Veterinary Clinical Medicine-I (General and Systemic)

COAGULATION CASCADE

• The coagulation cascade is a series of enzymatic reactions involving coagulation factors. This complex biochemical pathway plays three pivotal roles in the formation of fibrin from fibrinogen:
  • Acceleration of fibrin generation >10 million-fold
  • Regulation of fibrin plug size appropriate for injury
  • Localization of fibrin clot formation to site of injury
• The coagulation cascade can be divided into an extrinsic and intrinsic system which merge into the common pathway. When blood vessel walls are injured, the extrinsic coagulation system is initially activated by tissue factor (thromboplastin produced in the subendothelium), which combines with factor VII. The small amount of thrombin produced through Factor VIIa appears sufficient to activate factor XI to factor XIa and also to activate other cofactors (factors V, VIII, XIII). Through the action of factor XIa on factor IX, thrombin formation is maintained. The other contact phase coagulation factors (e.g., factor XII) are in vivo of lesser importance in the activation of the intrinsic system. The above described coagulation process explains why hemophilic (Factor VIII and IX deficient) or Factor VII deficient animals bleed, whereas Factor XII deficient animals do not.
• Coagulation factors are enzymes, cofactors, or substrates of particular reactions of the coagulation cascade. Most factors are given roman numerals from I-XIII, but the numbering is not sequential and there is no factor VI. Calcium (factor IV) is required for most reactions and is the reason why chelators, e.g., citrate and EDTA, are used for blood collection and processing, where plasma or blood cells are analyzed. All coagulation factors are synthesized in the liver and circulate as inactive precursors in the plasma. They need to be activated at the site of vessel injury. Vitamin K is needed for the functional synthesis of the coagulation factor II, VII, IX, and X. The half-lives of the coagulation factors vary from hours (Factor VII) to a few days (Fibrinogen). Following a fibrin plug formation, plasminogen will be activated and plasmin, an unspecific protease will commence breaking down fibrinogen as well as fibrin which results in fibrinogen lysis and fibrin (-ogen) split product (FSP) as well as D-dimer formation.