Thrombosis - Haemostasis in the wrong place

Question 1

Coagulation

Answer 1

• Coagulation is an inflammatory response which prevents blood loss.
• Coagulation is activated by inflammation - coagulation further promotes inflammation.

Question 2

Platelets and coagulation

Answer 2

• 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.

Question 3

Coagulation Vs fibrinolysis balance

Answer 3

• There is a constant balance between coagulationa and fibrinolysis.

Question 4

Arterial and venous thrombosis

Answer 4

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.

Question 5

Virchow’s triad

Answer 5

Question 6

Invlolvement of valves

Answer 6

• Contraction of muscles squashes veins, acting as a pump to return blood to the heart.

1. Valves in veins prevent backflow of blood.
2. Blood tends to eddy around the valves increasing the risk of stasis.
3. Damaged valves don’t close fully, which allows blood to flow in the wrong direction and pool in the legs.

Question 7

Deep vein thrombosis

Answer 7

• 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.

Question 8

Fate of a thrombus

Answer 8

Question 9

Proximal and distal deep vein thrombosis

Answer 9

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.

Question 10

Post thrombotic syndrome

Answer 10

• 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.

Question 11

Fate of venous thrombosis - pulmonary embolism

Answer 11

• 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.

Question 12

Tissue damage

Answer 12

Question 13

Platelet adherence

Answer 13

• 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.

Question 14

Platelet actvivation

Answer 14

• 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.

Question 15

Platelet aggregation

Answer 15

• Fibrinogen acts as a tether, holdinf platelets together –> aggregation.
• Fibrinogen is the soluble precursor to fibrin and is in circulation.

Question 16

Platelet substrate for coagulation

Answer 16

• 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.

Question 17

Common pathway

Answer 17

1. Clotting cascades produce activated factor 10 (Xa) —> this is a protease which catalyses the conversion of prothrombin to thrombin.
2. Thrombin is a protease that cleaves fibrinogen into fibrin. Once fibrinogen becomes fibrin, it is no longer soluble.
3. Fibrinogen promotes blood clotting by forming bridges between blood platelets through binding to their surface membrane fibrinogen receptor.
4. Fibrin forms long polymers which hold activated platelets together in a blood clot.
5. Enough thrombin present –> factor 13 (XIII) is activated and causes cross linking of fibrin which further stabilises the clot.

Question 18

Extrinsic and intrinsic pathways

Answer 18

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.

Question 19

Fibrinolysis and anticoagulation

Answer 19