1. Anticoagulants in the Treatment of Venous Thromboembolism
Gina Cragg
Pharmacy Practice Resident

2. 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.

3. Virchow’s Triad

4. 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)

5. 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

6. 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

7. 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

8. 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

9. 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)

10. 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

11. 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%

12. 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

13. 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
$$$

14. 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

15. 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
$$$

16. 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

17. References
Antithrombotic Therapy For Vte Disease: Chest Guideline And Expert Panel Report Kearon C, Akl EA, Ornelas J, et al. Chest. 2016;149(2):
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
Lexicomp on-line. Available at through VIHA intranet.
Uptodate. Available at through VIHA intranet.