High incidence of tumors in diabetic thrombin activatable fibrinolysis inhibitor and apolipoprotein E double‐deficient mice

Summary. Background: Activation of the complement system has been implicated in tumor growth. The antifibrinolytic protein, activated thrombin‐activatable fibrinolysis inhibitor (TAFIa), can modulate the activation of the complement system by inactivating the anaphylatoxins C3a and C5a. The apolipoprotein‐E (ApoE) genotype has been associated with carcinogenesis. Objective: The aim of this study was to evaluate whether TAFIa can affect the development of cancer in the ApoE‐deficient mouse model. Methods: TAFI and ApoE double‐knockout mice were generated. A group of mice was treated with the diabetogenic and carcinogenic compound streptozotocin (stz). Mice treated with saline, single knockout mice and wild‐type (wt) mice served as controls. Results: Six months after treatment with stz, mice were sacrificed. Hepatic tumors were found in male double‐knockout mice treated with stz but none was found in control animals that were not treated with stz or in single knockout of ApoE or wt animals. There was no significant difference in coagulation system activation between the groups of mice. The plasma concentrations of C5a, factor D and transforming growth factor‐β1 were increased in TAFI/ApoE double‐deficient mice treated with stz compared with the mice of the same genotype treated with saline. Conclusion: Apo‐E deficiency alone was not associated with tumors but the lack of TAFI appears to make the mice permissive for tumor formation in ApoE mice.     

Activation of single‐chain urokinase‐type plasminogen activator by platelet‐associated plasminogen: a mechanism for stimulation of fibrinolysis by platelets

Summary. Background and Objective: Platelets are essential for hemostasis, and they cause resistance to fibrinolysis by tissue‐type plasminogen activator. In contrast, platelets enhance fibrinolysis mediated by single‐chain urokinase‐type plasminogen activator (scu‐PA). This study investigated the mechanism behind this profibrinolytic role of platelets. Methods and Results: Platelets enhanced scu‐PA activity, but not urokinase‐type plasminogen activator (u‐PA) activity, in plasma clot lysis and chromogenic assays. We established, using the non‐cleavable scu‐PA mutant (Lys158→Glu) and protease inhibitors, that platelets increased activation to u‐PA by a serine protease. Activation of scu‐PA was platelet‐dependent, even in plasma. It occurred in platelet‐rich but not in platelet‐poor plasma, as assessed by sodium dodecylsulfate polyacrylamide gel electrophoresis and zymography after addition of plasminogen activator inhibitor‐1. Candidate proteases that are known to activate scu‐PA and are present in platelet preparations were investigated. Factor VII activating protease was detected in platelet preparations by western blotting, but its inhibition by antibodies did not inhibit activation of scu‐PA by platelets. Plasmin and plasma kallikrein both mimicked the platelet effect, but were distinguished by their responses to a range of inhibitors. Analysis of platelet‐associated protease activity and the time course of scu‐PA activation pointed towards plasminogen, and the data were consistent with a mechanism of reciprocal activation. The essential role of plasminogen was revealed using platelets from plasminogen‐deficient mice, which could not activate scu‐PA. Local plasminogen on platelet membranes was markedly more effective than solution‐phase plasminogen in activation of scu‐PA. Conclusions: Platelets enhance fibrinolysis by scu‐PA through reciprocal activation of scu‐PA and platelet‐associated plasminogen, a system that is potentially important in the lysis of platelet‐rich thrombi.     

原发性高血压和缺血性脑卒中患者凝血纤溶指标变化的研究

目的：观察原发性高血压和急、慢性缺血性脑卒中患者部分凝血纤溶指标的变化,为临床提供诊治依据。　　方法：对原发性高血压患者４５ 例（原发性高血压组）和急、慢性缺血性脑卒中患者９５ 例（缺血性脑卒中组）测定血浆部分凝血纤溶指标,以健康人３８例（正常对照组）为对照。　　结果：两组患者均存在不同程度的高纤维蛋白原血症,高血浆组织纤溶酶原激活物（ｔ－ＰＡ）和低活化蛋白Ｃ敏感度。原发性高血压患者血浆高纤溶酶原激活物抑制物－１（ＰＡＩ－１）含量亦升高。急性缺血性脑卒中血浆Ｄ－二聚体升高。　　结论：①原发性高血压患者存在纤溶抑制及高纤维蛋白原血症,可能是其并发缺血性脑血管病的原因之一。②活化蛋白Ｃ抵抗现象与动脉血栓形成有一定的相关性。     

Fibrinolytic measurements in Type 2 diabetic patients with acute cerebral infarction

The aim of this study was to investigate disturbances in fibrinolytic components in Type 2 diabetes patients with acute ischaemic stroke. Levels of plasminogen activator inhibitor-1 (PAI-1) activity and tissue PA (t-PA) antigen were measured in Type 2 diabetes subjects with (n=40) and without (n=80) acute stroke compared to non-diabetic subjects with (n=80) and without (n=80) acute ischaemic stroke. Diabetes was defined by WHO criteria and absence of diabetes by blood glucose <7.8 mmol⁻¹ and HbA_IC <6 % (reference range for assay 4.5–6.5 %). Levels of t-PA antigen were lower in healthy controls (9.2 ng ml⁻¹) than in either stroke group (non-diabetic stroke patient: 12.6 ng ml⁻¹; diabetic patient with stroke: 13.5 ng ml⁻¹ (each at p<0.05)) and intermediate in diabetic patients without stroke (11.1 ng ml⁻¹, ns). In a regression model levels of t-PA were related to stroke, BMI and age but not to diabetes or sex. Diabetic subjects without stroke had higher PAI-1 activity levels than either non-diabetic group (17.7 Uml⁻¹ vs 12.1 U ml⁻¹ and 9.2 U ml⁻¹ (each at p<0.05)). Levels were intermediate in diabetic subjects with stroke (12.8 U ml⁻¹, ns). In a regression model levels of PAI-1 were related to Type 2 diabetes, female sex, and body mass index but not stroke or age. These data suggest that further suppression of fibrinolysis does not occur with ischaemic stroke in Type 2 diabetes. The findings contrast with the importance of impaired fibrinolysis in coronary artery disease previously reported in both Type 2 diabetic patients and non-diabetic subjects. © 1998 John Wiley & Sons, Ltd.     

Use of antifibrinolytics in pediatric cardiac surgery: Where are we now?

Fibrinolytic activation is a major and preventable source of bleeding in neonates and children undergoing cardiac surgery with cardiopulmonary bypass. Based on the existing literature (adult and pediatric; cardiac and noncardiac), prophylactic administration of antifibrinolytic agents can help reduce fibrinolytic activation, and consequently reduces perioperative bleeding and the requirement for blood product transfusion. Due to the increased risk of renal failure and mortality reported in adults undergoing cardiac surgery, aprotinin should not be considered as a safe option in neonates and children. Further well‐designed studies would be required before the prophylactic administration of aprotinin could be considered in pediatric cardiac surgery. The lysine analogs, tranexamic acid and ?‐aminocaproic acid,, should be considered as safe and effective antifibrinolytic agents. Although no major side effects have been reported following the administration of lysine analogs in children undergoing cardiac surgery, high‐dose tranexamic acid should not be recommended in order to avoid the increased risk of clinical seizures. Despite the recent advances made in our understanding of the pharmacokinetics of tranexamic acid and ?‐aminocaproic acid,, the optimal plasmatic concentration to be targeted remains unknown. Further studies are therefore urgently needed to better define the optimal dose regimen to be used in neonates and children. In the meantime, the dose regimen published in the most recent pharmacokinetic studies can be used. Although no studies have assessed the effect of massive bleeding and transfusion on the plasmatic concentrations of the lysine analogs, additional boluses might be considered in the presence of bleeding and/or when signs of fibrinolytic activations are observed on viscoelastic hemostatic assays.     

动脉瘤病人围手术期凝血和纤溶状态及其与预后关系研究

目的 分析动脉瘤病人围手术期凝血与纤溶指标的变化特点及其与预后的关系。方法 回顾性分析2013年1-6月于中国医科大学附属第一医院重症医学科治疗的40例动脉瘤术后病人的临床资料,分析围手术期凝血及纤溶指标变化及其与预后的关系。结果 40例动脉瘤病人术后血小板及纤维蛋白原水平明显低于术前（P<0.05）,ISTH评分平均为（3.4±1.5）分,共7例病人诊断为弥漫性血管内凝血。动脉瘤破裂病人的ISTH评分明显高于未破裂者（P<0.05）。ISTH评分与APACHEⅡ、SOFA评分呈正相关关系（r=0.704、0.694,P<0.05）,ARDS、休克及死亡病人具有更高的ISTH评分。结论 动脉瘤病人围手术期凝血及纤溶系统激活,血小板及纤维蛋白原大量消耗,易发生出凝血功能障碍;ISTH评分高的病人更易发生器官功能损伤,且预后较差。     

舒血宁对AECOPD患者内皮功能和凝血纤溶系统的影响

目的探究舒血宁对AECOPD患者内皮功能和凝血纤溶系统的影响。方法收集于我院接受治疗的AECOPD患者120例为研究对象,随机分组;常规组患者60例,用常规方法进行治疗,舒血宁组患者60例,在常规组的基础上配合舒血宁进行治疗;之后对各组患者的各项指标[TM(血清血栓调节蛋白)、v WF(血管假血友病因子)、D-D(D-二聚体)、以及凝血四项指标)]进行比较。结果治疗结束后,舒血宁组的各项指标(TM、v WF以及D-D水平)的改善程度均显著好于常规组,差异有统计学意义(P0.05);治疗结束后舒血宁组的FBG改善程度显著好于常规组,差异有统计学意义(P0.05);TT、PT、APTT水平量组比较均没有显著差异,差异无统计学意义;治疗结束后舒血宁组总有效率为96.67%,常规组总有效率为56.67%,具有显著差异,有统计学的意义(P0.05)。结论在常规治疗的同时配合舒血宁,能够对AECOPD患者内皮功能和凝血纤溶系统起到明显改善效果,治疗总有效率较高值得推广。     

Components of the fibrinolytic system in the vitreous body in patients with vitreoretinal disorders

Purpose:  To assess components of the fibrinolytic system in the vitreous humour and serum of patients with vitreoretinal disorders.
Methods:  Forty-three samples of vitreous humour and plasma of 43 patients undergoing pars plana vitrectomy for macular hole, macular pucker, retinal detachment or proliferative vitreoretinopathy were evaluated for their content of plasminogen, a₂-antiplasmin, plasminogen-activator-inhibitor 1, plasmin-a₂-antiplasmin-complex, tissue plasminogen activator, total protein, albumin, d-dimer. Patient groups were compared with each other using the U -test (Mann and Whitney) for non-parametric testing of two independent samples.
Results:  The groups of retinal detachment and proliferative vitreoretinopathy had elevated vitreal levels of plasminogen-activator-inhibitor 1 (352.5 and 370.7 ng/mL vs. 1.86 and 56.6 ng/mL, P  = non-significant), plasmin-a₂-antiplasmin-complex (2416.5 and 1836.2 µg/L vs. 124.2 and 133.4 µg/L, P  < 0.001), albumin (0.08 and 0.15 g/dL vs. 0.03 and 0.07 g/dL, P  < 0.05) and d-dimer (4.76 and 1.64 µg/mL vs. 0.40 and 0.48 µg/mL, P  = non-significant) when compared with patients with macular hole and macular pucker.
Conclusions:  There are significant differences in the vitreal concentration of components of the fibrinolytic system in patients with vitreoretinal disorders. Breakdown of the blood–retinal barrier and complex disease-specific mechanisms are thought to be responsible for an increase of components of the fibrinolytic system in the vitreous.     

Endovascular management of the deep venous thrombosis: A new challenging role for the endovascular specialist in 2020

Over the last years, the endovascular approach to the management of the acute and chronic deep vein thrombosis (DVT) has gained more and more attention from the scientific community. DVT is the third most common cardiovascular disease after coronary heart disease and stroke, with classic treatment based on anticoagulation. Recent evidences have highlighted the risk of postthrombotic syndrome as high as 30%–50% in proximal ilio-femoral lesions, with irreversible clinical symptoms and impact on the quality of life of the population. Since 2000s, the new concept of thrombus removal in the acute phase has been supported by the introduction of different techniques based on the endovascular ablation of the clot by in-situ fibrinolysis and, more recently, fragmentation and aspiration. In the chronic phase, recanalization of the thrombosed segment is recommended by stent placement to remove the obstruction and eventually reduce the congestion. Immediate technical success of these procedures is widely satisfying, whereas the long-term clinical benefits are still debated. This paper presents an overview of the modern management of the DVT by endovascular approach with regard to the clinical contexts, interventional strategies and clinical outcomes. Endovascular specialist needs to be aware of this incoming challenge, as local expertise is demanded for the modern management of these patients in multidisciplinary theaters.