Haemostasis Flashcards
Define haemostasis
The endogenous process of stopping blood loss from damaged vessels and protecting against haemorrhage.
Is it vasoconstriction or vasodilation involved in haemostasis?
Vasoconstriction
Which is more solid, a platelet plug or clot?
Clot. Reinforced platelet plug with collagen and fibrin
Define thrombosis
Haemostasis in the wrong place. Formation of platelet plug / clot in the absense of vessel damage
Compare thrombus and embolus
Thrombus = clot that forms in the vessel and stays there Embolus = clot forms elsewhere in the body and travels to a vessel where it then gdts stuck and blocks blood flow
Define fibrinolysis
The break down of a clot
Compare red and white clots
Red = venous. Made mostly of erythrocytes White = arterial, made mostly of platelets
Thromboxane A2 is prothrombotic. True or false
True
Prothrombotic factors prevent the formation of clots. True or false?
False
Prostacyclin and nitric oxide are both ..?
Antithrombotic
Vessel injury causes exposed collagen. The collagen then activates platelets. Name 2 molecules that activated platelets release?
ADP and thromboxane A2
Do ADP and thromboxane activate platelets or prevent activation?
Activate. They attract more platelets to the site
The release of activated platelets is a positive feedback cycle resuLting in the formation of…?
The platelet plug
What prevents the platelet plug from continuing to grow and cover the non-injured area of the vessel?
The non-injured endothelium releases nitric oxide and prostacyclin which inhibit further platelet aggregation.
Aspirin prevents the platelets from releasing thromboxane by inhibiting which enzyme?
COX 1
COX 1 is the enzyme that turns arachidonic acid into PGG2. PGG2 is then turned in to which two molecules?
Thromboxane and prostacyclin
P2Y receptors are located where?
On platelets
Once activated by ADP, what effect do thr P2Y receptors have?
They release COX and also activate the GPIIb receptors
What do the GPIIb receptors do?
Once activated, these receptors join two platelets together via fibrinogen. Therefore, they cause platelet aggregation
MOA of clopidrogrel?
Prevents ADP from binding to P2Y receptors which prevents platelet aggregation
Abciximab and tirofiban are two drugs with which antiplatelet mechanism?
They prevent GPIIb receptor activation which prevents platelet aggregation
Aspirin inhibits the production of both thromboxane and prostacyclin. True or false?
True. However inhibition of prostacyclin is reversible, but thromboxane is not.
Name an ADP antagonist
Clopidogrel
Can clopidogrel or ticlopidine be used in cojunction with aspirin?
Yes
Finrinogen cross-linking occurs at which receptor?
GPIIb
Which drug class do abiciximab and tirofiban belong to?
GPIIb inhibitors
What reaction does Factor X facilitate?
Turns prothrombin into thrombin
What does thrombin do?
Turns fibrinogen (soluble) into fibrin (insoluble)
Thrombin activates clotting factor XIII. What role does this factor have?
It stabilises the fibrin network of the clot
Name a direct thrombin inhibitor and what action it has
Dabigatran. Stops thrombin from turning fibrinogen into fibrin
MOA of rivaroxaban?
Blocks factor Xa (which therefore blocks conversion of prothrombin into thrombin)
Anti-thrombin inactivates factor Xa. What drug enhances anti-thrombin?
Heparin
How does heparin enhance anti-thrombin’s inhibition of thrombin?
Due to heparin’s large size, it forms a complex with AT amd thrombin
Name a low molecular weight heparin
Enoxaparin
Antidote to heparin?
Protamine sulphate. Forms a complex with heparin and inactivates it.
Explain the role of vitamin K
Promotes the synthesis of vitamin K dependent clotting factors ( II, VII, IX, X)
Warfarin MOA?
Vitamin K antagonist. It competes with vitamin K for binding to vitamin K reductase
Why does it take around 48 hours for warfarin to reach peak effect?
It immediatelt blocks vitamin K reductase, but the body needs to use up the existing vitamin K for production of clotting factors. Once all the vitamin K stores are used up, then the effects of warfarin are apparent.
Why does warfarin have so mant drug interactions?
Because it is heavily bound to albumin. Therefore, competes for binding with other drugs that bind to albumin
Storage form of thrombin?
Prothrombin
How do fibrinolytic drugs work?
They convert plasminogen into plasmin, which breaks down fibrin, fibrinogen and some of the clotting factors
Example of fibrinolytic drugs?
Urokinase, alteplase, anistresplase
