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
