Lecture 2: Haemostasis Flashcards
what do endothelial cells do
- when intact, prevents clots
- when injured, promotes local clotting
- signals inflammatory cells to areas needing defence / repair
what is haemostasis
- stopping bleeding
- clotting and stopping blood from escaping
- first stage of wound healing
what are the platelet based pathways to repair blood vessels
- platelet adhesion
- platelet activation
- platelet aggregation
what are the non platelet based pathways of haemostasis
- enzyme cascade of coagulation
- vasoconstriction
what are the vasoconstrictors released by platelets
- serotonin
- ADP
- thromboxane A2
where are megakaryocytes found
bone marrow
what is low platelet count called
thrombocytopaenia
what happens during platelet activation
- platelets exocytose serotonin, ADP and calcium
- increase respiratory rate
- change shape to have protruding pseudopodia
what do platelets adhere to
exposed collagen
what is aggregation stimulated by
ADP
what is aggregation blocked by
Prasugrel
how do platelets aggregate
via fibrinogen
which clotting factors are not enzymes
factor V and VIII, as they are cofactors
what is an example of a thrombus
atrial fibrillation leads to thrombosis which leads to a stroke
what are examples of anticoagulants
- heparin
- citrate
what is serum and how is it different to plasma
- fluid left in blood after clotting
- lacks fibrinogen, clotting factors II, V and VIII
what does the extrinsic pathway of coagulation do and require
- requires secretion of tissue factor
- initiates coagulation
what does the intrinsic pathway of coagulation do
- all factors / proenzymes are already in place
- amplifies process through positive feedback
which factors activate thrombin
- factor Xa poorly activates it
- factor Va and Xa together activate thrombin well
what are the pathways to activate factor X
- extrinsic Xase enzyme
- intrinsic Xase enzyme
- thrombin through positive feedback
what is extrinsic Xase
tissue factor + factor VIIa
what is intrinsic Xase
factor VIIIa + IXa
which factors does thrombin activate
- factor VIII
- factor V
where are clotting factors made
liver
what is vitamin K
- a class of related fat-soluble vitamins
- is required to synthesise prothrombin (II), VII, IX and X
- essential for gamma carboxylation of clotting enzymes
what is plasmin
- lyses fibrin to stop or destroy clots
- starts as inactive plasminogen (made by liver)
- requires tissue plasminogen activator on endothelial cells to mature
what is protein C
- coagulation inhibitor
- works with cofactor protein S to inactivate Va
- inactivates factor VIIIa
- activated on surface of endothelial cells
what is antithrombin II
- works with heparin
- blocks activity of thrombin, Xa and IXa
what reverses the effects of heparin
protamine sulfate
what is haemophilia A caused by
- congenital lack of factor VIII
- X-linked so only males have symptoms
what is haemophilia B caused by
- genetic defect in factor IX
- also called christmas disease
what are symptoms of haemophilia A and B
- affects larger blood vessels in joints and muscles
- wounds that bleed for days
what are pharmalogical controls of blood clotting
- anti-platelet agents generally for arterial disease
- anti-coagulants generally for venous disease
- fibrinolytics generally to dissolve fibrin in arterial disease
what is aspirin
- anti-platelet agent
- blocks formation of thromboxane A2 in platelets
- lengthens bleeding time without lengthening coagulation time
- used after myocardial infarction
what are anticoagulant drugs and how do they work
- heparins inhibit factor Xa
- dabigatran inhibits thrombin
- rivaroxaban inhibits factor Xa
- warfarin is a vitamin K antagonist
examples of fibrinolytics
- tissue plasminogen activator
- streptokinase
- urokinase
