Overview of Anticoagulation Management

January 18, 2021

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A lot of noise was made when the Factor Xa drugs came out and there was no reversal agent.  We all feel comfortable with Vitamin-K reversing the effects of warfarin, but that can take a couple of days.  Just simply stopping the Factor Xa inhibitors will produce similar results!  Now that we have monoclonal antibodies to reverse dabigatran and the Xa inhibitors that worry should be gone.
A common question, though, in the family practice setting is when someone should stop their anticoagulant or antiplatelet therapy.  The chart below provides guidance on that front:

Aspirin 7-10 days before
Prasugrel (Effient®) 7-10 days before
Clopidogrel (Plavix®) 5 days before
Ticagrelor (Brilinta®) 5 days before
Warfarin (Coumadin®) 5 days before
Dabigatran (Pradaxa®) 12-17 hours 1-2 days before
3-5 days if CRCl is less than 50
Rivaroxaban (Xarelto®) 5-9 hours At least 24 hours (ideal=48hr) High risk= 2 days
Apixaban (Eliquis®) 8-15 hours At least 24 hours (ideal-48hr) High risk= 2 days
Edoxaban (Savaysa®) 6-11 hours At least 24 hours (ideal-48hr) High risk= 2 days

WHEN to RESTART:  Most experts say to restart therapy 24 hours after a low bleeding risk procedure.
Most agree that the anti-platelet drugs cannot be reversed.
ASPIRIN reversal… sort of
Intravenous DDAVP may be beneficial in some cardiac surgical patients with intractable microvascular bleeding due to platelet dysfunction that may be caused by aspirin use.
Vitamin-K: Reversal agent for Warfarin
Treatment: stop drug.

  • If minor bleeding progresses to major bleeding: Administer Vitamin-K at 5 to 25mg parenterally. May cause prolonged resistance to warfarin.
  • If INR is between 5 to 9, a low dose of oral Vitamin K (2.5mg) is given
  • Greater than 9 with no bleeding: give 5 mg orally.  Will reduce the INR within 12 to 24 hours.

Idarucizumab (Praxbind®)- reversal agent for dabigatran

  • Idarucizumab is a humanized monoclonal antibody fragment (Fab) indicated in patients treated with idarucizumab when reversal of the anticoagulant effects of dabigatran is needed:
    1. For emergency surgery/urgent procedures
    2. In life-threatening or uncontrolled bleeding

Coagulation factor Xa (recombinant), inactivated-zhzo) (Andexxa®)

  • ANDEXXA® is indicated for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding.
  • This indication is approved under accelerated approval based on the change from baseline in anti-Factor Xa activity in healthy volunteers. An improvement in hemostasis has not been established. Continued approval for this indication may be contingent upon the results of studies to demonstrate an improvement in hemostasis.

Limitation of Use:

  • ANDEXXA® has not been shown to be effective for, and is not indicated for, the treatment of bleeding related to any Factor Xa inhibitors other than apixaban (Eliquis®) and rivaroxaban (Xarelto®).

Prothrombin Complex Concentrate (PCC)   (Kcentra®)
Kcentra® is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (warfarin) therapy in adult patients with acute major bleeding or the need for urgent surgery or other invasive procedure.
Administration route:  intravenous use only. Online dosing calculator available.
Administer Vitamin-K to maintain Vitamin K-dependent clotting factor levels once the effects of Kcentra® have diminished
Source: human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent (mad cow disease), is possible
Plasma is frozen within hours after donation in order to preserve the clotting factors. The shelf life of FFP is 12 months, but it can be extended to 7 years if stored at − 65 °C (-85°F).    Most often used to treat bleeding disorders when a clotting factor or multiple factors are deficient, and no factor specific concentrate is available.
A unit of FFP contains near normal levels of all factors, including 400mg of fibrinogen.  It increases factor levels by 3%
Indications for use for FFP

  • Treatment of multiple or specific coagulation factor deficiency, with abnormal PT or APPT.  Either congenital or acquired (related to drug treatment)
  • Can be used for prophylaxis for planned surgical procedures.
  • Patients with massive transfusion who have clinically significant coagulation deficiencies.

Patients on warfarin who are bleeding or need to undergo an invasive procedure before Vitamin-K could reverse the warfarin effect or who need to have anticoagulation therapy after the procedure.

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