Docstoc

warfarin

Document Sample
warfarin Powered By Docstoc
					WARFARIN
 AN OVERVIEW
HEMOSTASIS

   VASCULAR SPASM

   PLATELET PLUG

   BLOOD COAGULATION

   GROWTH OF FIBROUS TISSUE IN CLOT
WHEN DOES BLOOD COAGULATE?


 Procoagulants > Anticoagulants
 Injury to blood vessel
 Blood stasis
   INITIATION OF BLOOD COAGULATION
Extrinsic Pathway                                      Intrinsic Pathway
 Tissue trauma                               Blood trauma/ contact with collagen


Leakage of Tissue Factor                                    Activation of factor
                Ca+2, factor VII                            XII, IX, VIII

  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          Fibrin Monomers

                             Ca+2, factor XIII



                         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




                       Vitamin K reduced

Inactive factors II,                       Active factors II,
  VII, IX, and X                            VII, IX, and X
 Proteins S and C                          Proteins S and C


Prevents the reduction of vitamin K, which is essential for
activation of certain factors
Has no effect on previously formed thrombus
  PLASMA HALF-LIVES OF VITAMIN K-
  DEPENDENT PROTEINS
     Factor II       72h
     Factor VII      6h
     Factor IX       24h

     Factor X        36h


Peak anticoagulant effect may be delayed by 72 to 96 hours
INDICATIONS

   Prophylaxis and treatment of venous
    thromboembolism (deep vein thrombosis and
    pulmonary embolism)
   Prophylaxis and treatment of Atrial fibrillation
   Valvular stenosis
   Heart valve replacement
   Myocardial infarction
WHY TO MONITOR WARFARIN THERAPY?


 Narrow therapeutic range
 Can increase risk of bleeding
MONITORING OF WARFARIN
THERAPY
   Prothrombin time
   PT ratio
   INR (International Normalized Ratio)
PROTHROMBIN TIME (PT)

   Time required for blood to coagulate is called PT
   Performed by adding a mixture of calcium and
    thromboplastin to citrated plasma
   As a control, a normal blood sample is tested
    continuously
   PT ratio (PTR) = Patient’s PT
                       Control PT
PROBLEMS WITH PT/PTR


 Thromboplastins are extracts from brain,
  lung or placenta of animals
 Thromboplastins from various
  manufacturers differ in their sensitivity to
  prolong PT
 May result in erratic control of
  anticoagulant therapy
INTERNATIONAL NORMALISED RATIO (INR)


INR = [PTpt]     ISI

       [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


 Inaccurate lab testing
 Poor patient compliance
 Concomitant medications
 Levels of dietary vitamin K
 Alcohol
 Hepatic dysfunction
 Fever
DURATION OF THERAPY

   Venous thromboembolism: Minimum 3 months,
    usually 6 months
   AMI: During initial 10-14 days of hospitalization
    or until patient is ambulatory
   Mitral valve disease/Mechanical heart valves:
    Lifelong
   Bioprosthetic heart valves: 3 months
   Atrial fibrillation: Lifelong
   Prevention of cerebral embolism: 3-6 months
CONTARINDICATIONS AND
PRECAUTIONS
   Hypersensitivity to warfarin
   Condition with risk of hemorrhage
   Hemorrhagic tendency
   Inadequate laboratory techniques
   Protein C & S deficiency
   Vitamin K deficiency
   Intramuscular injections
SIDE EFFECTS

 Hemorrhage
 Skin necrosis
 Purple toe syndrome
 Microembolization
 Teratogenecity
Agranulocytosis, leukopenia, diarrhoea,
nausea, anorexia.
SWITCHOVER FROM ONE BRAND OF
WARFARIN TO ANOTHER/
ACENOCOUMAROL
 Check patient’s INR
 Start with dose of 2 mg; increase dose
  slowly as required
COMPARISON WITH
ACENOCOUMAROL
THE OVERALL ANTICOAGULATION QUALITY
IS SIGNIFICANTLY BETTER WITH WARFARIN
AS COMPARED TO ACENOCOUMAROL

                             72%

                  72%
   % Responders




                  70%
                                                 67%
                  68%

                  66%

                  64%
                        Warfarin        Acenocoumarol


                         Thrombosis And Haemostasis 1994; 71(2): 188-191
RECENT TRIALS ON
   WARFARIN
    ANTICOAGULATION FOR VTE PROVOKED BY
    TRANSIENT RISK FACTORS (SURGERY etc) SHOULD
    BE CONTINUED FOR 3 MONTHS

    Group                    Incidence (%) per year

    Warfarin for 1 month     6.8%

    Warfarin for 3 months 3.2%

   There were no major bleeds in either groups
Follow-
up=11 mths



                           J Thromb Haemost. 2004; 2(5): 743-749
  THE PREVENTION OF RECURRENT VENOUS
  THROMBOEMBOLISM (PREVENT) TRIAL

Long-term use of low-intensity warfarin, prevents
  venous thromboembolism without increasing the risk
  of hemorrhage
    INCIDENCE OF VTES IN THE TWO TREATMENT GROUPS
         Drug                 Warfarin Placebo
         Events per 100         2.6       7.2
         person-years
         Bleeding requiring     0.9       0.4
         hospitalization


   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

				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:159
posted:3/30/2008
language:English
pages:27