Ting Hemostasis and Thrombosisis

What is the immediate hemostatic response to to damaged vessel?

What is the immediate hemostatic response to to damaged vessel?

Vasospasm

→Smooth muscle of the blood vessel wall tightens to stop bleeding Then platelets come

Platelet Sticking to exposed damaged blood vessel collagen

what happens when platelets encounter the site of blood vessel injury where collagen is exposed?

Platelet Adhesion

→Platelets stick to the exposed collagen of a damaged vessel

→ Usually, platelets float freely but when blood vessels are damaged they stick to exposed collagen and after they aggregate to form t a blood clot

Synthesized within platelets; promotes thrombogenesis and vasoconstriction

What is the compound made by platelets that encourage both the creation of blood clots and the narrowing of blood vessels?

Thromboxane A2

→Released when they become activated

1)Promotes platelet aggregation 

2)Causes vasoconstriction

Which glycoprotein is involved in platelet aggregation by binding to free fibrinogen?

GPIIb/IIIa →Fibrinogen bridges adjacent platelets →This glycoprotein binds fibrinogen to promote aggregation

Which receptor is responsible for the action of ADP on platelets?

P2Y1

→Receptor on the surface of platelets that binds to ADP

→ADP is like a rally cry (theatre director) for platelets, getting them ready andhelping them to work together to form a clot

What order is right for activation of the intrinsic pathway?

What is the correct sequence of factor activation in the intrinsic pathway of blood clotting

XII → XI → IX → VIII

12→11→9→8

→This pathway is one of the ways your body can start the process of forming a blood clot, involving a cascade of these factors to eventually lead to the formation of a stable clot.

Mechanism of action of Aspirin

Inhibits COX Enzyme which inhibits thromboxane A2 synthesis

→Thromboxane A2 is a substance that encourages platelets to clump together 

SO aspirin prevents clots

What is the effect of Aspirin on the synthesis of prostaglandins?

Reduces synthesis of all prostaglandins

→Prostaglandins are involved in inflammation, pain, and fever

Mechanism of action for clopidogrel?

The active metabolite of clopidogrel binds to the platelet ADP receptors 

→ADP promotes clots so clopidogrel prevents clots

Clopidogrel is a prodrug that is converted to its active metabolite by what enzyme?

CYP2C19

Abciximab is a monoclonal antibody fragment that inhibits platelet aggregation by binding to

Glycoprotein llb/lla receptor IRREVERSIBLY

→Those glycoproteins bind fibrinogen to promote aggregations

SO abciximab prevents clots

What is a cyclic heptapeptide that acts and a competitive inhibitor of the glycoprotein llb/lla receptor?

Eptifibatide

→ Binds COMPETITIVELY and is REVERSIBLE

Vorapaxar and Atopaxar target which receptor to exert their antiplatelet effect?

Protease-activated receptor (PAR-1)

→PAR-1 is activated by thrombin and leads to clots

Dipyridamole MOA

Inhibits PDE which increases cAMP to inhibit platelet activation and aggregation

→cAMP reduces platelet activation, and PDE breaks down cAMP

What drug has the most efficiency in catalyzing the inactivation of thrombin

Unfractionated Heparin (UFH)

→ most potent at inactivating thrombin (thrombin leads to clots)

How does protamine sulfate work to counteract the effects of heparin?

Protamine ionically binds to heparin

→Protamine is positively charged and heparin is negatively charged

What is the mechanism by which heparin-induced thrombocytopenia (HIT) occurs

Formation of heparin-platelet Factor 4 (PF4) complex that triggers antibody production, leading to platelet production in the bone marrow by heparin

→ HIT occurs when he body creates an immune response against a complex formed between heparin and Platelet Factor 4 (PF4) which leads to clots

Direct thrombin inhibitors

Dabigatran, Argatroban, Lepirudin

Warfarin inhibits the recycling of vitamin K by targeting which enzyme, leading to decreased synthesis of clotting factors?

Warfarin's anticoagulant effect is due to its action on which enzyme involved in vitamin K recycling?

Vitamine K Epoxide Reductase Complex (VKORC1)

→VKORC1 recycles vitamin K which causes clots so by inhibiting it we prevent clots

The anti-coag effect of warfarin results from its impact on the synthesis of which clotting factors?

II, VII, IX, X

2, 7, 9, 10

→These are Vitamin K dependent clotting factors

What is the MOA of direct Factor Xa inhibitors?

Directly Bind & Inhibit Factor Xa, preventing the conversion of prothrombin to thrombin

→ Factor XA catalyzes conversion of prothrombin to thrombin which causes clotting

How does streptokinase aid in fibrinolysis

Forming a complex with plasminogen, leading to the conversion of plasminogen to plasmin

→Fibrin holds clots together and plasmin breaks fibrin which breaks the clots