Normal Blood Clotting Process, Step-by-Step Guide to Coagulation

The body has several important mechanisms in place to prevent bleeding. This is collectively known as hemostasis and involves four major steps – vasoconstriction, platelet plug, blood clot formation and fibrous tissue growth. Some of these mechanisms take effect within seconds of a break in the blood vessel while others reach completion over minutes or even days. Although this process is known as hemostasis, it is commonly referred to as blood clotting. However it is important to note at the outset that blood clotting (coagulation) is actually only one step in the entire mechanism known as hemostasis.

A break in a blood vessel, either artery or vein, may occur for any number of reasons. Visible blood loss is more likely to occur with a cut of the skin that also severs a portion of the blood vessel. Internal bleeding is the term that is often used to describe bleeding within the  body which is not visible from the exterior. Micro-tears occur in blood vessels throughout the body on a daily basis and is unrelated to trauma but these tears are so small that it can be quickly and easily dealt with no significant blood loss.

Blood Clot Formation

A blood clot is a gelatinous mass of blood cells and components that seals a tear in a blood vessel. The process of forming this blood clot is known as coagulation. It is triggered by the formation of a platelet plug and exposure of the blood to the damaged blood vessel wall. Chemicals that circulate in the blood known as procoagulants (clotting factor) mediate this clotting process. It remains inactive because of the action of counter-chemicals known as anticoagulants, the constant flow of blood which prevents contact with the walls of the blood vessel and the lack of the appropriate triggers as discussed below.

Blood Clotting Pathways

There are two pathways known as the coagulation cascade that contribute to the formation of a blood clot – intrinsic pathway and extrinsic pathway. Both pathways yield the same effect, which is the formation of prothrombin activator, an important activator of prothrombin.

Extrinsic Pathway

  • Trigger : Factor III (tissue thromboplastin) released from the wall damaged blood vessel.
  • Activates Factor VII requiring the presence of calcium (calcium-dependent step) = Factor VIIa
  • Activates Factor X  = Factor Xa
  • Factor Xa + Factor V + platelet phospholipids = prothrombin activator.

Factor V requires the presence of thrombin (activated prothrombin) to become active.

Intrinsic Pathway

  • Trigger : Blood contact with collagen in the wall of the damaged blood vessel.
  • Activates Factor XII = Factor XIIa
  • Activates Factor XI in the presence of prekallikrein and kininogen = Factor XIa
  • Activates Factor IX in the presence of calcium = Factor IXa
  • Activates Factor X in the presence of calcium, Factor VIII and platelet phospholipds = Factor Xa
  • Factor Xa + Factor V + platelet phospholipds = prothrombin activator.

Both Factor V and VII are activated in the presence of thrombin but initially the prothrombin activator is able to function without it.

Thrombin and Fibrin

Fibrin is a long protein strand that forms the meshwork of a blood clot. It is laid over the platelet plug and traps blood cells and other particles in it to secure the site. Fibrin exists in the inactive form in the bloodstream known as fibrinogen. In order for fibrinogen to be activated, it requires the presence of the enzyme thrombin. In turn, thrombin remains inactive in the form of prothrombin. However, in the presence of prothrombin activator, prothrombin is converted into thrombin.


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