16. Haemostasis and thrombosis Flashcards
what does blood consist of?
blood cells (45%) and blood plasma (55%)
all coagulation factors/clotting factors reside in the plasma
which 2 categories do coagulation factors fall into?
PROCOAGULANTS
- promote clotting e.g. prothrombin, factors V, VII-XIII and fibrinogen
ANTICOAGULANTS
- prevent clotting e.g. plasminogen, TFPI, proteins C and S, antithrombin
what is haemostasis?
maintaining the balance between procoagulants and anticoagulants
prevents excessive blood loss by ensuring clot formation occurs at the site of injury
what is thrombosis?
a pathophysiological process where blood coagulates within a vessel leading to the obstruction of blood flow
where do thrombi form?
within the lumen of a vein or attach to the tunica intima of the vessel
what are venous thromboses referred to and why? what are they caused by?
red thrombi - they have a high erythrocyte content and high fibrin components
caused by decreased rate of blood flow and damage to the endothelium
what is atherosclerosis?
a pathophysiological process where a thrombus forms within an atherosclerotic plaque (between the tunica intima and the tunica media)
what are arterial thromboses referred to and why?
white thrombi - they have a high lipid content and high platelet components
what is virchow’s triad? outline it
reasons why a thrombus forms:
- rate of blood flow
- consistency of blood
- blood vessel wall integrity
why and when may a thrombus form due to rate of blood flow?
blood flow is slow –> no replenishment of anticoagulant factors so balance is tipped towards coagulation
may occur during long haul flights/when someone is immobile for a long time (e.g. injury)
why may a thrombus form due to consistency of blood?
there is a natural imbalance between procoagulation and anticoagulation factors (e.g. factor V leiden)
consistency of blood relates to the natural levels of clotting factors
why and when may a thrombus form due to blood vessel wall integrity?
damaged endothelia –> blood exposed to procoagulation factors
damage may occur during surgery/in individuals with consistent hypertension
what are the phases of coagulation?
INITIATION PHASE: small-scale production of thrombin. It occurs on the surface of tissue factor bearing cells
AMPLIFICATION PHASE: Large-scale production of thrombin, occurring on the surface of platelets
PROPAGATION PHASE: Thrombin mediated generation of fibrin strands. There is enough thrombin to convert fibrinogen to fibrin
what is involved in the initiation phase of coagulation?
- tissue factor bearing cells activate factors X and V to form the prothrombinase complex (FVa and FXa)
- the prothrombinase complex activates factor II (prothrombin) to produce factor IIa (thrombin)
- antithrombin (AT-III) comes and inactivates FIIa and FXa
describe some anticoagulant drugs
dabigatran - factor IIa inhibitor, taken orally
rivaroxaban - factor Xa inhibitor, taken orally
heparin - activates AT-III (decreasing FIIa and FXa)
low molecular weight heparins: activate AT-III (decrease FXa)
warfarin: vitamin K antagonist (vitamin K is needed to make clotting factors), taken orally
when are anticoagulants used?
- mainly venous thrombosis
- deep vein thrombosis and pulmonary embolism
- thrombosis during surgery
- atrial fibrillation
- heparin is used in an emergency because it is fast acting
- warfarin is used in the long term
what is involved in the amplification phase of coagulation at a cellular level?
PLATELET ACTIVATION AND AGGREGATION
- factor IIa (thrombin) –> activates platelets
- activated platelet changes shape and becomes ‘sticky’ –> attached to other platelets –> aggregation
what is involved in the amplification phase of coagulation at a molecular level?
- thrombin binds to protease-activated receptor (PAR) on the platelet surface
- PAR activation –> rise in intracellular Ca
- exocytosis of ADP from dense granules
- ATP activates P2Y12 receptors on platelet –> platelet activation/aggregation
- PAR activation also leads to liberation of arachidonic acid (AA) and activation of cyclo-oxygenase –> generates thromboxane A2 from AA
- thromboxane A2 activation –> expression of GPIIb/IIIa integrin receptor on the platelet surface which is involved in platelet aggregation
describe some antiplatelet drugs
clopidogrel: ADP (P2Y12) receptor antagonist, taken orally
aspirin: irreversible COX-1 inhibitor that inhibits production of TXA2, taken orally
abciximab: inhibits GPIIb/IIIa
when are antiplatelets used?
- arterial thrombosis
- acute coronary syndromes: MI
- atrial fibrillation
what is involved in the propagation stage of coagulation at a cellular level?
- large scale thrombin production
- thrombin binds to fibrinogen and converts fibrinogen to fibrin stands
fibrin strands form a net which trap many things to form a solid core
what do thrombolytics do? give an example
- convert plasminogen –> plasmin (a protease that degrades fibrin) which dissolves a pre-formed clot
alteplase is a recombinant tissue type plasminogen activator
when are thrombolytics used?
- arterial and venous thrombosis
- stroke (1st line treatment)
- ST-elevated MI
what is the main concern when using thrombolytics?
they can cause excessive bleeding
