Vascular Disease Two: Thrombosis And Embolism Flashcards
Thrombus definition
Solid mass composed of blood constituents aggregated together I’m the lumen of a blood vessel
Mainly platelets and fibrin
Thrombosis definition
The process leading to thrombus formation
Normal thrombosis mechanism
To prevent bleeding when a vessel wall is breached
Aggregation of platelets and fibrin
Once the defect is fixed the thrombus is removed by fibrinolysis
Normally PGI2 inhibits platelet aggregation
Normal thrombosis stage 1
Vessel wall is breached exposing collagen and von willebrand factor-> mediate adhesion of platelets
Platelets express glycoprotein 1a and 1b ligands
Adherent platelets undo shape change and aggregate to plug gap
Platelets release factors which trigger the coagulation cascade
Thromboxane is release by platelets-> increased platelet aggregation and vasoconstriction
Normal thrombosis stage 2
Coagulation cascade converts fibrinogen to insoluble fibrin stimulated by platelet factor 3
Platelets express receptors for fibrinogen-> help formation of haemostatic plug
Long fibrin molecules bind together platelets
Restricted to damage site
Normal fibrinolysis
Plasma inhibitor of coagulation cascade limit coagulation-> anti thrombin 3
Stimulated by plasmin activators released from endothelial cells (tPA)
->Inhibited by plasminogen activator inhibitor normally, this is prevented by activated protein C to allow fibrinolysis
Plasminogen and tPA bind to fibrin and tPA converts plasminogen to plasmin-> fibrin to fibrin degradation products
Controls the size of the thrombus
Inhibitors of fibrinolysis
Factor XIa and XIIIa, kallikrein-> plasminogen conversion
Anti plasma and narco globulin-> inhibit plasmin
Thrombin-activatable fibrinolysis inhibitor-> fibrin degradation
Endothelial prevention of thrombosis
Intact endothelium-> no collagen exposure-> no platelet aggregation
Prostacyclin and nitric oxide-> prevent adhesion and aggregation
Thrombomodulin-> binds to any thrombus formed on the surface and activates protien C-> fibrinolysis
Heparin like molecules-> inhibit elements of normal coagulation cascade
Plasminogen activators released by endothelium
Antithrombin III-> inactivates proteases
Coagulation cascade
Aim is to create a solid plug that seals the defect
Fibrin is generated from fibrinogen
Accelerate thrombus formation at site of injury
All proteases apart from V and VIII which are co factors
Intrinsic pathway of coagulation cascade
Coagulation is initiated by contact with surface agents such as collagen or by proteases such as kallikrein acting through Hageman factor
Seen mainly after severe damage
Extrinsic pathway of coagulation cascade
Coagulation is initiated by substances generated from damaged tissue-> tissue factor, by interaction with factor VII
Results in activation of factor X
Coagulation cascade, common pathway
Steps that lead to fibrin production
Key proteases is thrombin-> feeds back providing feedback application
Coagulation cascade 1
Coagulation initiated by tissue factor-> exposed following injury to vessel wall
Tissue factor and VIIa-> activate IX
-> activate X
Coagulation cascade 2
IXa and VIIIa and Ca ions act at phospholipid surface of platelets to activate X
VIII is activated by thrombin
Coagulation cascade 3
Ca completes with Va (also activated by thrombin (IIa)) and Ca ions to convert prothrombin to thrombin Thrombin: Cleaves fibrinogen Actives XIII-> cross links fibrin Activates XI,VII and V