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ANTICOAGULANT

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

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ANTICOAGULANT

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  1. ANTICOAGULANT BY :DR ISRAA OMAR

  2. Definition of Anticoagulation • Therapeutic interference with the clotting mechanism of the blood ("blood-thinning") 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 Da to 30k Da • 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 • 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. 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)

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

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

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

  16. Warfarin

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

  18. Warfarin: Major Adverse Effect—Haemorrhage • Factors that may influence bleeding risk: • Intensity of anticoagulation • Concomitant clinical disorders(liver disease ,thyrotoxicosis and fever ) • Quality of management • 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

  19. 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)

  20. 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)

  21. 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

  22. Contraindications to Warfarin Therapy • Pregnancy (it is a erotogenic 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

  23. 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

  24. 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

  25. Thank you

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