Oct 22: Warfarin, heparins, LMWH, heparinoids, direct thrombin inhibitors
Oct 29: How the coagulation system works
Nov 5: Anti-platelet agents
Bhatt, D.(2018). Advances in atherosclerosis, atrial fibrillation, and valvular disease. Nature Reviews Cardiology 15(2), 71-72. https://dx.doi.org/10.1038/nrcardio.2017.212
Platelets
Hemostasis
Engelmann, B., Massberg, S.(2013). Thrombosis as an intravascular effector of innate immunityNature Reviews Immunology 13(1), 34-45. https://dx.doi.org/10.1038/nri3345
McFadyen, J., Schaff, M., Peter, K.(2018). Current and future antiplatelet therapies: emphasis on preserving haemostasisNature Reviews Cardiology 15(3), 181-191. https://dx.doi.org/10.1038/nrcardio.2017.206
Meijden, P., Heemskerk, J.(2018). Platelet biology and functions: new concepts and clinical perspectivesNature Reviews Cardiology 16(3), 1. https://dx.doi.org/10.1038/s41569-018-0110-0
Strong activators
Thrombin *activates the core of the platelets*
Activated by:
PAR-1(Receptor) [Vorapaxar (antagonist)]
PAR-4 (Receptor)
Collagen *bear integrins e.g. GPIa/IIa and GPVIa that interact with platelets*
Weak activators:
ADP *acts on loosely packed platelets*
Binds GPcR:
P2Y1: Ca mobilization, platelet shape change, reversible aggregation
P2Y12: Platelet secretion and stable aggregation e.g. [Thienopyridine (antagonist)]
Platelet aggregation --> more ADP release --> more aggregation
Epinephrine
McFadyen, J., Schaff, M., Peter, K.(2018). Current and future antiplatelet therapies: emphasis on preserving haemostasisNature Reviews Cardiology 15(3), 181-191. https://dx.doi.org/10.1038/nrcardio.2017.206
Borissoff, J.I., Spronk, H.M. and ten Cate, H., 2011. The hemostatic system as a modulator of atherosclerosis. New England Journal of Medicine, 364(18), pp.1746-1760.
CLOTTING CASCADE
Melnikova, I.(2009). The anticoagulants marketNature Reviews Drug Discovery 8(5), 353-353. https://dx.doi.org/10.1038/nrd2851
FACTOR X
PROTHROMBIN --> THROMBIN
FIBRINOGEN --> FIBRIN