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