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AN OVERVIEW
HEMOSTASIS
VASCULAR SPASM
PLATELET PLUG
BLOOD COAGULATION
X Xa X Xa
Ca+2 Ca+2
Prothrombin activator
Prothrombin
Ca+2 activator
Prothrombin Thrombin Prothrombin Thrombin
(factor II) (factor II)
Activation of certain factors (VII, II, X and protein C and S) is essential for
coagulation. This activation requires vit K (reduced form)
BLOOD COAGULATION
Thrombin
Fibrinogen FibrinMonomers
Fibrin threads
ANTICOAGULANTS
Three classes
Heparin and Low Molecular Weight
Heparins (e.g. enoxaparin, dalteparin)
Coumarin Derivatves e.g. Warfarin,
Acenocoumarol
Indandione Derivatves e.g. Phenindione,
Anisindione
WARFARIN: MECHANISM OF ACTION
Vitamin K epoxide
WARFARIN
Vitamin K reduced
Factor X 36h
[PTRef ]
PTpt – prothrombin time of patient
PTRef – prothrombin time of normal pooled sample
ISI – International Sensitivity Index
OPTIMIZING WARFARIN THERAPY
Dosage to be individualized according to patient’s INR
response.
Use of large loading dose may lead to hemorrhage and
other complications.
Initial dose: 2-5 mg once daily
Maintenance dose: 2-10 mg once daily
Immediate anticoagulation required: Start heparin along
with loading dose of warfarin 10 mg. Heparin is usually
discontinued after 4-5 days. Before discontinuing, ensure INR
is in therapeutic range for 2 consecutive days
Monitor daily until INR is in therapeutic range, then 3 times
weekly for 1-2 weeks, then less often (every 4 to 6 weeks)
OPTIMAL THERAPEUTIC RANGE
Indication INR
Prophylaxis of venous 2.0-3.0
thromboembolism
Treatment of venous 2.0-3.0
thromboembolism
Atrial fibrillation 2.0-3.0
Mitral valve stenosis 2.0-3.0
Heart valve replacement
Bioprosthetic valve 2.0-3.0
Mechanical valve 2.5-3.5
Myocardial infarction 2.0-3.0
2.5-3.5 (high risk patients)
FACTORS INFLUENCING DOSE RESPONSE
Hemorrhage
Skin necrosis
Purple toe syndrome
Microembolization
Teratogenecity
72%
72%
% Responders
70%
67%
68%
66%
64%
Warfarin Acenocoumarol
N= 508
Target INR
1.5-2.0
NEJM 2003; 348 (15): 1425-1434
Warfarin Reduced the Risk of Recurrent Venous Thromboembolism,
Major Hemorrhage, or Death From Any Cause
0.25
P=0.02
Placebo
0.20
Cumulative Rate of Events (%) 48%
0.15 Low-intensity
warfarin
0.10
0.05
0.00
0 1 2 3 4
Years of Follow-up
NEJM 2003; 348 (15): 1425-1434