Thrombosis

In the cardiovascular system of the living body, blood coagulation or some process in the blood is formed and analyzed to form a solid mass, called thrombosis. The solid mass formed is called a thrombus. Unlike blood clots, blood clots form when blood flows. Thrombosis is an abnormal coagulation of blood in a flowing state due to activation of platelets and activation of blood coagulation factors. Conditions for thrombosis are currently recognized as three conditions proposed by Virchow: vascular endothelial cell damage, changes in blood flow status, and increased blood coagulability.

Thrombosis refers to a blood clot in which a human or animal is alive due to certain causes, blood has an abnormality in the circulating blood, or blood deposits occur on the inner wall or blood vessel wall of the heart. The understanding of the incidence of thromboembolic diseases is closely related to the medical technology and the diagnostic level of thrombosis. At present, the concept of thrombosis has been extensively distributed to the whole-body tissues and organs, and is no longer confined to myocardial infarction, deep vein thrombosis or cerebrovascular thrombosis. Forming equal lesions. Thrombosis can occur in blood vessels in any part of the body. The incidence of venous thrombosis is higher than that of arterial thrombosis, and the ratio can reach 4:1.

Pathogenesis of thrombosis

1. Vascular wall injury

The luminal surface of the vessel wall is covered by endothelial cells with a total area of more than 1000 m2. Normal vascular endothelial cells have antithrombotic properties, and they release various substances such as ATPase ADPase and tissue plasminogen activator through surface negative charges. (tpA), thrombin regulatory protein (TM), tissue factor pathway inhibitor (TFPI), endothelial-derived relaxing factor (EDRF) PGI2, etc., prevent adhesion, aggregation, promote fibrinolysis, inhibit blood coagulation, enhance Anticoagulant effect to maintain blood flow and prevent thrombosis.

2. Platelet factor

Platelets play a role in hemostasis and thrombosis by two mechanisms: (1) Platelets are a major component of emboli, particularly in arterial thrombosis, and in microthrombus formation in tiny blood vessels. (2) Through its thrombogenic effect and release of products, is conducive to platelet aggregation, emboli formation, stimulation of white blood cells and damage to endothelial cells, promote blood coagulation, and facilitate thrombosis.

3. White blood cells and red blood cell factors

Epidemiological survey data show that white blood cell count has a certain relationship with cardiovascular disease. Some studies have shown that white blood cell count is a valuable indicator of blood pressure and serum cholesterol in predicting myocardial infarction and is an independent risk factor.

Treatment

Thromboembolic disease is one of the causes of the current high risk of death, such as myocardial infarction, cerebral thrombosis, deep vein thrombosis, cerebral embolism, pulmonary embolism. In addition, thrombosis is an important pathological process involved in the pathogenesis of many diseases.

1. Anticoagulant therapy

(1) Heparin:

Heparin is a commonly used anticoagulant and is a highly sulfated glycosaminoglycan. Heparin is widely found in mammalian tissues, and mast cells are the main production site.

(2) Low molecular weight heparin:

The crude heparin is cleaved by chemical or enzymatic methods into fractions having a relative molecular mass of 1000 to 12,000 and then purified. There are at least 10 kinds of low molecular weight heparin prepared by different manufacturers and different methods.

2. Thrombolytic therapy

Thromboembolic disease is one of the common diseases that are harmful to health. The most effective treatment is thrombolytic therapy. The thrombolytic drug is applied to the formed thrombus, and the fibrinolytic activator is used to convert plasminogen into plasmin, so that the thrombus is dissolved in time, the local blood circulation is restored, and the function of the tissue and organs affected by the thrombus is improved. A large amount of data shows that after thrombosis, only 30% can be autolyzed, and about 50% can continue to develop. Therefore, in thromboembolic diseases, the earlier the treatment, the better the curative effect, especially the early recovery of important organs related to life such as brain, heart and kidney, which has great clinical significance.

(1) Commonly used thrombolytic drugs:

①Streptokinase (SK): is a single-chain protein that does not contain a glycosyl group and acts mainly on the peptide chain of plasminogen arginine (560)-valine (561) to cleave and single-chain. The plasminogen becomes a double-stranded plasmin and finally forms lysine (77). Plasmin is a biologically active plasmin. The thrombolytic effect of SK in the body is the process of SK thrombosis remaining after antibody neutralization. A large amount of plasminogen is adsorbed in the thrombus with fibrin, so a larger dose of SK is required to enter the thrombus and activate plasmin. Originally, it acts as a thrombolytic effect. SK has low binding capacity to fibrin and low specificity, which is easy to cause a widening of the fiber dissolution system.

②Contraindications for thrombolytic therapy: in the following circumstances, thrombolytic agents are not suitable or prohibited: 1 history of gastrointestinal or urinary tract bleeding, such as ulcer disease, esophageal varices, ulcerative colitis; 2 intracranial Lesions, trauma, tumor vasculopathy; 3 new surgery 7 to 10 days; 4 fractures; 5 large areas of skin grafts, burns without healing; 6 cardiopulmonary resuscitation; 7 pregnancy; 8 infectious thrombosis, bacterial Endocarditis; 9 newly formed tuberculosis cavity; 10 seniors with caution over 70 years old are generally not used.

3. Antiplatelet drugs

Antiplatelet therapy is an important component of the prevention and treatment of thromboembolic diseases, especially in white blood clots such as arterial thrombosis. Drugs that have been used clinically for many years to prevent platelet adhesion, aggregation and release, and thus prevent arterial thrombosis, are called antiplatelet drugs. The mechanism of action is the occurrence of thromboembolic disease. First, a variety of pathogenic risk factors damage endothelial cells, causing blood cell adhesion, aggregation, activation of platelets and release of various vasoactive substances, such as TXA2, 5-HT β-TG.

Author's Bio: 

Creative Animodel is specialized in providing an integrated portfolio of thrombosis models to improve the molecular understanding and treatment of thrombosis. With cutting-edge facilities and technologies, we have strong expertise in developing disease models suited for testing disease-modifying compounds or drugs. What’s more, customized thrombosis models can be designed and developed on your demand.