thrombosis - haemostasis in the wrong place Flashcards
describe platelets role in clotting cascade
- Platelets play a crucial role in the clotting cascade by forming the initial plug and supporting fibrin formation.
Key Functions:
* Adhesion – Platelets stick to exposed collagen at injury sites via von Willebrand factor (vWF).
* Activation – They release granules containing ADP, thromboxane A2, and serotonin, which recruit more platelets.
* Aggregation – Platelets bind together via fibrinogen bridges, forming the platelet plug.
* Coagulation Support – Provide a surface for clotting factors, enhancing thrombin generation and fibrin formation.
what is the purpose of the clotting cascade ?
to make lots of thrombin so that fibrinogen can be converted to fibrin. Fibrin forms strands which solidifies the agglutinated platelets to prevent blood loss.
describe the balance between coagulation and fibrinolysis
- There normally a constant balance between coagulation and fibrinolysis.
Some coagulation because of tissue damage or inflammation is always occurring and so there are anticoagulant and fibrinolytic agents constantly balancing against this.
describe arterial and venous thrombosis
Arterial thrombosis:
* Mostly result from atheroma rupture or damage to the endothelium (eg. MI, stroke).
* Platelet-rich ‘white’ thrombosis. 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
what is the involvement of valves in thrombosis ?
describe deep vein thrombosis
- If venous return is blocked, the affected organ becomes congested with fluid.
- Increased pressure so more filtration
- The risk is that the thrombosis might become dislodged and make its way back to the heart
what is the fate of a thrombus ?
describe proximal and distal deep vein thrombosis
proximal:
* Higher risk of pulmonary embolism
and post-thrombotic syndrome
(pain, swelling, maybe even ulcers)
deep:
* Rarely cause pulmonary embolism
Rarely cause post-thrombotic syndrome
what is 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 an increase of tissue permeability.
- Pain, swelling, discoloration, and even ulceration follow.
what is a pulmonary embolism ?
- A thrombus occurring in the veins will travel back to the right side of the heart if it is dislodged. From the right side of the heart it will pass into the pulmonary circulation.
- A pulmonary embolism is a blockage in one of the pulmonary arteries.
describe the coagulation and clotting process
- Damage to the vessel endothelium exposes underlying subendothelial cells.
- Damaged endothelium exposes Von Willebrand factor on subendothelial cells which activates platelets.
- Circulating Von Willebrand factor may bind to exposed subendothelial cells
- Activated endothelial cells can also express Von Willebrand factor.
- Activated platelets release Thromboxane A2 (TxA2) & Adenosine diphosphate (ADP) which induce receptors for fibrinogen (GPIIb/IIIa).
- These bind to receptors on adjacent platelets and increase expression of the glycoprotein complex GPIIb/IIIa.
- Fibrinogen acts as a tether, holding platelets together. This is aggregation.
- Fibrinogen is the soluble precursor to fibrin and is in the circulation.
- Once a clump of platelets aggregate they form a negatively charged surface which is required for coagulation.
- Exposure of Tissue Factor (TF) expressing cells during injury allows also allows the complex formation of TF with coagulation factor VII
- Coagulation involves the conversion of fibrinogen to fibrin and then crosslinking of the fibrin clot.
describe the common pathway
- The purpose of the clotting cascades is to produce activated factor ten (Xa) which is a protease that catalyses the conversion of prothrombin (II) to thrombin (IIa)
Thrombin (IIa) is important because is a protease that cleaves fibrinogen into fibrin. Fibrinogen is a large molecule present in plasma - once cleaved it becomes insoluble fibrin. - Fibrinogen promotes blood clotting by forming bridges between, and activating, blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor.
- Fibrin form long polymers which hold activated platelets together in a blood clot.
- Once there is enough thrombin present factor thirteen (XIII) which is activated and causes cross linking of fibrin which further stabilises the clot.
describe extrinsic and intrinsic pathways
describe TPA and antithrombin
