Thrombosis Flashcards
What is the purpose of clotting cascade
-makes lot of thrombin
-so that fibrinogen can be converted to fibrin
-fibrin form strands that solidify the agglutinated platelets to prevent blood loss
-produce activated factor X which is a protease that catalyses the conversion of prothrombin to thrombin p
How is thrombosis prevented
- anticoagulants
-endothelial cells have various factors that prevent coagulation - nitric oxide - inhibited platelets
*prostaglandin 12- inhibits platelet activation
*antithrombin-inhibits clotting when bound to heparan
What reverses thrombosis
Fibrinolysis ,
Clot is broken down by plasmin which is activated from plasminogen by tPA)
What factor activates platelets
Von willebrand ( tissue factor )
Arterial thrombosis
- occurs from atheroma rupture or damage to endothelium
-platelet rich
-primary
-may block down stream arteries
Venous thrombosis
-results from stasis or hyper coagulant state
-platelet poor
- secondary
-may move to lungs
Virchows triad
-stasis - static blood lacks kinetic energy and tends to clot
-hyper coagulant state - eg sepsis
-endothelial damage eg surgery or cannula
How is deep vein thrombosis caused
-venous return is blocked
-affected organ becomes congested with fluid
-increased pressure so more filtration
Risk of deep vein thrombosis
Thrombosis may become dislodged and make its way back to the heart
Different fates of a thrombus
-resolution eg thrombolysis
-embolism - moves to another location and blocks a vessel
-organised -becomes covered by endothelium
-recanalised and organised
Explain proximal dvt
-thrombus above the need is more at risk
- can lead to swelling , ulcers,pain
- higher risk of pulmonary embolism
Distal DVT
- thrombosis below knee
- less risk
-rarely cause pulmonary embolism or post thrombotic syndrome
Fate of a venous thrombus
- travel back to the right side of the heart if thrombus is dislodged
-passes through pulmonary circulation
-causing pulmonary embolism
What is pulmonary embolism
Blockage in one of the pulmonary arteries
Stages of coagulation
-damage to vessel , exposing subendothelial cells
-von willebrand factor binds to subendothelial cells , activating platelets
-activated platelets release thromboxane a2 & ADP , inducing receptors for fibrinogen
-txa2 and ADP bind to receptors on adjacent platelets and increase expression of glycoprotein complex GPIIb/IIIa
-aggregation- fibrinogens holds platelets together
-fibrinogen is a soluble precursor to fibrin which is insoluble and holds the clot firm
-one clump of platelets aggregate they form a negative charged surface
-exposure of tissue factor, forming TF with coagulation factor vii
Why is thrombin important
Cleaves fibrinogen into fibrin
How does fibrinogen promote blood clotting
-forming bridges between and activating blood platelets through binding to their GpIIb/IIIa surface membrane fibrinogen receptor
Explain extrinsic pathway
-beings In vessel wall
-damaged endothelial cells release tissue factor
-TF combines with calcium on negatively charged platelet surface
Activates factor vii
The viia factor can be inactivated by antithrombin
Intrinsic pathway
-begins in blood stream
- activates when blood exposed to collagen and put into charged surface
-
What is tissue plasminogen activator
-serine proteases found on endothelial cell s
-catalyse activation of circulating plasminogen into plasmin
Role of plasmin
Catalyses breakdown of cross linked fibrin clot into fragments called d dimers
How is herapan linked to antithrombin
-expressed by endothelial cells and binds to enzyme inhibitor antithrombin , resulting in AT activation
When antithrombin is activated what happens
-inactuves thrombin , factor xa,factor vii,and other components in the clotting cascade
