T Flashcards
Function of hemostasis
Limit blood loss
Define thrombosis
Formation of blood clot inside the vessel
Endothelium has a non-thrombogenic surface
If this is intact, it generates prostaglandin and nitric oxide which inhibits platelet aggregation
When endothelium is damaged, sub-endothelial collagen is exposed and platelets will adhere to this - this will activate the platelets
The platelets will begin to Aggregate
Platelets release agents which promote vasoconstriction and platelet aggergation
Then fibrin will form through enzymatic reaction, these get meshed within the platelet plug, which stops the flow
Haemostatic plug is dissolved by fibrinolytic system
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“Blood clot” slide
Shows EMG of RBC in fibrin mesh
Calcium is required for clotting
Calcium chelators can be used to prevent clotting
Thrombin acts on
Fibrinogen to form fibrin
Extrinsic factor = the Easy pathway
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Blood clotting disorders
Learn
Fibrinolytic system stops the clotting cascade overrunning
Plans in breaks down fibrin polymers
Venous thrombosis vs arterial thrombosis
Problem with venous thrombosis - can break off and enter pulmonary circulation
Anticoagulants are involved in vitro storage of blood, as well as in vivo
Heparin - is polyanionic (has lots of negative charges)
Calcium chelators and heparin are main anticoagulants in vitro
EDTA is a chelator
In vivo use of anticoagulants
Heparin - given intravenously Warfarin - given orally
Heparin binds to antithrombin 3
Heparin antithrombin 3 complex binds to various clotting factors, inhibiting clotting cascade
Low MW heparin works differently from heparin
Binds factor 10a
LMWH does not inactive thrombin, but Unfractionated heparin does
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Side effects of heparin
Allergic reactions Haemorrhage Heparin induced thrombocytopenia (reduced platelet level, therefore platelet plug less likely to form)
Main oral anticoagulant is Warfarin - a structural analogue of vitamin K
Blocks synthesis of coagulation factors in the liver
Vitamin K required for caboxylation of certain clotting factors
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S warfarin and R warfarin
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Warfarin ends up bound to plasma albumin, other drugs can displace warfarin from binding sites on albumin
Example is aspirin
NSAIDs and warfarin don’t mix
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New oral anticoagulants
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Aspirin irreversibly inhibits COX enzymes
Acetylation
Clopidogrel
Blocks platelet ADP receptors
Abciximab - MAB
Only used once??