状态下纤维蛋白原(Fbg)与D-二聚体(D-dimer)差异及其临床意义。方法43例单纯性、重型颅脑损伤病人随机分为亚低温治疗组和常温组,两组性别、年龄、GCS评分无显著差异。伤后5次(6h、12h、24h、48h、72h)检测Fbg和D-dimer,并记录GOS评分。结果①两组Fbg值在伤后6h、12h、24h、48h差异显著,但伤后72h两组差异不显著。两组Fbg值在伤后6h均较高,常温组升高幅度更明显。两组Fbg值在伤后12h下降,亚低温组降低程度较常温组小。②两组D-dimer在伤后6h明显升高,常温组升高更明显;其在伤后6h、12h、24h差异显著,而在伤后48h、72h差异不显著。③亚低温组GOS评分优于常温组,差异显著。结论在颅脑损伤后4h即开始实施亚低温治疗能改善伤后的高凝状态,并减轻继发纤溶亢进。亚低温治疗缓解了凝血功能紊乱,是其能起到脑保护作用和改善治疗效果的机制之一。     

Hemostatic variation during perioperative period of orthotopic liver transplantation without venovenous bypass

OBJECTIVES: To measure the variations of different parameters in the hemostatic system and to analyze their roles in the development of hemostatic disorder in patients with orthotopic liver transplantation (OLT) procedures routinely performed without venovenous bypass. METHODS: The blood coagulation and fibrinolysis parameters were analyzed in 20 patients who underwent liver transplantation. Blood samples were drawn from the radial artery at serial time points during perioperative period. Prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, vWF, antithrombin III (AT-III), protein C (PC), tissue factor pathway inhibitor (TFPI), plasminogen (PLG), alpha2-antiplasmin (alpha2-AP), and D-dimer were analyzed. RESULTS: Hemoglobin, platelet count, and fibrinogen were significantly decreased during anhepatic and reperfusion phases compared with preoperative values (P<0.01). VWF activity only showed significant increase during the reperfusion 60 min compared with preoperative value (P<0.05). PT, INR, aPTT, and TT were prolonged progressively, and they reached the maximum values at the beginning reperfusion 15 min compared with preoperative values (P<0.01). The AT-III, PC, TFPI, PLG, and alpha2-AP levels were decreased significantly and D-dimer level was elevated significantly throughout the intraoperative period. In the postoperative period, these parameters progressively returned to preoperative levels. CONCLUSIONS: In the entire process of OLT operation, coagulation defects, hyperfibrinolysis and platelet numbers decrease could develop hemostatic disorder. The data obtained in this study might contribute to a better understanding of the pathophysiology and assessment of bleeding risk in the OLT.     

轻中度颅脑损伤后凝血功能变化与手术预测的关系

目的探讨轻中度颅脑损伤(TBI)后凝血功能变化与手术预测之间的关系。方法 2013年10月~2015年9月在我院治疗的55例轻中度TBI患者,根据住院期间是否需要开颅手术分为手术组(8例)和非手术组(47例)。比较两组患者入院时血小板计数、纤维蛋白降解产物(FDP)、国际标准化比值(INR)、部分凝血活酶时间(APTT)、纤维蛋白原和D-二聚体之间的差异。结果手术组患者凝血功能明显低于非手术组,其中APTT、FDP和D二聚体明显低于非手术组(P0.05~0.01);而两组血小板计数、INR和纤维蛋白原比较,差异无统计学意义(均P0.05)。结论轻中度TBI患者凝血功能障碍和异常纤维蛋白原溶解与手术预测相关;临床应将其用于预测TBI患者的手术需要及预后。     

血清肾脏功能指标、炎症指标及凝血-纤溶指标与脑小血管病的关系

目的探讨血清肾脏功能指标、炎症指标及凝血-纤溶指标与脑小血管病(CSVD)的关系。方法收集68例CSVD患者及30例头颅MRI和神经系统查体均正常者的临床资料,并检测相关血液指标。入院后行头颅MRI检查,根据MRI结果将CSVD患者分为急性亚组和慢性亚组。结果对照组与CSVD组年龄、高血压病比率、胱抑素C、尿酸、肾小球滤过率、纤维蛋白原、D-二聚体、超敏C反应蛋白(hs-CRP)水平差异有统计学意义(均P<0.05)。CSVD组急性亚组及慢性亚组血肌酐水平、白细胞计数差异有统计学意义(均P<0.05)。调整混杂因素后,年龄、高血压病、胱抑素C、尿酸、hs-CRP及D-二聚体为CSVD的独立危险因素(均P<0.05);慢性CSVD的独立危险因素与CSVD相同(均P<0.05),而急性CSVD的独立危险因素为年龄、高血压病、胱抑素C、尿酸和D-二聚体(均P<0.05)。结论年龄、高血压病、胱抑素C、尿酸、CRP及D-二聚体是CSVD及慢性CSVD的独立危险因素,年龄、高血压病、胱抑素C、尿酸和D-二聚体是急性CSVD的独立危险因素。     

Replication and characterisation of genetic variants in the fibrinogen gene cluster with plasma fibrinogen levels and haematological traits in the Third National Health and Nutrition Examination Survey

Previous genetic association studies of the fibrinogen gene cluster have identified associations with plasma fibrinogen levels. These studies are typically limited to plasma fibrinogen measured among European-descent populations. We sought to replicate previous well-known associations with fibrinogen variants and plasma fibrinogen. We then sought to identify and characterise novel associations with fibrinogen variants with plasma fibrinogen and several haematological traits in three racial/ethnic populations. We genotyped 25 single nucleotide polymorphisms (SNPs) in the fibrinogen gene cluster in 2,631 non-Hispanic whites, 2,108 non-Hispanic blacks, and 2,073 Mexican-Americans from the Third National Health and Nutrition Examination Survey (NHANES). We performed single SNP tests of association for plasma fibrinogen, mean platelet volume, platelet distribution width, platelet count, white blood cell count, and serum triglycerides. Five previously identified associations with plasma fibrinogen replicated in our study in non-Hispanic whites and blacks. We identified two novel associations between genetic variants and decreased plasma fibrinogen: rs2227395 (p=0.0007; non-Hispanic whites) and rs2070022 (p=0.001; Mexican-Americans). Several fibrinogen SNPs were also associated with haematological traits: rs6050 with decreased platelet distribution width in non-Hispanic whites; rs6050 and rs2066879 with decreased and increased platelet distribution width, respectively, in non-Hispanic whites;rs2227409 with increased mean platelet volume, rs2070017 with decreased platelet count, and rs6063 with increased platelet distribution width in non-Hispanic blacks; and rs4220 and rs2227395 with decreased white blood cell count, rs2227409 with increased platelet distribution width, rs2066860 and rs1800792 with increased and decreased triclyceride levels, respectively, and rs1800792 with decreased platelet counts in Mexican-Americans. We successfully replicated and identified novel associations with fibrinogen variants and plasma fibrinogen. These data confirm the importance of the fibrinogen gene cluster for plasma fibrinogen levels as well as suggest this gene cluster may have pleiotropic effects on haematological traits.     

狼疮性脑病的临床特征及发生、发展的相关因素分析

目的 分析狼疮性脑病患者的临床特点及发生、发展的相关因素。方法 回顾性分析53例狼疮性脑病患者的临床资料,按随机配对原则分层抽取53例同期住院治疗诊断为系统性红斑狼疮(SLE)而无脑病的患者作为对照组,比较2组患者的临床资料,分析2组患者的临床差异,并进一步推断狼疮性脑病的可能危险因素。结果 神经系统症状中最为常见的分别是头痛38例(71.7%); 脑血管病24例(45.3%); 癫痫12例(22.6%); 狼疮性脑病组中血白细胞数升高、血小板计数减低、尿蛋白阳性率均明显高于对照组,抗核抗体(ANA)阳性例数低于对照组(P<0.05)。Logistic回归分析显示SLE患者白细胞计数、血小板计数以及尿蛋白阳性与狼疮脑病有关(P<0.05)。结论 头痛是狼疮性脑病最常见的神经系统症状; 血白细胞数升高、血小板计数减少可能是SLE患者发生狼疮性脑病的危险因素; 白细胞计数、血小板计数以及尿蛋白阳性可能与狼疮脑病有关。     

In vivo platelet release in myeloproliferative disorders

The in vivo platelet release reaction in 22 patients with myeloproliferative disorders has been studied by measuring plasma concentrations of the platelet release product beta-thromboglobulin (beta TG). Mean beta TG and mean beta TG: whole blood platelet count ratio were significantly raised in the patient group taken as a whole compared to an age matched control group. No significant increases were observed in the plasma concentrations of thrombin and plasmin sensitive fibrinogen fragments fibrinopeptide A (FpA) and B beta 1-42. The patients were divided into those who had normal, increased or decreased responses to in vitro ADP-induced platelet aggregation. Mean beta TG and the mean beta TG: whole blood platelet count ratio were higher in the increased and decreased responders to ADP than in the normal aggregation group, but the differences in means were not statistically significant. Aspirin given to six patients at a dose sufficient to eliminate the secondary phase of ADP-induced platelet aggregation reduced mean beta TG and the mean beta TG: whole blood platelet count ratio but did not alter mean FpA and B beta 1-42. It is concluded that the enhanced platelet release reaction seen in myeloproliferative disorders is independent of plasma protease activity that arises when coagulation and fibrinolytic systems are activated.     

Hemostatic markers and platelet aggregation factors as predictive markers for type of stroke and neurological disability following cerebral infarction.

We investigated the plasma levels of D-dimer, fibrinogen, beta-thromboglobulin (BTG) and platelet factor-4 (PF-4), indices of the occurrence of platelet activation in vivo, to find out their role in pathophysiology of ischemic stroke and whether or not such a role has any effect on the disability and the prognosis of stroke patients. A total of 76 patients with AIS aged from 26 to 85 (32 men, 44 women) and 30 cases as controls with similar age (18 men, 12 women) were included in the study. The plasma levels of D-dimer, BTG and PF-4 were measured by ELISA method using a special commercial kit. The cases were allocated into two groups as non-embolic (NEI) and cardioembolic stroke (CEI). The D-dimer levels in 76% of 42 patients in NEI group (p<0.05) and 85.2% of 34 patients in CEI group (p<0.05) were outside the confidence interval (CI) defined for the control group. The levels of BTG were elevated in 81% of 42 cases with NEI (p<0.05) and in 76% of 34 cases with CEI, with reference to CI of control group. The levels of PF-4 were significantly increased in 86% of cases with NEI (p<0.05) and in 88% of cases with CEI than controls (p<0.05). It was observed that the cases with high Rankin scores had higher levels of D-dimer (p<0.005), BTG (p<0.01) and PF-4 (p<0.01) than those with lower scores. There was a correlation between hemostatic markers, platelet activation and functional disability. D-dimer levels were an important marker that determined to degree of the activation of hemostatic system, especially in CEI subtype. The platelet aggregation had an important role in pathophysiology of ischemic stroke and this condition is significant in NEI subgroup and subjects with large infarcts and high disability scores.     

Platelet activation, coagulation and angiogenesis in breast and prostate carcinoma

In health, haemostasis and angiogenesis are tightly regulated processes, but may become deregulated in cancer. Recent evidence suggests that platelet activation may link these processes as platelets can release angiogenic factors such as vascular endothelial growth factor (VEGF). Furthermore, inflammation has also been implicated in regulating both coagulation and angiogenesis, possibly by activating platelets directly and increasing, for example, plasma fibrinogen. We hypothesized relationships between plasma markers of the processes in two common forms of cancer. Plasma levels of VEGF (reflecting angiogenesis), soluble P-selectin, (marking platelet activation), tissue factor [TF], fibrinogen and fibrin D-dimer (coagulation markers), and serum levels of IL-6 (inflammation) were measured by ELISA in 30 patients with biopsy-proven breast cancer, 30 patients with biopsy-proven prostate cancer, and 30 age- and sex-matched controls for each group. Prostate specific antigen was also measured in the men. Release of VEGF from IL-6 stimulated platelets was assessed by ELISA. Plasma levels of IL-6 (P <0.02), VEGF, soluble P-selectin, fibrinogen, and fibrin D-dimer (all p <0.01) were significantly raised in breast cancer, whereas VEGF, soluble P-selectin, fibrin D-dimer (all p <0.01) and fibrinogen (p <0.05) were significantly raised in prostate cancer. Significant correlations were found between IL-6 and VEGF (p <0.01), and IL-6 and soluble P-selectin (p = 0.038) in breast cancer. Further experiments demonstrated an in vitro IL-6 induced dose-dependent release of VEGF from platelets. In conclusion, strong relationships between IL6 and VEGF, but not with coagulation or platelet markers, and release of VEGF from IL-6 stimulated platelets, suggest a role for inflammation and platelets in angiogenesis.     

Effects of fixed low-dose warfarin, aspirin-warfarin combination therapy, and dose-adjusted warfarin on thrombogenesis in chronic atrial fibrillation

BACKGROUND AND PURPOSE: Recent clinical trials have established that adjusted-dose warfarin (international normalized ratio [INR] 2.0 to 3.0) is highly effective in the reduction of ischemic stroke in patients with nonvalvular atrial fibrillation (AF). We hypothesized that the introduction of fixed low-dose warfarin alone or in combination with aspirin (300 mg) could normalize hemostatic markers, namely plasma fibrin D-dimer (an index of thrombogenesis), plasminogen activator inhibitor-1 (PAI-1, an index of fibrinolysis), fibrinogen, and von Willebrand factor (vWf, an index of endothelial dysfunction), in a manner comparable to adjusted-dose warfarin (target INR 2.0 to 3.0). METJODS: Sixty-one patients with AF (44 men, mean+/-SD age 64+/-19 years) who were not receiving any antithrombotic therapy were prospectively randomized into 1 of 3 treatment groups: warfarin (2 mg) (n=23; group 1), combination 1 mg warfarin plus 300 mg aspirin (n=21; group 2) or combination 2 mg warfarin plus 300 mg aspirin (n=17; group 3). Subjects from all 3 AF groups were matched for sex, age, and blood pressure. Blood samples were taken for sequential measurements for changes in plasma fibrin D-dimer, PAI-1, fibrinogen, and vWf before and at 2 and 8 weeks after randomization (phase 1). All patients were subsequently offered adjusted-dose warfarin therapy (phase 2), and an additional blood sample was taken 6 weeks later. RESULTS: When pretreatment results were compared with those from 60 age- and sex-matched healthy control subjects in sinus rhythm, there were significant elevations in levels of fibrinogen (P=0.025), vWf (P<0.0001), and fibrin D-dimer (P<0.0001) in patients with AF compared with control subjects. There were no significant changes in the levels of various indices measured after 2 and 8 weeks of therapy in all 3 groups, except for an increase in PAI-1 level (P=0.024) in group 3. After 6 weeks of therapy with dose-adjusted warfarin (INR 2.0 to 3.0), there was a significant decrease in plasma fibrinogen (P=0.023) and fibrin D-dimer (P=0.0067) levels. There were no significant changes in the levels of PAI-1 (P=0.198) or vWf (P=0.33). CONCLUSIONS: The present results confirmed that high levels of vWf, fibrinogen, and fibrin D-dimer levels were present in patients with AF compared with control subjects. Moreover, the introduction of 300 mg aspirin plus low-dose warfarin (1 mg/d), low-dose warfarin alone (2 mg/d), or 300 mg aspirin plus low-dose warfarin (2 mg/d) did not significantly reduce any of the hemostatic markers studied (except PAI-1 levels), whereas conventional full-dose warfarin (INR 2.0 to 3.0) significantly reduced levels of fibrin D-dimer and fibrinogen. These results are in keeping with the disappointing ineffectiveness of low-intensity warfarin therapy, aspirin-warfarin combination, and ultralow-dose warfarin therapy in the recent prematurely terminated clinical trials and the established benefits of conventional adjusted-dose anticoagulation therapy.