Thrombosis Flashcards
Why does coagulation occur
- Coagulation prevents blood loss
- Inflammation activates coagulation which promotes inflammation
- Coagulation is an inflammatory response
Describe the two main phases of coagulation
- Circulating fibrinogen is not activated and so does not form strands
- When there is tissue damage/inflammation there is primary aggregation and activation of platelets - the surface of platelets is an important component enabling the clotting cascade which is needed to make thrombin
- There is also a secondary conversion of fibrinogen into fibrin caused by thrombin - the fibrin forms strands that solidify the agglutinated platelets to prevent blood loss
Describe how coagulation and fibrinolysis is balanced
- There is normally a balance between coagulation and fibrinolysis
- Coagulation is always happening to some degree because of tissue damage or inflammation
- Hence anticoagulant/ibrinolytic agents are also present to balance this
Describe how anticoagulants prevent thrombosis
- Endothelial cells express various factors inhibiting coagulation
- Nitric Oxide (inhibits platelets)
- Prostaglandin I2 (inhibits platelet activation)
- Antithrombin inhibits clotting when bound to heparan
Describe how fibrinolysis reverses thrombosis
The clot is broken down by plasmin which is activated from plasminogen by Tissue Plasminogen Activator (tPA)
Briefly describe coagulation
- If endothelial cells become damaged or inflamed, they may favour coagulation, subendothelial cells if disturbed release tissue factor or Von Willebrand factor
- Von Willebrand factor (activates platelets)
- Tissue Factor initiates clotting
Describe arterial and venous thrombosis
Arterial thrombosis -
* Mostly result from atheroma rupture or damage to the endothelium (eg. MI, stroke)
* Platelet-rich ‘white’ thrombus - mostly primary
* May block downstream arteries
Venous thrombosis -
* Often results from stasis or a hyper-coagulant state (eg DVT)
* Platelet-poor ‘red’ thrombus - mostly secondary
* May move to lungs
Describe Virchow’s Triad
- Stasis - static blood lacks kinetic energy and tends to clot
- Hyper-coagulant state - e.g. infection/sepsis, genetic predisposition or drugs like HRT
- Endothelial damage e.g. from surgery or a cannula
Describe the involvement of valves in thrombosis
- Contraction of nearby muscles constrict the veins acting as a pump to return blood to the heart
- Valves in the veins prevents backflow of blood
- The blood tends to eddy currents - blood contacts the valve and so changes direction - increases the risk of stasis
- Damaged valves may not close completely allowing blood to flow in the wrong direction and pool in the legs
Describe deep vein thrombosis
- If venous return is blocked, the affected organ becomes congested with fluid
- There is increased pressure so more filtration
- The risk is that the thrombus may become dislodged and make its way back to the heart
Describe what the fate of a thrombus may be
- Resolution e.g. thrombolysis
- Embolism e.g. moved to another location and blocks a vessel - more likely to go back to heart in vein and to block another vessel in an artery
- Organised - becomes covered by the endothelium - narrower vessel but blood flow is still possible
- Recanalised and organised - holes made in the thrombus and lined with endothelium to form a new lumen
State the difference between proximal and distal deep vein thrombosis
Proximal deep vein thrombosis - higher risk of pulmonary embolism and post thrombotic syndrome
Distal deep vein thrombosis- rarely cause pulmonary embolism and rarely cause post thrombotic syndrome
Describe the symptoms of post thrombotic syndrome
- Inflammation along with damage to the venous valves from the thrombus itself
- Valvular incompetence combined with persistent venous obstruction inducing a rupture of small superficial veins, subcutaneous haemorrhage and increased tissue permeability
- Pain, swelling, discoloration and ulceration can follow
Describe how a venous thrombosis can lead to a pulmonary embolism
- A thrombus in the veins will travel back to the right side of the heart if dislodged (an embolus)
- From the right side of the heart it will then pass into the pulmonary circulation
- A pulmonary embolism is a blockage in a pulmonary artery - can cause a decreased blood flow to a large area of the lungs which will reduce oxygen/carbon dioxide exchange so becomes life threatening
Describe what happens when there is tissue damage
- Endothelial cells are elongated cells that extend across many subendothelial cells which are exposed when endothelial cells are damaged
- These exposed subendothelial cells express von willebrand factors - glycoproteins that normally circulate in the blood
- The primary function of von willebrand factors is to bind to other proteins so binds to subendothelial collagen as well as collagen, platelets, and some coagulation proteins (especially VIII)
