The endothelium is continuously in contact with coagulation factors, which are glycoproteins and act as enzymes or co-factors.
But only when exposition of collagen or subendothelium takes place, the clotting cascade will be initiated.

Endothelial Lesion and Mediator Expression.

The damage of the endothelial surface leads to a release of tissue thromboplastin starting the extrinsic system, which converts factor VII to an activated state and initiates in combination with phospho-lipid and calcium the activation of factor X.
In addition there are other tissue factors like prekalli-kreine, kallikreine, kaoline and kiniogen (hmw) acting as a amplifier loop for the activation of the instrinsic system by Factor XII.

Contact Activation /
Release of Thromboplastin

The initial stage of activation of plasma coagulation is the activation of factor XII after binding to a foreign surface in the vascular system.
This surface activation is followed by socalled intrinsic activation” with formation of active factor IX. After the tissue lesion, tissue thrombo-plastin is released in parallel, with subsequent activation of factor VII.
This phase corresponds to the so called ”extrinsic coa-gulation activation”. Both initial phases of plasma coa-gulation, which are separate in theory, proceed in parallel ”in vivo”, however, and can reciprocally influence each other via the so called ”Josso loop”.

Tenase Complex
(Intrinsic System)

In the intrinsic system on the other hand, activation of factor IX is brought about by contact activation. Together with phospholipids and thrombin-activated factor VIII, the socalled tenase complex forms, which in turn can activate factor II (prothrombin).
Activation of Factor X
After activation of factor VII by tissue tr?hromboplastin, activation of factor X in the extrinsic system takes place.

Prothrombinase Complex
(Extrinsic System)

Together with phospholipids released from the cell membrane or phospholipids on the surface of the platelets and thrombin-activated factor V, activated factor X in the extrinsic system forms the socalled prothrombinase complex. This complex gives rise to the enzymatic cleavage of fragments 1 and 2 from prothrombin and therefore to the formation of activated factor II, thrombin.

Generation from Prothrombin to Thrombin.

The prothrombinase-complex converts prothrombin (factor II) to thrombin (factor IIa).
After generation of thrombin it cleaves plasma fibrinogen to generate fibrin, which exists first in a monomer structure, dissolved in plasma.

Generation from Fibrinogen to Fibrin

Thrombin, as the main enzyme of plasma coagulation, splits off fibrinopeptides A and B from fibrinogen, which is also named factor I. The resultant fibrin monomers can bind to each other covalently.

Polymerisation and Clot

Factor XIII, also activated by thrombin, leads to irreversible crosslinking of the fibrin monomers.