Blood Coagulation

Thrombin acts directly on the last step of the blood coagulation process, promoting the conversion of soluble fibrinogen in plasma into insoluble fibrin, so as to achieve the purpose of rapid hemostasis. It can also promote the mitosis of epithelial cells, accelerate wound healing, and is a quick acting local hemostatic. Thrombin is suitable for ligation of small blood vessels, capillaries, parenchymatous organs and other bleeding that is difficult to stop bleeding. It also has activated receptors, producing cell biological effects, such as inducing inflammation, inducing cell release of cytokines, causing cell proliferation, tissue and organ regeneration. Thrombin in the central nervous system is also neurotoxic, causing brain cell damage. Thrombin has a short half-life and is difficult to detect, so the complex formed by thrombin and antithrombin can be detected. The increase is related to DIC, DVT, PE and other coagulation system activation states such as atrial fibrillation.

Plasminogen is the inactive form of plasmin, synthesized primarily in the liver but also expressed in major organs and tissues.In physiology, plasminogen is converted to plasmin by shearing through the active loop.Activated plasmin has a wide range of substrate properties, including fibrin, fibrinogen, complement component 3, complement component 5, etc.Plasmin can also target key prothrombin activators tPA and uPA, resulting in a positive feedback loop.Active plasmin plays an important role in physiological and pathological processes such as fibrinolysis and hemostasis, extracellular matrix degradation, cell migration, tissue remodeling, wound healing, angiogenesis, inflammation, and tumor cell migration. Plasminogen has two different conformations, closed and open.Glycosylated plasminogen exists in the bloodstream in the closed conformation and cannot be activated by tPA and uPA.Glycosylated plasminogen exists in the open conformation only when it binds to fibrin or cell surfaces.Free plasmin is released from the surface and neutralizes almost simultaneously with the protease inhibitor α2-antithrombin in an irreversible complex.Their interaction rate is one of the fastest known (Ka: 2×107 mol-1 s-1). Activated plasmin has a very short half-life and cannot be directly detected in vivo, but it can be formed with plasmin inhibitors to form the complex PIC, which is relatively easy to detect. Elevations are common in DIC, DVT, PE, and thrombolytic therapy.

PAI-1 is initially produced in endothelial cells and platelets, and is the main PAI in plasma.PAI-1 is a glycoprotein with a molecular weight of 45-50 kDa, belonging to the serine protease inhibitor, and the reaction center is arginine. PAI-1 usually exists in two forms, active and inactive, with the latter being the majority.PAI-1 and PAI-2 inhibit tPA and uPA by substrate mechanisms.PAI-1 is inserted into the active site of PA to form a temporary Michaelis complex.As a protease inhibitor, PAI-1 can specifically act on tPA and uPA, inhibiting them at least 1000 times faster than other protease.PAI-1 rapidly and irreversibly inhibits PA, which is a major negative regulatory factor in the fibrinolytic system.PAI-1 is a potential therapeutic target and prognostic indicator in coagulation diseases.High levels of PAI-1 can prevent the formation of plasminogen. After fibrin formation, the fibrinolytic system is activated to form tissue plasminogen activator (t-PA), which further converts plasminogen into plasminogen, which is degraded into DD and FDP. PAI-1 is a physiological inhibitor of t-PA, and the two combine to form the complex tPAIC. The level of tPAIC is positively correlated with t-PA concentration and vascular endothelial injury [6]. Elevation is common in DIC, vascular endothelial injury, DVT, acute myocardial infarction, etc.

D-dimer is a specific molecular marker of fibrinolysis acting on cross-linked proteins. It contains two identical subunits, each of which is composed of three polypeptide chains: α, β, and γ. The so-called "D-dimer" is not a structurally simple and uniform substance in the circulation, but a mixture of fragments of different sizes containing D-dimer structures (such as DD, DY, XD, XY, DXD, YXD, DXXD, etc., with molecular weights ranging from 190 kDa to 720 kDa). For the past twenty years, D-dimer detection has been widely used in the exclusion of deep vein thrombosis (DVT) and pulmonary embolism (PE). In addition, D-dimer appears in secondary fibrinolysis and has important diagnostic value for other thrombotic diseases such as disseminated intravascular coagulation (DIC), cerebrovascular disease, liver disease and malignant tumors. At the same time, D-dimer detection can also be used as an indicator for monitoring thrombolytic drug therapy.

Fibrinolysin is a serine protease. When fibrinolysis is excessive, fibrinolysin will degrade fibrin or fibrinogen. The degraded products are collectively referred to as fibrinogen degradation products (FDP), which are composed of substances of different molecular weights such as X-fragment, Y-fragment, D-fragment, D-dimer, etc. FDP is an indicator of the activity of the fibrinolytic system and is often detected in coagulation tests. Especially for the diagnosis of disseminated intravascular coagulation syndrome (DIC) and the follow-up of postoperative patients, FDP is one of the important reference indicators.