Research Area

Coagulation


Introduction of coagulation

Blood coagulation is the process that blood changes from a flowing liquid state to a non-flowing jelly-like clot. This is a process of limited hydrolysis of a series of proteins involved by coagulation factors. The key process of blood coagulation is the conversion of fibrinogen in plasma to insoluble fibrin. Multimeric fibrin is interwoven into a network, and many blood cells are networked to form blood clots. Substances directly involved in blood clotting in blood and tissues are collectively referred to as coagulation factors. Blood coagulation has 12 kinds, and international nomenclatures for recognized them are numbered in Roman numerals. In addition, prekallikrein, kininogen and phospholipids derived from platelets are also directly involved in the blood coagulation process. In the coagulation factor, factor IV is an ion, and the remaining coagulation factors are proteins, wherein factors II, VII, IX, X, XI, and XII are endonucleases. Usually, in the blood, II, IX, X, XI, and XII are all in the form of inactive zymogens, which must be activated to be active. The activated enzymes are called active forms of these factors. One to two hours after the blood coagulation process, the blood clot shrinks and precipitates as a pale yellow liquid under the action of platelets. This liquid is called serum. Compared with plasma, serum lacks fibrinogen and a small amount of other plasma proteins involved in blood coagulation, and a small amount of substances released by platelets during hemagglutination.

Coagulation

Mechanism of coagulation

A lot of doctrines have been created about the blood coagulation mechanism. Until 1993, the International Blood Coagulation Factor Name Selection Committee published a pattern of human coagulation mechanisms that were widely accepted. According to the pattern, coagulation can be divided into four steps: 1. Prothrombin activator formation; 2. Thrombin formation; 3. Fibrin formation; 4. Fibrinolysis.

Prothrombin activator formation

From the beginning of coagulation to the formation of thrombin, it consists of endogenous and exogenous systems. Endogenous (intrinsic to blood) coagulation mechanism is a separate process of blood. When the blood comes into contact with the surface of the foreign body (collagen fiber of the blood vessel wall, etc.), the factor XII and factor XI of the contact factor are activated, and when the factor VI is activated, it activates the inactive factor IX. On the other hand, platelets also adhere to and agglomerate on the surface of foreign bodies and cause viscous metamorphosis to release platelet factor III. Immediately in the plasma, factor VIII and calcium ions react with these active factor XI and platelet factor III to activate the inactive factor X. And then factor V and platelet factor III act on factor X to convert prothrombin to thrombin. The mechanism of exogenous (tissue origin) is the process of tissue fluid entering the blood. The active component of tissue fluid promotes the interaction between thromboplastin and plasma factor VII, and then activates factor X. Finally, the factor V and calcium ion acts on activated factor X to convert prothrombin to thrombin.

Thrombin formation

The process by which prothrombin is converted to thrombin. Factor X and Factor V activated in the first step of coagulation and calcium ions acting on prothrombin break the bond of arginine-isoleucine in the prothrombin molecule to form thrombin.

Fibrin formation

The process by which fibrinogen is converted to a fibrin clot by the action of thrombin. Due to the action of thrombin, the arginine-glycine bond between the α bond and β bond in the fibrinogen molecule is cleaved, and the fibrin peptides A and B are released to form a fibrin monomer. Fibrin monomer polymerizes into a fibrin polymer. Factor VIII (transglutaminase) activated by the action of thrombin and calcium ions together with calcium ions promotes to form the bond between glutamine and lysine in the fibrin molecule. The process can form a strong fibrin block. In addition, in the third step of coagulation, the blood coagulates form a blood cake, but over time, due to the action of thrombus contractile proteins of the platelets, the blood cake shrinks.

Fibrinolysis

However, there is a fourth step in the body: a series of reactions involving fibrinolysis caused by plasmin, so these reactions are also included in the concept of blood coagulation.

Clinical Significance

The study of coagulation mechanisms has promoted the understanding of many hemorrhagic diseases, such as hemophilia (the patient's coagulation process is very slow or even minor damage is also bleeding), mainly due to the lack of factor VIII in plasma. In addition, it is found that coagulation factors II, VII, IX, and X are all synthesized in the liver, and vitamin K is required to participate in their formation. Lack of vitamin K, there will be bleeding tendency; the application of vitamin K can improve the symptoms of poor coagulation. In addition, in the laboratory or clinical work, different measures can be taken for each link in the blood coagulation process as needed to achieve the purpose of delaying coagulation or effectively stopping bleeding. If bleeding is prevented after surgery, coagulation substances such as thrombin and fibrin may be applied to the surgical site, and warm gauze, cotton or gelatin sponge may be used to pressurize the wound to promote coagulation.

Thrombosis is the pathological development of blood clots. These clots may break loose and become mobile, forming an embolus or grow to such a size that occludes the vessel in which it developed. An embolism is reported to occur when the thrombus (blood clot) becomes a mobile embolus and migrates to another part of the body, interfering with blood circulation and hence impairing organ function downstream of the occlusion. This causes ischemia and often leads to ischemic necrosis of tissue. Most cases of venous thrombosis are due to acquired states (older age, surgery, cancer, immobility) or inherited thrombophilias (e.g., antiphospholipid syndrome, factor V Leiden, and various other genetic deficiencies or variants).

References:

  1. Furie B, Furie BC. Thrombus formation in vivo. J. Clin. Invest. 2005, 115 (12): 3355–3362.
  2. Pallister CJ, Watson MS. Haematology. Scion Publishing. 2010, pp. 334–336.
  3. Long AT, et al. Contact system revisited: An interface between inflammation, coagulation, and innate immunity. Journal of Thrombosis and Haemostasis. 2015,14: 427–437.
  4. Shapiro SS. Treating thrombosis in the 21st century. N. Engl. J. Med. 2003, 349 (18): 1762–4.
  5. Giangrande PL. Six characters in search of an author: the history of the nomenclature of coagulation factors. Br. J. Haematol. 2003, 121 (5): 703–12.
  6. MacFarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature. 1964, 202 (4931): 498–9.

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