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ANTICOAGULANT

ANTICOAGULANT. Definition of Anticoagulation. Therapeutic interference ("blood-thinning") with the clotting mechanism of the blood to prevent or treat thrombosis and embolism. Indications of Anticoagulant Therapy. Treatment and Prevention of Deep Venous Thrombosis Pulmonary Emboli

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ANTICOAGULANT

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  1. ANTICOAGULANT

  2. Definition of Anticoagulation • Therapeutic interference ("blood-thinning") with the clotting mechanism of the blood to prevent or treat thrombosis and embolism.

  3. Indications of Anticoagulant Therapy • Treatment and Prevention of Deep Venous Thrombosis • Pulmonary Emboli • Prevention of stroke in patients with atrial fibrillation, artificial heart valves, cardiac thrombus. • During procedures such as cardiac catheterisation

  4. Enhances Antithrombin Activity

  5. Standard Heparin • Heterogeneous mixture of polysaccharide chains • MW 3k to 30k • Active in vitro and in vivo • Administration - parenteral- Do not inject IM - only IV or deep s.c. • Half-life 1 - 2 hrs - monitor APTT (activated partial thromboplastintime) • Adverse effect - haemorrhage – • antidote - protamine sulphate

  6. Heparin mechanism of action Heparin Antithrombin III Thrombin

  7. Monitoring Heparin • Activated Partial Thromboplastin Time (APTT) • Normal range: 25-40 seconds • Therapeutic Range: 55-70 seconds

  8. Low Molecular Weight Heparin • Changed management of venous thromboembolism • Standard (Unfractionated) heparin 30k • LMWH contains polysaccharide chains MW 5k • Enriched with short chains with higher anti-Xa:IIa ratio

  9. Differences in Mechanism of Action • Any size of heparin chain can inhibit the action of factor Xa by binding to antithrombin (AT) • In contrast, in order to inactivate thrombin (IIa), the heparin molecule must be long enough to bind both antithrombin and thrombin • the chains of LMWH are not long enough to bind antithrombin and thrombin

  10. Complications of Heparin • Hemorrhage(can be reversed by using protamine sulfate as an antidote) • Heparin-induced thrombocytopenia (HIT) and thrombosis • Osteoporosis (long-term only) more than 6 month; the explanation of this side effect is unknown • Hyperkalemia • Hypersensitivity reaction

  11. Heparin-Induced Thrombocytopaenia • Most significant adverse effect of heparin after haemorrhage • Most common drug-induced thrombocytopenia

  12. Major adverse effects of heparin

  13. Trreatment of HIT • Discontinue all heparin • If need to continue anti-coagulation, use danaparoid (orgaran). • Avoid platelet transfusions • Thrombosis: use danaparoid or thrombin inhibitor(Hirudin)

  14. Oral anticoagulant • Warfarin is an oral anticoagulant that prevent thrombosis • It inhibit the enzymatic reduction of vitamin K to its hydroquinone form, interfering with the post translational modification (carboxylation) of glutamic acid residues in clotting factors 2, 9, 7, 10. • Warfarin acts only in vivo

  15. Vitamin K-Dependent Clotting Factors Vitamin K VII Synthesis of Functional Coagulation Factors IX X II

  16. Warfarin Mechanism of Action Vitamin K Antagonism of Vitamin K VII Synthesis of Non Functional Coagulation Factors IX X II Warfarin

  17. Warfarin

  18. Side effects of warfarin • Bleeding • Hepatotoxicity • Warfarin induced skin necrosis(can be reduced by starting heparin and warfarin concomitantly)

  19. Warfarin: Major Adverse Effect—Haemorrhage • Factors that may influence bleeding risk: • Intensity of anticoagulation • Concomitant clinical disorders(liver disease ,thyrotoxicosis and fever ) • Concomitant use of other medications • Cimetidine and other enzyme inhibitors increase its action while rifampicin and other enzyme inducers inhibit the action of warfarin • aspirin increase its bleeding risk by working in synergistic fashion(PLATELETS INHIBITION) . • NSAIDS and chloral hydrate displace it from binding sites • Antibiotic eliminate the intestinal flora that produce vitamin k this will increase the risk of bleeding • Quality of management

  20. Prothrombin Time (PT) • Historically, a most reliable and “relied upon” clinical test However: • Proliferation of thromboplastin reagents with widely varying sensitivities to reduced levels of vitamin K-dependent clotting factors has occurred • Problem addressed by use of INR (International Normalized Ratio)

  21. Changing over from Heparin to Warfarin • May begin concomitantly with heparin therapy • Heparin should be continued for a minimum of four days • Time to peak antithrombotic effect of warfarin is delayed 96 hours (despite INR) • When INR reaches desired therapeutic range, discontinue heparin (after a minimum of four days)

  22. Warfarin: Dosing & Monitoring • Start low • Initiate 5 mg daily • Educate patient • Stabilize • Titrate to appropriate INR • Monitor INR frequently (daily then weekly) • Adjust as necessary • Monitor INR regularly (every 1–4 weeks) and adjust

  23. Contraindications to Warfarin Therapy • Pregnancy (it is a teratogenic drug can cause maxillofacial abnormality if given in the first trimester and increase the incidence of bleeding in the new born baby in the last trimester; but it can be given in the middle trimester of pregnancy but with higher doses to achieve the target INR because there is hyper-coaguability state during pregnancy • Situations where the risk of hemorrhage is greater than the potential clinical benefits of therapy • Uncontrolled alcohol/drug abuse • Unsupervised dementia/psychosis

  24. Signs of Warfarin Overdosage • Any unusual bleeding: • Blood in stools or urine • Excessive menstrual bleeding • Bruising • Excessive nose bleeds/bleeding gums • Persistent oozing from superficial injuries • Bleeding from tumor, ulcer, or other lesion

  25. Reversing action of warfarin • Plasma(fresh frozen plasma or clotting factors) • Rapid but short-lasting, used mainly for life threating bleeding • Vitamin K • Not rapid, but lasts 1-2 weeks. Do not use if wishing to restart warfarin within next week. In some cases only stopping the drug can be enough

  26. THANK YOU

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