高血压病患者血栓前状态的临床研究

目的 通过观察高血压病患者血栓前状态分子标志物的变化，探讨其易并发血栓性疾病的机制，为临床早期诊治提供客观依据。方法 对山东省血栓病防治工程技术研究中心与山东省交通医院2000—04—2004—05的1000例高血压病患者及100例健康对照者的血浆血栓前状态（PTS）分子标志物进行检测，包括：血管性血友病因子（vWF）、血小板α-颗粒膜蛋白-140（GMP-140）、11-去氢血栓烷B2（11-DH—TXB2）、纤维蛋白原（FIB）、抗凝血酶（AT）；组织型纤溶酶原激活剂（t—PA）、纤溶酶原激活剂抑制物-1（PAI-1）的活性水平及血液流变学指标，并进行分析与评价。结果 与对照组相比，高血压病患者的血浆vWF、GMP-140、11-DH—TXB2、FIB含量，PAI—1活性及血黏度均明显升高，而AT含量、t—PA活性均明显下降，差异极其显著（P〈0．01）。随着血压升高，PTS标志物变化越显著（P〈0．05）。结论 高血压病患者存在PTS，PTS与其病情进展、血栓性疾病的发生密切相关。     

老年原发性高血压患者血栓前状态的研究

目的 探讨老年原发性高血压（EH）患者血栓前状态（PTS）分子标志物的变化及其易并发血栓性疾病的机制。方法 测定100例老年EH患者及100例老年健康对照者的血浆血管性血友病因子（vWF）、血小板α-颗粒膜蛋白-140（GMP-140）、纤维蛋白原（Fg）、凝血酶原片段1＋2（F1＋2）的含量，抗凝血酶（AT）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）的活性及血液流变学指标，并进行了分析与评价。结果 老年EH病人血浆vWF、GMP-140、Fg、F1＋2含量、PAI-1活性、血黏度较对照组均明显升高，而AT、t-PA活性均明显下降（P〈0.01）。随着血压水平升高，PTS标志物水平变化越明显。结论 PTS与老年EH患者的病情发展及血栓性疾病的发生密切相关。     

阻塞性睡眠呼吸暂停综合征患者血栓形成前状态分子与颈动脉内膜中层厚度关系

目的： 探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血栓形成前状态(PTS)分子标志物与颈动脉内膜中层厚度关系。方法： 选择OSAHS患者56例和对照组28例,采用采用酶联免疫吸附法测定血清血小板颗粒膜蛋白-140(GMP-140)、血管性血友病因子(vWF)和抗凝血酶Ⅲ(ATⅢ)水平,采用底物发光法测定组织型纤溶酶原激活剂(t-PA)和血浆纤溶酶原激活物抑制剂1(PAI-1)水平；使用彩色多普勒超声检测颈动脉内膜中层厚度(IMT)。结果：OSAHS组血清GMP-140、vWF、Fbg、PAI-1水平高于对照组,血清ATⅢ、t-PA水平低于对照组,颈动脉内膜中层厚度高于对照组(P均＜0.05)。血清GMP-140、vWF、Fbg、PAI-1水平与IMT呈正相关(r=0.507,0.411,0.392和0.458,均P＜0.05)。血清ATⅢ、t-PA水平与IMT呈负相关(r=-0.401,-0.367,均P＜0.05)。OSAHS患者GMP-140、vWF、t-PA水平与IMT成线性回归关系。结论：OSAHS患者存在着明显的PTS,同时颈动脉内膜增厚明显。PTS是导致患者颈动脉内膜增厚的重要因素之一。     

老年高血压并发脑梗死患者凝血、抗凝、纤溶系统功能改变及意义

目的分析老年高血压并发脑梗死患者凝血、抗凝、纤溶系统分子标志物指标的变化及意义，为临床早期诊断治疗提供客观依据。方法检测100例老年高血压患者、100例老年高血压合并脑梗死患者及100例健康老年对照者血管性血友病因子抗原（vWF：Ag）、血小板α-颗粒膜蛋白-140（GMP-140）、纤维蛋白原（FIB）的含量及抗凝血酶（AT）、蛋白S（PS）、蛋白C（PC）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活剂抑制物-1（PAI-1）的活性，并进行分析与评价。结果与对照组相比，老年高血压患者、老年高血压合并脑梗死患者血浆vWF：Ag、GMP-140、FIB含量、PAI-1活性均明显升高，而AT、PS、PC、t-PA活性明显降低，差异具有统计学意义（P〈0．01）。结论老年高血压患者存在明显的凝血、抗凝及纤溶功能失衡，这与其病情进展及脑梗死的发生密切相关，早期防治具有重要的临床意义。     

阻塞性睡眠呼吸暂停综合征患者血栓形成前状态分子与颈动脉内膜中层厚度的关系

目的:探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血栓形成前状态(PTS)分子标志物与颈动脉内膜中层厚度的关系。方法:选择OSAHS患者56例和健康体检者28例为对照组,采用酶联免疫吸附法测定血清血小板颗粒膜蛋白-140(GMP-140)、血管性血友病因子(v WF)和抗凝血酶(AT)水平,采用底物发光法测定组织型纤溶酶原激活剂(t-PA)和血浆纤溶酶原激活物抑制剂1(PAI-1)水平;使用彩色多普勒超声检测颈动脉内膜中层厚度(IMT)。结果:OSAHS组血清GMP-140、v WF、Fbg、PAI-1水平高于对照组,血清AT、t-PA水平低于对照组,颈动脉内膜中层厚度高于对照组(P均0.05)。血清GMP-140、v WF、Fbg、PAI-1水平与IMT呈正相关(r=0.507,0.411,0.392和0.458,均P0.05)。血清AT、t-PA水平与IMT呈负相关(r=-0.401,-0.367,均P0.05)。OSAHS患者GMP-140、v WF、t-PA水平与IMT成线性回归关系。结论:OSAHS患者存在着明显的PTS,同时颈动脉内膜增厚明显,PTS是导致患者颈动脉内膜增厚的重要因素之一。     

H型高血压患者血栓前状态分子标志物的变化

血栓前状态(PTS)是指多种因素引起的凝血、抗凝及纤溶系统平衡失调,有利于血栓形成的病理状态.近年来研究表明,通过检测血栓前状态的一些分子标志物可反映体内高凝状态或血栓形成[1].H型高血压(同型半胱氨酸≥10 μmol/L)是引发心脑血管疾病,尤其是脑卒中最重要的危险因素,但有关H型高血压患者血栓前状态的研究报道不多.我们通过检测H型高血压患者血浆血管性假性血友病因子(vWF)、血小板α颗粒膜蛋白-140(GMP-140)、纤维蛋白原(FIB)、D-二聚体(DD)、纤溶酶原激活物抑制物-1( PAI-1)和组织纤溶酶原激活物(t-PA)等指标,探讨其在H型高血压患者中的变化及其临床意义.     

在H型高血压患者中检测血栓前状态分子标志物的意义

目的 观察H型高血压患者血栓前状态分子标志物中的血管性假性血友病因子(vWF)、血小板α-颗粒膜蛋白-140(GMP-140)、组织型纤溶酶原激活物抑制物(PAI-1)以及纤维蛋白原(FIB)的变化,分析其临床意义.方法 连续选取120例H型高血压患者为观察组,以同期住院的60例同型半胱氨酸(Hcy)正常的原发性高血压患者为对照组,30例体检健康者为空白对照组.检测3组入选者血浆vWF、GMP-140、PAI-1、FIB,并予以比较、分析.结果 从观察组到对照组、空白对照组,受试者血浆vWF 、GMP-140、PAI-1、FIB依次降低,两两比较差异有统计学意义(P＜0.01).结论 H型高血压患者可能具有更高的血栓形成风险.     

脑梗死高危人群血栓前状态的检测

目的探讨血栓前状态者(PTS)在脑血管病高危人群防治中的作用和意义。方法使用酶联免疫吸附法和凝固法检测40例原发性高血压病人和25名正常者(对照组)外周血小板α颗粒膜蛋白(GMP-140)、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-1)和纤维蛋白原(Fg)的水平变化。结果与正常对照组相比,高血压组血浆GMP-140,Fg,PAI-1水平均显著升高(P<0.05或P<0.01),t-PA较正常对照组下降(P<0.01)。结论原发性高血压病人存在PTS,降压的同时给予抗凝、降低血液黏稠度治疗可能会降低其血栓并发症的发生率。     

血栓形成前状态分子标志物变化在不稳定性心绞痛合并糖尿病患者中的意义

目的观察不稳定性心绞痛(UAP)合并糖尿病(DM)患者体内血栓形成前状态分子标志物水平的变化及临床意义。方法随机选择2015年1月～2016年9月于海南省人民医院住院的40例UAP合并DM患者(合并症组),40例UAP患者(UAP组),40例健康对照者(对照组)。分别测定各组体内假性血友病因子(vWF)、纤溶酶原(Plg)、抗凝血酶Ⅲ(ATⅢ)、Ⅷ因子相关抗原(Ⅷ:Ag)、血小板颗粒膜蛋白-140(GMP-140),蛋白C(PC),Ⅱ因子活性(FⅡa)、组织型纤溶酶原激活物(t-PA)、组织型纤溶酶原激活物抑制剂(PAI)、D-二聚体(D-dimer)、血栓素B2(TXB2)。结果合并症组vWF,Ⅷ:Ag,GMP-140,FⅡa,PAI-1,D-Dimer,TXB2水平与UAP组以及对照组相比,明显升高(P0.05),而ATⅢ,PC,t-PA水平与UAP组以及对照组相比,明显降低(P0.05);UAP组vWF,Ⅷ:Ag,GMP-140,FⅡa,PAI-1,D-Dimer,TXB2水平与对照组相比,明显升高(P0.05),而UAP组ATⅢ,PC,t-PA水平与对照组相比,明显降低,差异具有统计学意义(P0.05)。结论 UAP合并DM患者体内存在更明显的止凝血分子标志物水平的变化,可能是影响其预后不良的重要因素。     

瑞舒伐他汀对血脂正常阻塞性睡眠呼吸暂停综合征合并高血压患者血栓前状态的影响

目的 研究瑞舒伐他汀对血脂正常的阻塞性睡眠呼吸暂停综合征（OSAS）合并高血压患者血栓前状态的影响.方法 血脂正常的OSAS合并高血压患者75例,随机分成瑞舒伐他汀组40例,常规治疗组35例,另选取25名门诊健康体检者作为对照组.检测一氧化氮（NO）、内皮素（ET-1）及血管性假性血友病因子（vWF）、血小板颗粒膜蛋白（GMP-140）、组织型纤溶酶原激活剂（t-PA）、纤溶酶原激活物抑制剂-1（PAI-1）的水平变化.结果 ①治疗前两组OSAS合并高血压患者NO、t-PA低于健康对照组,差异有统计学意义（P＜0.05）;ET-1、vWF、GMP-140、PAI-1水平均高于健康对照组,差异有统计学意义（P＜0.01）.②治疗后瑞舒伐他汀组及常规治疗组NO、t-PA水平均较治疗前升高,瑞舒伐他汀组NO、t-PA高于常规治疗组,差异有统计学意义（P＜0.05）.③治疗后瑞舒伐他汀组及常规治疗组ET-1及vWF、GMP-140、PAI-1均较治疗前降低,瑞舒伐他汀组ET-1、vWF,GMP-140低于常规治疗组,差异有统计学意义（P＜0.01）.结论 对于血脂正常的OSAS合并高血压患者,瑞舒伐他汀可通过提高血浆NO、t-PA浓度和降低ET-1、vWF、GMP-140、PAI-1浓度等非调脂机制改善血栓前状态.     

血栓形成标志物与原发性高血压的关系

目的判断原发性高血压患者是否存在血栓前状态(pretbrombotic state,PTS),并探讨PTS在原发性高血压患者中的意义。方法运用酶联免疫吸附双抗体夹心法(ELISA)、酶联免疫吸附竞争法、发色底物法、凝固法等检测手段,检测了1 000例原发性高血压患者和100例健康成人的6-酮-前列腺素F1α(6-K-PGF1α)含量、血栓素B2(TXB2)含量、纤维蛋白原(Fib)含量、组织型纤溶酶原激活剂(t-PA)及纤溶酶原激活抑制物-1(PAI-1)的含量和活性及血液流变学等指标的变化进行分析与评价。结果与对照组比较,1~2级高血压组及3级高血压组患者血浆TXB2、Fib水平、PAI-1含量及活性、血黏度均显著升高(P<0.01);而6-K-PGF1α含量t、-PA含量及活性均显著下降(P<0.01)。结论高血压病患者存在PTS,PTS与高血压病患者的病情发展,血栓栓塞性疾病的发生密切相关。     

Blood coagulation and fibrinolysis in patients with hyperthyroidism

Several papers concerning abnormalities of blood coagulation and fibrinolysis during hyperthyroidism, have been published. Increased von Willebrand Factor (vWF) activity and high fibrinogen levels have been reported. However, there is controversy concerning the presence of a hypercoagulable state in hyperthyroidism. We investigated various hemostatic parameters in 41 hyperthyroid patients and compared them to 20 euthyroid controls. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX and X activities, vWF, antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor-1 (PAI-1), as well as common lipid variables, were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with control subjects, fibrinogen, factor IX, vWF, AT III and PAI-1 were significantly increased in patients (p<0.05, p<0.0001, p<0.05, p<0.01 and p<0.0001; respectively), whereas factor X and t-PA were decreased (p<0.05). We showed that free T4 (FT3) levels were correlated with factor VIII activity (r=0.35, p<0.05). FT4, FT3 and TSH did not correlate with fibrinogen, vWF, AT III, t-PA, or PAI-1. AT III was inversely correlated with factor VII activity (r=-0.48, p<0.01). Protein C and S were correlated with vWF levels (r=0.58, p<0.0001; r=0.55, p<0.0001, respectively). Protein C was inversely correlated with t-PA (r=-0.39, p<0.01). There was a negative correlation between triglycerides, LDL-C and F X (r=-0.45, p<0.05; r=-64, p<0.01, respectively). Mean platelet volume (MPV) was correlated with anti-thyroid peroxidase (TPO) antibodies (in Graves'disease) and F IX activity (r=0.57, p<0.05 and r=0.39, p<0.05; respectively). We found important differences in the coagulatory /fibrinolytic parameters between the hyperthyroid patients and healthy controls. Hyperthyroid patients may experience vascular endothelial dysfunction and decreased fibrinolytic activity in blood. This endothelial activation may represent a situation with a higher thromboembolic potential.     

2级高血压患者血栓前状态分子标志物的变化

目的 探讨2级高血压患者血栓前状态相关指标的改变及其临床意义.方法 采用流式细胞仪、酶联免疫吸附双抗体夹心法(ELISA)、全自动血凝分析仪等检测2级高血压血小板表面P-选择素(P-selectin,CD62P)、血浆组织型纤溶酶原激活剂(t-PA)、抑制剂(PAI-1)和凝血四项即血浆纤维蛋白原(FIB)水平、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT).结果 2级高血压组CD62P的表达、血浆PAI-1、FIB三项指标均较正常组增高(P＜0.05),而t-PA水平较正常组降低(P＜0.05);2级高血压APTT和PT时间明显缩短(P＜0.05);正常组与2级高血压组TT时间比较无统计学意义(P＞0.05).结论 2级高血压患者血小板活化、凝血功能增强、纤溶功能减退,存在明显的血栓前状态;测定血小板表面CD62P的表达、血浆t-PA和PAI-1和凝血四项有助于早期发现2级高血压患者血栓前状态并有助于导临床早期干预治疗.     

Effects of perindopril treatment on hemostatic function in patients with essential hypertension in relation to angiotensin converting enzyme (ACE) and plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms

BACKGROUND AND AIM: An imbalance in the hemostatic system is a frequent finding in untreated essential hypertension (HT), and it has been shown that treatment with angiotensin converting entyme (ACE) inhibitors improves hemostatic function. In order to elucidate the role of genetic factors, we studied hemostasis in patients with untreated and treated HT and correlated the results with ACE I/D and plasminogen activator enhibitor-1 (PAI-1) 4G/5G gene polymorphisms. METHODS AND RESULTS: Forty-three males with HT (mean age 31.7 +/- 6.8 years) were compared with 34 age and gender-matched controls. All of the patients were treated with perindopril (4 mg/day) and, after one and six months of therapy, their levels of plasma fibrinogen (Fb), t-PA antigen, PAI-1 antigen, von Willebrand factor (vWF), ACE activity and blood pressure were measured. ACE and PAI-1 genotypes were identified by means of the polymerase chain reaction on DNA isolated from peripheral blood lymphocytes. Untreated patients had significantly higher levels of Fb, PAI-1 (p < 0.01) and t-PA (p < 0.05) regardless of their ACE or PAI-1 genotypes. Perindopril reduced blood pressure regardless of ACE or PAI-1 genotype (p < 0.001). ACE II homozygotes showed the greatest decrease in ACE activity (p < 0.01) and a significant reduction in Fb levels (p < 0.05) after just one month of treatment. Analysis of the group as a whole revealed an increase in t-PA antigen levels after six months of treatment, regardless of ACE or PAI-1 genotype (p < 0.01). CONCLUSIONS: Our results show that essential hypertension predisposes to the procoagulant state characterized by hyperfibrinogenemia and hypofibrinolysis. Perindopril reduced fibrinogen levels in ACE II homozygotes due to its more potent inhibitory action on the renin-angiotensin system in such patients. It improved fibrinolysis by increasing t-PA levels regardless of ACE and PAI-1 genotype.     

In patients with deep-vein thrombosis elevated levels of factor VIII correlate only with von Willebrand factor but not other endothelial cell-derived coagulation and fibrinolysis proteins.

Several studies have shown that patients with venous thrombosis have elevated levels of factor VIII (FVIII) at an increased frequency. Most such patients also have high von Willebrand factor (vWF) levels. Since vWF is synthesized by the vascular endothelium, we hypothesized that elevated FVIII levels would also be associated with an increase of other endothelial cell-derived coagulation proteins suggesting perturbation of the endothelium. In 100 healthy individuals and 129 patients with venous thromboembolism, we have determined antigenic FVIII levels along with several endothelial proteins including vWF, soluble thrombomodulin (sTM), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1). Levels of FVIII, vWF, PAI-1 and t-PA were significantly increased in patients compared with the controls (FVIII, vWF, and PAI-1,P < 0.001; t-PA, P < 0.05). Levels of sTM, however, were higher in the controls than in the patients (P < 0.001). Whereas the FVIII levels correlated well with the vWF levels in the patients (correlation, 0.61; P < 0.001) and the controls (correlation, 0.70; P < 0.001), there was neither a relevant correlation between FVIII and sTM, PAI-1, and t-PA, nor between vWF and sTM, PAI-1, and t-PA in the patients and the controls. In conclusion, although levels of PAI-1 and t-PA can be found, on average, at increased levels in patients with thrombosis, FVIII levels correlate only with vWF but not other endothelial cell-derived coagulation and fibrinolysis proteins including sTM, PAI-1, and t-PA.     

Anticoagulant therapy modifies fibrinolytic dysfunction in chronic atrial fibrillation

OBJECTIVE: We evaluated the changes in fibrinolytic activation markers before starting anticoagulation, at 1 and 6 months following the introduction of anticoagulant therapy. DESIGN AND METHODS: Tissue plasminogen activator (t-PA), its endothelial inhibitor (PAI-1), plasmin:antiplasmin complexes (PAPc), modified antithrombin III (ATM), D dimer (D-D) and fibrinogen (FIB) were measured in 36 patients with chronic atrial fibrillation. Fifteen of them had rheumatic mitral stenosis and 21 had nonrheumatic atrial fibrillation. Basal levels were compared with a sex- and age-matched healthy control group. RESULTS: At baseline, patients with atrial fibrillation showed significantly higher plasma levels of PAI-1, ATM, D-D and FIB levels (p < 0.05) than controls, and no differences in t-PA and PAPc concentrations. Levels of t-PA, PAI-1, ATM and D-D decreased significantly under anticoagulant therapy, whereas FIB levels were not significantly modified. PAPc levels were significantly increased at 6 months in the rheumatic group but did not differ significantly in the nonrheumatic group. CONCLUSIONS: Patients with chronic atrial fibrillation show a hypercoagulant state and a relatively low fibrinolytic function. After 6 months of anticoagulant therapy, an improvement in fibrinolytic function markers was detected.     

Plasma t-PA/PAI-1 complex and blood coagulability in patients with coronary artery disease.

The t-PA/PAI-1 complex is a good indicator of the release of fibrinolysis activators and inhibitors from the vascular wall, but its clinical significance in chronic ischemic heart disease is unclear. The plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and the t-PA/PAI-1 complex (including various coagulation factors) were assayed in 72 patients with coronary artery disease (CAD) and 29 control (C) subjects. The CAD patients were subdivided into 3 groups: single-vessel disease (G1, n = 30), double-vessel disease (G2, n = 20), and triple-vessel disease (G3, n = 22). The patients with triple-vessel disease had higher fibrinogen values (G3: 318 +/- 75 mg/dl, C: 263 +/- 56), factor VII activity (G3: 143 +/- 36%, C: 123 +/- 14), and t-PA antigen levels (G3: 4.7 +/- 0.8 ng/ml, C: 3.3 +/- 0.7) than controls. Patients with double- and triple-vessel disease also showed higher levels of factor VIII, vWF antigen, thrombin-antithrombin III complex (G1: 2.3 +/- 0.6 ng/ml, G2: 2.7 +/- 0.5, G3: 3.1 +/- 0.5, C: 2.0 +/- 0.5), and t-PA/PAI-1 complex (G1: 13.9 +/- 6.1 ng/ml, G2: 16.4 +/- 4.6, G3: 18.2 +/- 5.9, C: 10.7 +/- 4.9) than control subjects. The t-PA/PAI-1 complex levels were correlated significantly with the activities of factors VII and VIII and the thrombin-antithrombin III complex. These findings suggest that patients with CAD have greater blood coagulability than controls, and that this difference is related to the severity of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)