Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 554

Glycoprotein can associate with thrombin, high-molecular-weight

kininogen, coagulation factor-XI and -XII, and thrombospondin-1. Ligand
binding activates the GP1b-GP5-GP9 receptor complex for calcium mobilization,
cytoskeleton rearrangement, granule release, and activation of

GP1b α

α 2 β 3 -integrin, the
main integrin implicated in platelet aggregation that interacts with von Willebrand
factor. Collagen receptor GP6 needs GP1b for platelet adhesion. von Willebrand

factor carries coagulation factor-VIII at sites of vascular lesions and protects it
against proteolysis. Platelet adhesion receptor GP1b

α

that binds to von Willebrand
factor can act independently of von Willebrand factor for platelet recruitment under
high hemodynamic stress in sites of exposed subendothelium after vascular injury
and adhesion to the extracellular matrix and growing thrombus [ 1020 ].
von

α

Willebrand factor possesses binding sites for collagen and platelet

glycoproteic subunit GPIb for platelet crosslinking and platelet plug formation.

Binding of von Willebrand factor to platelets must withstand strong hydrodynamic
forces. The vWF-GPIb

α

α bond is specialize in force resistance. Two states of the

vWF-GPIb bond indeed exist [ 1021 ]: (1) a state at low force and (2) another state

that begins to be involved at 10 pN with aboout 20-fold longer lifetime and greater
force resistance.
Fibrinogen (Fng) links adjacent platelets by binding with

α

α 2B β 3 -integrins.
Primary hemostasis thus involves a set of adhesion receptors (platelet plasmalemmal
glycoprotein GP1b [CD42b], 133 α 2B β 3 -integrins, etc.) and proteins

(von Willebrand factor, collagen, fibronectin, fibrinogen, laminin, homotrimeric
thrombospondin TSP2, etc.). Once released from activated platelets, ADP is a potent
inducer of platelet aggregation (self-perpetuating process). Platelet-activating factor
and adrenaline act together to relieve the effect of inhibitors of platelet aggregation.

GP9 [CD42a],

9.8.1.2 Secondary Hemostasis

Secondary hemostasis has 2 pathways — intrinsic and extrinsic — that join in a
common pathway leading to fibrin (Fn or activated factor-I [FIa]) formation. This
fibrillar protein polymerizes to form a mesh around platelets that stabilizes the
hemostatic plug over the breach.

Intrinsic Pathway

The intrinsic pathway is characterized by the formation of the primary complex
on collagen by high-molecular-weight kininogen (HMWK), prekallikrein (preKK),

133 Glycoprotein-1b, or cluster of differentiation CD42b, complexes with glycoprotein-9 to function
as a receptor for von Willebrand factor. It is a component of the GP1b-GP5-GP9 complex on
platelets.