WHAT IS THE COAGULATION CASCADE? FACTORS AND STAGES - BIOLOGY - 2025

The coagulation cascade is a set of successive enzymatic reactions interspersed in the process of closing and healing the wounds produced in the walls of the vessels. They can produce significant blood losses that compromise the integrity of the body.

The staunching of vascular wounds and the arrest of bleeding are integrated into a global process that is called hemostasis. This begins with a set of reactions aimed at the production of a platelet plug or "white thrombus" that rapidly covers the wound and hinders the blood flow.

In vivo coagulation cascade (Source: Dr Graham Beards via Wikimedia Commons)

This initial process is called primary hemostasis, but the consistency and stability of the plug that forms almost immediately must be improved by fibrin deposits and the production of a "red thrombus", which result precisely from the coagulation cascade, which comes from then to constitute the so-called secondary hemostasis.

The coagulation process occurs in a series of successive stages of sequential activation of enzymatic factors that are in inactive form. In an initial step, a factor is activated that later, with other elements, becomes an activating complex for another factor, and so on.

Coagulation factors

Coagulation factors are called substances that for the most part are present in blood plasma or that make their appearance during the process and participate in some stage of it. These are usually enzymes in their inactive form.

The factors are given their proper names, which are often related to the function they fulfill in the cascade, but they are also designated, in their inactive form, with the generic name "factor" followed by a Roman numeral that identifies it and that can go from I to XIII (Ia to XIIIa, in the case of activated factors).

The first four factors are named more by their "proper" names than by their "Roman" nomenclature. Thus, factor I is fibrinogen, II is prothrombin, III is thromboplastin or tissue factor, and IV is ionic calcium.

The rest of the factors are better known by their Roman numeral (V, VI does not exist, VII, VIII, IX, X, XI, XII and XIII). In addition to those mentioned, we should include high molecular weight kininogen (HMW), prekallikrein, kallikrein and platelet phospholipids, factors for which there is no “Roman” identification.

Stages of coagulation

The coagulation cascade is accomplished in three successive stages including: the activation phase, the coagulation phase, and the retraction of the clot.

Activation phase

This includes a set of steps that conclude with the formation of a prothrombin activation complex (Xa, Va, Ca ++ and phospholipids). The conversion of factor X to activated factor X (Xa, the proteolytic enzyme that converts prothrombin to thrombin) is the critical step here.

Factor X activation can occur in two different ways: one called the external route and the other internal route, depending on whether the blood leaves the vessel and comes into contact with extravascular tissue or whether the process is activated within the vessel without the blood get out of it.

In the external pathway or extrinsic activation system, the blood leaves the vessel and comes into contact with tissue whose injured cells release thromboplastin or tissue factor (FT or III) which, when joined to factor VII, activate it and constitute, together with it, the Ca ++ and tissue or platelet phospholipids, a factor X activation complex.

In the internal pathway or intrinsic system, when factor XII contacts negatively charged surfaces such as collagen in the vascular wall, or glass, if it is blood in a test tube, it is activated and passes to factor XIIa, for which Kallikrein and HMW kininogen collaborate.

Extrinsic and intrinsic pathway of the coagulation process (Source: Dr Graham Beards via Wikimedia Commons)

Factor XIIa proteolytically activates factor XI which becomes Factor XIa and which in turn activates factor IX. Factor IXa together with factor VIIIa, Ca ++ and platelet phospholipids constitute a factor X activation complex.

It is evident that the end result of both activation pathways is the formation of a complex that, although different in each case (FT, VIIa, Ca ++ and phospholipids for the external pathway and IXa, VIIIa, Ca ++ and phospholipids for the internal pathway), fulfills the same function of conversion of factor X into factor X activated.

The activation phase thus concludes with the conformation of the complex Xa, Va, Ca ++ and phospholipids, which is known as the prothrombin activator complex.

Coagulation phase

This begins when the prothrombin activator complex converts prothrombin into thrombin, a proteolytic enzyme among whose functions is the decomposition of plasma fibrinogen and liberating fibrin monomers from it that will later form polymers of said peptide.

At the beginning, the fibrin polymers are joined together by non-covalent electrostatic bonds, and they form an unstable and not well consolidated network, but the thrombin produced activates factor XIII and this XIIIa promotes the formation of covalent bonds that stabilize the network and consolidate the clot.

At first, coagulation occurs relatively slowly, but the thrombin produced acts as a positive feedback mechanism, accelerating the activation of factors V, VIII, and XI, with which the intrinsic pathway cascade proceeds faster, even without involvement. factor XII.

This means that even when the coagulation cascade is initiated by the activation of the extrinsic pathway, thrombin also ends up recruiting to the intrinsic mechanism by activating factor XI in the absence of factor XIIa.

Clot retraction phase

The coagulation process occurs mainly on the platelet plug. In addition, platelets that bind to fibrin are trapped during the formation of the fibrin network. Platelets have a contractile apparatus that, when activated, bring closer and closer the contact between the fibrin fibers.

Clot retraction is like a "squeezing" process that expels fluid, but usually traps blood cells, especially red blood cells or red blood cells, in the network, giving the thrombus a color from which it derives the name "red thrombus".

The expelled fluid is no longer plasma, since it lacks fibrinogen and the other coagulation factors that have been consumed during the process. Rather, it is called a serum.

References

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