thrombosis
Introduction
Introduction to thrombosis Thrombosis refers to a blood clot that occurs when a human or animal is alive due to certain causes, blood forms an abnormality in the circulating blood, or blood deposits occur on the inner wall or blood vessel wall of the heart. Thrombosis can be divided into venous thrombosis, arterial thrombosis and microthrombus according to the anatomy of the body. It can also be divided into platelet thrombus, erythrocyte thrombosis, mixed thrombus and fibrin thrombus according to the composition of the thrombus, and some are divided into white thrombus according to the color seen by the naked eye. , red blood clots and mixed blood clots. basic knowledge The proportion of the disease: 0.01%-0.05% (the incidence rate is about 0.01%-0.05% among the middle-aged and elderly people over 60 years old, and the incidence rate of hypertension is higher) Susceptible people: no specific population Mode of infection: non-infectious Complications: pulmonary embolism
Cause
Cause of thrombosis
Endocrine factors (25%):
Deficiency of anticoagulant substances includes: antithrombin III deficiency, abnormal antithrombin III disease, protein C deficiency, protein S deficiency, and heparin cofactor II deficiency. Abnormal fibrinolytic causes: plasminogen deficiency, lack of fibrinolytic substances, increased fibrinolysis inhibitors, abnormal fibrinogenemia.
Physical factors (20%):
Stasis of blood flow: pregnancy, obesity, trauma, surgery, congestive heart failure, bedriding too long. Embolization: more common in arterial thrombosis.
Disease factors (35%):
Coagulation: malignant tumors, myeloproliferative diseases. Abnormal blood vessel wall: atherosclerosis, hyperlipidemia, diabetes. Increased blood viscosity: polycythemia vera, plasma cell disease, burns. Platelet dysfunction: essential thrombocytosis.
Other factors (15%):
Oral contraceptives, hemolytic crisis. Causes of increased blood coagulation: bacterial endotoxin, virus, hemolysis, necrotic tissue, tumor cells, thrombotic thrombocytopenic purpura, serum disease, disseminated intravascular coagulation.
Pathogenesis
1. Vascular wall damage The luminal surface of the vessel wall is covered by endothelial cells, and its total area exceeds 1000 m2. Normal vascular endothelial cells have antithrombotic properties, which release various substances such as ATPase and ADPase through surface negative charges. Tissue plasminogen activator (tpA), thrombin regulatory protein (TM), tissue factor pathway inhibitor (TFPI), endothelial-derived relaxing factor (EDRF), PGI2, etc., prevent platelet adhesion, aggregation, and promote fibrin Dissolve, inhibit blood coagulation process, enhance anticoagulant effect to maintain blood flow and prevent thrombosis. When endothelial cells are damaged by machinery, infection, immunity, chemicals and metabolites, endothelial cells fall off and cause subendothelial When tissue exposure, or defects in endothelial function in various congenital diseases, the vessel wall loses these antithrombotic effects, and the potential thrombogenic mechanisms present in the vessel wall produce favorable thrombotic changes, such as vWF, tissue. Factor (TF), etc., changes in blood vessels that favor thrombosis may be through the following mechanisms:
(1) Promote platelet adhesion and aggregation: After normal endothelial cells are detached, the subendothelial tissue is exposed to the blood. Platelet adhesion is one of the earliest reactions leading to thrombosis. The components of platelets adhering to the endothelium include collagen, laminin, micro Fiber and vWF, heparan sulfate form a strong negative charge on the surface of blood vessels. ATPase ADPase and PGI2 on the surface of endothelial cells are another mechanism for normal blood vessels to prevent platelet adhesion and aggregation. ATPase and ADPase promote endothelial cell damage. And the release of ADP from blood cell damage to AMP prevents platelet aggregation, and these functions decline when endothelial cells are damaged or shed.
(2) vasoconstriction and sputum: endothelial cells can secrete endothelin, a substance with strong vasoconstriction, which can cause arterial and venous vasoconstriction. The vasoconstriction of endothelin is 10 times stronger than that of angiotensin, and the effect is long lasting. The vasoconstrictor is a platelet-activating factor (PAF), a product of endothelial cell injury. This substance is also an inducer of platelet aggregation, which promotes the accumulation of platelets at local lesions. The vascular endothelial cells secrete PGI2 and EDRF (the essence). In the case of NO), when endothelial cells are damaged, the amount of release is also decreased, thereby losing the function of regulating normal vasodilation. Many substances can stimulate endothelial cells to produce PGI2, such as ATP, ADP, PAF, thrombin, endothelin and NO. PGI2 exerts antithrombotic effects by dilating blood vessels and inhibiting platelet aggregation. The ability of vascular wall to synthesize PGI2 is arterial>venous>capillary, inner layer of vessel wall>middle layer>outer layer, upper limb blood vessel>lower limb blood vessel. These differences may be different. The incidence of thrombosis is different.
(3) Fibrinolytic activity: two important physiological plasminogen activators, namely t-PA and urokinase plasminogen activator (u-PA), are synthesized and secreted by endothelial cells to clear normal blood circulation. The formation of a small amount of fibrin is an important fibrinolytic system in the body. About 95% of the t-PA released by endothelial cells is rapidly bound by excess plasminogen inhibitor (PAI) and loses its activity, and also loses its binding to fibrin. Ability, many factors can stimulate endothelial cells to synthesize PAI-1 at the level of gene transcription, such as interleukin-1, tumor necrosis factor, thrombin, endotoxin, lipoprotein alpha, glucocorticoids, while insulin and insulin-like growth factors pass Post-transcriptional regulation of genes promotes the production of PAI-1. In thrombotic diseases, the plasma t-PA activity of patients decreases, which may be related to the increase of PAI.
(4) Procoagulant effect of the blood vessel wall: The involvement of the normal blood vessel wall in hemostasis is related to its procoagulant effect. Under pathological conditions, this effect becomes a factor contributing to thrombosis. This procoagulant effect includes:
1 After endothelial cells are stimulated by thrombin and endotoxin, the cell surface can express tissue factor (TF), a transmembrane glycoprotein that binds to factor VII/VIIa to form a complex that leads to factor IX and Activation of factor X, starting the clotting waterfall,
2 Endothelial cells have the function of binding to factor IXa, in the presence of factor VII, promoting the activation of the factor, the latter and the factors Va, Ca2 constitute prothrombin, promote the blood coagulation process,
3 The surface of endothelial cells contains activating factor XII, which promotes activation of factor XII.
(5) Anticoagulant effect of blood vessel wall: The strong anticoagulant effect of vascular endothelial cells plays an important role in protecting blood flow in blood vessels. They pass through proteoglycans, thrombomodulin (TM), tissue factor present on the surface of vascular endothelium. The anticoagulant effect of factors such as pathway inhibitor (TFPI) prevents the occurrence of intravascular coagulation. Heparan sulfate is the most important type of glucosamine polysaccharide, which has the effect of enriching the surface of the endothelium such as AT-III, and constitutes on the surface of the endothelium. The anticoagulant system of heparan sulfate-AT-III rapidly inactivates intravascular activated coagulation factors. TM present on the surface of endothelial cells is the main cofactor for accelerating thrombin-activated protein C. In addition, TM also enhances factor Xa-activating protein. The role of C, the reduction of thrombin formation, in recent years, extensive research on TFPI, TFPI synthesis site in endothelial cells and liver, is a powerful inhibitor of TF, it can block the activation process of exogenous coagulation pathway, when endothelial cells When the injury or detachment occurs, the above anticoagulant effect is significantly reduced or lost, resulting in a change that favors blood coagulation.
2. Platelet factors Platelets play a role in hemostasis and thrombosis by the following two mechanisms:
1 platelets are the main component of emboli, especially in arterial thrombosis, and in microthrombus formation of 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.
In thrombotic diseases, platelet activation is closely related to thrombosis. In coronary heart disease, platelet shape changes are stimulated (platelet pseudopodia formation), platelet adhesion and platelet aggregation inhibitors (ADP, adrenaline) , collagen or arachidonic acid) increased aggregation, plasma platelet release products (ADP, 5-HT, -TG, TXA2, etc.) increased in concentration, platelet alpha granule membrane protein (GMP-140) on platelet surface and plasma The increase of medium concentration indicates that platelet activation is one of the important pathological mechanisms of thrombosis, and there are basically two reasons for platelet activation:
1 special plateau causes platelet activation,
2 A variety of irritants, including drugs, bioactive substances, chemicals and immunosuppressive agents, have been reported in clinical studies leading to platelet activation.
3. Leukocyte and red blood cell factors Epidemiological investigation data in recent years show that white blood cell count has a certain relationship with cardiovascular disease. Some studies have shown that white blood cell count is a similar blood pressure and serum cholesterol in predicting myocardial infarction. Risk factor.
(1) White blood cells are a component of blood clots. The following effects may be the mechanism by which white blood cells participate in thrombosis:
1 Adhesion of leukocytes: It has long been known that white blood cells have the function of adhering to the blood vessel wall. This adhesion is very mild under normal conditions, and is more common in slow-flowing veins. When veins are stagnant or small arteries When oppressed and occluded, leukocyte adhesion mainly depends on the adhesion function of leukocytes and endothelial cells on the surface. The adhesion receptors on the surface can be affected by leukotriene B4, collagen, 5-HT, adrenaline, kinin, CSA, TNF, etc. The substance is stimulated and upregulated within a few minutes, thereby increasing its adhesion to the surface of endothelial cells.
2 Release of toxic oxidative substances: Mononuclear cells activated and adhered to the surface of blood vessels release reactive superoxide metabolites. These O2- can inactivate EDRF and reduce endothelial cell function, and activated monocytes release a variety of Cytokines, including interleukin-1, TNF and proteolytic enzymes, cationic proprotein, collagenase, damage endothelial cells, impair vasodilatation, and cause adhesion, aggregation and activation of platelets and neutrophils.
3 The rheological properties of white blood cells: the diameter of white blood cells is about 8m, and the diameter of small capillaries is only 5 ~ 6m. Therefore, when microvessels pass, the deformability of white blood cells determines its degree of circulation in blood vessels. When white blood cells are activated, pseudo-genesis occurs. Foot protrusion, cytoplasmic hardness increases, white blood cells are easily trapped in the microvessels, causing slow flow.
4 The procoagulant effect of leukocytes: In acute leukemia, especially acute promyelocytic leukemia, there is a serious anticoagulant dysfunction, complicated by DIC. In the early years of research, it has been recognized that the cause of concurrent DIC exists in the release of leukemia cells. Substance, procoagulant substances of leukemia cells can be divided into two categories: one through the exogenous coagulation pathway and the other through the endogenous coagulation pathway, but both types of procoagulant substances promote coagulation by activating factor X.
(2) The role of red blood cells in thrombosis:
1 red blood cell aggregation: in myocardial infarction, Waldenström macroglobulinemia, tumor and other diseases, a large pile of red blood cell aggregates can be seen in the blood circulation, which play a role like platelet aggregates in the microcirculation, affecting the microcirculation Normal blood perfusion.
2 Whole blood viscosity increases: Whole blood viscosity depends mainly on red blood cells. The increase in the number of red blood cells and the decrease in deformability can increase the viscosity of whole blood. When the blood viscosity increases, the blood flow resistance increases, the flow speed is slow, and the tissue is deficient. Blood, hypoxia, so that various metabolites in the tissue accumulate.
3 promote platelet adhesion, aggregation and release: red blood cells promote platelet adhesion and aggregation, which is conducive to hemostasis and thrombosis, its promotion through the following mechanisms: A. physical effects: the collision of red blood cells and platelets, strengthen the transport of platelets to the inner wall of blood vessels Speed and frequency, the number of red blood cells increases, and the deformability decreases. This effect is greater. B. Chemical action: red blood cells release ADP to cause platelet aggregation. This mechanism mainly works under high shear stress. Recently, it has been proposed. A small amount of hemoglobin released by red blood cells induces platelet aggregation by the formation of free radicals, and the presence of red blood cells can also enhance the platelet release response.
4. Factors in the formation of blood clots in thrombosis
(1) lack of coagulation factors:
1 Congenital coagulation factor XII deficiency: This disease was first described by OD Rathoff in 1955, and the factor lacking in the name of the patient is the Hagemam factor. The patient has prolonged APTT but no bleeding, and factor XII deficiency in the population. There is a high incidence, the disease is autosomal recessive, divided into two types: type I cross-reactive substance negative (CRM-), its factor XII content and activity decreased in parallel; type II cross-reactive substance positive (CRM), Due to abnormal molecular structure, factor XII activity is less than 1% in homozygotes, antigen is not detected, APTT>120s; in heterozygotes, factor XII activity is 25%-50%, antigen content is 35%-65 %, while APTT is prolonged by 5% to 20%, and the deficiency of factor XII leads to a thrombotic mechanism associated with decreased endogenous fibrinolytic activity.
2 kininogen deficiency: no reports of thromboembolism, but in the case of congenital kallikrein deficiency, there are reports of thromboembolism, of the 35 reported cases, 3 ( 8.6%) thrombosis occurred.
(2) Increased clotting factor:
1 increased fibrinogen: in thrombotic diseases, there is an increase in fibrinogen concentration, the cause is not cleared, and many related factors have been found, such as obesity, diabetes, smoking, increased lipids, increased blood pressure, etc., fibrinogen Increased concentration is conducive to the mechanism of thrombosis, including increased plasma and whole blood viscosity, changes in blood flow and increased shear stress on the vascular endothelium, and LDL binding is beneficial to atherosclerosis, which is the substrate of thrombin and platelet aggregation. The basic components are chemotactic components such as endothelial cells, fibroblasts, and smooth muscle cells.
Increased activity of factor VII: increased activity of factor VII in thrombotic diseases was proposed by the Northwick Park Heart Research Center in the United Kingdom. They found that factor VII activity was significantly higher in patients who died of myocardial infarction or tumor than in survivors (P< 0.01), the factor VII activity of patients with diabetes or microvascular disease was significantly higher than that of normal people (P<0.01). Smoking, drinking, and contraceptives all increased the activity of factor VII. There are factors V, IX in oral contraceptives. Reports of elevated X, age, ethnicity, and blood type are also associated with factor VII activity.
(3) abnormal molecular structure of blood coagulation factor:
1 abnormal fibrinogenemia: At least 250 patients with this disease have been reported, the disease is autosomal recessive, in the reported cases, about 20% of patients have recurrent thromboembolic disease, 25% There is bleeding, 7% of simultaneous bleeding and thrombosis, and half of the patients are asymptomatic, fibrinogen functional defects include the following four: A. abnormal release of fibrin peptide chain, B. fibrin monomer polymerization or factor XIIa mediated Cross-linking abnormality, C. is not sensitive to the fibrin effect of plasmin degradation and cross-linking, D. and the ability to bind to plasminogen is reduced, which is characterized by abnormal polymerization of fibrin monomer and insensitivity to plasmin degradation. Functional defects are the most common.
2 Factor VIII Molecular Abnormalities: In 1991, a literature reported that Sweden had a family of factor VIII defects with thrombophilia. The patient was 44 years old, male, with multiple thrombosis, and his brother and uncle also had a history of thromboembolism. The reason may be that a point mutation of the Factor VIII molecule leads to an abnormal molecular production, resulting in a factor VIII that is insensitive to the degradation of activated protein C.
(4) Coagulation factor activation: major surgery, tissue factor enters the blood circulation during trauma, promotes the activation of blood coagulation factors, blood coagulation, severe intravascular hemolysis, phospholipids of red blood cells play a role in promoting coagulation, tumors and acute leukemia, especially in acute early The myeloid leukemia cells release a direct activating factor X or a factor VII procoagulant. The prosthetic valve activates factor XII, initiates an endogenous coagulation process, and infusion of excess prothrombin complex induces thrombosis. Since the preparation consists of activated coagulation factors Xa, IXa and VIIa, the incidence of thrombosis is 5% to 10%.
5. Factors in antithrombin factors in thrombosis
(1) Reduced or lack of antithrombin III:
1 Hereditary antithrombin-III (AT-III) deficiency: In 1965, O Egeberg reported the first family of hereditary AT-III deficiency in Norway. The patient's AT-III level dropped to 50% of normal. Repeated venous thrombosis, the incidence of AT-III deficiency in the normal population is 1 / 5000, most patients with thromboembolic disease before the age of 35, according to AT-III function and antigen content determination, combined with genetic analysis, will It is divided into type I and type II (a, b, c3 subtypes), genetic abnormalities are the cause of type II and some type I AT-III deficiency, due to decreased plasma concentration of AT-III or activity, leading to blood Increased coagulability is the cause of thrombosis.
2 Acquired AT-III deficiency: It can be caused by the following three reasons: A. Reduction of AT-III synthesis, mainly in various liver diseases (hepatitis, cirrhosis), oral contraceptives, receiving asparaginase (L-asparaginase) Treatment, taking levamisole, etc., B.AT-III loss too much, mainly seen in digestive tract diseases and kidney disease, C.AT-III excessive consumption, found in heparin treatment and DIC patients.
(2) Heparin cofactor-II deficiency: Two patients with repeated venous thrombosis or cerebral infarction due to heparin cofactor-II (HC-II) deficiency were reported by Tran et al and Sie et al in 1985, respectively. The patient's HC-II level and activity decreased in parallel to 47% to 66% of the normal value. The proband had cerebral infarction at 40 years old. Among the 5 members of the family, 3 had a history of thrombosis, but the HC-II content and activity. Parallel decline, it is considered to be caused by decreased ability of synthetic HC-II, acquired HC-II deficiency is seen in liver disease, DIC, kidney transplantation, and the cause of reduction is related to increased consumption.
(3) Protein C deficiency:
1 hereditary protein C deficiency: patients with this disease have a history of repeated venous thrombosis, deep vein thrombosis of the lower extremities, pulmonary embolism is more common, in neonates with homozygotes, manifested as fulminant purpura, prone to occur in such patients Thromboembolic skin necrosis, according to protein C activity and concentration determination combined with genetic analysis, is divided into type I and type II, genetic abnormalities are the cause of this disease, autosomal dominant inheritance is the main genetic mode of the disease, but it may also There is a recessive inheritance.
2 acquired protein C deficiency: can be caused by 3 reasons, reduced liver synthesis, seen in severe liver disease, vitamin K deficiency or taking anti-vitamin drugs, such as warfarin, dicoumarin, excessive consumption, such as DIC, major surgery After, deep vein thrombosis, etc., activation of protein C formation disorders, in adult respiratory distress syndrome, severe infection, vascular endothelial injury and other diseases, due to TM reduction leading to protein C activation disorders.
(4) Activated protein C cofactor II deficiency: This disease is caused by a point mutation of the plasma factor V gene, which produces an abnormal factor V molecule of Arg506Gln replacement, so that activated protein C (APC) cannot act on the cut. Point and lose the role of the degradation factor V molecule, resulting in decreased blood anticoagulant activity, easily lead to thrombosis, the incidence of this disease in venous thrombosis can reach 40%.
(5) Protein S deficiency: Hereditary protein S deficiency was first reported by Comp et al in 1984. Venous thrombosis is a characteristic of this disease. The incidence of thrombotic diseases is 5% to 10%, all of which are heterozygous. , pregnancy, oral contraceptives, acute inflammation and vitamin K deficiency can lead to secondary protein S deficiency.
(6) Antiphospholipid antibodies: Antiphospholipid antibodies include lupus anticoagulant (LA) and anticardiolipin antibodies (ACA), both of which cause thrombosis, thrombocytopenia and fatal failure. Cardiolipin thrombosis syndrome (ACAS) and lupus anticoagulant thrombosis syndrome (aLA).
6. Factors in the formation of fibrinolysis system in thrombosis
(1) Abnormal plasminogenemia: due to abnormal plasminogen molecules, the amount of plasmin converted to activator is reduced, resulting in decreased fibrin (original) solubility and prone to thrombosis. The disease is autosomal dominant. The plasma plasminogen level is normal, but the activity is decreased, only 40% of normal people, indicating abnormal molecular structure of plasminogen.
(2) Defects in release of plasminogen activator: In 1978, Johansson et al. first reported a family of repeated deep vein thrombosis in the release of plasminogen activator (PA) in Sweden. Among the 59 members of the family, 23 Thrombus formation in humans, 12 of these 23 people in the intravenous drip DDAVP or venous block, can not increase the blood PA, indicating the release of PA.
(3) Too many plasminogen activator inhibitors: Since 1983, Nilsson and Tengborn reported congenital plasminogen activator inhibitor hypertoxia until 1993, and six families were reported in the literature. Autosomal dominant inheritance, the cause of excessive PAI-1 is not cleared, may be related to gene defects, and the acquired plasminogen activator inhibitor is not uncommon, in coronary heart disease, especially myocardial infarction, unstable angina High blood pressure, diabetes, atherosclerosis, and increased PAI-1 in obese individuals.
7. Changes in blood rheology Factors in thrombosis Blood rheology is a science that studies blood rheology, including the biological significance of blood viscosity and blood flow, in the body, blood vessels are narrow, curved, bifurcation Or atherosclerotic plaques, often a good site for thrombosis, blood viscosity is mainly affected by plasma large molecular weight proteins, whole blood viscosity is affected by blood cells and plasma proteins, in many diseases, there are Factors that increase plasma or whole blood viscosity, such as macroglobulinemia, multiple myeloma, congenital fibrinogenemia, primary or secondary polycythemia, pulmonary heart disease, leukemia, leukemia, burns, Severe dehydration and red blood cell shape, membrane structure and deformation changes are seen in various hereditary red blood cell diseases such as sickle cell anemia, hereditary spherocytosis, abnormal hemoglobinemia, etc. The increase in whole blood viscosity caused by some diseases is multifactorial Such as coronary heart disease, cerebral infarction, hypertension, atherosclerosis, peripheral arterial disease, diabetes, tumor, hyperlipidemia, etc., blood When the viscosity increased, reducing blood flow, perfusion unfavorable, resulting in tissue ischemia, venous thrombosis favor.
Prevention
Thrombosis prevention
The prevention and treatment of thrombotic diseases aims to improve the hypercoagulable state, and then clear or rebuild the blood flow pathway to prevent tissue ischemia and necrosis. The prevention and treatment measures have been greatly developed in the past 20 years, and many experiences have been gained in clinical practice. Lessons and prevention measures generally include anticoagulant therapy, thrombolytic therapy, antiplatelet therapy, etc. The choice of antithrombotic therapy is closely related to the stage of the disease. All limbs and venous thrombosis can be removed for more than 48 hours. Suppository therapy is also mainly used for newly formed acute venous and venous thrombosis. Antiplatelet and anticoagulant are mainly used to prevent thrombosis, and have little effect on the formed thrombus.
Indications
(1) DIC: Most patients with early acute DIC, especially those with hypercoagulable state, are mainly treated with heparin; thrombolytic therapy is only suitable for patients with advanced DIC or patients with sequelae after DIC recovery.
(2) thrombosis: deep vein thrombosis, peripheral arterial thrombosis, cerebrovascular thrombosis, etc., anticoagulation and thrombolysis have a certain effect.
(3) thromboembolism: detached emboli may cause acute vascular embolism, common pulmonary embolism, cerebral embolism, spleen embolism, renal artery embolization, mesenteric artery embolization, etc., usually based on thrombolytic therapy, anticoagulant therapy Supplemented.
(4) Heart disease: such as myocardial infarction in the past with heparin treatment, recently advocated in the early stage of infarction, thrombolytic drugs for coronary perfusion treatment, have higher efficacy, heart valve disease, cardiopulmonary bypass, open heart surgery , arterial repair, coronary artery bypass grafting, etc., anticoagulation (oral anticoagulant) and antiplatelet therapy can be used to prevent postoperative thrombosis.
(5) Acute nephritis: There is no satisfactory effect at present. The combination of anticoagulant and antiplatelet therapy may have some effects.
(6) malignant tumors: the release of tissue thromboplastin has the risk of thrombosis. Anticoagulant therapy has a tendency to prevent metastasis in some patients with malignant tumors, usually treated with oral anticoagulants.
2. Contraindications
(1) Heparin and antithrombin III: hemorrhagic disease or bleeding tendency, poor hemostasis after wound operation, severe liver and kidney dysfunction, and increased heparin-like substances.
(2) oral anticoagulant: coagulopathy, hypertension with retinopathy, hemorrhagic encephalopathy and recent craniocerebral trauma and surgery, severe liver disease, after pregnancy and childbirth.
(3) antiplatelet therapy: active ulcer, active tuberculosis and associated with cavity formation, platelet dysfunction, coagulopathy.
(4) thrombolytic therapy: hemorrhagic encephalopathy, visceral hemorrhagic injury, postoperative wound hemostasis, active ulcer, pregnancy, severe liver and kidney dysfunction, coagulopathy.
At present, most of the cases focus on postoperative surgery. According to recent papers with more cases, the use of anticoagulants to prevent deep venous thrombosis and pulmonary infarction has achieved good results, such as low-dose heparin, dextran-40, etc. In the traditional Chinese medicine, a number of research work on exploratory prevention of thrombosis has also been carried out. The drugs currently used in clinical practice include Salvia miltiorrhiza, Sanqi, Ginkgo biloba capsules, etc., but no large case reports have been reported.
Complication
Thrombosis complications Complications pulmonary embolism
1. Post-thrombotic syndrome: It is the most common and most important complication. During the process of thrombosis, the venous valve is damaged or even disappears or adheres to the wall of the vessel, resulting in secondary deep venous insufficiency, ie venous thrombosis. Form the post-syndrome.
2, pulmonary embolism: pulmonary embolism refers to a pathological process caused by obstruction of the pulmonary artery or its branches by embolism. Its diagnostic rate is low, misdiagnosis rate and mortality are high.
3, hemorrhagic: the main complication in thrombolytic therapy is bleeding. Special attention should be paid to gastrointestinal and intracranial hemorrhage.
Symptom
Symptoms of thrombosis Common symptoms Dyspnea atherosclerosis Varicose veins Internal carotid artery Traumatic thrombosis Chest pain Skin pale sudden pain Renal vascular malformation Cough
1. Venous thrombosis is a clinically common thrombus, usually caused by slow or stagnant blood flow. Venous thrombosis is characterized by a large amount of red blood cells and fibrin, platelet aggregation and degranulation, and its number is small; The whole blood clot inside, the color is dark red, called red thrombus, venous thrombosis often causes vascular occlusion, so the proximal end of the thrombus is mainly red blood cells, and the new end of the platelets adheres to the surface. Large veins, common such as iliac vein, femoral vein, hip vein, can be characterized by lower extremity edema, pain, skin color changes, thrombus detachment can flow into the pulmonary artery with blood, causing pulmonary embolism.
(1) superficial thrombophlebitis: varicose veins of the lower extremities, irritant drugs with excessive concentration of intravenous infusion, etc., prone to thrombophlebitis, local skin redness, increased skin temperature, lesions are cord-like, beating Sexual pain and tenderness, severe venous occlusion can occur.
(2) deep venous thrombosis of the lower extremities: most manifested as gastrocnemius pain and tenderness, calf muscle induration, ipsilateral lower extremity edema and superficial venous engorgement; in pregnancy, the elderly, prolonged bed, trauma, more common after surgery .
(3) Pulmonary infarction: pulmonary embolism and infarction, thrombosis of venous thrombophlebitis or venous thrombosis, or right embolus, along the bloodstream into the pulmonary circulation, block the pulmonary artery and its branches, clinical manifestations in addition to the primary disease In addition to the symptoms, most of them are non-specific lung symptoms, such as sudden chest pain, dyspnea, cough, hemoptysis or bloody sputum. Half of the patients have a second (P2) enhancement in the pulmonary valve area. Pulmonary embolism does not necessarily occur in the lungs. Infarction, and therefore the symptoms of this disease and whether there is pulmonary infarction, the extent of infarction and the original disease of the patient's heart and lungs, chest X-ray examination is one of the routine diagnostic methods of pulmonary infarction, pulmonary angiography is the basis for the diagnosis of this disease For example, there is a defect in the pulmonary blood vessels or pulmonary artery occlusion.
(4) Others: such as superior mesenteric vein thrombosis, hepatic vein thrombosis, portal vein thrombosis, etc., thrombosis in these areas, the onset is slow, often accompanied by thrombophlebitis lesions and other signs.
2. Arterial thrombosis Also known as white thrombus, it is mainly composed of platelets and fibrin. It usually occurs in areas where blood flow is fast and the blood vessel wall is damaged, or abnormal parts of blood vessels. Platelets adhere only to the blood vessel wall of the lesion, forming Platelet thrombosis, fibrin can form locally when blood passes, and adhere to the surface of platelet thrombus. The thrombin remaining on the fibrin wire can cause platelets in the bloodstream to adhere to the fibrin wire, resulting in the formation of platelets and fibrin. Repeatedly covering layer by layer, fibrin wire can also mesh part of red blood cells and white blood cells. If the head, body and tail of the thrombus are obviously called mixed blood clots, and when the platelet thrombosis grows up, the blood vessels can be occluded and the blood flow can be affected. Causes tissue ischemia, hypoxia, severe ischemic injury, and common myocardial ischemia, infarction, cerebral artery embolization, mesenteric artery embolization and limb arterial embolism, manifested as angina pectoris, hemiplegia, Consciousness disorder, acromegaly and limb ischemic necrosis, etc., thrombus shedding can enter with arterial blood flow Smaller arteries cause embolism, which is common in the brain, spleen, kidney and other organs. If embolism occurs in the coronary artery or cerebral artery branch, it can often be life-threatening. Arterial thrombosis and embolism are arterial occlusion caused by two different causes. Lesion.
(1) Arterial thrombosis: mainly an abnormality of the arterial wall, which is common in atherosclerosis. The lesion is mostly in the inner side of the opening of the blood vessel branch or the blood vessel is fixed in the surrounding tissue, so the intermediate artery such as the coronary artery and the easily involved The cerebral arteries, when thrombosis occurs, lead to myocardial infarction and cerebrovascular thrombosis, and the lesions in the aorta and its main arteries are prone to cause thrombosis of the mesenteric artery and limb arteries.
(2) Arterial embolism: an embolus that is detached from other parts. The stenosis of the branch of the artery is occluded with arterial blood flow. The severe symptoms can cause typical symptoms within one to several hours, which are sudden pain and pale skin. Sense of numbness, paralysis and vascular pulsation disappear, etc., can also appear collapse, occlusion time can cause distal tissue necrosis, tissue necrosis on the surface of the body is more obvious, easy to diagnose.
3. Microcirculation thrombus Fibrin thrombosis, or transparent thrombus, which is mainly composed of fibrin deposition, may cause intravascular coagulation due to microcirculatory disorders; it may also block small blood vessels by detached emboli, or due to certain factors Direct damage to microvascular endothelial cells leads to fibrin deposition, common with DIC, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura and the like.
Examine
Thrombosis examination
There is no unified understanding of hematological examination and laboratory diagnosis of thrombosis. At present, there seems to be a lack of laboratory-specific diagnostic indicators, and the results of laboratory findings in the process of thrombosis are highly variable, and the method of detection is not sensitive enough, especially In the early stage of thrombosis, there are still many difficulties in accurately determining the pre-thrombotic or hypercoagulable state. The following blood tests can confirm or predict thrombosis.
1. Endothelin-1 assay: Endothelin-1 (ET-1) is the only endothelin synthesized and secreted by vascular endothelium. ET-1 has strong vasoconstrictive activity and stimulates endothelial cells to release t-PA. In the population distribution, the plasma level of ET-1 in the elderly is higher than that of the population, which may be one of the factors that are susceptible to thrombosis in the elderly.
2. Increased thrombin regulatory protein: thrombin regulatory protein or thrombomodulin (TM) is a receptor for thrombin, a single-chain anticoagulant protein present on the surface of endothelial cells, TM and thrombin The surface of endothelial cells binds to form a complex that specifically converts protein C into activated protein C (APC). TM is one of the sensitive and specific molecular markers that reflect endothelial cell damage. Plasma or endothelial cell surface TM is increased. , indicating hypercoagulable state and thrombosis.
3. Platelet examination: including platelet adhesion, increased aggregation; increased plasma platelet release, especially alpha-specific thrombin (-TG) and platelet factor 4 (PF4) in alpha particles and platelet alpha particles Membrane protein GMP-140 increased, plasma serotonin release of serotonin was increased and platelet concentration decreased; plasma TXA2 metabolite TXB2 increased and/or prostacyclin product (6-keto-PGF1) ) reduced; both respond to platelet activation.
4. Increased activation of coagulation factors: the levels of coagulation activity (F:A) and antigenicity (F:Ag) of human coagulation factors are generally 100%. In thrombotic diseases, F:A and F:Ag can be significantly increased. Prothrombin fragments 1+2 (F1+2) and fragment 2 (F2) are elevated, F1+2 is a reflection of thrombin activity, F1 and F2 are endogenous thrombin activities, and clotting time and APTT are shortened.
5. Plasma anticoagulant factor reduction: antithrombin-III, protein C, protein S, HC-II, APC sensitivity and cl-inhibitor determination of thrombosis, especially for hereditary, familial The diagnosis of thrombosis has certain clinical significance.
6. Fibrinolytic activity decline: fibrin (original) degradation products (FDP) can be used to determine fibrinolytic activity. Increased D-dimer in FDP is a marker of cross-linked fibrin degradation. Increased fibrin peptide A content suggests Thrombin formation is an early indicator of fibrinogen conversion to fibrin. Positive serum co-coagulation test indicates an increase in soluble fibrin monomer complex, suggesting an increase in thrombin and plasmin production, in addition to plasminogen Activity measurement, t-PA and PAI measurements can also be used as indicators of fibrinolysis.
7. Changes in hemorheology: changes in blood rheology usually apply hematocrit (HCT), whole blood viscosity, whole blood reduction viscosity, plasma viscosity, erythrocyte electrophoresis time, fibrinogen quantification, erythrocyte thixotropy and adhesion Indexes such as elasticity to reflect changes in blood rheology in patients with thrombotic diseases. In thromboembolic diseases, whole blood or plasma viscosity is increased, erythrocyte thixotropy, and viscoelasticity are often reduced.
8. Angiography: It is one of the more accurate and reliable methods for diagnosing thromboembolic disease. It can be used to understand the location, size, shape, degree of occlusion and the establishment of collateral circulation. In addition, retrograde venography of the lower extremity can also diagnose veins. The degree of valve damage and blood reflux are of great value to the treatment and prognosis of this disease, but angiography is a method of traumatic examination. Disadvantages:
1 contrast agent can cause allergic reactions, mild urticaria, itching, hiccups, bronchospasm, severe anaphylactic shock,
2 a small cause deep, superficial phlebitis, injection of contrast agent extravasation, can cause local hematoma and venous thrombosis after angiography,
3 There are often false positive results for gastrocnemius venous thrombosis in the knee below the lower extremity.
9. Radioactive fibrinogen test: This is a non-invasive test method, which uses fibrinogen to infiltrate the thrombus and use its labeled radionuclide to scan the body surface and count the local measurement value for more than 24 hours. It indicates that there is thrombosis in this place. This test is easy to operate, sensitive and correct. It is often used for screening examination. Its shortcomings are often due to limb inflammation, surgical incision, ulcer, fracture, cellulitis, etc. It has diagnostic value for acute calf, distal extremity and iliac vein thrombosis, but has less sensitivity for the diagnosis of thrombus formation in the femoral, iliac, iliac and inferior vena cava.
10. Electrical impedance plethysmography: The principle of inspection is to use blood to have electrical conductivity, and when the blood flow changes, it can cause changes in resistance (impedance) and affect the voltage. Indirectly understand the change in blood volume according to the result of voltage measurement. After the pressure is applied to the middle of the thigh, the blood volume of the deep venous blood is increased. When the thigh is decompressed, the blood of the lower leg of the normal person is rapidly returned; if there is thrombosis, the blood flow of the lower leg is slow or the circulation of the collateral is refluxed. Results An abnormal curve appeared on the impedance plethysmogram. This is a non-invasive examination method. It has diagnostic value for sputum, femoral and venous thrombosis, but has poor sensitivity to calf vein thrombosis. The disadvantages are:
1 The detection of proximal venous occlusion with a large number of collateral veins can be false negative.
2 can be false positive when the blood flow of severe arteries is reduced and the venous filling is poor.
3 can not distinguish between thrombotic and non-thrombotic obstruction.
11.Doppler Ultrasound: Ultrasound Doppler flowmeter uses the Doppler effect to observe changes in blood flow velocity versus frequency difference. When venous blood flows smoothly, limb pressurization can increase blood flow rate, and ultrasonic signal is enhanced; if blood vessel is occluded, signal If it is weakened or disappeared, it can be judged whether the blood vessel has thrombosis. This method is simple and easy to perform. It has diagnostic value for thrombosis of the iliac vein, femoral vein and iliac vein. Especially the complete occlusion of the blood vessel has a high diagnostic rate. In patients with circulatory or superficial venous thrombosis, false negatives may occur.
12Duplex Scanning Double-Density Scan: This is a non-invasive test. It is a valuable and accurate method for confirming arterial and venous occlusion. This method can accurately identify the anatomy of arteriovenous thrombosis. It can also measure the amount of venous reflux (m1/s). It is proved that when the venous flow rate is lower than 10ml/s, skin changes and ulcer formation do not occur, and allergic to angiographic agents cannot be performed, but angiography is especially possible. Be applicable.
13. CT and MRI: can determine the location of brain lesions and can be distinguished from other brain tumors, cerebral hemorrhage and other diseases, but can not clearly visualize the arteriovenous thrombosis of the limbs, correct diagnosis.
Diagnosis
Diagnosis of thrombosis
Diagnostic criteria
In addition to the clinical diversification of the diagnosis of thrombosis, most rely on instrumental diagnostic tests. According to the autopsy data, there are about half of the patients with clinical thrombosis. There is no clinical manifestation before birth, and there is no clear diagnosis until after death, especially Early diagnosis has some difficulties, early detection of hypercoagulable state, thrombosis and determination of thrombosis.
Differential diagnosis
1. Functional stenosis of the mitral valve.
2. Pulmonary hypertension.
3. The thick left ventricle makes the heart chamber smaller.
4, active rheumatic mitral valvitis.
5, hyperthyroidism.
6, Lutembacher syndrome.
7, constrictive pericarditis in the atrioventricular sulcus.
8, left atrial myxoma.
9. Left atrial spherical thrombosis.
