2.13 Pharmacology of Anticoagulants
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What is the mechanism of action for heparin?
- Antithrombin binds to and inactivates ACTIVATED clotting factors: XIIa, XIa, IXa, XA, and IIA (Thrombin)
- Binds to antithrombin and speeds up these reactions
- Increases activity of antithrombin 3 of 1000X
- Inactivate, activating clotting factors
What is the mechanism of action for warfarin?
- Inhibits Vitamin K Oxide (epoxide) Reductase
- Means decreased levels of Active Vitamin K
- Means decreased levels of Vitamin K Dependent Clotting Factors II, VII, IX, X (also anticoagulant proteins C & S)No effect on already synthesized clotting factors; so therapeutic effects not seen until these factors are depleted
- 3-4 days until effect is seen
What are the main adverse effects from heparin?
- HIT (Heparin-induced thrombocytopenia) - Heparin binds to platelet factor 4. And body makes antibodies for it. Which binds to platelets.
- 1. Removed by the spleen and drops platelet count. Outcome is Thrombocytopenia
- 2. Platelet is activated and stimulates blood clotting. Outcome is Thrombosis
- Cause of HIT is having a thromboembolic event
What are the main adverse effects from warfarin?
Warfarin Skin Necrosis - caused by depletion of Protein C by Warfarin
What is the time to steady-state anticoagulant effects during a heparin IV infusion?
What is the time to steady-state anticoagulant effects during a oral warfarin regimen?
How does warfarin have a pro-coagulant effect early in therapy?
Decreases level of Protein C (Anticoagulant)
What are the lab tests used to monitor and adjust doses for heparin?
- Activated partial thromboplastin time (aPTT or PTT)
- Anti-Factor Xa levels
What are the lab tests used to monitor and adjust doses for warfarin?
- Prothrombin Time (ProTime or PT) - measured in seconds
- INR = International Normalized Ration
- ISI = International Sensitivity Inde
How do you reverse anticoagulation from heparin?
How do you reverse anticoagulation from warfarin?
- 1. Vit K Dependent Clotting Factor (acts faster) - FFP (Fresh Frozen Plasma), NovoSeven (Recombinant Factor VIIa), PCC (Prothrombin Complex Concentrate)
- 2. Active Vit K - Phytonadione
Which anticoagulant is injectable?
Which anticoagulant is orally taken?
What is the MOA of Fondaparinux?
- Inactivates 10a
- Fondaparinux = Heparin with 5 saccharides
How many saccharides does Heparin need to bind to both thrombin and antithrombin?
What is the MOA of Low Molecular Weight Heparin?
- Primarily Xa reactions
- Some IIa (Thrombin)
Is Heparin or Warfarin safe to give during pregnancy?
- Heparin is safe
- Larger molecules so can't cross placenta
What should you check during heparin therapy?
Patient platelet count
What is the treatment approach for deep vein thrombosis and/or pulmonary embolism?
- IV infusion heparin immediately
- Add oral warfarin
- Stop heparin once therapeutic warfarin effect attained
- Outpatient warfarin therapy
Why do you sometimes give Heparin and Warfarin at the same time?
- Warfarin has a slow onset
- Warfarin initially drops level of Protein C; so give Heparin until Factors 2, 10 are depleted
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