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TRAUMA DUE TO TREATMENT Prof.S.Ramaswamy’s unit,M1 Dr.Sangeetha.C.Joseph
Case  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
History of presenting complaints ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
History of presenting complaints (contd.) ,[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
On Examination ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CNS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
INVESTIGATIONS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
1.7 2.1 3.64 4.65 INR 21 21.2 22.4 21.3 aPTT Control-21 12.1 18.2 38.4 40.7 PT Control-11 DAY 8 DAY 6 DAY 3 DAY 1 INV
[object Object],[object Object],[object Object],[object Object]
 
[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object]
[object Object]
HEMOSTASIS ,[object Object],[object Object],[object Object],[object Object]
WHEN DOES BLOOD COAGULATE? ,[object Object],[object Object],[object Object]
INITIATION OF BLOOD COAGULATION Extrinsic Pathway Tissue trauma Leakage of Tissue Factor X Xa Prothrombin activator Ca +2 ,   factor VII Ca +2 Prothrombin    Thrombin (factor II) Ca +2 Intrinsic Pathway Blood trauma/ contact with collagen Activation of  factor XII, IX, VIII X Xa Ca +2 Prothrombin activator Prothrombin   Thrombin (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)
Vitamin K-Dependent Clotting Factors Vitamin K Synthesis of Functional Coagulation Factors VII IX X II
Warfarin Mechanism of Action Warfarin Synthesis of Non Functional Coagulation Factors Antagonism of Vitamin K Vitamin K VII IX X II
WARFARIN: MECHANISM OF ACTION Inactive factors II, VII, IX, and X Proteins  S and C Proteins  S and C Active factors II, VII, IX, and X Vitamin K epoxide Vitamin K reduced WARFARIN ,[object Object],[object Object]
PLASMA HALF-LIVES OF VITAMIN K-DEPENDENT PROTEINS Peak anticoagulant effect may be delayed by 72 to 96 hours 36h Factor X 24h Factor IX 6h Factor VII 72h Factor II
Warfarin - Pathophysiology ,[object Object],[object Object],[object Object],[object Object]
INDICATIONS ,[object Object],[object Object],[object Object],[object Object],[object Object]
WHY TO MONITOR WARFARIN THERAPY? ,[object Object],[object Object]
MONITORING OF WARFARIN THERAPY ,[object Object],[object Object],[object Object]
PROTHROMBIN TIME (PT) ,[object Object],[object Object],[object Object],[object Object],[object Object]
PROBLEMS WITH PT/PTR ,[object Object],[object Object],[object Object]
INTERNATIONAL NORMALISED RATIO (INR) INR = [PT pt ]  ISI   [PT Ref ] PT pt  – prothrombin time of patient PT Ref  – prothrombin time of normal pooled sample ISI – International Sensitivity Index
OPTIMIZING WARFARIN THERAPY ,[object Object],[object Object],[object Object],[object Object],[object Object]
How frequently we should monitor? ,[object Object],[object Object],[object Object]
Commencement & discontinuation of AC  guidelines british committee for hematology ,[object Object],[object Object],[object Object]
Guide lines for dosing RECOMMENDATIONS american college of cardiology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
OPTIMAL THERAPEUTIC RANGE 2.0-3.0 2.5-3.5  (high risk patients) Myocardial infarction,recurrent DVT and PTE 2.0-3.0 2.5-3.5 Heart valve replacement Bioprosthetic valve Mechanical valve 2.0-3.0 Mitral valve stenosis 2.0-3.0 Atrial fibrillation 2.0-3.0 Treatment of venous thromboembolism 2.0-3.0 Prophylaxis of venous thromboembolism INR Indication
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],2.5 2.5 2.5 2.5 / 3.0 2.5 2.5 3.0 – 3.5 2.5 – 3.0 2.5 Target INR . Warfarin Indications – Systemic
Usually indefinite Oral Anticoagulation for prevention of   Thromboembolism   ,[object Object],[object Object],[object Object],[object Object],[object Object],INR – 2 to 3 INR – 2.5 to 3.5 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Oral Anticoagulants inAtrial Fibrillation
FACTORS INFLUENCING DOSE RESPONSE ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
CONTARINDICATIONS AND PRECAUTIONS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
SIDE EFFECTS ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Bleeding risk high in elderly d/t ,[object Object],[object Object],[object Object]
Etiology in elderly ,[object Object],[object Object]
May begin  concomitantly with Heparin  Therapy Heparin should be continued for a minimum of four days Time to peak antithrombotic effect of Warfarin  therapy is delayed 96 hours (despite INR) When INR reaches desired therapeutic range, discontinue heparin ( after a minimum of four days ) Conversion from Heparin to Warfarin
SWITCHOVER FROM ONE BRAND OF WARFARIN TO ANOTHER/ ACENOCOUMAROL ,[object Object],[object Object]
Signs of Warfarin Overdosage ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Causes of excessive anticoagulation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
THE OVERALL ANTICOAGULATION QUALITY IS SIGNIFICANTLY BETTER WITH WARFARIN AS COMPARED TO ACENOCOUMAROL 72% 67% 64% 66% 68% 70% 72% %  Responders Warfarin Acenocoumarol Thrombosis And Haemostasis 1994; 71(2): 188-191
New Anticoagulation Drugs ,[object Object],[object Object],[object Object],[object Object],[object Object]
Why do we need new anticoagulation drugs? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Synthetic Pentasaccharide ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Ximelagatran ,[object Object],[object Object],[object Object],[object Object],[object Object]
Dilemma for the physician in SDH ,[object Object],[object Object],[object Object]
Neurological complications of ac ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
How safely and for how long can W be withheld in pts when admitted with major bleeds ? ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object]
[object Object],[object Object]
Withdrawal of oral anticoagulant treatment ,[object Object],[object Object],[object Object],[object Object],[object Object]
Discontinuation of ac british committee  standards of hematology ,[object Object],[object Object],[object Object],[object Object],[object Object]
Reversal Options ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object]
Recommendations for reversal guide lines on oral ac by british society of hematology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],Message  ……
[object Object]

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A Case of Warfarin induced SDH

  • 1. TRAUMA DUE TO TREATMENT Prof.S.Ramaswamy’s unit,M1 Dr.Sangeetha.C.Joseph
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  • 10. 1.7 2.1 3.64 4.65 INR 21 21.2 22.4 21.3 aPTT Control-21 12.1 18.2 38.4 40.7 PT Control-11 DAY 8 DAY 6 DAY 3 DAY 1 INV
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  • 18. INITIATION OF BLOOD COAGULATION Extrinsic Pathway Tissue trauma Leakage of Tissue Factor X Xa Prothrombin activator Ca +2 , factor VII Ca +2 Prothrombin Thrombin (factor II) Ca +2 Intrinsic Pathway Blood trauma/ contact with collagen Activation of factor XII, IX, VIII X Xa Ca +2 Prothrombin activator Prothrombin Thrombin (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)
  • 19. Vitamin K-Dependent Clotting Factors Vitamin K Synthesis of Functional Coagulation Factors VII IX X II
  • 20. Warfarin Mechanism of Action Warfarin Synthesis of Non Functional Coagulation Factors Antagonism of Vitamin K Vitamin K VII IX X II
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  • 22. PLASMA HALF-LIVES OF VITAMIN K-DEPENDENT PROTEINS Peak anticoagulant effect may be delayed by 72 to 96 hours 36h Factor X 24h Factor IX 6h Factor VII 72h Factor II
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  • 29. INTERNATIONAL NORMALISED RATIO (INR) INR = [PT pt ] ISI [PT Ref ] PT pt – prothrombin time of patient PT Ref – prothrombin time of normal pooled sample ISI – International Sensitivity Index
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  • 35. OPTIMAL THERAPEUTIC RANGE 2.0-3.0 2.5-3.5 (high risk patients) Myocardial infarction,recurrent DVT and PTE 2.0-3.0 2.5-3.5 Heart valve replacement Bioprosthetic valve Mechanical valve 2.0-3.0 Mitral valve stenosis 2.0-3.0 Atrial fibrillation 2.0-3.0 Treatment of venous thromboembolism 2.0-3.0 Prophylaxis of venous thromboembolism INR Indication
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  • 44. May begin concomitantly with Heparin Therapy Heparin should be continued for a minimum of four days Time to peak antithrombotic effect of Warfarin therapy is delayed 96 hours (despite INR) When INR reaches desired therapeutic range, discontinue heparin ( after a minimum of four days ) Conversion from Heparin to Warfarin
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  • 48. THE OVERALL ANTICOAGULATION QUALITY IS SIGNIFICANTLY BETTER WITH WARFARIN AS COMPARED TO ACENOCOUMAROL 72% 67% 64% 66% 68% 70% 72% % Responders Warfarin Acenocoumarol Thrombosis And Haemostasis 1994; 71(2): 188-191
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Notas del editor

  1. The four Vitamin K dependent clotting factors are synthesized in the liver.
  2. Warfarin acts as an anticoagulant by blocking the ability of Vitamin K to carboxylate the Vitamin K dependent clotting factors, thereby reducing their coagulant activity.
  3. The signs of warfarin overdosage are listed on this slide. Hemorrhagic complications from warfarin therapy are more likely to occur with excessive degrees of anticoagulation, but even with an INR in the therapeutic range, bleeding can occur. Because of the likelihood of finding an underlying lesion in an individual who has gastrointestinal bleeding or significant genito-urinary bleeding in the face of therapeutic levels of anticoagulation, one is advised to consider and evaluate for underlying abnormalities predisposing to the bleeding. The return on such evaluations in the face of an excessive degree of anticoagulation diminishes, and one must use judgement whether or not to pursue an evaluation.