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Anticoagulants

Andrea Brianne Katie Kim

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?

Significance & Relevance to lecture


Significance
Blood clots (thrombus) could be fatal Myocardial infarction (heart attack) Cerebrovascular accident (stroke)

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

B. Extrinsic initiation of coagulation cascade:


1) Tissue damage 2) Release of thromboplastin
Thrombin Fibrinogen

Fibrin threads

Thromboxane (paracrine) aggregates platelet

Intrinsic

Extrinsic Thromboplastin Later slide

pg. 537, See also pg. 129 in packet

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

Intrinsic and Extrinsic mechanisms converge here

Detail of Coagulation Cascade

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

Inhibits both intrinsic and extrinsic pathways to clot formation


(Used to prevent embolus formation, e.g. atrial fibrillation and varicose veins)

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)

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