Coagulation And Antiplatelets Flashcards
What is haemostasis and its role?
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.
What are the 4 main steps of primary haemostasis?
Vasospasm, platelet adhesion, platelet activation and platelet aggregation.
What happens in vasospasm?
Reflex vasoconstriction, loss of antithrombotic properties (less PGI2 and NO synthesised). Inhibition of fibrinolysis (less tPA production)
What happens in platelet adhesion?
Platelets adhere to exposed collagen (mediated by GP1a) and von Willebrand factor (mediated by GP1b).
What happens in platelet activation?
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.
What happens in platelet aggregation?
Fibrinogen binds to glycoprotein IIb/IIIa receptor on platelets, forms a direct bridge between platelets. Platelet plug formation at the site of injury.
What does ADP and Thromboxane do on the platelets?
Increase intracellular Ca+2.
Activate additional degranulation, increase expression of GPIIb/IIIa receptors and increases TxA2 production.
What is the process of secondary haemostasis?
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)
What is fibrinolysis?
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.
What is virchow’s triad of thrombosis?
Hypercoagulability of blood (cancer, inflammatory disease), Vessel wall injury (surgery, irritation, inflammation), Stasis of blood (immobility, varicose veins.
What are 3 differences between a white thrombus and red thrombus
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.
What is idiopathic thrombocytopenia purpura?
Autoimmune disorder characterized by abnormally low platelet levels. It can be shorter or longer than 6 months.
What are the different haemophilias?
Inherited: type A, factor VIII deficiency, Type B, Factor IX deficiency.
Acquired: Liver failure, Vit K deficiency, DIC
What are the uses of antiplatelet agents?
Prevent cerebrovascular incidents, prevent cardiovascular incidents
What is the MoA of Aspirin?
At low doses, it irreversibly inhibits COX-1, which inhibits TxA2 formation. And its inhibits platelets activation and recruitment to injury site.
What are 3 aspirin associated adverse effects?
Gastric irritant dyspepsia, nausea. (Take with meals, enteric coated tablets)
Hypersensitivity, bleeding and may precipitate gout.
What is the difference between thienopyridines and non-thienopyridines?
Thienopyridines antagonize receptor irreversibly. Non-thienopyridines do it reversibly.
What are some similarities and differences between clopidogrel and prasugrel?
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.
What are some indications of ADP-receptor antagonists?
Alternative in aspirin intolerance patients.
Secondary prevention for TIA, thromboembolic stroke.
What is the mechanism of dipyridamole?
Inhibits Phosphodiesterase 3 enzyme. This increases cAMP and decreases Ca+2. This is a coronary vasodilator and has weak antiplatelet activity.
What are the adverse effects of dipyridamole?
Headache, hypotension, dizziness, muscle pain, flushing.
What is the mechanism of action of eptifibatide and tirofiban?
Reversible GPIIb/IIIa antagonists, main adverse effects are bleeding and thrombocytopenia.
What is the mechanism of action of heparins?
Heparina bind to inactive antithrombin III and activates it. Binds to Factor Xa and thrombin and blocks its effect.
What is the significance in size between unfractionated and low molecular weight heparins?
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.
What are some indications and monitoring needed for heparins?
Treat DVT and pulmonary embolism. Treat ACS (unstable angina/Non-STEMI.
What needs monitoring is your activated partial thromboplastin time.
What is the adverse effects of unfractionated heparin?
Bleeding, thrombocytopenia, osteoporosis and fractures (long-term use)
What is heparin-induced thrombocytopenia?
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.
What is the reversal of heparin effects?
Stop heparin, administer protamine sulphate, closely monitor aPTT
What is rivaroxaban and apixaban’s mechanism of action and indications?
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.
What are some drug interactions of direct Factor Xa?
CYP3A4 Inducers and Inhibitors, P-glyprotein inducers/inhibitors.
What is dabigatran’s mechanism of action and indications?
Direct inibitor of thrombin. Prevents VTE after knee/hip replacement. Prevent and treat DVT, PE.
What are warfarin’s indications?
Prevent and manage venous thromboembolism.
What is warfarin’s mechanism of action?
Warfarin is a vitamin K antagonist. It reduces vitamin-K mediated hepatic synthesis of clotting factors (II,VII,IX and X)
How should the international normalised ratio be measured?
Measure at baseline, then alternate days for 2 weeks, then weekly for 2 weeks, then twice weekly for 1 month then monthly.
