What is Hemostasis and Blood Coagulation?

Hemostasis

The hemostatic system consists of blood vessels, platelets and the plasma coagulation system, including fibrinolytic factors and their inhibitors. The hemostasis process is complex. In the initial stage, the constriction of damaged blood vessels leads to a reduction in blood flow. Then a plug is formed, which consists in the adhesion and addition of platelets and fibrin, this leads to a complete control of blood loss and allows the repair of the vascular and tissue defect

• A series of reactions to stop the bleeding

• During hemostasis, rapid sequence phases occur

• Vascular spasms: instant vasoconstriction in response to injury

• Formation of platelet plugs

• Coagulation (blood clotting)

Three mechanisms operate locally at the site of injury to control bleeding, when a blood vessel is injured:   

• Vessel wall contraction
• Platelet adhesion and aggregation (platelet plug formation)
• Plasmatic coagulation to form a fibrin clot

All three mechanisms are essential for normal hemostasis. Abnormal bleeding is usually due to defects in one or more of these three mechanisms. For a better understanding of the pathogenesis of pathological bleeding, it is customary to divide hemostasis into two stages: primary and secondary hemostasis

Primary hemostasis is the term used for instant plug formation after vessel wall injury, which is achieved through vasoconstriction, platelet adhesion, and aggregation. Fibrin formation is not required for haemostasis at this stage. However, primary haemostasis is only temporarily effective. Unless secondary haemostasis strengthens the platelet plug by forming a stable fibrin clot, bleeding may start again. Ultimately, the mechanisms within the fibrinolytic system lead to the dissolution of the fibrin clot and the restoration of normal blood flow

Coagulation  

When a blood vessel is damaged, various mechanisms combine to stop the bleeding. Platelets start sticking together, blocking small holes. The plasma then produces a filamentous protein, fibrin, which forms a network capable of retaining red blood cells and therefore constitutes a blood clot

• A set of reactions in which the blood changes from liquid to gel

• Coagulation follows intrinsic and extrinsic pathways

• The last three steps of this series of reactions are:

• The prothrombin activator is formed
• Prothrombin is converted into thrombin
• Thrombin catalyzes the binding of fibrinogen in a fibrin network

The fibrin clot is the end product of a multiplicity of complex plasma protein reactions called coagulation or clotting factors. Most clotting factors are serine protease zymogens and become active enzymes during the blood clotting process. The six serine proteases are the activated forms of coagulation factors II, VII, IX, X, XI and XII. The letter "a" accompanying a Roman numeral (for example, factor Xa) indicates that the factor is in its activated form. Factors V and VIII are not enzymes but cofactors which, after activation, modify the speed of the coagulation reaction

Plasma coagulation has traditionally been divided into two different pathways: the intrinsic and the extrinsic pathway. This understanding of coagulation was based on in vitro studies of coagulation in a relatively cell-free plasma system. However, this division does not actually occur in vivo because the factor VIIa-TF complex is a potent activator of factor IX and factor X

The coagulation factor reactions take place on the surface of the phospholipids. After platelet activation, some phospholipids (phosphatidyl ethanolamine, phosphatidyl serine and phosphatidyl choline) that were not present on the resting platelet surface are exposed on the platelet surface. These newly exposed phospholipids provide the appropriate phospholipid surface on which coagulation factor reactions take place

The principal initiating pathway of blood coagulation in vivo is the extrinsic system. The critical component is TF, an intrinsic component of the membrane expressed by cells in most extravascular tissues. TF functions as a cofactor for the major plasma component of the extrinsic pathway, factor VII. A complex of these two proteins leads to the activation of factor VII into factor VIIa, which then converts factor X into factor Xa, the product identical to that formed by the intrinsic pathway. As mentioned above, the factor VIIa-TF complex also activates factor IX to factor IXa. However, as factor Xa levels increase, the factor VIIa-TF complex is subject to inhibition by factor Xa-dependent TFPI