Mechanism Of Thrombus Formation Research Articles

Coronary thrombosis. Effects of blood flow on the mechanism of thrombus formation.

The mechanism of arterial thrombosis, including coronary thrombosis, is different from that of thrombosis which occurs at sites of blood stasis such as deep venous thrombosis. Considering the onset of arterial thrombus formation, soluble coagulant factors may not play important roles for its onset since they are diluted by the effect of blood flow and cannot reach high enough concentrations to form insoluble fibrin. Platelets, which can stick to damaged vascular lumen even in the presence of shearing effects of blood flow, may play a crucial role in the onset of arterial thrombus formation. Thus, the mechanism of platelet thrombus formation should be assessed in the presence of blood flow. However, current dogma that fibrinogen binding to activated GP IIb/IIIa is the final common pathway for platelet thrombus formation was developed by using the function assay system of aggregometer, in which the effects of blood flow were not seriously considered. We are proposing in this review that plasma ligand protein of von Willebrand factor (vWF) and its interactions with platelet GP lb and GP IIb/IIa, which become apparent only in assays systems under influence of high shear rates of flow condition such as flowchambers or coneplate viscometers, are the key events leading to the onset of arterial thrombosis. A better understanding of the vWF-mediated mechanism of platelet thrombus formation is important for the development of better clinical tools to prevent ischemic heart disease as well as for a complete understanding of the mechanism of coronary thrombosis.

Plaque と組織因子

Rupture of the atherosclerotic plaque is closely related to thrombus formation and subsequent ischemic disease, such as acute coronary syndrome. However, the mechanism of thrombus formation after plaque rupture is not well understood. We examined the immnohistochemical localization of tissue factor (TF) in the human atherosclrotic lesion with monoclonal antibody against human TF. We also examined TF activity in the atherosclerotic intima that is experimentally induced by cholesterol feeding in rabbits, and in the coculture system of human umbilical vein endothelial cells (HUVEC) and human peripheral blood monocytes (PBMC) which are stimulated by oxidized LDL. TF was mainly localized in the foam cells, most of which are derived from macrophages, and its localization is well correlated with that of fibrin. Less amount of TF was also seen in the extracellular matrix. Experimentally induced atherosclerotic intima showed TF activity more intensely than non-atherosclerotic intima. The TF activity was thought to be derived from subendothelial tissue which was full of foamy macrophages, as scanning electron microscopy demonstrated exposure of subendothelial tissue. In vitro studies revealed that oxidized LDL stimulated TF activity in coculture of HUVEC and PBMC and that this stimulation required direct contact between the two cells. These findings suggest that TF localizing in atherosclerotic intima plays an important role not only in fibrin formation within atherosclerotic plaque but also in thrombus formation at the rupture site of plaque.

Platelet and Thrombin Inhibitors as Adjuncts to Thrombolytic Therapy and Percutaneous Coronary Interventions: A Review

A large body of evidence supports the critical role of thrombus formation in the pathogenesis of acute MI as well as the early ischemic complications after percutaneous coronary interventions. Both platelets and the plasma proteins involved in fibrin formation are intimately involved in the thrombotic process. Recently, pharmacological agents that hinder fibrin formation and platelet activation or aggregation have been developed. These drugs are being tested in patients with acute MI, in conjunction with thrombolytic agents, and in patients undergoing percutaneous coronary interventions. So far, the antiplatelet agents appear very promising in the area of percutaneous coronary intervention. Information on their role in acute myocardial infarction is still too preliminary to draw conclusions. Results with antithrombin agents have been less promising. This article will briefly describe the mechanisms of thrombus formation, detail the mechanism of action of available antithrombotic pharmacological agents, and review recent clinical trials of these agents.

Models to Study Thrombotic Disorders

Experimental models of thrombosis and vascular injury are important research resources that have enhanced our understanding of this pathophysiological process. Animal models provide insights into the prevalence of mechanisms that have been outlined in isolated cell and protein studies. The availability of transgenic and gene knockout animals will allow to pinpoint the relative functional importance of single changes in specific gene products in the pathophysiological process. The advances generated in our understanding of vascular injury and blood interaction with the vascular wall will facilitate the formulation of new strategies for cardiovascular protection an the prevention and treatment of thrombosis. The importance of thrombosis is highlighted by its dramatic consequences, which are the concern of numerous studies aimed at improving both treatment and diagnosis (1-3). Ultimately these studies are based on the evolving research on the mechanisms of thrombus formation. Blood factors, vessel wall factors, and cell-cell interactions in the context of fluid dynamics regulate thrombus formation and should be thoroughly investigated.

Risk of thromboembolism in new onset or transient atrial fibrillation

Atrial fibrillation (AF), potentially serious cardiac arrhythmia, occurs in 2% to 4% of persons greater than 60 years of age. The risk of systemic thromboembolism from chronic AF has long been recognized. Little is known about the thromboembolic risk of new onset Af. However, the results of prior studies support a significant risk of thromboembolism because of recent onset or paroxysmal AF. The mechanism of thrombus formation, embolization, and resolution in AF is illdefined, particularly that of new onset. The traditional concept holds that atrial thrombus forms only after greater than 2 days of AF and embolizes by dislodgement from increases in shear forces. This prevailing concept further proposes that newly formed atrial thrombus, in the setting of AF, organizes over a span of 14 days. The results of recent transesophageal echocardiographic studies have given insight into the temporal sequence of atrial thrombus formation, embolization, and resolution in AF and have expanded the traditional concept of thromboembolism in AF. Namely, left atrial thrombus may form before the onset of AF in the face of sinus rhythm. Conversion to sinus rhythm may increase the thrombogenic millieu of the left atrium. Importantly, atrial thrombus may form in the acute phase of AF. Lastly, thrombus may require more than 14 days to become immobile or to resolve. On the basis of these emerging insights by transesophageal echocardiography, it appears appropriate to consider anticoagulation in patients presenting with new onset or acute AF.

Effect of magnetic fields on viscous liquid column with finite length in a vertical straight tube

The formation of thrombus is closely related to the hydrodynamical conditions. Chandler’s experiment and further research shows that the cause thrombus formed in the lower meniscus may be that the fluid particles at relatively high speed strike on the lower meniscus leading to the gathering of platelet and red blood cells (RBC). This paper deals with the motion of viscous liquid column with finite length and two free surfaces in a vertical straight tube under the action of magnetic fields, numerical solution is obtained by the time-dependent method in a finite difference techniques. The results show that under the action of a proper magnetic field, the axial velocity at the lower meniscus near the axis will decrease, strike on the lower meniscus will be reduced and then thrombus formation at the lower meniscus can be avoided. This result provides a guide to further experimental research on the mechanism of thrombus formation and medical treatment to thrombus.

Mechanisms of cerebral artery thrombosis: a histopathological analysis on eight necropsy cases.

The mechanisms of thrombus formation in atherosclerotic cerebral arteries are still controversial, although intraplaque haemorrhage and rupture of the atheromatous plaques have been proposed. A histopathological analysis of segments of the thrombosed large intracranial arteries was carried out on eight patients who died within 28 days after brain infarction. The study revealed occlusive thrombi in six and mural thrombi in two, developing mostly at the site of greatest stenosis or just distal to it. The histological characteristics of the thrombosed arteries were plaque rupture in three, intramural haemorrhage in one, ulceration in one, and thrombosis in the absence of plaque rupture or intramural haemorrhage in three. Occlusive emboli distal to the site of cerebral artery thrombosis (intracranial artery-to-artery thromboembolism) were observed in two. The following conclusions were drawn from the study: 1) plaque rupture or intraplaque haemorrhage is not a sine qua non for cerebral artery thrombosis; 2) occlusions occur at the site of greatest luminal compromise or just distal to it, and 3) non-occlusive mural thrombosis can occur in the absence of plaque rupture and eventually lead to local occlusion or distal embolisation.

Chapter 3 Mechanisms of thrombus formation and dissolution

This chapter presents a brief overview of the process of thrombogenesis. Emphasis is placed on the balance between prothrombotic and antithrombotic pathophysiological reactions. The rheologic considerations are reviewed in chapter 2, and the process of thrombus formation in devices composed of biomaterials is summarized in chapter 15.

Development of Anthron, an antithrombogenic coating for angiographic catheters.

A new heparinized hydrophilic polymer (Anthron) which contains a large amount of heparin ionically bound to the polymer matrix has been developed. Anthron showed excellent and long-term blood compatibility both in animal and clinical tests. It has been clarified that the long-term blood compatibility of Anthron results from its negative membrane potential and continuous release of heparin from its surface into the blood at the rate of more than 0.01 unit/cm2 min. The application of Anthron for angiographic catheters was studied, and we evaluated the effects of our antithrombogenic angiographic catheter (AAC). As controls, polyurethane catheters (PUC), and polyethylene catheters (PEC), were studied in a similar manner. In addition, the mechanisms of thrombus formation and its complications are discussed.

Mechanisms of thrombus formation and lysis

Maintenance of a patent vasculature is critical to provide nutrient blood flow to dependent tissues. This is normally facilitated by vessels composed of actively nonthrombogenic endothelium and blood that contains both nonactivated platelets and inactive coagulation proenzymes. Following vessel injury, active hemostasis results from vasoconstriction, adherence and aggregation of activated platelets, and coagulation enzyme activation. The resulting thrombus contains a mixture of blood cells and the insoluble product of coagulation, fibrin, which further stimulates the activation of another blood enzyme system known as the fibrinolytic system. This results in the conversion by plasminogen activators of the circulating plasma proenzyme plasminogen into the active fibrinolytic enzyme plasmin, which dissolves the clot into degradation products. Vascular patency ultimately is restored and healing is thus facilitated. The hemostatic system is highly regulated by a variety of processes. Derangement of regulation can lead to disease manifesting either as thrombosis or hemorrhage. Furthermore, improved understanding of the molecular interactions involved in these processes has led to design of newer therapeutic interventions targeted toward amelioration of the sequelae of thromboembolic disease.

Arteriovenous difference in levels of vascular and platelet factors of hemostasis

The authors study arteriovenous differences that lie at the basis of the mechanism of thrombus formation in arteries and veins. The experiments were carried out on rats. ADP-induced platelet aggregation, the malonic dialdehyde concentration, and the cAMP concentration, the last by radioimmunoassay, were determined in the platelet-enriched plasma. The antiaggregation activity of the aorta and posterior vena cava was estimated by determination of the antiaggregation properties and cAMP level in the vessel walls by radioimmunoassay. It is concluded that great importance in the mechanism of white thrombus formation must be ascribed to disturbance of the vascular-platelet component of the hemostasis system, and in the mechanism of formation of the red thrombus - to disturbance of the coagulation component.

The role of platelet hyperfunction in thrombus formation in hyperlipidemia

The mechanism of thrombus formation in hyperlipidemia was studied. Attempts at artificial creation of an arterial thrombus in control rabbits stenosing the femoral artery by ligature were not successful unless ellagic acid was administered by injection. Howevere, in rabbits with hyperlipidemia, mere creation of stenosis in the femoral artery resulted in a high percentage of thrombus formation. In rabbits with hyperlipidemia, both thromboxane (Tx) A 2 biosynthesis in platelets and prostacyclin (PGI 2) biosynthesis in the aorta were increased and these changes were noted at the level of cyclooxygenase in the arachidonic acid metabolic pathway. Therefore, these results suggest that thrombi are likely to be formed in hyperlipidemia and that such thrombus formation is due largely to platelet hyperfunction.

高脂血症およびこれに伴う動脈硬化症の血せん症発現における血小板の関与について

The mechanism of thrombus formation in hyperlipidemia and atherosclerosis was studied using rabbits.Attempts at artificial creation of arterial thrombus in control rabbits using Maekawa's technique of stenosing the femoral artery by ligature were not successful unless ellagic acid was administered by injection. Howevere, this thrombus formation could be prevented by oral administration of aspirin.In rabbits with hyperlipidemia, mere creation of stenosis in the femoral artery resulted in a high percentage of thrombus formation with the prophylactic effect of aipirin being considerably decreased.In rabbits with hyperlipidemia, both thromboxane (Tx) A2 biosynthesis in platelets and prostacyclin (PGI2) biosynthesis in the aorta were increased and these changes were noted at the level of cyclo-oxygenase in the arachidonic acid metabolic pathway. A diminished inhibitory effect of aspirin on TxA2 and PGI2 production was observed. In hyperlipidemia, although PGI2 biosynthesis was increased, mere creation of stenosis in the artery resulted in a high percentage of thrombus formation. Therefore, these results indicate that platelet hyperfunction is largely accountable for thrombus formation.In rabbits with experimental atherosclerosis, TxA2 bsosynthesis of platelet was increased but PGI2 biosynthesis of aorta was decreaed.These results indicate that thrombi are likely to be formed in hyperlipidemia, which may lead to atherosclerosis, and that such thrombus formation is due largely to platelet hyperfunction.

Functional and Morphological Studies of Platelet Reactivity with Vessel Wall Subendothelium in Chronic Myeloproliferative Disease

Mechanisms of thrombus formation in myeloproliferative disease were studied using a technique which visualized platelet-vessel wall interactions under physiological conditions of blood flow. Whole blood from four patients with chronic myelogenous leukaemia and three with thrombocythaemia were pumped through perfusion chambers containing de-endothelialized artery segments. Platelet reactivity with vessel walls (thrombus formation) was measured in sections of vessels by light microscopy and quantitative morphometric analysis. Five patients produced platelet reactivity values of 130--258% of controls while two gave decreased values. The two highest platelet reactivity values occurred in samples with elevated platelet counts and normal haematocrits. In contrast, when anti-platelet drugs were administered to three patients with high platelet counts, reactivity values decreased to 11--34% of controls. Clinical correlations revealed that patients with highest platelet reactivity values (165--258%) were those subjects who also exhibited thrombotic or haemorrhagic complications. Thus absolute platelet count and haematocrit may be major determinants in predicting these complications. Qualitative evaluations of thrombus formations by light and electron microscopy provide further evidence that platelets in myeloproliferative disease also possess qualitative abnormalities.

An introduction to blood compatible polymer surfaces for use in artificial internal organs

AbstractWhile the body is a hostile environment for all types of polymers, an even more serious problem is that of thrombus formation induced by all foreign surfaces, including polymeric surfaces. This is a still largely unsolved problem which hinders the development of artificial internal organs. The thromboresistant materials presently proposed and used in artificial organs include heparinized surfaces and materials found to be thromboresistant in certain implantation cites. In this article tissue‐polymer interactions are first discussed and then followed by a discussion of blood‐polymer interactions. The mechanism of thrombus formation is presented and some of the possible interactions of blood with surfaces are suggested. Representative nonthrombogenic and thromboresistant materials are discussed.

Possible mechanism of thrombus formation.

IT has often been observed that after trauma (and possibly under other conditions) the thrombi which form in the vascular system consist of a small white head (the white embolus) and a longer red tail1. The predominant constituent of the embolus is generally aggregated platelets, and some recent experiments may throw light on the mechanism of formation of the red tail, which consists primarily of red cells.

Thromboembolic disease in pregnancy

The mechanism of thrombus formation and the predisposing factors of thrombophlebitis were discussed.The various forms of treatment proposed for this condition were presented.In pregnancy the incidence of thrombophlebitis was found to be surprisingly low. Diagnosis, prognosis, and treatment during gestation were reviewed.The effectiveness of anticoagulant treatment in preventing embolism and death in the expectant mothers was demonstrated after careful analysis of a large number of cases reported in the literature.The dangerous effects of coumarin derivatives on the fetus were recognized, and the relative safety of heparin was shown after tabulation of the cases reported in sufficient details.The use of dextran was proposed for prevention of pulmonary embolism in pregnancy complicated by thrombophlebitis or phlebothrombosis.

POINTS FROM LETTERS: Boxing Injuries

Endovascular treatment of aneurysms with flow diverters or coiling is sometimes complicated by intraprocedural or postprocedural thrombosis along or within the devices. Thrombus composition and structure associated with such complications may provide insights into mechanisms of thrombus formation and clinical strategies to remove the thrombus. We present a retrospective histopathologic study of 4 patients who underwent mechanical thrombectomy due to acute occlusion of either implanted flow diverter devices or along coils during the treatment of intracranial aneurysm.

THE ELECTROPHORESIS OF THE BLOOD PLATELETS OF THE HORSE WITH REFERENCE TO THEIR ORIGIN AND TO THROMBUS FORMATION

1. The cataphoretic velocity of blood platelets (horse) in plasma has been found to be between 40 and 51 micro per sec. per volt per cm. The mean velocity obtained from five horses is . 45 micro per sec. per volt per cm. 2. The cataphoretic velocity of polymorphonuclear leucocytes in similar specimens is practically identical with that of the platelets. This is noteworthy because of the fact that lymphocytes and red cells have different speeds. 3. With spontaneous agglutination of platelets, white cells and red cells, there is no change in the cataphoretic velocity incidental to aggregation. 4. The possible surface composition of platelets and white cells is briefly discussed. 5. The bearing of these findings on the origin of blood platelets and the mechanism of thrombus formation is demonstrated.