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79 Cards in this Set
- Front
- Back
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what is hemostasis |
prevention of bleeding due to vessel damage |
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what three components lead to hemostasis |
formation of platelet plug to block hole formation of fibrin clot from proteins present in plasma reinforcing plug (fibrinogen and platelets) contraction of blood vessels to limit blood flow |
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what drugs are used to reduce clotting |
anticoagulants antiplatelet thrombolytics |
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what drugs are used to facilitate clotting |
replacement factors plasminogen inhibitors |
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what is a thrombosis |
unwanted hemostatic plug in blood vessel or heart |
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what does a thrombus consist of in the venous circulation |
predominantly fibrin |
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what does a venous thrombus associate with |
blood flow stasis |
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what does an arterial thrombus predominantly consist of |
platelets |
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what is an arterial thrombus assoc with |
atherosclerosis |
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what does thrombosis cause |
ischaemia tissue infarction |
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what is used to treat a thrombus |
anticoagulants |
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what is used to treat ischaemic tissue infarction |
antiplatelet |
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what causes deep vein thrombosis |
immobile for long time so blood clots due to slower blood flow |
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what causes a PE |
clot dislodged and travels to lungs |
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what happens in blood coagulation |
conversion of fluid blood to solid gel or clot conversion of soluble fibrinogen to fibrin |
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when is the intrinsic coagulation pathway activated |
contact with exposed collagen |
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when is the extrinsic coag pathway activated |
upon tissue damage causing release of tissue factor, VIIa, phospholipid and Ca |
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outline the extrinsic pathway |
tissue damage leads to activation of X to Xa |
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outline the intrinsic pathway |
contact with collagen leads to activation of XII which activates XI which activates IX which activates X in presence of VIIIa phospholipid and Ca |
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how does Xa lead to stabilised fibrin |
activates prothrombin to thrombin in presence of Va phospholipid and Ca thrombin acivates fibrinogen to form fibrin and XIII to form XIIIa in presence of Ca XIIIa catalyses fibrin to form stabilised fibrin |
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how are the inactive precursors of the clotting cascade activated |
proteolysis |
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what is PL provided by in clotting cascade |
activated platelets |
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what allows tissue factors to bind to platelets |
gamma-carboxyglutamic acid residues on tissue factors |
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outline tissue factor activation |
platelet finds area of cell damage and activates Va sits on surface -ve charge on platelet allows ca to bind TF bind to Ca by y-carboxyglutamic acid residues proteolytic cleavage of factor X to Xa Xa activates II thrombin stabilises fibrin |
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why do factors need to be carboxylated |
otherwise cannot be bound to platelets |
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what factors are carboxylated in the liver |
II VII IX and X
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outline carboxylation of TF |
when made have glutamic acid residue cyclic reaction of vit K from quinone to hydroquinone to epoxide and then again catalysed by Vit K reductase provides material required |
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name an oral coagulant |
warfarin |
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what does warfarin do |
inhibits Vit K reductase hence inhibiting carboxylation of tissue factors VII II IX and X so cannot interact with platelets |
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how is warfarin administered |
orally |
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what does the rate of onset of warfarin depend on |
factor haldf life |
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where is warfarin metabolised |
liver |
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how do you measure the action of warfarin |
prothrombin time |
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what is the prothrombin time |
clotting time of plasma from patient following addition of ca/thromboplastin |
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what is PT expressed as |
ratio of clotting time compared with healthy subjects or international normalized ratio |
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what are the INR value for prophylaxis of DVT |
2-2.5 |
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what are INR value for treatment of DVP/PE |
2.5 |
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what is the INR value for recurrent DVT / PE |
3.5 |
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how is INR determined |
initially daily then at longer intervals then every 12 weeks |
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what is warfarin potentiated by |
drugs which displace it from plasma proteins, which interfere with liver function, with platelet function and liver disease and decreased vit K availability |
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what drugs displace warfarin from plasma proteins q |
aspirin |
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what drugs interfere with liver funvtoin |
sulphonamides |
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what drugs interfere with platelet functions |
NSAIDs |
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why is warfarin potentiated by liver disease |
decreases factor production and warfarin clearance |
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what are warfarin actions decreased by |
drugs which induce metabolising enzymes promoted clotting factor synthesis reduced warfarin adsorption |
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what drugs induce metabolising enzymes |
barbituates |
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what drugs promote clotting factor syntheesis |
vit K |
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what drugs reduce warfarin adsorption |
colestipol |
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what are the side effects of warfarin |
bowel or brain haemorrhage teratogenic contraindicated in pregnancy |
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if theres major bleeding after warfarin what do you do |
stop warfarin give vit K and replacement tissue factors |
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if the INR>8 what do you do |
stop warfarin until 5 give vit K |
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if INR is 6-8 what do you do |
stop warfarin until 5 |
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name an injectable anticoagulant |
heparin or LMW heparin |
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what family is heparin part of |
glycosaminoglycan proteins |
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what is the mechanism of heparin |
binds and activates antithrombin III both undergo conformational changes then bind to IIa so it removes IIa and ATIII from blood stream |
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what does ATIII do |
inhibits IIa |
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where is heparin more potent |
at IIa than Xa |
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what is the difference between heparin and LMW |
LMW cannot inhibit IIa but can inhibit Xa |
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how is heparin administered |
IV or SC or in vitro to clear blocked IV catheter |
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what are the limitations of heparin |
activity modified by IV released from platelets-inhibition if factor Xa already bound to fibrin cannot interact with ATIII/heparin complex |
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why can heparin not be administered orally |
charge and large size mean not absorbed in gut |
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what is heparins initial rapid removal due to |
binding to endo/macrophage cells |
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what is heparins slower removal due to |
renal excretion |
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why does LMW have simpler kinetics |
heparin binds to plasma proteins LMW does not |
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what is heparins onset of action |
immediate if IVq |
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what is the disad of LMW |
only acts on X |
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what is the ad of LMw |
not neutralised by IV can administer SC less complex pharmacokinetics |
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what are examples of heparin drugs |
heparin calciparine minihep monoparin |
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what are examples of LMW heparin drugs |
certoparin dalterparin enoxaparin |
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how does hirudin work |
inhibts thrombin by binding to active site |
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what is hirugen |
synthetic peptide derived from hirudin |
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what is bivalirudin |
derivative of hirugen |
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what are the effects of bivalirudin |
potent arterial and venous antithrombotic with fewer bleeding problems |
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what did clinical trials of bivalirudin show |
no greater efficacy over pre existing therapies |
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where may bivalirudin be used for |
patients with heparin antibody production |
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what is bivalirudin used for now |
percutaneous cornoary intervention due to rapid on off effects |
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what is heparin used for |
acute therapy |
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what is warfarin used for |
long term therapy |
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what are heparin and warfarin used for |
prevention of pre op DVT treatment of DVT prevention of PE prevention of thrombosis on prosthetic heart valves |
