Antithrombin is high

Antithrombin is a relatively important substance in human blood. It can control the coagulation and dissolution of blood. If the amount of antithrombin in the human body changes, it will cause various problems in the human body. For example, if the antithrombin increases, it may be caused by oral anticoagulants and acute bleeding. If the antithrombin level is low, it may be congenital, or it may be caused by diseases such as myocardial infarction, cerebrovascular disease, nephrotic syndrome, etc.

1. Clinical significance

Antithrombin III (AT III) is the most important inhibitor of active coagulation factors in the blood, which controls blood coagulation and fibrinolysis. The level of ATIII in the blood varies depending on various diseases and symptoms, and decreases in disseminated intravascular coagulation (DIC), liver disease, nephrotic syndrome, and the like. Reduced ATⅢ levels in the blood may result in the inability to exert the therapeutic effect of heparin. Therefore, it is of great significance to understand the activity of ATIII as an indicator for monitoring such diseases, pathological analysis, prognosis determination, and heparin treatment or administration of ATIII concentrate preparations.

1. Pathological increase: indicates that the anticoagulant activity of the blood is enhanced, which is mainly seen in the acute bleeding period of oral anticoagulants and etc.

2. Pathological reduction:

(1) Congenital AT-III deficiency.

(2) In the prethrombotic state and thrombotic diseases, the anticoagulant effect of the blood is weakened, such as in the hypercoagulable phase of DIC, myocardial infarction, angina pectoris, cerebrovascular disease, pregnancy, deep vein thrombosis, nephrotic syndrome, etc.

(3) Reduced synthesis, such as severe liver disease.

2. Working Principle

Antithrombin III (AT III). ATⅢ is an inhibitor of thrombin and serine-containing proteases such as factors XIIα, XIα, IXα, and Xα. It binds to thrombin via an arginine-serine peptide bond. The ATⅢ thrombin complex is formed, which inactivates the enzyme. Heparin can accelerate this reaction by more than a thousand times. Heparin binds to the lysine contained in ATⅢ, causing a conformational change in ATⅢ, making the arginine residues contained in ATⅢ easier to bind to the serine residues of thrombin. Once the heparin-ATⅢ thrombin complex is formed, heparin dissociates from the complex and combines with another ATⅢ molecule again for repeated use. The ATIII-thrombin complex is eliminated by the reticuloendothelial system. The inhibitory effect on thrombin activity is related to the length of heparin molecules. The longer the molecule, the greater the enzyme inhibition.

3. Deficiency

1. Hereditary ATⅢ deficiency can be divided into two types: (1) CRM-type: both antigen and activity are decreased. (2) CRM+ type: normal antigen, decreased activity.

Hereditary ATⅢ deficiency is an autosomal dominant genetic disease with a prevalence of approximately 1/5000. It mostly occurs in patients aged 10-25 years. Patients often develop venous thrombosis after surgery, trauma, infection, pregnancy or delivery, and thrombosis may occur repeatedly. The biological activity and antigenicity of ATⅢ in the plasma of CRM- patients are about 50% of that of normal people. There are many types of ATⅢ structural and functional abnormalities in CRM+, and the common manifestation is a reduced affinity for heparin, thereby significantly weakening the ability to inactivate serine proteases.

2. Acquired ATⅢ deficiency:

(1) Reduced ATⅢ synthesis is seen in liver diseases, liver dysfunction, mainly in cirrhosis, severe hepatitis, and advanced liver cancer. It is often related to the severity of the disease and may be accompanied by thrombosis.

(2) Increased loss of ATⅢ: seen in nephrotic syndrome.

(3) Increased ATⅢ consumption is seen in prethrombotic and thrombotic diseases, such as angina pectoris, myocardial infarction, cerebrovascular disease, DIC, postoperatively, oral contraceptives, deep vein thrombosis, pulmonary infarction, and pregnancy-induced hypertension.

(4) Increased ATⅢ level is seen in hemophilia A and hemophilia B, oral anticoagulants, and the use of progesterone drugs.