S2: Thrombosis Flashcards
What is a thrombosis?
Solid mass of blood formed within the cardiovascular system involving the interaction of endothelial cells, platelets and coagulation cascade and it impedes blood flow
Why are blood clots (coagulation) important?
- Blood clots prevent blood loss. e.g. A cut will get haemostasis which is normal. However, if you start clotting in your artery (e.g. brain)-> thrombosis -> dangerous (as can lead to infarct). Coagulation is therefore an immunological response (you close up wound to prevent infection).
- ## Inflammation activates coagulation and coagulation promotes inflammation so they are linked very closely
What are blood clots made of?
- Fibrinogen and this is cleaved into fibrin by thrombin
2. Platelets which become activated and aggregate together
Describe arterial thrombosis
- Most likely to result from atheroma rupture which ends up blocking downstream smaller arteries which stop blood flow and can cause MI or stroke as oxygenated blood cannot reach tissue
- Described as platelets rich ‘white’ thrombosis
Describe venous thrombosis
- Results from stasis or hypercoagulant state of blood
- If clot blocks flow then there will be back pressure causing oedema
- If this dislodges (embolism), as blood in veins returns to the heart, it will move to RV and get stuck in pulmonary artery or further smaller arteries in the lungs.
What are the 4 key components to a blood clot?
- Endothelium
- Platelets
- Coagulation (protein involved)
- Fibrinolysis (coagulation cascade)
How is normal haemostasis a state of equilibrium?
It is a balance of:
- Fibrinolytic factors, anticoagulant proteins
- Coagulation factors, platelets
What is the response to injury?
- Vessel constriction
- Formation of unstable platelet plug - Primary Haemostasis (platelet adhesion and aggregation)
- Stabilisation of the plug with cross linked fibrin - Secondary Haemostasis (blood coagulation)
- Dissolution of clot and vessel repair (fibrinolysis)
What is Virchow’s triad?
There are three things which make a person prone to having a thrombosis:
- Stasis - changes to normal blood flow (static blood lacks kinetic energy and tends to clot)
- Endothelial damage e.g. vessel wall injury due to surgery of cannula
- Hypercoagulant state - alterations in the constiutent of blood e.g. infection, herdity, drugs (e.g. HRT) etc
Describe Virchow’s Triad: Endothelial damage
Platelets and coagulation are activated by the similar things in different ways, this is where we get the idea of primary and secondary haemostasis.
The activation of platelets and fibrinogen is by tissue damage/inflammation but this is done in different ways (triggering mechanisms different).
- Coagulation and fibrinolysis
Explain coagulation and fibrinolysis
Fibrinolysis (thrombolysis) is getting rid of the clot, Plasminogen gets activated to plasmin by an enzyme called tPA. It involves an enzyme plasmin cleaving fibrin. D-dimers are just fragments of fibrin which tell you a clot has happened somewhere in the body.
Coagulation is a dynamic process, we are constantly clotting and unclotting (coagulation and fibrinolysis).
What enzyme activates plasminogen?
tPa activates plasminogen to plasmin
What is the platelet release reaction?
Vessel injury causes collagen to be exposed which causes the patelet release reaction.
Negatively charged phospholipids on activated platelet provide surface for clotting reactions to take place (coagulation cascade of thrombin and fibrin).
Also platelets release serotonin which causes vasoconstriction and thromboxane A2 and ADP which causes vasocontriction and platelet aggregation (primary plug).
What is the cell based model of coagulation?
EXTRINSIC (small amount of thrombin) AND INTRINSIC (large release of thrombin)
At the surface where the damage is:
- Tissue factor exposed during damage binds to factor 7a
- This leads to a small amount of thrombin being released
- Thrombin on the surface of platelets will activate them (platelets)
- Thrombin with factor 9a and co factor 8a (tenase complex) will lead to the activation of 10a with its co-factor 5a (prothrombinase complex). These complexes need phospholipid and calcium to work.
- This leads further thrombin being synthesised from prothrombin
- Thrombin converts fibrinogen to fibrin. Thrombin also converts factor 13 in factor 13a helping crosslink fibrin.
What does the intrinsic and extrinsic pathway for coagulation mean?
Intrinsic = factors in the blood Extrinsic= factors that occur when tissue damage occurs
Name some blood coagulation inhibitors
INTRINSIC
Protein C + S = Activated protein C
Activated protein C degrades co factor 5a and co factor 8a
EXTRINSIC
Antithrombin III is important for inhibiting factor 10a and thrombin
Describe Virchow’s Triad: Hypercoagulability
Normal haemostasis balance leans towards coagulation factors and platelets (e.g. malignancy increases clotting factors). There is also a decrease in fibrinolytic factors and anticoagulant proteins (ATIII deficiency, FV Leiden - resistant to activated protein C, Protein C and protein S deficiencies).
List factors that may cause Virchow’s Triad: Stasis
- Prolonged immobility
e. g. surgery, travel - Stroke
- Cardiac failure
- Pelvic obstruction
- Dehydration
- Hyperviscosity
- Polycythaemia (increase Hb either through reduction of plasma volume or increase in red cell numbers)
Involvement of valves in thrombosis
Valves in veins prevent backflow of blood, the contraction of nearby muscles squashes the veins acting as a pump to return blood to the heart (as blood can’t go back due to valves)
However you have turbulence around the valves (tends to “eddy” around valves) and it is the turbulence behind the valve that is important, this increases the risk of stasis.
Lack of movement in veins causes it to clot (like water in a canal that doesn’t move is more likely to freeze than a river that flows).
This is why people commonly get thrombosis on planes due to lack of movement.
Clinical features of DVT (symptoms)
Pain, tenderness of veins Limb swelling Superficial venous distension Increased skin temperature Skin discoloration All reflect obstruction to the venous drainage
Fate of venous thrombosis in lungs
A venous thrombosis that moves to the lung can have two fates. If it is small, it can move through RA -> RV -> PA -> block of part of your lung (small pulmonary artery), this can be asymptomatic. If there is a large venous thrombosis then this can block off a large PA and cut off perfusion to the whole lung -> rapid death.
Describe proximal and distal DVT
Proximal DVT = Higher risk of pulmonary embolism and post-thrombotic syndrome (pain, swelling, possibly ulcers) – as closer to heart and more likely to move to lungs – you should therefore be more worried as it is more dangerous than distal DVT. [External iliac, common femoral, deep femoral, great saphenous, femoral, popliteal] Distal DVT (anything below the knee)= Rarely causes a pulmonary embolism and rarely causes post-thrombotic syndrome [Tibial and small saphenous vein] -> more likely to respond to treatment.
Describe antithrombin and heparin
Antithrombin inhibits clotting by binding to proteases and inhibiting it.
Although we can give antithrombin to patients we tend to activate antithrombin that is already present, this is what heparin does. Heparin mimics a similar endogenous molecule heparan which binds antithrombin on endothelial cell surface.
Therefore giving heparin means more antithrombin exposed which will prevent blood clotting.
Name some anticoagulants and clot busters
Anti-coagulants STOP blood from clotting
“Clot busters” undo a clot
Anticoagulants:
- warfarin
- heparin
- direct oral anticoagulant
‘Clot busters’ reverse:
- plasminogen activators
- streptokinase
Describe bleeding
Increase fibrinolytic factors or anticoagulation proteins causes excess plasmin to be formed which is a proteolytic enzyme which can degrade fibrin and other things if in excess causing bleeding.
