Haemostasis and thrombosis Flashcards
What is haemostasis?
Essential physiological process.
Blood coagulation prevents excessive blood loss.
What is thrombosis?
Pathophysiological process.
Blood coagulates within blood vessels and obstructs blood flow.
What are the procoagulants (plasma clotting factors)?
Prothrombin
Factors V, VII-XIII
Fibrinogen
What are the anticoagulants (plasma clotting factors)?
Plasminogen
TFPI (tissue factor pathway inhibitor)
Proteins C and S
Antithrombin
What is atherosclerosis?
Pathophysiological process.
Thrombus forms within atherosclerotic plaque.
When may a clot become life-threatening?
If it dislodges from the vessel- embolism.
What is a feature of venous thromboses?
High fibrin components
High erythrocyte content
(Red thrombi)
What is a feature of arterial thromboses?
High platelet components
High lipid content
(White thrombi)
Why does a thrombus form?
Virchow’s triad.
What is Virchow’s triad?
Rate of blood flow.
Consistency of blood.
Blood vessel wall integrity.
What is the cell-based theory of coagulation?
Three stages: initiation, amplification, propagation.
What is involved in the initiation stage of the cell-based theory of coagulation?
Small scale production of thrombin.
Tissue factor bearing cells activate factors X and V, forming prothrombinase complex.
Prothrombinase complex activates factor II (prothrombin) creating factor IIa (thrombin).
Antithrombin (AT-III) inactivates factors IIa and Xa.
Anticoagulants work here.
What is involved in the amplification stage of the cell-based theory of coagulation?
Large scale thrombin production on the surface of platelets.
Factor IIa (thrombin) activates platelets.
Activated platelets change shape and become ‘sticky’, attaching other platelets.
Antiplatelets work here.
What is involved in the propagation stage of the cell-based theory of coagulation?
Thrombin mediated generation of fibrin strands from fibrinogen.
Activated platelets are involved in large-scale thrombin production.
Thrombolytics work here.
What are the constituents of blood?
Blood cells (45%)- 99% erythrocytes. Blood plasma (55%)- 90% water.
How does the rate of blood flow affect the risk of thrombus formation?
If blood flow is slow/stagnating, there is slow turnover of clotting factors- no replenishment of anticoagulant, balance adjusted in favour of coagulation.
e.g. long haul flight, DVT.
Increased likelihood of thrombus formation.
How does the consistency of blood affect the risk of thrombus formation?
Natural imbalance between pro-coagulation and anticoagulation factors, e.g. factor V leiden.
Increased likelihood of thrombus formation.
How does the blood vessel wall integrity affect the risk of thrombus formation?
Damaged endothelia leads to blood being exposed to pro-coagulation factors. Increased likelihood of thrombus formation.
What is dabigatran?
Factor IIa inhibitor
Oral
Inhibits initiation phase of cell-based theory of coagulation.
What is rivaroxaban?
Factor Xa inhibitor
Oral
Inhibits initiation phase of cell-based theory of coagulation.
What is heparin?
Activates AT-III (decreased factors IIa and Xa)
i.v., s.c.
Inhibits initiation phase of cell-based theory of coagulation.
What are low molecular weight heparins?
Activate AT-III (decreased Xa)
e.g. dalteparin
Inhibits initiation phase of cell-based theory of coagulation.
What is warfarin?
Vitamin K antagonist
Vitamin K is required for generation of factors II, VII, IX and X.
Oral
Inhibits initiation phase of cell-based theory of coagulation.
List anticoagulant drugs.
Dabigatran
Rivaroxaban
Heparin
Low molecular weight heparins, e.g. dalteparin
Warfarin
These inhibit initiation phase of cell-based theory of coagulation.
