Download - Blood clots
Why does blood clot?
How does blood clot?
Controlling blood clots
Pharmaceutical intervention
Virchow’s Triad... Endothelial injury
○ Stress, turbulent flow, scarred valves
○ Increased collagen exposure Altered blood flow
○ Turbulence, due to plaques, aneurysms, sickle-cell Hypercoaguability
○ Genetic or acquired○ Mutations in factors, MI, heparin, AF, COCP, sickle
cell
Vascular Spasm
Platelet Plug Formation
Coagulation Cascade
Damage to arteries = Circular muscle contraction
Caused by - platelet secretions - nociceptor inhibition
Damaged endothelium exposes ECM Platelets adhere via von Willebrand factor
Thromboxane A2 + Serotonin Vasoconstriction
Thromboxane A2 + ADP Platelet Aggregation
* Primary Haemostatic Plug
Clotting factors
ADPSerotonin
Fibrin-stabilising factor (XIII)
Thromboxane A2
X
II
I
TF + Ca2+
VII TF - VIIa
Damaged tissue...
Xa + Va
IIa
Ia
XIII
XIIIa
XII
XIXIa
XIIa
IXIXa
X
VIIIa + Thrombin (IIa) catalyses the conversion of...
V Va
VIII VIIIa
Damaged cells...
Clot retraction
Fibrinolytic system○ Dissolves clots via fibrinolysis○ Thrombin, XIIa, tissue plasminogen activator (t-Pa)
activate plasminogen plasmin○ Plasmin breaks down fibrin and inactivates Ia, IIa,
Va, XIIa WBC/endothelium secrete prostcyclin
(inhibit thromboxane A2) Antithrombin inhibits IIa, Xa, XIIa PC + Thrombomodulin inactivates Va & XIIIa
X
II
I
TF + Ca2+
VII TF - VIIa
Damaged tissue...
Xa + Va
IIa
Ia
XIII
XIIIa
XII
XIXIa
XIIa
IXIXa
X
VIIIa +
Damaged cells...
Antithrombin
Activated Protein C
Plasmin
Heparin○ Speeds up antithrombin action○ Immediate action○ 2 types: unfractioned and LMWH○ Use for DVT prophylaxis post-op
Warfarin○ Inhibits vitamin K reductase, so inactivates clotting
factors○ 3 days before action○ Use as long term anticoagulant, e.g. Prophylaxis,
AF, hip surgery, prosthetic heart valves.
Used within 12hours of MI, thromboembolic stroke, arterial clots
Streptokinase○ Catalyses conversion of plasminogen to plasmin○ Increased risk of bleeds and allergic reaction
Alteplase○ Cleaves plasminogen into plasmin○ Increased risk of stroke