Vascular Disease Two: Thrombosis And Embolism Flashcards Preview

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Flashcards in Vascular Disease Two: Thrombosis And Embolism Deck (23)

Thrombosis definition

The process leading to thrombus formation


Thrombus definition

Solid mass composed of blood constituents aggregated together I'm the lumen of a blood vessel
Mainly platelets and fibrin


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
Cleaves fibrinogen
Actives XIII-> cross links fibrin
Activates XI,VII and V


Coagulation cascade 4

Fibrin is cross linked by action of XIII (transglutaminase)


Three main factors that predispose thrombus formation

Endothelial dysfunction-> damage to endothelium
Changes in blood flow pattern->
stasis allows aggregation and contact with epithelium
turbulent flow may cause damage
Change in potential blood coagulability->
increased throbbing or fibrinogen
decreased protein C
Anti phospholipid antibodies


Predisposing factors to thrombus relating to sites of thrombus

Artery-> Atheroma, aneurysms
Hear valve-> inflammation caused by infection
Ventricle-> inflammation following infection, ventricular aneurysm
Atrium-> atria fibrillation-> stasis, mitral valve stenosis
Ventricle-> slow flow, changes in coagulability
Cerebral vein sinus-> inflammation following infection, changes in coagulability


Outcomes following vascular occlusion by thrombus

Propagation-> enlarges along vessel
Lyses by intrinsic fibrinolysis-> rare
Organisation-> in growth of granulation tissue from vessel wall-> thrombus replaced by granulation tissue-> fibroblasts invade and lay down collagen
Recanalisation-> new vascular channels develop in granulation tissue and reestablish flow


Embolism definition

Occlusion of a vessel by material travelling in the circulation
Most commonly due to circulating thrombus-> thromboemboli



Thromboemboli form:
Systemic veins-> travels round to heart-> impacts pulmonary arterial system
Heart-> via aorta to systemic circulation-> brain, kidneys, spleen, gut, lower limbs
Common carotids-> cerebral arteries
Abdo aorta-> renal and lower limbs


Other material which may cause embolism

Tumour cells
Fat and bone marrow-> may occur after big fractures
Air-> accidental pumping of air into venous circulation during intravenous injection
-> pressure change cause air to dissolve in plasma in divers-> bubbles when they get back up-> the bends


VTE risk assessment

Active cancer/cancer treatment
>60 yrs
Know thrombophilliass
BMI >30
One of more significant medical co morbidities

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