Blood Clotting Process

Binding of GPIa/IIa to collagen results in

Swelling and development of pseudopods in platelets

Platelets binding to exposed subendothelium causes

platelet activation and aggregation

Overall process: Step 4

Fibrin network is formed- secondary hemostatic plug

Cleavage by thrombin effect on fibrinogen

Fibrinopeptides A and B are released

ADP in platelets binds

P2Y12, stimulating production of more GIIb/IIIa

Activates fibrinogen

Thrombin

When thrombin binds to PAR1/PAR it activates

A Gq signaling pathway that results in increased Ca2+, which activates phospholipase A2 and granule release

Overall process: Step 3

Activation of platelets initiates clotting cascade

Plavix

Anti-platelet drug Antagonist of P2Y12 (ADP) receptor

Aspirin

Anti-platelet drug Inhibits COX, preventing formation of thromboxane 2

Platelet granules contain

Ca+2 ADP serotonin heparin antagonist fibrinogen some clotting factors platelet derived growth factor vWF

Fibrinogen structure

Dimer of heterotrimers, linked by disulfide bonds

Fibrin is cross linked by

Factor XIIIa

Activated fibrinogen forms

Fibrin

Ca2+, clotting factors, fibrinogen, and heparin antagonist released from granules will facilitate

Formation of the secondary hemostatic plug

COX

In platelets Produces thromboxane A2 after platelet activation

Overall process: Step 1

Injured vessel contracts, restricting blood flow

PAR1/PAR

Platelet receptor Binds activated thrombin

GPIa GP=glycoprotein

Platelet receptor Binds collagen

GPIIb/GPIIIa GP=glycoprotein

Platelet receptor Binds fibrinogen and vWF (vonWillebrand factor)

GPIb GP=glycoprotein

Platelet receptor Binds vWF (vonWillebrand factor)

Overall process: Step 2

Platelets aggregate at site, forming a primary hemostatic plug

Granules are released when

Platelets are activated

Primary hemostatic plug formation begins when

Platelets bind to exposed subendothelium

Platelet derived growth factor

Stimulates repair of endohethelium

Fibrin is produced from

The proteolytic cleavage of fibrinogen by thrombin

Activation of prothrombin forms

Thrombin

thromboxane 2 and serotonin are

Vasoconstrictors

Both ADP and thromboxane 2 have

autocatalytic functions, they stimulate further activation and aggregation of platelets

Binding of GPIb to vWF results in

increased GPIIb/IIIa exposure on PM surface