Blood Clotting Flashcards
Why interfere with blood clotting?
The thrombin-fibrin clot can cause complications such as venous thrombosis, myocardial infarction, cerebral artery occlusion, peripheral artery thrombosis.
How do clots form?
Damaged endothelium reveals underlying collagen and other proteins. Platelets aggregate and adhere to surface it form a temporary seal. Blood clotting factors from strong, durable thrombin-fibrin clots.
How to prevent and treat thrombosis?
Agents that deplete functional clotting factors
- warfarin, heparin, direct enzyme inhibitors such as dabigatrin and rivaroxaban
Agents that accelerate clot lysis
- tissue plasminogen activator
Antiplatelet drugs
- aspirin, clopidogrel
What is warfarin?
A drug that prevents clotting factor synthesis by inhibiting vitamin K recycling from KO (inactive) to KH2 (active).
Vitamin K is a cofactors for post-translational carboxylate on of glutamic acid group on factors II, VII, IX and X.
Uses and adverse effects of warfarin?
Uses:
Prevents thromboses from extending. Oral administration so it can be used in the long term.
Adverse effects:
Risk of bleeding, coagulation needs regular monitoring.
Teratogenic, can’t be used in pregnancy
What is heparin?
Strong acid, mixture of glycosaminoglycans.
Causes the inactivation of Xa and thrombin.
What is the mechanism of action of heparin?
Binds to lysine on antithrombin III
Conformational change to ATIII
increases affinity for activated factors of intrinsic arm, esp Xa and thrombin.
Accelerated inactivation of these
Prevents conversion of fibrinogen to fibrin
Stops clot propagation
What are the uses and adverse effects of heparin?
Uses: Venous and arterial thrombosis Given parenterally. Can only be given as injection. Rapid coagulation Not teratogenic in pregnancy Adverse effects: Bleeding
What is dabigatrin?
Direct enzyme inhibitor of thrombin (IIa)
What is rivaroxaban?
Direct enzyme inhibitor of thrombin for factor Xa
What is tissue plasminogen activator (t-PA)?
Promotes clot lysis. Recombinant human protein IV administration Immediate onset of action Relieves blockage of critical vessels e.g. Coronary artery occlusion.
Explain how aspirin impairs the function of blood platelets?
Aspirin is an anti platelet drug.
At low levels of aspirin, it has inhibited platelet TXA2 synthesis by irreversible acetylation of a serine residue at the active site of cycloxygenase I (COX-1). The permanent loss of TXA2 production causes defective platelet clot formation as it affects the platelet aggregation and adhesion. Thus protection from thrombotic disorders.
What is clopidogrel?
Clopidogrel is an oral, antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. The drug works by irreversibly inhibiting a receptor, an adenosine diphosphate (ADP) chemoreceptor on platelet cell membranes.
Clopidogrels active metabolite blocks platelet ADP receptors irreversibly.
Adverse effects include hemorrhage, severe neutropenia, and thrombotic complications.
