2型糖尿病患者血浆凝血酶激活的纤溶抑制物变化观察

目的评价血浆凝血酶激活的纤溶抑制物(TAFI)在2型糖尿病患者凝血及纤溶功能变化中的作用。方法检测90例2型糖尿病患者和30例与患者年龄相匹配的健康者血浆中TAFI、组织纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制物(PAI-1)。结果TAFI的活性在2型糖尿病各组患者血浆中高于对照组(P<0.05),高蛋白尿组较尿蛋白正常组和低蛋白尿组升高(P<0.05)。t-PA在无并发症组低于对照组,但无统计学意义(P>0.05),高蛋白尿约较尿蛋白正常组和低蛋白尿组低(P<0.05)。PAI-1在2型糖尿病各组患者高于对照组(P<0.05),高蛋白尿组较尿蛋白正常组利低蛋白尿组升高(P<0.05)。TAFI的活性与t-PA和PAI-1含量有较好的相关性。结论检测2型糖尿病患者血浆中TAFI活性水平,对于预测2型糖尿病患者的微血管病变程度,防治2型糖尿病并发症有着重要意义。     

冠心病患者血浆中凝血酶活化的纤溶抑制物测定的意义

目的 了解冠心病患者急性期血浆中凝血酶活化的纤溶抑制物(TAFI)活性与抗原水平的变化.方法 用ELISA与发色底物法分别检测72例急性心肌梗死(AMI)患者、54例心绞痛患者和45名对照血浆中TAFI抗原及活性;同时用Clauss法检测血浆中的纤维蛋白原(Fib).结果 AMI组与心绞痛组之间以及二者与对照组之间的血浆TAFI抗原及活性水平的差异无统计学意义(P＞0.05),男性与女性之间差异也无统计学意义(P＞0.05);血浆TAFI抗原与活性之间有一定的相关性(r=0.692,P＜0.05);AMI组、心绞痛组与对照组之间血浆Fib水平的差异有统计学意义(P＜0.05).结论 冠心病患者发生AMI时,血浆中TAFI的活性与抗原水平没有显著的变化.     

中药降糖通脉方对2型糖尿病大鼠凝血和纤溶功能影响的实验研究

目的 观察2型糖尿病大鼠凝血和纤溶活性及降糖通脉方的干预作用.方法将Wistar大鼠随机分为正常对照组、糖尿病模型组、胰激肽原酶组及降糖通脉方组,每组10只.经尾静脉注射链脲佐菌素(STZ)并以高糖高脂饲料喂养诱导制备2型糖尿病大鼠模型.采用发色底物法检测大鼠血浆凝血酶激活的纤溶抑制物(TAFI)水平;用逆转录-聚合酶链反应(RT-PCR)测定主动脉组织型纤溶酶原激活物(t-PA)及其抑制物纤溶酶原激活物抑制剂1(PAI-1)的mRNA表达.结果糖尿病模型组血浆TAFI水平和主动脉PAI-1 mRNA表达均较正常对照组明显增高,主动脉t-PA mRNA表达较正常对照组明显降低(P<0.05或P<0.01).与糖尿病模型组比较,胰激肽原酶组和降糖通脉方组TAFI水平和PAI-1 mRNA表达均明显下降,t-PA mRNA表达明显增高,且降糖通脉方组作用明显(P<0.05或P<0.01).结论 2型糖尿病大鼠存在血栓前状态且纤溶功能受抑制;降糖通脉方能明显改善纤溶功能及血栓前状态,其疗效优于胰激肽原酶.     

水蛭素对凝血过程中凝血酶活化的纤溶抑制物的影响

凝血酶活化的纤溶抑制物（TAFI）是一种最近被证实的血浆中的纤溶抑制物，在凝血和纤溶方面具有重要的作用。van Tilburg等的研究显示，TAFI升高可使静脉血栓的危险性轻度增加。Hori等发现2型糖尿病患者TAFI血浆浓度和活性显著高于健康对照组，肥胖患者TAFI浓度和活性显著高于非肥胖的糖尿病患者和非肥胖的健康个体。     

凝血纤溶系统标志物动态变化在冠状动脉粥样硬化性心脏病的应用研究

目的探讨凝血纤溶系统的动态变化监测在冠状动脉粥样硬化性心脏病(CAHD)诊断和治疗中的应用价值。方法采用发色底物法对152例CAHD患者(CAHD组)及40例健康对照者(对照组)血浆抗凝血酶Ⅲ(ATⅢ)、蛋白C(PC)、纤溶酶原激活物抑制物-1(PAI-1)、凝血酶激活的纤溶抑制物活性(TAFI:A)水平进行检测。结果与对照组比较,CAHD组患者治疗前血浆ATⅢ、PC水平明显降低(P<0.05),PAI-1、TAFI:A水平明显升高(P<0.05);CAHD组患者治疗后,仅血浆PC水平与对照组比较差异有统计学意义(P<0.05)。结论血浆ATⅢ、PC、PAI-1、TAFI:A水平检测应用于CAHD的诊断和治疗具有一定的临床意义。     

葛根素治疗2型糖尿病及对凝血纤溶活性和内皮功能的影响

目的:观察葛根素对2型糖尿病患者的临床疗效并着重从其对凝血纤溶活性和内皮功能影响的角度探讨葛根素改善胰岛素抵抗的机制。方法:68例T 2DM患者随机分为治疗组和对照组各34例。分别检测治疗前及治疗后4周空腹血糖、空腹胰岛素、餐后2 h血糖、餐后2 h胰岛素、糖化血红蛋白、尿微量白蛋白、HOM A模型胰岛素抵抗指数、胰岛素敏感指数,血浆中凝血纤溶活性及内皮功能指标包括纤溶酶活组织型纤溶酶原激活剂活性、纤溶酶原激活物抑制剂活性、内皮素及一氧化氮。结果:经葛根素治疗后,T 2DM患者凝血纤溶系统活性改善、内皮素明显下降、一氧化氮明显增加,与对照组比较差异显著(P<0.05);尿微量白蛋白和HOM A模型胰岛素抵抗指数明显下降,胰岛素敏感指数明显提高,与对照组比较差异显著(P<0.05)。结论:葛根素可通过改善2型糖尿病患者凝血纤溶系统活性,调节血管内皮舒缩功能,减轻尿微量白蛋白的作用,发挥改善减轻胰岛素抵抗,提高胰岛素敏感性作用。     

凝血纤溶功能与2型糖尿病患者的关系

[目的]观察2型糖尿病(T2DM)患者凝血纤溶功能的变化.[方法]分析30例T2DM患者及30例健康对照者临床资料.比较两组血浆凝血酶激活的纤溶抑制物(TAFI)、血管性血友病因子(vWF)、纤维蛋白原(FIB)、(D)二聚体(D-D)水平.[结果]T2DM组TAFI、vWF、FIB、D-D水平校正常对照组均明显增高(P＜0.01).[结论]高水平的血浆TAFI、vWF、FIB、D-D与T2DM尤其是大血管病变风险增加有关.     

慢性肾小球疾病患者血浆中部分抗凝和纤溶指标变化的探讨

目的研究慢性肾小球疾病患者血浆中部分抗凝和纤溶物质与其止凝血障碍的关系。方法在STAGO-STA全自动血凝仪上检测79例慢性肾小球疾病患者和60名正常对照的血浆蛋白C(PC)、蛋白S(PS)、抗凝血酶(AT-)、纤溶酶原(PLG)和抗纤溶酶(AP)活性。结果与正常对照比较肾病综合征患者PC、PLG活性升高,有显著性差异(P<0.01);PS和AT活性降低(P<0.01),有显著性差异;AP升高,与正常对照无显著性差异。慢性肾炎患者PC升高(P<0.05),PLG升高(P<0.01),与正常组比较有显著性差异;PS和AT降低(P>0.05)与正常组比较无显著性差异,AP无变化。结论慢性肾小球疾病患者存在不同程度的凝血亢进和纤溶亢进,测定抗凝和纤溶系统的一些项目可帮助了解疾病的进展及指导治疗。     

急性白血病纤溶系统检测的临床意义

目的探讨急性白血病(AL)患者纤溶系统的异常. 方法发色底物法和ELISA法测定93例患者血浆一系列纤溶指标. 结果患者血浆组织纤溶酶原激活物活性、D-二聚体(D-D)水平显著升高;纤溶酶原活性(PLG)、α2抗纤溶酶活性(α2-PI)、纤溶酶原激活抑制物活性(PAI)水平降低;缓解后均恢复正常. 结论 AL患者存在纤溶系统的激活,部分指标与AL分型、出血程度和预后有关.     

冠心病患者凝血及纤溶系统功能的变化

为探讨冠心病(CHD)患者凝血及纤溶系统的变化,我们对20例稳定性心绞痛(SA),19例不稳定性心绞痛(UA),51例急性心肌梗死(AMI)患者作组织型纤溶酶原激活物(t-PA)、组织型纤溶酶原激活物抑制物(PAI)、纤溶酶原(PCG)、α_2抗纤溶酶(α_2AP)、纤维蛋白原(Fg)、D二聚体(D-Dimer)等凝血及纤溶指标的测定,结果显示与SA相比,UA及AMI患者t-PA活性、t-PA/PAI比值明显降低(P<0.05),血浆PAI活性、Fg含量及D-Dimer含量均明显增高(P<0.05),说明μA及AMI患者存在明显凝血活性增强及纤溶系统功能减退,这对冠心病的发生和发展起着重要作用。     

罗格列酮对2型糖尿病患者血浆tPA和PAI1活性的影响

目的:运用胰岛素增敏剂罗格列酮治疗2型糖尿病患者,观察罗格列酮对2型糖尿病患者血浆tPA和PAI1活性水平的影响。方法:48例2型糖尿病患者,口服罗格列酮(文迪雅)4mg/d,共12周,观察治疗前后的血浆tPA和PAI1活性、血糖和胰岛素等,计算胰岛素敏感指数和胰岛素抵抗指数,并将各指标进行分析比较。结果:罗格列酮治疗后2型糖尿病患者血浆tPA活性升高(P<0.05),PAI1活性及PAI1/tPA活性比值降低(P<0.05,P<0.01)。血糖、胰岛素水平降低(均P<0.05);胰岛素敏感指数明显升高(P<0.05);胰岛素抵抗指数降低(P<0.05)。结论:罗格列酮在降低血糖、改善胰岛素抵抗、提高胰岛素敏感指数的同时,能增强糖尿病患者纤溶系统的活性,对心血管起到保护作用。     

Metabolic syndrome accompanied by hypercholesterolemia is strongly associated with proinflammatory state and impairment of fibrinolysis in patients with type 2 diabetes: synergistic effects of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor

OBJECTIVE: To determine whether plasma concentrations of thrombin-activatable fibrinolysis inhibitor (TAFI) in patients with type 2 diabetes were associated with components of metabolic syndrome (MS), including high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI)-1, and LDL cholesterol. RESEARCH DESIGN AND METHODS: We studied 136 consecutive patients with type 2 diabetes. Diagnosis of MS was diagnosed by current criteria. Hypercholesterolemia (HC) was defined as serum LDL cholesterol >140 mg/dl (3.6 mmol/l) or treatment with a statin. For comparisons, diabetic patients were divided into four groups: those with no MS and no HC (n = 38), with MS but not HC (n = 39), with no MS but with HC (n = 26), and with both MS and HC (n = 33). RESULTS: Considering all patients with type 2 diabetes, plasma PAI-1 was strongly associated with MS components such as BMI, triglyceride, alanine aminotransferase, a homeostasis model assessment of insulin resistance, and hs-CRP. Plasma TAFI only correlated positively and independently with LDL cholesterol. Plasma concentrations of plasmin-alpha2-antiplasmin complex (PAP), a measure of fibrinolytic activity in blood, showed a significant negative correlation with plasma PAI-1 but not TAFI. Diabetic patients with both MS and HC had the highest serum hs-CRP concentrations and the lowest plasma PAP concentrations. CONCLUSIONS: LDL cholesterol is a main determinant of plasma TAFI in patients with type 2 diabetes. Coexistence of MS and HC synergistically accelerates inflammation and impairment of fibrinolysis via elevated concentrations of both TAFI and PAI-1, which inhibit fibrinolysis.     

Shelf-life of bank blood and stored plasma with special reference to coagulation factors

Whole blood and plasma drawn into plastic bags containing citrate- phosphate-dextrose (CPD) and stored at 4 degrees C for various periods were studied for variations of coagulation factor and fibrinolytic activity. The blood was collected and processed in the conventional way. The most labile component, factor VIII coagulant activity, decreased to about 50 percent of its original value within the first 24 hours in whole blood, but thereafter, it decreased more slowly. Storage of whole blood for 6 hours at 4 degrees C had an insignificant effect on VIII coagulant activity; an even slower decrease was found for factor VIII coagulant antigen. The major fall in VIII coagulant activity occurred between 6 and 24 hours of whole blood storage. Factor VIII-related antigen remained normal for about 1 week, but on further storage showed signs of proteolytic degradation. In plasma, there was a successive decrease in VIII coagulant activity with its minimum level (about 50% decrease as compared with the original level) after 7 to 14 days of storage. All other factor VIII activities in plasma remained unchanged throughout the study. Factor V retained its activity for about 1 week in the whole blood. Factors II, VII, IX, X, XII, XIII and fibrinogen did not fall below normal during a storage period of 35 days, nor was there any indication of increased fibrinolytic activity in either whole blood or plasma. Storage of whole blood and plasma at 4 degrees C for 1 to 2 weeks seems to have relatively little effect on the levels and function of various coagulation components with the possible exception of factor VIII coagulant activity.     

川崎病患儿血浆D-二聚体与纤维蛋白原的变化及临床意义

目的 通过检测川崎病患儿D-二聚体和纤维蛋白原(Fib)含量,探索D-二聚体和纤维蛋白原改变与川崎病合并冠状动脉病变之间的关系.方法 采用酶联免疫吸附实验(ELISA)分别检测65例川崎病患儿、30例健康对照组小儿的D-二聚体和纤维蛋白原含量,并同时检测血小板计数(PLT).结果 川崎病组的D-二聚体和纤维蛋白原含量高于健康对照组,差异有统计学意义(P<0.01);合并冠状动脉病变(CAL)组D-二聚体和纤维蛋白原含量高于无冠状动脉损伤(NCAL) 组, 差异有统计学意义(P<0.01);D-二聚体和纤维蛋白原含量与血小板计数无相关性.结论 D-二聚体和纤维蛋白原与川崎病冠状动脉损伤有着密切的关系,对川崎病合并冠状动脉病变具有较好的预测价值.     

A new functional assay of thrombin activatable fibrinolysis inhibitor

New thrombin activatable fibrinolysis inhibitor (TAFI) assays are necessary for studying the role of this fibrinolysis inhibitor in cardiovascular disease. The identification of a functional single nucleotide polymorphism (SNP) (1040C/T) leading to a TAFI-variant with increased stability but lower antigen levels has made the determination of functional activity even more essential. Therefore, we developed a new assay for the functional activity of TAFI in citrated plasma samples. This assay is based on the retardation of plasma clot lysis by TAFIa. TAFI activation was induced simultaneously with fibrin formation and lysis was mediated by rt-PA. The variability of other plasma components was minimized by a 20-fold dilution of the samples in TAFI-depleted plasma. Lysis times (-/+ potato carboxypeptidase inhibitor) and the TAFI-related retardation of clot lysis, the functional parameter of the assay, were determined in a group of 92 healthy volunteers, as well as TAFI antigen levels (electroimmunoassay) and two TAFI SNPs (-438A/G and 1040C/T). TAFI-related retardation was 19.8 +/- 5.6 min (mean +/- SD) and was correlated with the antigen level. The specific antifibrinolytic activity of TAFI was associated with the -438A/G and 1040C/T genotypes. Individuals with the 325Ile-variant had on average a 34% higher TAFI-specific antifibrinolytic activity than individuals with the 325Thr-isoform. The TAFI-related retardation in the two groups of individuals did not differ, as a lower level compensated for the higher specific antifibrinolytic activity of the 325Ile-isoform. This assay provides valuable information about the performance of different TAFI isoforms and constitutes a new method for studying the role of TAFI in cardiovascular disease.     

急性白血病患者止血功能检测的临床意义

目的：探讨急性白血病（ＡＬ）患的止血功能及其与出血症状及预后的关系。方法采用ＥＬＩＳＡ或发色底物法对９３例ＡＬ患浆凝血、抗凝和纤溶指标进行了检测。结果治疗前血浆Ｐ－选择素、可溶性纤维蛋白单体复合物（ＳＦＭＣ）、凝血酶调节蛋白（ＴＭ）、组织型纤溶酶原激活剂、Ｄ－二聚体（Ｄ－Ｄ）水平显升高;高白Ｃ抗原（ＰＣ：Ａｇ）、纤溶酶原活性（ＰＬＧ）、α２抗纤溶酶（α２－ＰＩ）、纤溶酶原激活剂抑制物（ＰＡ）     

血浆纤溶标志物在原发性膜性肾病疾病进展中的变化

目的分析原发性膜性肾病(IMN)患者不同慢性肾脏病(CKD)分期血浆纤溶标志物水平的差异。方法选取200例IMN患者(IMN组,其中CKD1期103例、CKD2期53例、CKD3期30例、CKD4~5期14例)和97名体检健康者(健康对照组),检测血浆纤溶酶-α2抗纤溶酶复合物(PIC)、组织型纤溶酶原激活物抑制剂-1复合物(tPAIC)、纤维蛋白原(Fib)、纤维蛋白降解产物(FDP)、D-二聚体(DD)水平。结果IMN组Fib、FDP、DD与PIC水平显著高于健康对照组(P<0.01),tPAIC水平显著低于健康对照组(P<0.01)。IMN组不同CKD分期之间Fib和tPAIC水平差异均有统计学意义(P<0.05),随CKD分期的进展,Fib水平逐渐升高,tPAIC水平逐渐下降。Fib和tPAIC水平CKD1期与CKD3期、CKD4~5期之间差异有统计学意义(P<0.05),FDP、DD和PIC水平各CKD分期之间差异无统计学意义(P>0.05)。结论IMN患者存在纤溶系统功能低下的情况,易发生血栓栓塞。Fib和tPAIC与疾病分期有关,可作为IMN疾病进展及血栓栓塞预防的监测指标。     

Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats

Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, we used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. We conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.     

Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways

Summary. Background: Activation of coagulation and fibrinolysis play a role in the pathophysiology of experimental arthritis. Objective: To determine the extent of activation of the coagulation and fibrinolytic pathways in different joint diseases in humans and to ascertain the factors that may influence fibrin deposition within the joint. Methods: Plasma from normal subjects (controls, n= 21) and plasma and synovial fluid samples from patients with rheumatoid arthritis (RA; n = 64), osteoarthritis (OA; n = 29), spondyloarthropathy (SpA; n = 22) and crystal arthritis (CA; n = 25) were analyzed for the levels of TF (tissue factor) and tissue factor pathway inhibitor (TFPI) activities, thrombin–antithrombin III (TAT) complexes, and F1 + 2 (thrombin fragment), fibrin d ‐dimer and thrombin‐activated fibrinolysis inhibitor (TAFI) antigenic levels. The measurements were analyzed by pairwise correlation with each other as well as with standard parameters of inflammation [C‐reactive protein (CRP), joint leukocyte count]. Inter‐group comparisons were performed to look for disease‐specific differences. Results: Compared with healthy controls, patients with joint diseases had higher levels of TAT, F1 + 2 and d ‐dimers in their plasma. In the synovial fluid, TF activity, TAT, d ‐dimers, and TAFI were significantly higher in inflammatory arthritides than in OA. The levels were highest in RA patients. In the plasma, TF activity was correlated with TAT and d ‐dimer levels with CRP, TFPI, and TAT. In the synovial fluid, TF activity correlated with plasma CRP levels, synovial fluid leukocyte count, and synovial TAT and TAFI levels. In addition, synovial d ‐dimers correlated with CRP, and synovial TAFI levels were correlated with synovial F1 + 2 and TAT. Conclusions: Activation of the coagulation and fibrinolytic cascades in the joint and in the circulation is evident in both inflammatory and degenerative joint diseases. Within the joint, inflammatory mechanisms leading to TF‐mediated activation of the coagulation pathway and subsequent fibrin deposition is the most likely explanation for the observed findings. In the plasma, the link between inflammation (CRP increase) and TF activation is weak, and a non‐TF‐mediated mechanism of coagulation activation could explain these findings. RA is characterized by significantly higher levels of TAT in the synovial fluid and plasma than other arthritides. Although fibrinolytic activity is linked to inflammation, the increased amounts of TAFI in the joint, particularly in RA, may explain why fibrin formation is so prominent in this condition compared with other joint diseases.