扩张性心肌病患者内皮功能和纤溶活性的变化及其与脑卒中相关性研究

目的:探讨扩张性心肌病患者内皮功能和纤溶活性的变化与脑卒中的关系。方法:38例扩张性心肌病患者随访1.5年,记录脑卒中的发生情况,采用酶联免疫吸附法测定血浆血管性血友病因子、D-二聚体抗原水平,并与正常健康组(20例)对照。结果:扩张性心肌病患者血浆血管性血友病因子、D-二聚体抗原水平高于正常健康组,血管性血友病因子与心功能状态有关(P<0.01)。脑卒中的发生率11%,经logistic多元逐步回归分析提示脑卒中的发生与血管性血友病因子、D-二聚体抗原水平和心房颤动有关(P<0.05)。结论:扩张性心肌病患者血浆血管性血友病因子、D-二聚体抗原水平增高并与脑卒中相关。     

孕妇血浆和羊水凝血、抗凝血及纤维蛋白溶解状态研究

目的探讨孕妇血浆和羊水中凝血、抗凝血及纤溶状态。方法采用磁珠法检测孕妇第一产程末血浆和羊水中活化部分凝血活酶时间、血浆凝血酶原时间、纤维蛋白原、抗凝血酶Ⅲ活性、蛋白C活性、蛋白S活性、凝血酶时间、D-二聚体和血管性血友病因子的水平。结果孕妇血浆纤维蛋白原、蛋白C活性、D-二聚体、血管性血友病因子显著高于健康对照组(P0.01)。羊水中活化部分凝血活酶时间、血浆凝血酶原时间和凝血酶时间超出了试剂盒的检测上限,未检测到蛋白S活性,纤维蛋白原、抗凝血酶Ⅲ活性、蛋白C活性、D-二聚体和血管性血友病因子的水平分别为(0.27±0.46)g/L、(2.07±1.22)、(1.80±1.52)、(0.22±0.05)μg/mL和(0.32±0.09)。结论孕妇是发生深静脉血栓的高危人群,孕妇血浆和羊水中凝血、抗凝血及纤溶活性成分的变化可作为孕妇和胎儿健康状况的监测指标。     

心房颤动患者高敏C反应蛋白与血栓前状态标志物相关性分析

目的:观察心房颤动(简称房颤)患者血浆高敏C反应蛋白(hs-CRP)、血管性假血友病因子(v WF)、D-二聚体及纤维蛋白原(Fbg)的变化情况并分析其相关性。方法 :选取房颤组95例患者及窦性心律对照组55例患者,比较两组血浆hs-CRP、v WF、D-二聚体及Fbg水平。结果:房颤组hs-CRP、v WF、D-二聚体均高于对照组(P0.05);Fbg水平在房颤组与对照组的差异无统计学意义(P0.05)。在房颤组中,hs-CRP与血栓前状态相关指标v WF、Fbg及D-二聚体存在正相关(P0.05)。结论:房颤患者存在血栓前状态,与炎症反应相关。     

急性冠状动脉综合征冠状动脉支架置入术凝血指标变化

目的 了解急性冠状动脉综合征患者行支架置入术(PCI)凝血指标变化的规律,为临床抗凝治疗提供依据.方法 急性冠状动脉综合征行支架置入术患者34例,分别于介入前及术后1、4、24、48 h留取血样,检测凝血酶-抗凝血酶复合物(TAT)、血管假性血友病因子(vWF)、蛋白C、抗凝血酶、纤维蛋白原、D-二聚体不同时间段水平并进行统计分析.结果 PCI术后TAT持续增高,蛋白C、抗凝血酶持续下降,vWF、D-二聚体持续升高与TAT相一致,纤维蛋白原呈一过性降低.结论 PCI术后存在凝血酶产生增加与vWF、D-二聚体的增高时相一致,同时抗凝血系统蛋白活性下降.凝血高活性至少持续48 h,以后逐渐恢复正常.     

小儿急性白血病vWF、D-二聚体的检测及临床意义

目的 探讨急性白血病(AL)患儿血浆血管性假血友病因子(vWF)、D-二聚体的水平变化对其病情进展、疗效观察及预后的意义.方法 采用ELISA法检测血浆vWF,采用免疫比浊法检测血浆D-二聚体水平.结果 白血病患儿化疗前血浆vWF、D-二聚体水平升高,与对照组比较差异有统计学意义(P＜0.01),缓解后血浆vWF、D-二聚体水平比治疗前有明显降低(P＜0.01),但血浆vWF仍高于正常水平(P＜0.05),而D-二聚体缓解后差异无统计学意义(P>0.05).结论 白血病患儿存在不同程度的血管内皮细胞损伤及凝血和纤溶系统的激活,并随病情的好转而改善,血浆vWF、D-二聚体可作为白血病患者病情进展、疗效观察及预后的指标之一.     

急性冠脉综合征介入治疗前后止凝血分子标志物的检测及意义

目的 观察急性冠脉综合征患者经皮冠状动脉介入治疗前后止凝血分子标志物的检测及意义。方法 选择行PCI治疗的ACS患者（31）例，分别于术前、术后24小时采血测定血管性血友病因子（vWF）、纤维蛋白原（FBG）、抗凝血酶-Ⅲ（AT-Ⅲ）和D-二聚体。结果PCI术后血浆vWF、FBG、D-二聚体的含量显著高于PCI术前，AT-Ⅲ显著低于PCI术前（P〈0．05）。PCI术前、术后血浆vWF、FBG、D-二聚体、AT-Ⅲ有显著性差异（P〈0．05）。结论 ACS患者处于血栓前状态，PCI后患者存在血管内皮损伤、高凝状态和纤溶功能受损，对术后治疗有指导作用。     

血浆D-二聚体在临产孕妇分娩前后及分娩方式中的应用研究

目的 评价孕妇分娩前后以及分娩方式体内血浆D-二聚体水平变化的临床意义.方法 收集184例临产孕妇和非孕健康对照组40例,将临产孕妇分成自然分娩组(n=83),剖宫产组(n=101);采用酶免荧光法和凝固法检测孕妇血浆D-二聚体和纤维蛋白原水平,评价D-二聚体与纤维蛋白原的相关性,并随访其妊娠结局,行弥散性血管内凝血(DIC)追踪.结果 剖宫产组年龄、孕龄、住院天数明显大于自然分娩组;所有孕妇体内D-二聚体和纤维蛋白原水平明显高于健康对照组(P<0.01),孕妇产后D-二聚体水平高于分娩前,而且剖宫产组产后第1天D-二聚体水平也显著高于自然分娩组产后第1天(P<0.01);临产孕妇中共有5例发生产后DIC,D-二聚体与纤维蛋白原无相关性(P>0.05).结论 妊娠妇女机体处于高凝状态,体内血浆D-二聚体和纤维蛋白原水平明显高于非孕健康人群,然而对于高危人群应该动态监测D-二聚体水平,降低血栓事件的发生.     

D-二聚体的临床应用

D-二聚体(D- dimer,DD)是纤溶酶水解交联蛋白后形成的一种特异性降解产物。DD水平的增高表明体内有纤维蛋白血栓形成和纤溶发生,DD含量变化可作为体内高凝状态和纤溶亢进的分子标志物之一。DD对血栓性疾病如DIC、肺栓塞、深静脉血栓、急性心肌梗塞、冠心病等具有早期诊断价值,对恶性肿瘤观察也有重要价值,综述如下。1　D-二聚体的形成D-二聚体是交联纤维蛋白经纤溶酶作用后的终末产物。在凝血过程中,凝血酶在水解纤维蛋白原后,即相继释放出纤维蛋白肽A(FPA)和肽B(FPB) ,剩余部分为可溶性纤维蛋白单体(SFM) ,在转行酰胺酶作用下,S…     

尿毒症患者血栓前状态的相关研究

目的探讨尿毒症患者止血功能的调节及其临床意义。方法用ELISA法测定59例尿毒症患者血浆血管性血友病因子(vWF)、高半胱氨酸(Hcy)、P-选择素、血栓前体蛋白(TpP)、纤维蛋白肽A(FPA)、凝血酶-抗凝血酶复合物(TAT)、蛋白C(PC)、蛋白S(PS)、D-二聚体的水平,并比较各指标在尿毒症组与正常组(n=30)间的差异。结果尿毒症患者的血浆vWF、Hcy、TpP、FPA、TAT、PS、D-二聚体含量显著高于正常对照组(P<0.05或P<0.01),P-选择素和PC含量显著低于正常对照组(P<0.01)。结论尿毒症患者止血功能变化以凝血亢进为主,其出血倾向与血小板活化功能受损密切相关。     

降纤酶治疗急性脑梗死血粘度与纤溶凝血指标的变化

目的 观察急性脑梗死用降纤酶治疗后血粘度及纤溶、凝血系统的变化。方法 对28例急性脑梗死患者治疗前后的全血粘度、血浆粘度、纤维蛋白原、血小板聚集、白陶土部分凝血活酶时间(KPTT)、血浆凝血酶原时间(PT)、血管性假血友病因子相关抗原(vWF：Ag)、D-D二聚体进行测定。结果 全血粘度、血浆粘度、血小板聚集、纤维蛋白原、血管性假血友病因子相关抗原下降，D-D二聚体升高。白陶土部分凝血活酶时间、血浆凝血酶原时间则延长。结论 降纤酶是治疗急性脑梗死的有效方法之一。     

Tissue factor pathway inhibitor and other endothelium-dependent hemostatic factors in elderly individuals with normal or impaired glucose tolerance and type 2 diabetes

OBJECTIVE: Impaired glucose tolerance (IGT) is believed to be a prediabetic phase that precedes the development of type 2 diabetes. In elderly subjects, IGT and diabetes are both independently associated with the occurrence of cardiovascular disease. Endothelial damage precedes atherosclerotic changes of the vascular wall. Therefore, several markers of endothelial dysfunction were examined in elderly subjects with IGT and elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), and thrombomodulin were studied as markers of endothelial dysfunction in a population-based study of elderly subjects with normal glucose tolerance (NGT) or IGT and type 2 diabetes. In addition to these endothelium-dependent factors, we also investigated tissue factor pathway inhibitor (TFPI) activity in relation to metabolic parameters and cardiovascular risk factors. RESULTS: All data were adjusted for age. Increased levels of vWF antigen, t-PA antigen, and PAI-1 activity were seen in the IGT and diabetic group compared with the NGT group. TFPI activity and thrombomodulin levels were increased in all elderly subjects, and no differences were seen between the groups. There was a positive association between HbA(1c) and TFPI activity and vWF antigen. Fasting blood glucose levels correlated with vWF antigen, t-PA antigen, and PAI-1 activity, whereas urine albumin excretion correlated with TFPI activity, vWF antigen, and PAI-1 activity. Serum insulin levels correlated strongly not only with vWF antigen and t-PA antigen but also with PAI-1 activity. This correlation did not change after further adjustment for serum glucose and HbA(1c), which may suggest that in the elderly subjects, impaired fibrinolysis is probably associated with insulin resistance. There were no associations between the endothelium-dependent hemostatic factors and lipids, except for a negative correlation between HDL cholesterol and thrombomodulin. CONCLUSIONS: In elderly subjects with IGT, several endothelium-dependent hemostatic factors are already consistently increased, indicating endothelial damage in this stage.     

Coagulation, fibrinolysis, and kallikrein systems in sepsis: relation to outcome

Fatal multiple organ failure after severe infection may be related to an early activation of protease cascade systems. This study aimed to relate changes in coagulation, fibrinolysis, and kallikrein to shock and outcome. Of 53 patients with severe infection, 30 did not develop shock, 12 survived septic shock, and 11 died from organ failure after septic shock. No patient had overt disseminated intravascular coagulation. We measured 17 components of the coagulation/fibrinolysis/kallikrein pathways on admission and on the next 2 days. High values for fibrinogen, factor VIII:C, von Willebrand factor antigen, and D-dimer were seen in all patients; factor XII, prekallikrein, factor VII, antithrombin, protein C, and fibronectin were low. The patients thus appeared to be hypercoagulable. These disturbances were more pronounced in septic shock survivors, who also had low plasminogen and antiplasmin, indicating ongoing fibrinolysis. Nonsurvivors of sepsis were distinguished mainly by high plasminogen activator inhibitor values; this suggests an impaired functional fibrinolysis in fatal sepsis, with possible therapeutic implications. Cryoprecipitate infusion increased the fibronectin concentration, but did not influence the other factors studied.     

Effects of older age on fibrin D-dimer, C-reactive protein, and other hemostatic and inflammatory variables in men aged 60–79 years

BACKGROUND: Previous studies have suggested that several hemostatic and inflammatory variables, which are risk predictors for arterial or venous thrombosis, increase with age. However, there is a lack of data from large population studies for reliable estimates of reference ranges. OBJECTIVES: To establish reliable reference ranges of hemostatic and inflammatory variables for 5-year age groups in older men and their implications for pathogenesis and diagnosis. PATIENTS AND METHODS: A total of 3861 men aged 60-79 years at the 20 years follow-up of the British Regional Heart Study. RESULTS: Several variables increased with age. The greatest median increases between 60-64 and 75-79 years age groups were observed for fibrin D-dimer (91%) and C-reactive protein (CRP) (57%). Significant median increases were also observed for von Willebrand factor antigen (23%), tissue plasminogen activator antigen (11%), factor VIII (10%), and fibrinogen (8%). In contrast, levels of classical cardiovascular risk factors neither decreased nor increased substantially with age, with the exception of systolic blood pressure (median increase 10%). CONCLUSIONS: The exponential increases in risk of arterial and venous thrombotic events in men between age 60 and 79 years (when most such events occur) may be related in part to increasing activation of blood coagulation, fibrinolysis, and inflammation; possibly related to the increasing inflammatory burden of both atherosclerotic and non-vascular disease. These increases also have implications for diagnosis of suspected acute venous thromboembolism (D-dimer), and recently proposed screening for prediction of coronary heart disease risk and detection of occult disease (CRP).     

绝经后女性冠心病与非冠心病患者雌激素水平与凝血及纤溶功能分析

背景绝经后女性冠心病发病率及死亡率升高多认为与雌激素降低有关,但确切机制不明.目的探讨绝经后女性冠心病与非冠心病患者血中内源性雌激素水平与凝血及纤溶功能的变化.设计以诊断为依据,非随机对照试验.地点、对象和方法选择2001-09/2002-05,以因胸闷痛收住本院的正常绝经≥1年的妇女为研究对象.纳入标准均为绝经后妇女;2周内未用抗凝剂;未服用免疫抑制剂、雌激素.排除标准肝、肾、内分泌、神经及生殖系统疾病.根据冠状动脉造影结果,将62例绝经后的妇女分为冠心病(32例)与非冠心病(30例)两组.清晨空腹取静脉血,抽提血浆和血清后测定雌二醇、孕酮、促卵泡刺激素和促黄体生成素,凝血系统的纤维蛋白原、血管性血友病因子抗原(von Wille-brand factor antigen,vWFAg)及纤溶系统的组织纤溶酶原激活剂(tissue plasminogen activator,tPA)、纤溶酶原激活剂抑制物-1(plasminogen activator inhibitor-1,PAI-1)和D-二聚体等.主要观察指标两组患者凝血及纤溶系统指标比较及雌激素水平.结果冠心病组血中雌二醇[(39.97±9.73)ng/L],孕酮[(6.42±1.14)nmol/L]明显低于非冠心病组[(64.92±9.77)]ng/L,(7.01±0.85)nmol/L(t=10.6860,2.3960,P＜0.01,0.05);冠心病组患者凝血系统的纤维蛋白原,vWFAg,PAI-I,D-二聚体明显高于非冠心病组(t=2.3377～4.3560,P＜0.05);冠心病组患者纤溶系统的tPA水平明显低于非冠心病组(t=2.4307,P＜0.05).结论绝经后女性冠心病较非冠心病组血中雌二醇水平明显降低,凝血功能亢进及纤溶功能低下.     

Genetic influence on thrombotic risk markers in the elderly – a Danish twin study

OBJECTIVE: Several hemostatic variables are identified as cardiovascular risk markers. In young and middle-aged individuals, plasma concentrations of these variables are partly determined by genetic factors. The genetic contribution to cardiovascular disease (CVD) decreases with increasing age, and it is therefore important to determine the heritability of hemostasis also in the elderly. METHODS: The heritability of plasma levels of factor VII, fibrinogen, tissue factor, tissue factor pathway inhibitor, von Willebrand factor, thrombin activatable fibrinolysis inhibitor (TAFI), and D-dimer was determined in 130 monozygotic and 155 dizygotic same-sex twin pairs, aged 73-94 years, who participated in the Longitudinal Study of Aging of Danish Twins. Furthermore, we determined the influence of promoter polymorphisms in corresponding genes on the plasma level variation. RESULTS: Genetic factors accounted for 33% (D-dimer) to 71% (TAFI) of the variation in plasma levels. Polymorphisms were associated with concentrations of FVII and TAFI in sib-pair based analyses, but in linkage analyses the polymorphisms did not explain a significant part of the genetic variation for any of the variables. CONCLUSIONS: Concentrations of hemostatic variables have a substantial genetic variation in the elderly, but in this study the promoter polymorphisms only explained a minimal part of this variation.     

Induction of a hypercoagulability state and endothelial cell activation by granulocyte colony-stimulating factor in peripheral blood stem cell donors

In June, 1997, we initiated a prospective study to analyze the effect of granulocyte colony-stimulating factor (G-CSF) on coagulation system in peripheral blood stem cells (PBSC) donors following G-CSF administration. Since, 25 consecutively healthy donors received G-CSF (filgrastim) to mobilize and collect PBSC and 20 donors were finally included in the study. Blood samples were collected immediately before starting G-CSF and prior to PBSC collection to analyze the following parameters: prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, hypercoagulability markers (D-dimer, TAT complex, F1 + 2), natural anticoagulants (antithrombin, protein C, protein S), endothelial activation markers [von Willebrand factor antigen (vWF:Ag) and angiotensin converting enzyme (ACE)], and resistance to activated protein C. We found a significant increase in F1 + 2 and D-dimer while a significant decrease of antithrombin and protein C activity was evidenced. Regarding endothelial cell activation markers, a significant increase of vWF:Ag with a slightly significant decrease of ACE were also observed. Therefore, in PBSC donors receiving G-CSF our results reveal activation of both coagulation and endothelial cells that could favor the developing of thrombotic events. In consequence, a careful monitoring should be considered in those cases with risk factors for thrombosis.     

Circulating inflammatory and hemostatic biomarkers are associated with risk of myocardial infarction and coronary death, but not angina pectoris, in older men

Summary.  Aims : The extent to which hemostatic and inflammatory biomarkers are related to angina pectoris as compared with myocardial infarction (MI) remains uncertain. We examined the relationship between a wide range of inflammatory and hemostatic biomarkers, including markers of activated coagulation, fibrinolysis and endothelial dysfunction and viscosity, with incident myocardial infarction (MI) or coronary heart disease (CHD) death and incident angina pectoris uncomplicated by MI or CHD death in older men. Methods : A prospective study of 3217 men aged 60–79 years with no baseline CHD (angina or MI) and who were not on warfarin, followed up for 7 years during which there were 198 MI/CHD death cases and 220 incident uncomplicated angina cases. Results : Inflammatory biomarkers [C-reactive protein (CRP), interleukin-6, fibrinogen], plasma viscosity and hemostatic biomarkers [von Willebrand factor (VWF) and fibrin D-dimer] were associated with a significant increased risk of MI/CHD death but not with uncomplicated angina even after adjustment for age and conventional risk factors. Adjustment for CRP attenuated the relationships between VWF, fibrin D-dimer and plasma viscosity with MI/CHD death. Comparisons of differing associations with risk of MI/CHD deaths and uncomplicated angina were significant for the inflammatory markers ( P  < 0.05) and marginally significant for fibrin D-dimer ( P  = 0.05). In contrast, established risk factors including blood pressure and high-density lipoprotein (HDL)-cholesterol were associated with both MI/CHD death and uncomplicated angina. Conclusion : Circulating biomarkers of inflammation and hemostasis are associated with incident MI/CHD death but not incident angina uncomplicated by MI or CHD death in older men.     

普通冰冻血浆与新鲜冰冻血浆部分血浆组分的比较

目的:比较普通冰冻血浆(FP)和新鲜冰冻血浆(FFP)中血浆组分的差异。方法:随机选择北京市红十字血液中心提供的FP和FFP各20份,血浆融化后即刻分别检测凝血因子、纤溶系统及抗凝蛋白指标等12种血浆组分,即活化的部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血因子Ⅷ(FⅧ)活性、凝血因子Ⅴ(FⅤ)活性、纤维蛋白原(FIB)水平、血管性血友病因子裂解蛋白酶(ADAMTS-13)活性、血管性血友病因子(v WF)活性、D-二聚体(D-dimer,DD)、纤维蛋白降解产物(fibrin degradation products,FDP)、抗凝血酶(antithrombin,AT)、蛋白C(protein C,PC)、蛋白S(protein S,PS),并进行比较分析。结果:与FFP相比,FP中APTT明显延长(t=3.428,P<0.01),PT延长(z=-2.140,P<0.05),FⅧ活性明显降低(t=-3.372,P<0.01),但均在参考区间内;PS活性降低(t=-2.458,P<0.05);两种血浆中其余组分的差异无统计学意义(P>0.05)。结论:与FFP相比,FP缺乏某些凝血因子和抗凝蛋白,但可替代FFP应用于部分疾病的治疗。     

人工髋关节置换术围手术期凝血、抗凝活性变化

目的:检测人工髋关节置换术围手术期凝血、抗凝活性,探讨手术方式本身对凝血、纤溶活性的影响规律,为评估人工关节置换后的血栓性疾病并发症提供理论依据。方法:选择人工髋关节置换患者50例,分别于术前、术后即刻、术后24 h、术后3 d检测凝血指标(凝血酶原时间、活化部分凝血活酶时间、纤维蛋白原),抗凝指标(抗凝血酶Ⅲ、抗Ⅱ因子活性),纤溶指标(D-二聚体),并进行分析比较。结果:术前、术后凝血酶原时间、活化部分凝血活酶时间比较差异无统计学意义(P>0.05),纤维蛋白原术后即刻减低(P<0.05),术后24 h,3 d增高(P<0.05);术后抗凝血酶Ⅲ、抗Ⅱ因子活性较术前降低(P>0.05);D-二聚体术后即刻、术后24 h增高(P<0.05),术后3 d恢复正常(P>0.05)。结论:人工髋关节置换术围手术期存在凝血活性增强,抗凝活性变化不明显、纤溶活性增强的失动态平衡状态,血栓性疾病的发生倾向明显增强。     

内皮素D-二聚体在婴幼儿肺炎并发心力衰竭进展中的作用及意义

目的研究婴幼儿肺炎并发不同程度心力衰竭时内皮素(ET)、D-二聚体(D-dimer)等变化及其内在联系,探讨该阶段血管内皮功能、凝血、纤溶功能的变化。方法选择肺炎及肺炎并发不同程度心力衰竭患儿80例作为试验组,健康婴幼儿20例作为对照组,均抽血检测ET、D-dimer值。结果各组间ET、D-dimer差异有统计学意义;心衰程度越重,ET、D-dimer越高,其中以肺炎并发重度心衰组明显,ET与D-dimer间呈正相关(r=0.42,P<0.01)。结论婴幼儿肺炎并发心力衰竭时存在内皮细胞功能紊乱和凝血、纤溶系统的激活。