对70例激素性骨坏死患者凝血纤溶系统改变的分析

目的测定激素性骨坏死患者血栓形成和低纤溶倾向的指标,探讨激素性骨坏死的病因学,以用于对非创伤性骨坏死患者的早期预防诊断以及易感人群的筛选。材料和方法对70例激素性骨坏死患者抽取空腹肘静脉血,另取52名健康人作为对照。应用自动凝血仪测定凝血、纤溶指标。结果激素性骨坏死患者血液学因素改变明显,其中活化部分凝血活酶时间(APTT)、抗凝蛋白C(PC)、抗凝血酶Ⅲ(AT-Ⅲ)、纤溶酶原激活抑制物(PAI)、活化蛋白c抵抗(APC-R)、纤溶酶原(PLG),两组比较有显著性差异。结论激素性骨坏死患者的凝血纤溶指标异常,对激素性骨坏死易感人群可以进行高凝和低纤溶的筛选,APTT、PC、AT-Ⅲ、PAI、APC-R、PLG可以作为骨坏死易感因素的筛选指标。     

妊娠高血压综合征患者凝血、抗凝及纤溶系统的变化及其临床意义

目的探讨妊娠高血压综合征(妊高征)患者凝血、抗凝、纤溶功能指标的改变及其临床意义。方法分别应用凝固法、发色底物法和免疫法检测85例妊高征患者、50例晚期妊娠者及50名正常非孕妇女血浆凝血酶原时间(PT)、活化的部分凝血酶原时间(APTT)、凝血酶时间(TT)、纤维蛋白原(Fbg)、抗凝血酶Ⅲ(AT-Ⅲ)、纤溶酶原(PLG)、α2-抗纤溶酶(α2-AP)、D-二聚体(D-dimer)。所有测定均在SysmexCA-7000全自动血凝仪上完成。结果与对照组比较,晚孕组及妊高征各组PT、APTT、Fbg、AT-Ⅲ、PLG、α2-PI、D-dimer差异有统计学意义(P<0.05或P<0.01);与晚孕组比较,妊高征及各组PT、APTT、Fbg、AT-Ⅲ、PLG、α2-PI、D-dimer差异亦有统计学意义(P<0.05或P<0.01);且随病情加重差异有增高趋势。结论正常晚孕妇女处于高凝状态,而妊高征患者存在明显的高凝状态,且有血栓形成倾向。产前进行凝血与纤溶功能的检查对妊高征的监测和治疗有一定临床意义。     

慢性阻塞性肺疾病与凝血-纤溶功能异常

慢性阻塞性肺疾病（COPD）是以气道、肺实质和肺血管的慢性炎症为特征。因肺内通气血流比例失调致慢性缺氧，可继发红细胞增多和血黏滞度增高，引起血流高黏、高聚、高凝及微血栓形成。COPD急性加重期凝血-纤溶功能异常进一步恶化，对病情进展的影响已经为临床高度关注。研究同时发现COPD与静脉血栓栓塞症（VTE）关系密切，其合并深静脉血栓（DVT）甚至肺血栓栓塞症（PTE）已成为重要的医疗保健问题。     

Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study.

AIMS: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. METHODS AND RESULTS: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. CONCLUSIONS: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.     

Effects of lipids and lipoproteins on thrombosis and rheology

Atherosclerotic plaque rupture and erosions precipitate thrombus formation and may lead to an acute ischemic syndrome. Lipids and lipoproteins modulate the expression and/or function of thrombotic, fibrinolytic and rheologic factors, and thereby influence hemostasis and potential tissue damage resulting from vascular injury. Triglyceride-enriched lipoproteins are accompanied by elevations in factor VII clotting activity, plasminogen activator inhibitor (PAI-1) and viscosity of blood and plasma. Low density lipoprotein (LDL) promotes platelet activation and tissue factor expression and LDL levels correlate with levels of vitamin K dependent coagulation factors and fibrinogen. Conversely, LDL inhibits tissue factor pathway inhibitor (TFPI) which limits activation of the extrinsic coagulation pathway. High density lipoprotein (HDL) has anti-atherothrombotic properties that result from inhibition of platelet and erythrocyte aggregation, reduced blood viscosity and suppression of tissue factor activity and PAI-1 activity and antigen levels. The effects of lipids and lipoproteins on hemostasis and rheology may have important implications for the clinical sequelae following plaque disruption and erosion.     

The contribution of leukocyte proteases to fibrinolysis

Summary Polymorphonuclear leukocytes accumulate within blood clots and may contribute to fibrinolysis. The primary fibrinolytic enzymes of neutrophils are cathepsin G and elastase. Fibrin can be exposed to these granular enzymes as a result of cell lysis, phagocytosis of fibrin, or secretion of the enzymes from the cells. Neutrophil secretion occurs in association with blood coagulation and is dependent upon a plasma factor(s) and calcium. After secretion, the enzymes can degrade fibirn within a plasma environment. This is demonstrated by the inhibition of fibrinolysis by specific inhibitors of elastase and the augmentation of fibrinolysis by neutralization of the primary plasma inhibitor of elastase, ₁-proteinase inhibitor. A radioimmunoassay which discriminates elastase from plasmic degradation products of fibrinogen has been developed. In this assay, elastase elicited degradation products of fibrin(ogen) were detected in certain pathophysiologic plasma samples. Taken together, these findings indicate a role for leukocyte proteases in physiological fibrinolysis.Abbreviations PMN polymorphonuclear leukocytes - PK prekallikrein - FDP fibrin(ogen) degradation products This work was supported by HL 17 964 from the National Heart, Lung and Blood Institute     

Effect of blood passage through the pulmonary circulation on fibrinolytic parameters

The lung vasculature bed has a unique fibrinolytic potential, which has not yet been completely elucidated. We investigated the effect of blood passage through the pulmonary circulation on the values of fibrinolytic parameters in plasma. Forty-seven patients (16 women, 31 men, mean age 54 years, range 21–67 years) who had undergone elective cardiac catheterization were included in the study. The blood samples were taken simultaneously from the right atrium and the left ventricle. The following fibrinolytic parameters were measured: tissue-type plasminogen (t-PA) antigen and activity, plasminogen activator inhibitor-1 (PAI-1) antigen and activity, and euglobulin clot lysis time (ECLT). No difference was found between the samples obtained from the right atrium and the left ventricle with respect to t-PA antigen: 8.1 (6.7–11.3) vs 8.4 (5.9–11.0)ng/ml; t-PA activity: 92 (5–680) vs 62 (32–696)IU/ml; PAI-1 antigen: 8.4 (5.5–14.3) vs 8.7 (6.2–13.1)ng/ml; and ECLT: 5.5 (4.1–9.1) vs 5.6 (4.1–8.5) 1000/min. In contrast, PAI activity decreased significantly: 7.9 (5.8–10.3) vs 7.4 (6.0–10.4)IU/ml, P 0.01. Patients with and without pulmonary hypertension did not differ in any of measured parameters, either in the right atrium or in the left ventricle. These results show that under basal conditions fibrinolytic activity which is not attributed to t-PA is elevated in lung vasculature. Further, basal fibrinolytic activity in the lungs is not influenced by pulmonary hypertension.     

非瓣膜性心房颤动患者凝血-纤溶系统活性的变化及临床意义

目的:探讨非瓣膜性心房颤动患者凝血-纤溶系统改变及其意义.方法:选择慢性非瓣膜性心房颤动患者(心房颤动组)54例,其中男28例,女26例,平均年龄(58.4±12.3)岁;存在相同心血管疾病(高血压或冠心病)的窦性心律者(窦性心律组)40例,男20例,女20例,平均年龄(57.6±11.7)岁;健康体检者35例为对照组,其中男17例,女18例,平均年龄(52.4±18.5)岁.测定以上3组患者血浆纤维蛋白原、D-二聚体、组织纤溶酶原激活剂、组织纤溶酶原抑制剂水平及凝血酶原时间、凝血酶时间和部分凝血活酶时间.结果:非瓣膜性心房颤动患者血浆纤维蛋白原、D-二聚体和组织纤溶酶原抑制剂水平显著升高,血浆组织纤溶酶原激活剂水平显著降低.凝血酶原时间、凝血酶时间和部分凝血活酶时间则无显著变化.结论:非瓣膜性心房颤动患者存在高凝和低纤溶状态.     

高血压脑出血微创手术治疗进展

高血压脑出血具有很高的发病率、病死率和致残率,为社会、家庭带来了沉重的健康及经济负担,但高血压脑出血也是脑卒中亚分类中仅有的没有明确治疗标准的疾病,传统开颅手术在高血压脑出血中应用广泛,但目前没有明确证据支持其可以提升患者的神经功能及预后。微创手术逐渐得到了越来越为广泛的应用。本文主要探讨了立体定向血肿抽吸、神经内镜技术以及纤溶药物治疗高血压脑出血的发展及现状。随着神经影像学的快速发展,立体定向血肿抽吸治疗高血压脑出血的治疗效果愈发理想;通过不断的改进,神经内镜清除血肿的效果愈发理想,而内镜手术入路的选择仍无统一标准;rtPA/尿激酶纤溶治疗尽管可以减少一定量的血肿,但是纤溶治疗与再出血及水肿加重之间的关系仍颇具争议。目前,仍需要更多的临床研究以进一步证实微创手术在治疗高血压脑出血中的作用。     

Active PAI-1 as marker for venous thromboembolism: Case–control study using a comprehensive panel of PAI-1 and TAFI assays

Background

Both activated Thrombin Activatable Fibrinolysis Inhibitor (TAFI) and active Plasminogen Activator Inhibitor-1 (PAI-1) attenuate fibrinolysis and may therefore contribute to the pathophysiology of Venous ThromboEmbolism (VTE). Whether increased TAFI and/or PAI-1 concentrations are associated with VTE is unclear.

Objective

To study an association of impaired fibrinolysis and VTE using a comprehensive panel of in-house developed assays measuring intact TAFI, activation peptide of TAFI (AP-TAFI), PAI-1 antigen, endogenous PAI-1:t-PA complex (PAI-1:t-PA) and active PAI-1 levels in 102 VTE patients and in 113 healthy controls (HC).

Results

Active PAI-1 was significantly higher in VTE patients compared to HC (20.9 [9.6-37.8] ng/ml vs. 6.2 [3.5-9.7] ng/ml, respectively). Active PAI-1 was the best discriminator with an area under the ROC curve and 95% confidence interval (AUROC [95%CI]) of 0.84 [0.79-0.90] compared to 0.75 [0.68-0.72] for PAI-1:t-PA, 0.65 [0.58-0.73] for PAI-1 antigen, 0.62 [0.54-0.69] for AP-TAFI and 0.51 [0.44-0.59] for intact TAFI. Using ROC analysis, we defined an optimal cut-off of 12.8 ng/ml for active PAI-1, with corresponding sensitivity of 71 [61–79] % and specificity of 89 [82–94] %. A lack of association with the time between VTE event and sample collection or with the intake of anticoagulant treatment suggests that active PAI-1 levels are sustainable high in VTE patients.

Conclusions

This case–control study emphasizes the clinical importance of measuring active PAI-1 instead of PAI-1 antigen and identifies active PAI-1 as a potential marker of VTE. Prognostic studies will need to address the clinical significance of active PAI-1 as biomarker.