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Reference: PATHOPHYSIOLOGY
Harrison’s Principles of Internal Medicine - Trauma to the veins
Old Trans - Venous stasis
- Decreased oxygen supply to the avascular valve cusps
ANTIPLATELET, ANTI-COAGULANT AND FIBRINOLYTIC DRUGS - Endothelial cells express adhesion molecules on surface
INTRODUCTION - Tissue factor-bearing leukocytes adhere to activated
endothelial cells
ANTI-THROMBOTIC THERAPY - Coagulation
1. Anti-platelets
2. Anti-coagulants MANAGEMENT
3. Fibrinolytic agents - ANTI-COAGULANT
o Mainstay
INDICATION: o
- Prevent thrombotic events
- Prevent complications THROMBUS FORMATION
- Restore vascular patency - Impaired blood flow
- Reduced clearance of activated clotting factors
- Extends into proximal veins
ARTERIAL THROMBOSIS - Thrombus fragments dislodge
- To lungs -> Pulmonary Embolism
- Rich in platelet d/t high shear in the injured arteries.
- White in color
ANTI-PLATELETS
Most common cause of: INTRODUCTION
o MI
o CVA - Inactive platelets are maintained by:
o Limb gangrene o NO
Potent vasodilator
PATHOPHYSIOLOGY Potent inhibitor of platelet aggregation
- Plaque rupture o Prostacyclin
- Exposes thrombogenic material to blood - Endothelial Cells release:
- Triggers platelet aggregation & fibrin formation o Prostacyclin
- Results to platelet-rich thrombus o CD39
- Occlude bloodflow Membrane-associated ADPase
Degrades ADP released from
MANAGEMENT activated platelets
- Inhibit platelet formation
o ANTI-PLATELET AGENT ROLE OF PLATELETS IN ARTERIAL THROMBOSIS
ACUTE SETTING: - Injury
Anti-platelet - Vessel wall damage
Anti-coagulants - Exposure of subendothelial matrix and Tissue Factor
Fibrinolytic - Platelets adhere to exposed collagen by:
o A2b1
o Glycoprotein (GP) VI
VENOUS THROMBOSIS o vWF
o GPIba
- Forms under low-shear conditions o GPIIb/IIIa (aIIbB3) – most abundant receptor
- Few platelets - Conformational change (adhered platelet)
- Composed predominantly of RBCs. - Secrete ADP and TxA2
- Red in color o Activate ambient platelets and recruit to vascular
injury
DEEP VEIN THROMBOSIS - TF initiates coagulation where activated platelets potentiate
- Complication: coagulation by binding clotting factors
o Pulmonary Embolism - In activated platelets, GPIIb/IIIa – conformational change
o Post-phlebitic Syndrome o Binds to:
Fibrinogen
vWF
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THIENOPYRIDINES
2. Clopidogrel
o Reduces risks by 8.7% > aspirin
o Expensive > Aspirin
o S/E : rare
- THIENOPYRIDINE RESISTANCE
ASPIRIN o Variability in the capacity of the thienopyridines
to inhibit ADP-induced platelet aggregation and
- Most widely used genetic polymorphisms in the CYP isoenzymes
- Cheap involved in the metabolic activation of the drugs.
- Effective
- Mechanism of Action:
o Irreversibly acetylating and inhibiting COX-1 DIPYRIDAMOLE
Enzyme for biosynthesis of TxA2
o High doses: - Weak anti-platelet agent
Inhibits COX-2 - Extended-release formulation of dypiridamole combined
Decrease synthesis of with low-dose aspirin
prostacyclin o Aggrenox for prevention of stroke in patients with
TIA
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- Mechanism of Action:
o Inhibits phosphodiesterase
o Blocks the breakdown of cAMP
Increased levels of cAMP reduce IC Ca
and inhibit platelet activation
o Blocks adenosine uptake by platelets and other
cells
Further increase in local cAMP levels
because of platelet adenosine A2
receptor – adenylate cyclase coupling.
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HEPARINOIDS
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FIRBRINOLYTIC DRUGS
INTRODUCTION
- Streptokinase
- Urokinase
- tPA
STREPTOKINASE
UROKINASE
tPA
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