treatment of thrombosis Flashcards
what are the three processes that occur to limit blood loss after BV damage?
- vasoconstriction
- platelet adherence and aggregation to plug hole
- blood coagulation to lay down fibrin in the hole and providing a scaffold for repair
what is a red thrombus?
the occlusion of veins by fibrin
what is a white thrombus?
the occlusion of an artery by platelet aggregation
fast flow deters fibrin deposition
what activates the intrinsic pathway of the blood coagulation cascade?
atherosclerosis via suface contact activating factor XII
what activates the extrinsic pathway of the blood coagulation cascade?
when factors are introduced into circulation, those factors come from damaged cells, those activate factor VII
what are the factors that promote coagulation (that can be deficient)
factor VIII (type A haemophilia) factor IX: type B haemophilia Vitamin K: this is required for the carboxylation of glutamic acid residues
what are the endogenous anti-coagulants?
thrombomodulin:
- inhibits factor II,V and VII
- prevents coagulation in the extrinsic pathway and the common pathway
anti-thrombin III:
- inhibit thrombin, by stimulating factors that inhibit thrombin
- inhibits all activated factors of intrinsic pathway and factor X
- does not affect extrinsic pathway
heparin co-factor II:
- inhibits activated thrombin
how does heparin work?
combines with and accelerates the action of anti-thrombin III
- increases rate of complex formation - so that thrombin inactivation is almost instantaneous
- inactivates IIa, Xa, IXa and XIIa
- pro-thrombin III must be present for heparin to work
how is heparin administered?
onset?
when is it used?
duration?
heparin can be administered SC or IV (but IV is preferred)
has immediate onset
low dose heparin is used pre-operatively to reduce risk of deep vein thrombosis
works for 2-4 hours
what is the antagonist of heparin?
protamine sulphate
what is a major problem of using heparin? alternatives?
heparin sensitisation/resistance is a problem. so substitute compounds are used instead (e.g. dalteparin/ this has a longer duration of action)
other alternatives: - hirudin blocks factor II - danapiroid blocks factor X - ancrod causes fibrinolysis
how does warfarin work?
interfere with the reduction of vitamin K
- prevents the gamma carboxylation of factor II, VII, IX and X
- if those factors are not carboxylated they become non-functional
how is warfarin different to heparin
heparin increases the rate of a physiological process
warfarin inhibits the reduction of vitamin K
heparin is given IV warfarin is given orally
also warfarin is inactive in vitro will heparin is
warfarin has a half life of 40 hours, while heparin has a duration of action of 2-4 hours
rate of onset of warfarin s much longer than for heparin
what are the main dangers of using warfarin?
main hazard is bleeding, but can be treated with vitamin K
- the vitamin K is given IV
- but no response is illicited until new factors are synthesised
- haemorrhage may require immediate treatment by whole blood transfusions
explain the reason behind the rate of onset of warfarin? how do clinicians deal with this?
how can the rate of onset by altered?
the rate of onset of warfain depends on the half life of the factors (because it can only prevent carboxylation of the factors, it does NOT decarboxylate)
- the half life of factors X and II is 40 and 60 hours
- meaning for warfarin to decrease the efficacy of the clotting cascade (some of the carboxylated clotting factors must be reduced)
therefore, if an immediate effect is required heparin is given in addition to warfarin
the rate of onset of warfarin can be quicker in patients with fever of hyperthyroidism
