Thrombosis Flashcards
Describe varicose veins and deep vein thrombosis
Varicose veins- lots of branches
Deep vein thrombosis- red, deep, inflamed veins
Explain coagulation
Coagulation prevents blood loss by causing inflammation.
Inflammation activates coagulation which promotes the inflammatory response
Explain the process of coagulation
1) Circulating fibrinogen is not activated and doesnt form strands- there is inactive fibrinogen in blood stream
2) There is primary aggregation and activation of platelets as response to tissue damage/trauma
3) Secondary conversion of fibrinogen to fibrin caused by thrombin
What is the purpose of the clotting cascade
the purpose of the clotting cascade is 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
Explain how anticoagulants prevent thrombosis
-endothelial cells express various factors inhibiting coagulation
-nitric oxide (inhibits platelets)
-prostaglandin 12 (inhibits platelet activation)
-anti thrombin inhibits clotting when bound to heparan.
Explain coagulation
-if endothelial cells become damaged or inflamed they may favour coagulation.
-subendothelial cells if disturbed they may release tissue factor/ Von Willebrand factor
-tissue factor initiates clotting
Explain how fibrinolysis reverses thrombosis
-clot is broken down by plasma which is activated from plasminogen by ‘Tissue Plasminogen Activator’ (tPA)
Explain arterial thrombosis
Arterial thrombosis: mostly result from atheroma rupture or damage to the endothelium
-platelet rich ‘white’ thrombosis (mostly primary)
Explain venous thrombosis
Venous thrombosis:
-often results from stasis or hyper-coagulant state
-platelet poor ‘red’ thrombosis Arterial thrombus (mostly secondary)
-may move to lungs
Explain three components of Virchow’s triad:
1) Stasis
2) Hyper-coagulant state
3) Endothelial
Explain the involvement of valves in thrombosis
1) contraction of nearby muscles squashes veins, acting as a pump to return blood to the heart.
2) valves in veins prevent backflow of blood
3) Blood tends to move in a circular motion (eddy) around valves increasing risk of stasis
4) damaged valves may not close successfully allowing blood to flow in the wrong direction and pool in the legs
What does the fate of thrombus depend on
The fate of thrombus is a blood clot and depends on several biological processes:
-resolution
-embolism
-organised
-recanalised and organised
Explain proximal and distal DVT in deep vein thrombosis
Proximal DVT (occurs below knee):
-higher risk of pulmonary embolism and post- thrombotic syndrome
Distal DVT (occurs above knee):
-rarely causes pulmonary embolism, rarely causes post-thrombotic syndrome
Explain 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
-pain, swelling, discoloration and even ulceration follow
What will happen to a thrombus occurring in the veins
A thrombus occurring in the veins will travel back to the right side of the heart if it dislodged.
From the right side of the heart it will pass into the pulmonary circulation
What is a pulmonary embolism
pulmonary embolism- is a blockage in one of the pulmonary arteries
Explain platelet adherence
Platelet adherence:
-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
Explain platelet activation:
-activated platelets release Thromboxane A2 and Adenosine diphosphate (ADP) which induce receptors for fibrinogen.
-these bind to receptors on adjacent platelets and increase expression of the glycoprotein complex
Explain platelet aggregation
-fibrinogen acts as a tether, holding platelets together (this is aggregation)
-fibrinogen is the soluble precursor to fibrin and is in circulation
Explain platelet substrate for coagulation
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 also allows the complex formation of TF with coagulation factor VII
Explain a common pathway in coagulation
1) Thrombin is important because it is a protease that cleaves fibrinogen into fibrin. Fibrinogen is a large molecule present in the plasma.
2) Fibrinogen promotes blood clotting by forming bridges between and activating blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor
3) Fibrin form long polymers which hold activated platelets together in a blood clot
4) Once there is enough thrombin present factor which is activated and causes cross linking of fibrin which further stabilises the clot
Explain extrinsic pathway
extrinsic pathway:
-begins in the vessel wall
-damaged endothelial cells release tissue factor. The greater the amount of damage, the more is released.
-tissue factor combines with Ca2+ on negatively charged platelet surface and activates factor VII
Explain the intrinsic pathway
intrinsic pathway:
-begins in the blood stream
-activated when blood is exposed to collagen
-activated when blood is put onto a charged surface such as glass
-defects in the factors of extrinsic pathway have far larger physiological effects than mutations in the enzymes of the intrinsic pathway
