Oral Anticoagulants In Pulmonary Embolism

1. Oral AnticoagulantsIn Pulmonary Embolism Presnted by Marianne Adly Under the supervision of Prof. Seham Hafez

2. Oral Anticoagulant Warfarin Marevan Caumadin • Mechanism of Action: Factor II Facrtor VII Factor IX Factor X 1- Vit. K Warfarin Interferes with hepatic synthesis of vitamin K-dependent coagulation factors (factor II, VII, IX and X)

3. Oral Anticoagulant – Warfarin • Mechanism of Action: 2- Protein C Naturally occurring anticoagulant Hypercoagulable State Warfarin Protein S Cofactor for activation of Protein C Warfarin also inhibits the formation of the naturally occurring anticoagulant protein C and its cofactor protein S.

4. Oral Anticoagulant – Warfarin • Initiation of Warfarin • Warfarin should be started on the first day of hospitalization • Either heparin or LMWH/fondaparinux therapy should be continued for at least 5 days in the setting of PE, and until warfarin therapy is therapeutic and stable. Never give warfarin to patient with thrombosis until after patient has been anticoagulated fully with heparin

5. Oral Anticoagulant – Warfarin There are several reasons to overlap heparin and warfarin therapy: The onset of warfarin activity depends on: - Its pharmacokinetic characteristics (half-life >36 hours - The rate of elimination of previously circulating clotting factors. The effect of warfarin can be delayed for several days. By overlapping a quick onset anticoagulant such as heparin or LMWH with warfarin therapy, adequate anticoagulation can be continued with heparin/LMWH until warfarin therapy reaches a therapeutic intensity. 1-

6. Oral Anticoagulant – Warfarin There are several reasons to overlap heparin and warfarin therapy – cont’: 2- Protein C Naturally occurring anticoagulant Hypercoagulable State Warfarin Protein S Cofactor for activation of Protein C Thrombus extension To prevent this complication, heparin and warfarin therapy should overlap.

7. Oral Anticoagulant – Warfarin • Protocols of Warfarin • First protocol: • starting treatment at 5 mg per day and titrating the dosage every three to seven days to achieve an INR between 2.0 and 3.0. • Second protocol: 10-mg initiation dose for the first 2 days, with the INR on day 3 used to guide dosing on days 3 and 4, and the INR on day 5 used to guide the next three doses ( target INR 2- 3 ) This hepls to achieve a therapeutic INR more quickly

8. Oral Anticoagulant – Warfarin • Protocols of Warfarin – Cont’ • Pediatric dose: Administer weight-based dose of 0.05-0.34 mg/kg/d PO and adjust dose according to desired INR Infants may require doses at high end of this range

9. Oral Anticoagulant – Warfarin • Duration of Warfarin • The optimal duration of oral anticoagulant treatment after a first episode of pulmonary embolism remains uncertain. • The appropriate duration of warfarin therapy is based on: • the likelihood of a recurrent venous thromboembolic event • the risk of bleeding in each patient.

10. Duration of Warfarin

11. Oral Anticoagulant – Warfarin • Contraindication of warfarin 1- Pregnancy. Therefore, long-term treatment with LMW heparin is used when PE occurs in a pregnant woman 2- Cancer patient. LMWH is used 3- Sever liver or kidney disease. 4- Gastrointestinal ulcer. • Adverse effects: • Hemorrhage • Skin necrosis • Purple toe syndrome (rare )

12. Oral Anticoagulant – Warfarin • Precautions: • Avoid or use extreme caution in patients with hereditary or acquired deficiencies of protein C or protein S, because these deficiencies are associated with higher incidence of tissue necrosis following warfarin administration • Do not switch brands after achieving satisfactory therapeutic response; use caution in patients with active TB or diabetes; exercise caution in patients with protein C or S deficiency, because they are at high risk of developing skin necrosis • Warfarin is teratogenc and contraindicated in pregnancy

13. Oral Anticoagulant – Warfarin • Drug interactions: Many medications may affect warfarin activity Drugs that may decrease anticoagulant effects include: griseofulvin, phenytoin, rifampin, barbiturates, carbamazepine, estrogens, oral contraceptives, vitamin K, and sucralfate Some medications that may increase anticoagulant effects include: oral antibiotics, miconazole, clofibrate, sulfonylureas, allopurinol, chloramphenicol, disulfiram, metronidazole, and acetaminophen.

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