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