activation of blood coagulation via clotting cascade

Definition

Target type: biologicalprocess

Any process that initiates the clotting cascade of blood coagulation, a cascade of plasma enzymes that is triggered following damage to blood vessels, leading to formation of a clot. [GOC:jal, ISBN:0781735149]

The coagulation cascade, also known as the clotting cascade, is a complex series of enzymatic reactions that ultimately lead to the formation of a stable fibrin clot. This process is essential for hemostasis, preventing excessive blood loss after injury. The coagulation cascade is initiated by either the intrinsic or extrinsic pathway, converging at the activation of factor X to form activated factor X (Xa), which then acts as a catalyst for the final common pathway, ultimately leading to the formation of fibrin.

**Intrinsic Pathway:**

The intrinsic pathway is activated by contact with negatively charged surfaces, such as collagen exposed after injury. This activation begins with the activation of factor XII, a zymogen (inactive enzyme precursor) that converts to activated factor XII (XIIa). XIIa activates factor XI, which then activates factor IX, which then activates factor X, in the presence of factor VIII and calcium ions. The activation of factor X marks the point where the intrinsic pathway converges with the extrinsic pathway.

**Extrinsic Pathway:**

The extrinsic pathway is initiated by the release of tissue factor (TF), a membrane-bound protein that is exposed at the site of injury. TF binds and activates factor VII, converting it to activated factor VII (VIIa). VIIa then activates factor X in the presence of calcium ions.

**Final Common Pathway:**

Activated factor X (Xa) combines with factor V, calcium ions, and phospholipid membrane to form the prothrombinase complex. This complex activates prothrombin, converting it to thrombin. Thrombin then cleaves fibrinogen, a soluble protein, into fibrin monomers. These monomers polymerize to form fibrin strands, which then cross-link to create a stable fibrin clot.

**Regulation:**

The coagulation cascade is tightly regulated by a complex interplay of procoagulant and anticoagulant factors. This ensures that clotting occurs only when necessary, preventing uncontrolled clotting and thrombosis. Anticoagulants such as antithrombin and protein C inhibit the activity of various coagulation factors, while proteins such as tissue factor pathway inhibitor (TFPI) specifically inhibit the extrinsic pathway.

**Clinical Significance:**

Defects in the coagulation cascade can lead to a variety of bleeding disorders, such as hemophilia, or thrombotic disorders, such as deep vein thrombosis. Understanding the intricate mechanisms of the coagulation cascade is crucial for the diagnosis and treatment of these conditions.'
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Compounds (39)