Anticoagulants in the Treatment of Venous Thromboembolism

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Presentation transcript:

Anticoagulants in the Treatment of Venous Thromboembolism Gina Cragg Pharmacy Practice Resident 2015-16

Learning Objectives To understand to different mechanisms of action of anticoagulants used in the out-patient antithrombotic clinic. To describe the medication doses and durations of treatment. To describe key monitoring parameters for each of the medications. To discuss any patient specific questions relevant to your practice.

Virchow’s Triad

Generalized Duration of Treatment Provoked (first episode): Cause reversible: 3-6 month Cause irreversible: Treat as unprovoked Unprovoked: Isolated distal DVT (1st episode): 3-6 months Isolated distal DVT (recurrence): consider extended Proximal DVT/PE (first episode or recurrence): consider extended (extended depends on bleed risk and additional factors)

Dalteparin (Fragmin) A low molecular weight heparin (LMWH) Indirectly blocks factor Xa through increasing activity of anti-thrombin Must monitor platelets as risk of heparin induced thrombocytopenia (HIT) Monitor hemoglobin (early indicator of bleed) Used in bridging to warfarin, cancer associated VTE and pregnancy Renal dose adjustment required

XII XIIa Intrinsic Pathway XI XIa Extrinsic Pathway IX IXa VIIa VII X Xa X LMWH (primary target) Prothrombin (II) Thrombin (IIa) LMWH Fibrinogen (I) Fibrin (Ia) XIIIa Cross-Linked Fibrin Clot

Fondaparinux (Arixtra) Synthetic pentasaccharide containing active portion of LMWH Indirectly blocks factor Xa through increasing activity of anti-thrombin Monitor hemoglobin (early indicator of bleed) Used in place of LMWH following heparin induced thrombocytopenia (HIT) Contraindicated eGFR < 30ml/min

XII XIIa Intrinsic Pathway XI XIa Extrinsic Pathway IX IXa VIIa VII X Xa X Fondaparinux Prothrombin (II) Thrombin (IIa) Fibrinogen (I) Fibrin (Ia) XIIIa Cross-Linked Fibrin Clot

Warfarin Decreases synthesis of vitamin K dependent factors in the liver (factors II, VII, IX, X, Protein S and C) No effect on pre-existing clotting factors These factors may take up to 5 days to be removed from the body Often bridge with LMWH or fondaparinux for minimum 5 days and 2 consecutive therapeutic INRs (2-3) Monitor hemoglobin (early indicator of bleed)

XII XIIa Intrinsic Pathway XI XIa Extrinsic Pathway Warfarin IX IXa VIIa VII Warfarin Warfarin X Xa X Warfarin Prothrombin (II) Thrombin (IIa) Fibrinogen (I) Fibrin (Ia) XIIIa Cross-Linked Fibrin Clot

Dabigatran (Pradaxa) Direct thrombin (IIa) inhibitor Contraindicated eGFR < 30ml/min Monitor hemoglobin (early indicator of bleed) Dyspepsia is a common side effect (consider with meals Administer 2hrs prior to antacids (interaction) Can cause abdominal pain and diarrhea Cannot open capsule and mix with food as this increases the bioavailability by 75%

XII XIIa Intrinsic Pathway XI XIa Extrinsic Pathway IX IXa VIIa VII X Xa X Prothrombin (II) Thrombin (IIa) Dabigatran Fibrinogen (I) Fibrin (Ia) XIIIa Cross-Linked Fibrin Clot

Rivaroxaban (Xarelto) Direct factor Xa inhibitor Contraindicated eGFR < 30ml/min Non-inferior to warfarin with less risk serious bleed Taken twice daily in acute treatment of VTE then once daily Monitor hemoglobin (early indicator of bleed) No bridging with LMWH necessary $$$

XII XIIa Intrinsic Pathway XI XIa Extrinsic Pathway IX IXa VIIa VII X Xa X Rivaroxaban Prothrombin (II) Thrombin (IIa) Fibrinogen (I) Fibrin (Ia) XIIIa Cross-Linked Fibrin Clot

Apixaban Direct factor Xa inhibitor Contraindicated eGFR < 15ml/min Non-inferior to warfarin with less risk serious bleed Taken twice daily Monitor hemoglobin (early indicator of bleed) No bridging with LMWH necessary $$$

XII XIIa Intrinsic Pathway XI XIa Extrinsic Pathway IX IXa VIIa VII X Xa X Apixaban Prothrombin (II) Thrombin (IIa) Fibrinogen (I) Fibrin (Ia) XIIIa Cross-Linked Fibrin Clot

References Antithrombotic Therapy For Vte Disease: Chest Guideline And Expert Panel Report Kearon C, Akl EA, Ornelas J, et al. Chest. 2016;149(2):315-352. Saseen JJ and MacLaughlin EJ. Chapter 9: Venous Thromboembolism. Dipiro JT, editor. Pharmacotherapy: A Pathophysiological Approach. 9th edition. New York: McGraw Hill Medical;2014.p 245-278. Lexicomp on-line. Available at http://online.lexi.com through VIHA intranet. Uptodate. Available at http://www.uptodate.com through VIHA intranet.