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Question
What are the different anticoagulative functions of aspirin, coumarin, heparin, EDTA, and citrate? Which is most effective for test-tube (in vitro) anticoagulation? Which is most effective for in vivo anticoagulation?
Relevance to lecture
Intrinsic and Extrinsic Pathways for blood clotting homeostasis Vasoconstriction Temporary blockage of rupture by platelet plug Blood clotting to seal the hole until tissue repair
Hemostasis: 3 Processes
1. Damage to blood vessel wall causes VASOSPASM 2. PLATELET PLUG FORMATION 3. 2 possible CLOTTING pathways: A. Intrinsic initiation of coagulation cascade:
1) Collagen exposure (platelets) 2) Release of platelet factors
Fibrin threads
Intrinsic
Aspirin
Form of Functioning:
Binds to platelets and inhibits platelet aggregation (early in hemostasis) Inhibits COX enzymes that promote synthesis of platelet activator: Thromboxane A2 Butextrinsic pathway with platelet aggregation still possible
(Daily ASA used to prevent clot formation in cardiac arteries)
(Platelets)
Aspirin
pp 539
Coumarin
Form of Functioning: Antagonizes the biosynthesis in the liver of several Vitamin K-dependant clotting factors
Vitamin K is a co-factor in the synthesis of various clotting proteins
Coumarin
Heparin
Form of Functioning:
Inhibits thromboplastin (tissue factor III) which starts the extrinsic pathway Works with antithrombin II to block various platelet active factors (IX XII) Produced naturally by the body (basophils)
Heparin
Thromboplastin
EDTA
(Ethylene diamine Tetra-acetic Acid)
Form of Functioning:
Causes structural, biochemical and functional injury to blood platelets, including irreversible dissociation of the fibrinogen receptor Chelates calcium ions - making them unavailable to clotting enzymes
EDTA
Citrate
Form of functioning:
Chelates calcium ions - making them unavailable to clotting enzymes Used to store blood in a refrigerator
Citrate
Effective anticoagulants
Test tube (in vitro) Citrate Inactivates (chelates) Ca2+ EDTA Medications (in vivo) Aspirin Blocks the production of thrombin Coumarin Heparin
Analogy
Blood clotting is like a busy intersection after a power-outage of the stop lights. * A police officer (anticoagulant) is called to direct traffic (blood flow) to prevent a blockage of the intersection (blood clot)