肾素血管紧张素系统与静脉血栓关系的研究进展

既往认为肾素血管紧张素系统是人体内一个重要的调节系统,近年来的研究表明该系统与机体静脉血栓形成尚具有一定联系,经典的ACE-AngⅡ-AT1轴具有促血栓形成的作用,而ACE2-Ang( 1-7)-Mas轴具有与其相反的抗血栓作用。本文总结了目前肾素血管紧张素系统与静脉血栓关系的相关研究,以寻求对静脉血栓形成影响因素的进...     

The relationship between exercise and risk of venous thrombosis in elderly people

OBJECTIVES: To study whether exercise is associated with the risk of venous thrombosis in elderly people.
DESIGN: Observational study with a median follow-up of 11.6 years.
SETTING: The Cardiovascular Health Study in four U.S. communities.
PARTICIPANTS: People aged 65 and older without prior venous thrombosis (deep venous thrombosis or pulmonary embolism).
MEASUREMENTS: Self-reported exercise was measured two or three times during follow-up and was defined as expending more than 500 kcal/wk on exercise, including walking for exercise. Venous thrombosis cases were verified using medical record review.
RESULTS: Of 5,534 participants, 171 developed a first venous thrombosis. Self-reported exercise at baseline was not related to the risk of venous thrombosis after adjustment for sex, age, race, self-reported health, and body mass index (adjusted hazard ratio (HR_adj)=1.16, 95% confidence interval (CI)=0.84–1.61), although with exercise modeled as a time-varying exposure, overall results were in the direction of greater risk of venous thrombosis (HR_adj=1.38, 95% CI=0.99–1.91). For mild-intensity exercise, such as walking, there was a nonsignificant finding in the direction of benefit (HR_adj=0.75, 95% CI=0.49–1.16), but strenuous exercise, such as jogging, was associated with greater risk of venous thrombosis (HR_adj=1.75, 95% CI=1.08–2.83) than no exercise at all.
CONCLUSION: In elderly people, strenuous exercise was associated with a higher risk of venous thrombosis than no exercise at all. Future studies are needed to explain this unexpected higher risk.     

Aortic wall injury and thrombogenesis in catheterization: experimental study

Arterial and venous catheterization is a very useful procedure in the diagnosis of heart diseases. However, some complications with thrombogenesis have been reported. Two kinds of Mikaelson-type non-heparin-coated angiographic catheters (with 6.5 Fr. and 80 cm length) were used for the experiments. One was of polyurethane (PUC) and the other of polyethelene (PEC). Eight experimental dogs were used for each group. The catheter was inserted into the ascending aorta through the femoral artery. No antithrombogenic drugs were given to the animal. One hour later, sodium heparin (100 U/kg) was administered intravenously. The animal was sacrificed by acute exanguination. The aorta was opened longitudinally. The position of the thrombi on the aortic wall was macroscopically observed and the weight of the thrombi attached to the catheters were measured. A piece of the aorta at each level was excised for light and scanning electron microscopic observations. Mural thrombi of various lengths still remained on the aortic wall of every dog after the removal of the catheters. Microscopic observation revealed that the mural thrombus was formed on the aortic wall, where the endothelial cells had peeled off and the internal elastic membrane was partially destroyed. SEM observation also showed that fibrin network on the aortic wall where the endotherial cells were peeled off. Microscopic observation of aortic wall also revealed intimal tears, inner elastic membrane injury and bleeding in the elastic membrane. This damage could worsen leading to dissection of the aorta, thrombosis of the abdominal organs. The injury is considered due to mechanical irriation by the catheter.(ABSTRACT TRUNCATED AT 250 WORDS)     

The close relationship of heparin and the vessel wall

For over 100 years heparin has attracted interest because of its anticoagulant powers. Commercial heparin has now been shown to be a mixture of over 100 different closely related sulfated polysaccharides of which only 10% activate antithrombin-III. Fifty years ago the original research teams in Toronto and Stockholm in demonstrating the clinical uses of heparin observed that antithrombotic activity did not correspond to levels of anticoagulation. It has been shown that: (a) Heparin accumulates rapidly and specifically in the endothelium against a concentration gradient of hundreds- to thousands-fold. (b) Experimental thrombosis, however produced, is accompanied by a marked decrease in the electronegative charge of the vessel wall and the charge is restored in all cases by heparin. (c) The normal electronegative charge is due to glycosaminoglycans. Heparin possesses the strongest electronegative charge of these substances and is present in the vessel wall as a component of a larger heparitin (sulfate) proteoglycan molecule. (d) Maintenance of the normal electronegative charge depends on adequate supply of oxygen (adequate blood flow). (e) Commercial heparin releases enzymes from the endothelium, lipoprotein lipase and histaminase (D.A.O.). Lipoprotein lipase changes the composition of plasma lipids and lipoproteins and histaminase provides a check for fat absorption. The release of these enzymes decrease and prevent atherosclerotic changes. (f) After administration of commercial heparin, heparin isolated from the plasma has higher antithrombin activity than that injected. The heparin taken up by the endothelium is returned with greater activity. The anticoagulant effect of administered heparin does not produce hemorrhage since this requires simultaneous occurrence of defects in the vascular factor of hemostasis (the result of stress or pituitary-adrenal imbalance) or platelet defect. Thus, clinical effectiveness of heparin is an expression of its close relationship to the vessel wall.     

Deep venous thrombosis: an overview

The patients at high risk of deep venous thrombosis are defined. Factors in the formation of intravenous thrombi are described. The roles of endothelium, formed elements, clotting factors, and their interrelationships are correlated. Diagnostic modalities and their application are described, and the commonly used medical and surgical therapies are specifically outlined.     

Morphometric and ultrastructural study of experimental venous thrombosis. Effects of defibrotide, an antithrombotic agent

Defibrotide is a profibrinolytic agent which has potent stimulatory effects on vascular prostacyclin (PGI2) production and secretion. We have studied the effects of this substance on the morphological organization of venous thrombi by combining ultrastructural evaluation with histometric analysis. Thrombosis was induced by inserting a collagen-coated thread into the femoral vein of rabbits 2 h before sacrifice. The results show that Defibrotide is highly effective in reducing the size of the thrombus. This is due to combined profibrinolytic action and interference with platelet and leukocyte adhesion as indicated by results showing that: (i) large deposits of fibrin-like material are smaller and less abundant; (ii) platelet aggregates are smaller, and (iii) the density of leukocytes in thrombus is strongly decreased. Polymorphism is prominent in platelets which are indistinguishable from control suggesting that the primary site of action of Defibrotide is on adhesion. The inhibitory effect on leukocyte participation to the thrombotic process is probably due to PGI2 release and may be of relevance on maturation and aging of the thrombus.     

红细胞微粒与深静脉血栓形成关系的研究进展

红细胞微粒是在各种刺激因素下由红细胞释放的小囊泡，其产生和释放贯穿于红细胞的整个老化过程。相关研究证明红细胞微粒具有调节血管内皮细胞功能及激活凝血系统的作用，其与心血管疾病的发生、发展有这密切联系，尤其在深静脉血栓形成等血栓性疾病中发挥着重要作用。随着对红细胞微粒研究的不断深入，其可能作为一种深静脉血栓形成诊断外周血生物标志物。现主要对红细胞微粒与深静脉血栓形成的关系研究进行一概述。     

The relationship between gene polymorphism of MTRR A66G and lower extremity deep venous thrombosis

ABSTRACT

Objective: To investigate the relationship between gene polymorphism of MTRR A66G and lower extremity deep venous thrombosis (DVT).

Methods: Two hundred and two patients with DVT as experimental group and 240 normal adults (control group) were enrolled in this study and white blood cells were collected, respectively. Polymorphism of the 66 loci in MTRR gene was detected by polymerase chain reaction-sequence-specific primers (PCR-SSP) in two groups. The frequency of genotype and allele distribution of each group was compared.

Results: The frequency of AA, AG and GG genotypes in 66 sites of MTRR gene were 26.76%, 4 3.66% and 29.58% in DVT group and 43.57%, 44.28% and 12.14% in control group, respectively. There was no significant difference in the distribution frequency between two groups (χ?=?3.2, P?>?.5).

Conclusions: The gene polymorphism of MTRR A66G may not be an independent genetic risk factor in DVT in China.     

The effect of predilatation on coronary angioplasty-induced vessel wall injury

Fifty-four patients presenting with stenotic lesions in a major coronary artery visually estimated by diagnostic angiography to be greater than 90% but less than 100% were randomized to one of two angioplasty regimens, predilatation (group 1) or no predilatation (group 2). In group 1, the artery was initially dilated with a 2 mm balloon followed by a balloon that was considered by the operator to be the definitive size to fully dilate the target vessel. In group 2, the artery was dilated with a balloon deemed the definitive size to complete the angioplasty procedure. There were no statistical differences between groups with respect to age, sex, history of unstable angina, or prior acute myocardial infarction. There were also no significant differences in the angiographic characteristics of the coronary lesions including artery location, lesion length, concentric or eccentric morphology, tubular versus discrete stenosis, calcium in lesions, or lesions on a bend. Following angioplasty, luminal filling defects were present in 5% of the predilated group and in 9% of the nonpredilated group (p = NS). The incidence of luminal border haziness at the dilatation site did not differ between groups, seven (35%) in group 1 versus eight (24%) in group 2. Angiographic evidence of a linear dissection at the angioplasty site was also similar between groups, one (5%) in group 1 versus five (15%) in group 2. Occlusive complications were witnessed in 10% of the predilated group and 12% of the nonpredilated group (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fibrinolytic activity after vessel wall injury.

The goal of this study was to assess fibrinolytic activity after vessel wall injury and to correlate changes in fibrinolytic activity with angiographic and histologic findings. Accordingly, in 18 atherosclerotic rabbits, vessel wall injury was produced by means of iliac artery balloon angioplasty (the injury group), whereas 8 atherosclerotic rabbits served as a control group. In all rabbits from the injury group, deep vessel wall injury was documented by either angiography or histologic study. Plasminogen activator inhibitor-1 activity in plasma increased significantly, from 21.79 +/- 1.29 arbitrary units/ml (AU/ml) at baseline study to 32.05 +/- 1.47 AU/ml at 6 h after vessel wall injury (p less than 0.01), whereas activity remained unchanged throughout the 24-h period in the control group. Plasma levels of tissue plasminogen activator activity were similar in both groups. Intravascular thrombus was found in five of six additional rabbits 6 h after vessel wall injury, that is, at the time of impaired fibrinolytic activity, whereas no thrombus was found in the control group (p less than 0.05). It is concluded that deep vessel wall injury is associated with reduced fibrinolytic activity. In addition to other procoagulant factors, elevated plasminogen activator inhibitor-1 activity may lead to intravascular thrombosis and impaired resolution of thrombus.     

Association between venous and arterial thrombosis: clinical implications

Venous and arterial thromboses have traditionally been regarded as separate diseases with different causes. However, recent epidemiological studies have documented an association between these vascular complications, probably due to the presence of more overlapping risk factors than previously recognized. This narrative review first focuses on the risk factors associated with both arterial and venous thrombotic events. In addition, it summarizes the more recent data on the risk of incident venous thromboembolism in patients with asymptomatic atherosclerosis or clinical manifestations of atherothrombosis, as well as on the risk of incident atherothrombotic events in patients with previous manifestation of venous thromboembolism. The potential clinical implications are also discussed.