Thrombosis and Embolism Flashcards
Haemostasis is?
Normal, physiological process that stops leaks of vessels (by plugging leaks), and is the normal response to injury.
In healthy vessels is actively switched off to maintain the blood in a fluid state.
In healthy vessels, what inhibits haemostasis?
Endothelial Cells
1) Physically Insulating tissues from blood
2) Produce enzymatic and chemical inhibitors of platelet activation; Nitric Oxide (NO) and prostacyclins
3) Produce antithrombin on their surface which binds and inactivates the coagulation enzyme thrombin.
After vessel injury, how do endothelial cells promote haemostasis?
1) Produce endothelin > vasoconstriction
2) Loss of endothelial barrier, exposing underlying tissue, activates > platelets and coagulation cascade
3) Produce von Willebrand factor > promotes platelet adhesion to the ECM proteins exposed by vessel injury.
4) Produce Tissue Factor “thromboplastin”, which activates the coagulation cascade
PLatelets are?
-Produced by cytoplasmic fragmentation of megakaryocytes in the bone marrow.
~7day lifespan
-alpha and dense granules contain chemical mediators of haemostasis > choco-chip like structures
How are the platelets important in haemostasis, after vessel injury?
- They become activated by ECM proteins (esp. collagens) that are exposed when the endothelial monolayer is damaged
- Secrete chemical signals “thromoxane A, vasoactive amines and ADP”
- these promotes > vasoconstriction and platelet aggregation
What happens to haemostasis if there’s reduced platelets?
Purpura: bleeding from skin capillaries
Major Spontaneous Haemorrhage.
Haemostasis is achieved via a combination of
Endothelial cells
Platelets
Coagulation cascade
Basis of the clotting cascde?
Several different pathways can activated CC (including Tissue factor).
- Cascade of proteolytic reactions
- Inert circulating zymogens (precursors) are sequentially activated.
Turns on a series of enzymatic cleavage events thrombin > catalyses fibrinogen > fibrin web > with platelets form plug.
*thrombin also activates platelets
THrombosis
Haemostasis inappropriately activated
Thrombi may form in arteries or veins. May cause damage by obstructing vessel lumens (either where they form, or by breaking off and travelling as an embolus.
A “thrombus” is?
A mass formed from blood constituents within the circulation during life.
- fibrin and platelets
- entrapped red and white blood cells
Is a thrombus the same thing as a blood clot??
NO!
Blood clot: formed in static blood, involves primarily th e coagulation system.
Has NO platelet interaction with the vessel wall.
eg) in vitro when blood is placed in a test tube
Clot is soft, jelly-like and unstructured. Composed of a random mix of blood cells suspended in serum proteins.
Constituents of Virchows Triad? What is the virchow’s Triad
1) Endothelial injury
2) Hypercoagulability
3) Abnormal Blood Flow
These are the3 main factors that cause thrombosis (turn on haemostasis inapropriate,y
Types of endothelial cell injury…
Atherosclerosis Hypoxia Infection/inflammation Physical damage Chemical Damage
How is it that thrombi can form on vascular implants in vessel walls?
Artificial Surfaces can…
- Activate the intrinsic coagulation cascade
- Bind pro-inflammatory compliment cascade proteins
- Bind other proteins that may activate platelets.
So A.Ss do tend to promote thrombus formation and inflammation
Patients must take “anti-coagulant drugs”
What causes changes in blood flow?
Turbulence (arteries and cardiac chambers)
- narrowing
- aneurysms
- infarcted myocardium
Stasis (veins)
- Failure of right side of heart
- compressed or varicose veins
- blood viscosity
