Anti-Coagulants Flashcards
What is thrombosis?
the pathological formation of a haemostatic plug
- occurs within the vasculature
- forms in the absence of bleeding
What is Virchow’s triad?
describes the risk factors that predispose thrombosis formation
hypercoagulability
- increased tendency of the blood to thrombus
- can be in the absence of bleeding
- can have genetic or environmental factors causing it
endothelial injury/vessel damage (atherosclerosis)
- alters the dynamics of blood flow
= turbulent blood flow
haemostasis/venous stasis
- alteration of normal blood flow
= e.g. can allow the accumulation of procoagulant factors
What is haemostasis?
arrest of blood loss from damaged blood vessels
- wound causes vasoconstriction
= adhesion/platelet activation and fibrin formation
forms a haemostatic plug
- occurs to prevent/stop bleeding
What is the difference between an arterial and venous thrombus?
arterial - high vascular flow - fibrin meshwork = contains mainly platelets and leukocytes and very few red blood cells = known as a white thrombus - associated with atherosclerosis
venous
- low vascular flow
- jelly-like red tail
- fibrin meshwork = contains mainly red blood cells
= known as a red thrombus
- can detach and forma emboli (deep vein thrombosis)
What are the two pathways of blood coagulation?
extrinsic = in vivo pathway
- some components in this pathway are from outside the blood
intrinsic - contact pathway
- all components in this pathway are from inside the blood
What is the extrinsic pathway of blood coagulation?
2 methods
- rupture of atherosclerotic plaque in artery
- adhesion, activation and aggregation of platelets
- secretion of preformed mediators (e.g. ADP) and synthesis of mediators (TXA2 and PAF)
- further aggregation of platelets
- thrombus formation
- rupture of atherosclerotic plaque in artery
- platelet acidic phospholipid exposure facilitates factor X activation (surface catalysis)
- active factor Xa activates factor II
- factor IIa converts soluble fibrinogen to soluble fibrin
- thrombus formation
What is the intrinsic pathway of blood coagulation?
- rupture of atherosclerotic plaque in artery
- activation of factor XI by factor XIIa (hageman factor)
- factor XI activates factor X
- factor Xa activates factor II
- factor IIa converts soluble fibrinogen to insoluble fibrin
- thrombus formation
What are the types of haemostatic drug therapy? What do they affect?
pro-haemostatic drug therapy
- used in haemophilia
- is an excessive anti-coagulant therapy
anti-haemostatic drug therapy
- are also known as anti-thrombotics
they affect: blood coagulation, platelet function and fibrin removal (fibrinolysis)
What are the different types of haemophilic caused by? What are their common causes?
haemophilia A
- caused by a lack of factor VIII (8)
haemophilia B
- caused by a lack of factor IX (9)
= Christmas factor
haemophilia C
- caused by a lack of factor XI (11)
= Rosenthal syndrome
causes
- liver disease, vitamin K deficiency (common in neonates), excessive oral anticoagulants
What are the different anti-coagulants?
heparin low molecular weight heparins - enoxaparin - dalteparin - synthetic pentasaccharide = fondaparinux
hirudin lepirudin argatroban melgatron/ximelagatron biralirudin
What is the mechanism of action of heparin?
target is the factors of the intrinsic/contact pathway
anti-thrombin III (AT III) inhibits thrombin (IIa) by binding to active serine
- anti-thrombin is a serine protease inhibitor
heparin binds to AT III and thrombin II and accelerates this rate of action
inhibits serine proteases
= factors IX, X, XI and XII
What is the mechanism of action of low molecular weight heparins (LMWHs)?
target is the factors of the intrinsic/contact pathway
mechanism of action is similar to heparin
- increase the action of AT III on factor Xa but not on factor IIa
= factor IIa is too large for lmwh to act on
inhibits serine proteases
= factors IX, X, XI and XII
What is the mechanism of action of hirudin? What is the mechanism of action of melagatran/ximelagatran?
hirudin
- is a direction thrombin (IIa) inhibitor
melagatran/ximelagatran
- is an orally active thrombin inhibitor
How does Vitamin K act?
acts as a cofactor for carboxylase enzymes
- catalyses the reaction of oxygen, carbon dioxide and glutamic acid residues to form gamma carboxyglutamic acid residues
hydroquinone (vitamin k reduced form) catalyses the reaction and is oxidised to epoxide (vitamin k oxidised form) in the process
vitamin k reductase reduces epoxide to quinone (vitamin k) then to hydroquinone to be used again
What is warfarin used for?
is an anti-coagulant = Vitamin K antagonist
- interferes with the gamma carboxylation of glutamic residues in factors II, VII, IX and X (glycoproteins)
has competitive inhibition with vitamin k due to their similarities in structure
- inhibits vitamin k reductase
Why do the effects of warfarin take several days to be seen?
occurs due to the degradation of preformed gamma carboxylated factors (factors II, VII, IX and X)
onset of action depends on the half life of the protein factor
- factor VII = 6 hours
- factor IX = 24 hours
- factor X = 40 hours
- factor II = 60 hours
