Blood clotting (hemostasis)

An essential property of the blood is the ability to clot, which aids in preventing blood loss. Precisely regulated interactions between blood vessel walls, circulating platelets, and clotting proteins in the plasma account for the ability to quickly stop blood loss (i.e., hemostasis).

Overview of hemostasis

Three physiologic mechanisms interact to prevent hemorrhage: 

( 1 ) Vasoconstriction of small vessels and platelet plug formation

There are three phases of Platelet plug formation:

( a ) Platelet adhesion (sticking) to the exposed subendothelial extracellular matrix occurs at a site of injury

Adhesion is mediated by a variety of different platelet receptors, including: 

• Receptors for binding to extracellular matrix proteins (e.g., collagen). The von Willebrand factor (vWF) is a ligand present in plasma and is released by endothelial cells and by activated platelets. 
• The binding of vWF to a type of platelet receptor promotes platelet adhesion; vWF forms crosslinks between platelets and with collagen. 
• Other receptors

( b ) Platelet activation.

Activated platelets release many factors that promote hemostasis, including: Adenosine diphosphate (ADP) is a potent activator of other platelets, amplifying the platelet activation response. Serotonin and thromboxane A2 assist hemostasis as vasoconstrictors. vWF augments platelet adhesion and aggregation. Platelet-derived growth factor promotes wound healing by stimulating growth and migration of fibroblasts and smooth muscle cells at the site of injury.

( c ) Platelet aggregation (joining).

completes the formation of a platelet plug. The signaling molecules released during platelet activation amplify the platelet adhesion and activation responses and recruit more platelets to the site of injury.

( 2 ) Platelet plug formation :

The platelet plug is prevented from extending beyond the site of injury by prostacyclin and nitric oxide, which are secreted from intact endothelial cells and inhibit platelet activation.

( 3 ) The Clot formation.

 (= blood coagulation mechanism = secondary hemostasis)

The blood coagulation mechanism ( secondary hemostasis ) is formed when the plasma protein fibrinogen is cleaved to produce fibrin, which subsequently becomes cross - linked in to a stable mesh ( blue color on the picture ) .

Сlotting may be initiated by one of two pathways: the intrinsic pathway or the extrinsic pathway.

Each pathway consists of a cascade of reactions, in which inactive circulating precursor proteins (“clotting factors”) become activated. These chain reactions normally are not activated in the circulation because clotting factors are present at low concentration in plasma. 

• The intrinsic pathway is triggered when blood contacts substances inside the vessels, a negatively charged surface (e. g., exposed subendothelial collagen; aggregations of platelets). 
• The extrinsic pathway is activated when blood contacts cells outside the vascular endothelium; nonvascular cells express a protein called tissue factor, which initiates the extrinsic pathway.

The intrinsic and extrinsic pathways converge at the common pathway for coagulation, which begins with the activation of factor X.

The plasma protein prothrombin is cleaved by activated factor X to produce the protease thrombin

Thrombin is responsible for the cleavage of fibrinogen and for the activation of factor XIII, which cross-links fibrin into a stable mesh.

Anticoagulants

 Fibrinolysis