Coagulation And Antiplatelets

Question 1

What is haemostasis and its role?

Answer 1

It facilitates repair of vascular injury, maintains blood fluidity, limits blood loss and prevents vessel occlusion. Primary haemostasis is for platelet plug formation, while secondary heamostasis is for the stabilisation of the clot.

Question 2

What are the 4 main steps of primary haemostasis?

Answer 2

Vasospasm, platelet adhesion, platelet activation and platelet aggregation.

Question 3

What happens in vasospasm?

Answer 3

Reflex vasoconstriction, loss of antithrombotic properties (less PGI2 and NO synthesised). Inhibition of fibrinolysis (less tPA production)

Question 4

What happens in platelet adhesion?

Answer 4

Platelets adhere to exposed collagen (mediated by GP1a) and von Willebrand factor (mediated by GP1b).

Question 5

What happens in platelet activation?

Answer 5

ADP induces platelet aggregation, thromboxane stimulates platelet activation and vasoconstriction, serotonin stimulate platelet aggregation and vasoconstriction. Also the expression of glycoprotein IIb-IIIa receptor on the platelets.

Question 6

What happens in platelet aggregation?

Answer 6

Fibrinogen binds to glycoprotein IIb/IIIa receptor on platelets, forms a direct bridge between platelets. Platelet plug formation at the site of injury.

Question 7

What does ADP and Thromboxane do on the platelets?

Answer 7

Increase intracellular Ca+2.

Activate additional degranulation, increase expression of GPIIb/IIIa receptors and increases TxA2 production.

Question 8

What is the process of secondary haemostasis?

Answer 8

Extrinsic pathway: Factor 3 (Tissue factor), Factor 7, then Factor 10

Intrinsic pathway: Factor 12, 11, 9, 8 then Factor 10.

Common pathway Factor 5, 2(Thrombin), 1(Fibrinogen)

Question 9

What is fibrinolysis?

Answer 9

Natural breakdown of fibrin within clots, activated by the presence of fibrin. Tissue plasminogen activator released from endothelial cells. Plasmin breaks down plasmin into fibrin and fibrinogen degradation products.

Question 10

What is virchow’s triad of thrombosis?

Answer 10

Hypercoagulability of blood (cancer, inflammatory disease), Vessel wall injury (surgery, irritation, inflammation), Stasis of blood (immobility, varicose veins.

Question 11

What are 3 differences between a white thrombus and red thrombus

Answer 11

Arterial thrombus: Moves in direction of flow of blood, forms in high pressure arteries, results from endothelial cell injury.

Venous thrombus: moves in the direction of the heart, venous stasis, tail breaks off easily to form an emboli. More RBC’s and fewer platelets.

Question 12

What is idiopathic thrombocytopenia purpura?

Answer 12

Autoimmune disorder characterized by abnormally low platelet levels. It can be shorter or longer than 6 months.

Question 13

What are the different haemophilias?

Answer 13

Inherited: type A, factor VIII deficiency, Type B, Factor IX deficiency.

Acquired: Liver failure, Vit K deficiency, DIC

Question 14

What are the uses of antiplatelet agents?

Answer 14

Prevent cerebrovascular incidents, prevent cardiovascular incidents

Question 15

What is the MoA of Aspirin?

Answer 15

At low doses, it irreversibly inhibits COX-1, which inhibits TxA2 formation. And its inhibits platelets activation and recruitment to injury site.

Question 16

What are 3 aspirin associated adverse effects?

Answer 16

Gastric irritant dyspepsia, nausea. (Take with meals, enteric coated tablets)
Hypersensitivity, bleeding and may precipitate gout.

Question 17

What is the difference between thienopyridines and non-thienopyridines?

Answer 17

Thienopyridines antagonize receptor irreversibly. Non-thienopyridines do it reversibly.

Question 18

What are some similarities and differences between clopidogrel and prasugrel?

Answer 18

Similarities: both prodrugs and both bind irreversibly.

Differences: C: Oral, slow onset, needs CYP2C19 for activation.
P: Parenteral, rapid onset, CYP3A4 and CYP2B6. Greater risk for bleeding.

Question 19

What are some indications of ADP-receptor antagonists?

Answer 19

Alternative in aspirin intolerance patients.
Secondary prevention for TIA, thromboembolic stroke.

Question 20

What is the mechanism of dipyridamole?

Answer 20

Inhibits Phosphodiesterase 3 enzyme. This increases cAMP and decreases Ca+2. This is a coronary vasodilator and has weak antiplatelet activity.

Question 21

What are the adverse effects of dipyridamole?

Answer 21

Headache, hypotension, dizziness, muscle pain, flushing.

Question 22

What is the mechanism of action of eptifibatide and tirofiban?

Answer 22

Reversible GPIIb/IIIa antagonists, main adverse effects are bleeding and thrombocytopenia.

Question 23

What is the mechanism of action of heparins?

Answer 23

Heparina bind to inactive antithrombin III and activates it. Binds to Factor Xa and thrombin and blocks its effect.

Question 24

What is the significance in size between unfractionated and low molecular weight heparins?

Answer 24

UFH: Because of its larger size, it has similar antithrombin and anti-factor Xa activity. LMWH is too short to bridge to thrombin and antithrombin. Has greater activity for anti-factor Xa activity.

Question 25

What are some indications and monitoring needed for heparins?

Answer 25

Treat DVT and pulmonary embolism. Treat ACS (unstable angina/Non-STEMI.

What needs monitoring is your activated partial thromboplastin time.

Question 26

What is the adverse effects of unfractionated heparin?

Answer 26

Bleeding, thrombocytopenia, osteoporosis and fractures (long-term use)

Question 27

What is heparin-induced thrombocytopenia?

Answer 27

Platelet factor 4 complexes with heparin, antibodies form against PF4-heparin complex (immune response). IgG-PF4-heparin complex binds to platelets and activates platelets. Patient goes into a hypercoagulability state.

Question 28

What is the reversal of heparin effects?

Answer 28

Stop heparin, administer protamine sulphate, closely monitor aPTT

Question 29

What is rivaroxaban and apixaban’s mechanism of action and indications?

Answer 29

Directly binds factor Xa, does not require AT to exert its effects. Its indicated to prevent VTE after knee/hip surgery, prevent stroke, treat DVT, PE.

Question 30

What are some drug interactions of direct Factor Xa?

Answer 30

CYP3A4 Inducers and Inhibitors, P-glyprotein inducers/inhibitors.

Question 31

What is dabigatran’s mechanism of action and indications?

Answer 31

Direct inibitor of thrombin. Prevents VTE after knee/hip replacement. Prevent and treat DVT, PE.

Question 32

What are warfarin’s indications?

Answer 32

Prevent and manage venous thromboembolism.

Question 33

What is warfarin’s mechanism of action?

Answer 33

Warfarin is a vitamin K antagonist. It reduces vitamin-K mediated hepatic synthesis of clotting factors (II,VII,IX and X)

Question 34

How should the international normalised ratio be measured?

Answer 34

Measure at baseline, then alternate days for 2 weeks, then weekly for 2 weeks, then twice weekly for 1 month then monthly.