Thrombosis Flashcards
What’s thrombosis?
Solid mass of blood formed within the CVS involving interaction of endothelial cells, platelets, coagulation cascade which impedes blood flow
Features of arterial thrombosis?
Result from atheroma rupture (MI, stroke)
Platelet-rich “white” thrombosis
Block downstream arteries
Features of venous thrombosis?
Result from stasis or hypercoagulant state
Platelet-poor “red” thrombus
May move to lungs
What makes a blood clot?
Endothelium
Platelets
Coagulation
Fibrinolysis
What’s normal haemostasis?
state of equilibrium
fibrinolytic factors, anticoagulant proteins vs coagulation factors, platelets
Describe process of haemostasis
- response to injury –> vessel constriction
- formation of unstable platelet plug : platelet adhesion + aggregation
- fibrin stabilises plug : blood coagulation
- fibrinolysis : dissolution of clot + vessel repair
What does development of a thrombus depend on?
Changes in normal blood flow
Alterations in blood constituents
Damage to endothelial layer
Risk factors of endothelial dysfunction?
smoking + hypertension
Risk factors of endothelial damage?
surgery, catheter (PICC lines), trauma
eg of hereditary factors of hypercoagulability?
factor V Leiden, prothrombin G20210A, protein C + S deficiency
eg of acquired factors of hypercoagulability?
cancer, chemo, oral contraceptive/hormone replacement therapy, pregnancy, obesity, HIT
Risk factors of stasis?
immobility, stroke, cardiac failure, pelvic obstruction, dehydration, hyperviscosity, polycythemia –> endothelial injury
What’s Virchow’s Triad?
endothelial damage
hypercoagulability
stasis
Mechanism when endothelial damage?
1º
-collagen + vWF binds, activates platelets
-platelets enlarge + release granule contents
-exposing phospholipid surface + express receptors
-TF + collagen initiate coagulation cascade
2º
-activated platelet + fibrin form mesh
Describe the fibrinolytic system
- endothelial cells release tPA
- tPA activates plasminogen
- plasminogen -> plasmin
- plasmin breaks up clot
- forming fibrin fragments + D-dimers
What’s PL?
charged phospholipids on platelet surface for coagulation
Describe the cell based model of coagulation
- damaged tissue releases TF
- TF activates 7a
- 7a initiates thrombin required for amplification
- 8a + 9a on platelet surface activates 10a
- 10a has cofactor 5a
- 10a + 5a induces prothrombin
- prothrombin -> thrombin
- thrombin induces fibrinogen -> fibrin
What’s initiation of cell based model of coagulation?
TF released with 7a activating thrombin
What’s amplification of cell based model of coagulation?
generating more thrombin
9a + 8a on platelet activates 10a
What’s propagation of cell based model of coagulation?
10a + 5a propagate more induction of thrombin
What’s the common pathway of coagulation?
- 10a with cofactors: 5a, PL, Ca2+ on platelet surface
- 10a activates prothrombin -> thrombin
- thrombin activates fibrinogen -> fibrin
What’s the extrinsic pathway of coagulation?
- tissue damage activates TF
- TF, 7a, Ca2+ activates 10 -> 10a
What’s the intrinsic pathway of coagulation?
- 12 -> 12a
- 12a activates 11 -> 11a
- 11a activates 9 -> 9a
- 9a with cofactors: 8a, PL, Ca2+
- 9a activates 10 -> 10a
- 10a activates prothrombin -> thrombin
How’s 10 activated?
EXTRINSIC : TF, 7a, Ca2+ activates 10 -> 10a
INSTRINSIC : 9a with cofactors: 8a, PL, Ca2+ activates 10 -> 10a
What’s activated protein C (APC)?
formed from protein C + S
inhibits 8a + 5a -less amplification
What’s antithrombin III?
inhibit 10 + thrombin
What are the natural coagulation inhibitors?
activated protein C (APC), antithrombin III
What’s antithrombin III deficiency?
factor 5 Leiden - mutation in 5, which is resistant to APC so induces clotting
Why’s there increased risk of stasis at valves?
blood eddy around valves
Where is the riskier DVT?
above knee increases risk of PE
What’s the annual incidence DVT?
1:1000
What’s inherited thrombophilia?
8:100
Clinical features of DVT?
pain, tenderness of veins, limb swelling, superficial venous distension, increased skin temp, discoloration due to obstruction to the venous drainage
What are anticoagulants + eg?
prevent
warfarin, heparin, direct oral anticoagulants
What are ‘clot busters’ + eg?
reverse
plasminogen activators, streptokinase
What are the bleeding complications from anticoagulants?
👁, bruising, intracerebral bleeding
