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Flashcards in Thrombosis Deck (10):
1

Define haemostasis.

Arrest of blood flow from damaged blood vessels which involved platelet aggregation, vasoconstriction and coagulation.

2

How does damage to a BV lead to formation of a soft platelet plug?

Damage to BV
Exposure of platelets to +ve charge on ECM and (later) thrombin
Platelets adhere and activate
release mediators (ADP, TxA2) (+ve feedback on platelets)
vasoconstriction and aggregation of platelets
Soft platelet plug

3

Explain the 2 stages of coagulation

1) Initial phase; platelets cause - TF causes VII to VIIa
VIIa causes X to Xa
Xa causes prothrombin to thrombin

2)Amplification phase; (on the surface of activated platelets)
Thrombin (IIa) causes fibrinogen to fibrin to fibrin stable clot. Also causes further activation of other clotting factors.

4

What is a thrombosis?

formation of a blood clot (thrombus) inside a BV usually due to injury of a vessel wall, slowed blood flow or hypercoagubility of blood.

5

Describe how venous and atrial thrombi are formed

Stasis of blood
Coagulation and platelet aggregation
Fibrin rich thrombus
Oedema, inflammation and a pulmonary embolism

6

Describe the anticoagulant treatments available and what they are good for treating

1) Heparin - large glycosaminoglycan family
clotting factors can interact with antithrombin to inactivate them but not very active normally. Heparin increases activity x1000.
Give iv in minutes, can cause haemorrhage and if sever - gievn protamine which binds and inhibits heparin.

2)Warfarin - vitamin K antagonist. Cofactor required in some clotting factor synthesis,
Vit K isn't regenerated therefore Ca can't bind the co factors and thereifre they are less active.
1-3 days to work, orally, many drug interactions therefore patients need to be monitored.

3) Xa inhibitors
- indirect; via antithrombin - enoxaprin
-direct; rivaroxaban

4)IIa inhibtors - hirudin

5) Dabigatran - as effective as warfarin but less chance of haemorrhage

7

Describe the time course of arterial thombosis

Rupture of atherosclerotic plaque
Exposure of matrix and thrombin
Coagulation and platelet aggregation
Formation of occlusive thrombus
Regional ischemia
Cell death - MI in heart or in brain = stroke.

8

Describe anti-platelet drugs

They inhibit platelet aggregation to limit the growth of or decrease the risk of arterial thrombosis.

a) Aspirin - irreversibly inhibit COX2 - blocks production of TxA2 and PGI2. Endothelial cells can produce new protein which decreases the TxA2/PGI2 ration...antiaggregatory effct of PGI2 dominates

b)P2Y12 Receptor agonists - clopidogrel (prodrug)
Blocks ADP which normally activates aggregation

c)Inhibitors of platelert GP IIb/IIIa receptors
Normally platelets aggregate due to cross links forming by fibrinogen binding to glycoprotein receptors - blocked by abciximab

9

Describe thrombolytic drugs

Use them to remove thormbi and act by promoting the production of plasminogen.

Streptokinase - binds to plasminogen and activates it
Alteplase - nautral tpa - activates plasminogen bound fibrils
Reteplase - like alteplase but given as a single bolus injection

Toxicity - if severe bleeding - tranexamic acid

10

How would you treat MI?

Aspirin and iv fibrinolytic drugs
Clopodogrel and maybe an anticoagulant aswell (heparin)
emergency PCI (better than thrombolytics!)