Thrombosis - Haemostasis in the wrong place Flashcards
Coagulation
- Coagulation is an inflammatory response which prevents blood loss.
- Coagulation is activated by inflammation - coagulation further promotes inflammation.
Platelets and coagulation
- Platelets enable the clotting cascade.
- The clotting cascade makes thrombin which converts fibrinogen to fibrin.
- Fibrin forms strands which solidifies the agglutinated platelets to prevent blood loss.
Coagulation Vs fibrinolysis balance
- There is a constant balance between coagulationa and fibrinolysis.
Arterial and venous thrombosis
Arterial thrombosis: mostly from atheroma damage to the endothelium (stroke). platelet-rich. primary. Blocks downstream arteries.
Venous thrombosis: mostly from stasis or a hyper-coagulant state(DVT). platelet-poor. secondary. Moves to lungs.
Virchow’s triad
Invlolvement of valves
- Contraction of muscles squashes veins, acting as a pump to return blood to the heart.
- Valves in veins prevent backflow of blood.
- Blood tends to eddy around the valves increasing the risk of stasis.
- Damaged valves don’t close fully, which allows blood to flow in the wrong direction and pool in the legs.
Deep vein thrombosis
- If venous return is blocked, the affected organ becomes congested with fluid –> increases pressure and therefore filtration.
- The risk is that the thrombosis might make its way back to the heart.
Fate of a thrombus
Proximal and distal deep vein thrombosis
Proximal deep vein thrombosis (DVT): Higher risk of pulmonary embolism and post-thrombotic syndrome (pain, swelling etc)
Distal deep vein thrombosis: Rarely cause pulmonary embolism and post thrombotic syndrome.
Post thrombotic syndrome
- Inflammation and damage to venous valves from the thrombus.
- Valvular incompetence and persistent venous obstruction inducing a rupture of small superficicial veins, subcutaneous haemorrhage and increase of tissue permeability.
- Followed by pain, swelling, discoloration etc.
Fate of venous thrombosis - pulmonary embolism
- A thrombus occuring in the veins will travel back to the right side of the heart if it’s dislodged. –> from the right of heart it will pass into pulmonary circulation.
- Pulmonary embolism is a blockage in one of the pulmonary arteries.
Tissue damage
Platelet adherence
- Damaged endothelium exposes Von Willebrant factor om subendothelial cells which activates platelets.
- Circulating Von Willebrand factor may bind to exposed subendothelial cells.
- Activated endothelial cells can also express Von Willebrand factor.
Platelet actvivation
- Activated platelets release A2 and ADP which induce receptors for fibrinogen.
- These bind to receptors on adjacent platelets and increase expression of the glycoprotein complex.
Platelet aggregation
- Fibrinogen acts as a tether, holdinf platelets together –> aggregation.
- Fibrinogen is the soluble precursor to fibrin and is in circulation.
Platelet substrate for coagulation
- Clump of platelets aggregate –> form negatively charged surface which is required for coagulation.
- Exposure of Tissue Factor (TF) –> complex formation of TF with coagulation factor VII.
Common pathway
- Clotting cascades produce activated factor 10 (Xa) —> this is a protease which catalyses the conversion of prothrombin to thrombin.
- Thrombin is a protease that cleaves fibrinogen into fibrin. Once fibrinogen becomes fibrin, it is no longer soluble.
- Fibrinogen promotes blood clotting by forming bridges between blood platelets through binding to their surface membrane fibrinogen receptor.
- Fibrin forms long polymers which hold activated platelets together in a blood clot.
- Enough thrombin present –> factor 13 (XIII) is activated and causes cross linking of fibrin which further stabilises the clot.
Extrinsic and intrinsic pathways
Extrinsic pathway:
* Begins in vessel wall.
* Damaged endothelial cells release tissue factor (TF), the greater the amount of damage, the more is released.
* TF combines with Ca++ on negatively charged platelet surface, and activats factor VII.
* The Vlla-tissue factor complex can be quickly inactivated by antithrombin in vivo.
Intrinsic pathway:
* Begins in blood stream.
* Activated when blood is exposed to collagen (or other damaged surfaces.)
* Activated when blood is put onto a charged surface such as glass.
* Deflects in the factors of extrinsic pathway have fat larger physiological effects than mutations in the enzynes of the intrinsic pathway.
Fibrinolysis and anticoagulation
