Reversal Agents for Anti-coagulation

For Reversal of Major Bleeding

Definition: Major Bleed(s) are all bleeds associated with hemodynamic compromise, occurring in an anatomically critical site (e.g., intracranial), or associated with a decrease of hemoglobin >2 g/dL (when baseline is known) or requiring transfusion of >2 U of packed RBCs.

Bleeding due to Vitamin K antagonists (VKA):

Vitamin K: 10 mg IV over 30 min in 50 mL NS
1. Can give PO but then longer reversal times (18-24 hrs)
2. IV formulation can be given PO if slower reversal times are ok
Give 4F-PCC (K-Centra):
1. Comes as 500 or 1000 unit kit
2. Weight based:
  1. INR 2-4 = 25 U/kg
  2. INR 4-6 = 35 U/Kg
  3. INR >6 = 50 U/kg
3. Low Dose Fixed
  1. 1500 Units for ICH
  2. 1000 Units for all other major bleeds
Alternate to PCC: FFP 10-15 ml/kg (not “2 units”)
Alternate to PCC: FEIBA (contains VIIa)
1. Give for STD Dosing INR < 5 = 500 IU, INR > 5 = 1,000 IU.
2. Lyophilized powder in single-use vials of 500, 1000, or 2500 units per vial
3. Compared to Wt based dosing of 4F-PCC, FEIBA showed no difference (N=158; 118 FEIBA pts; 78% ICH)
  1. Crit Care Med 2018; 46:943–948

Dabigatran:

Idarucizumab 2.5 g IV repeat 10 min after 1st dose for total of 5g
4F-PCC [K-Centra] 50 Units/kg IV
aPCC (FEIBA) 50 Units/kg IV
Activated Charcoal

Xa-Inhibitors

4F-PCC [K-Centra] 50 Units/kg IV
aPCC (FEIBA) 50 Units/kg IV
Activated Charcoal [within 2-4 hours of exposure]
Dialysis for Edoxaban
1. NOT for rivaroxaban, or apixaban
Andaxanet fXa Inhibitor (FDA approved 2018 limited release until 2019)
1. Apixaban and >7 hours since Rivaroxaban (low dose)
  1. 400 mg Bolus at 30 mg/min followed by Infusion of 480 mg over 2 hours
  2. Cost for low dose estimated $25,000
1. Rivaroxaban < 7 hours OR enoxaparin (high dose)
  1. 800 mg Bolus at 30 mg/min followed by Infusion of 960 mg over 2 hours
  2. Cost for high dose estimated at $49,500
Ciraparantag (“Universal Agent”? No yet FDA approved)
1. Binds anticoagulants via Hydrogen bonds
2. Made up of 2 L-arginine units
3. Works on Edoxaban, riva, apixa, dabigatran, lovenox and heparins
  1. Not warfarin or agratroban
4. Works within 30 min
5. 300 mg IV Bolus
6. FDA fast track designation 4/2015

Condition	Intervention
INR > goal but < 5 No significant bleeding or risk of bleeding	· Lower dose or omit next dose
INR ≥ 5 or < 9 AND No significant bleeding or risk of bleeding	· Preferred: Omit next 1-2 doses · Alternatively, omit 1-2 doses & give Vitamin K (1-2.5 mg po) · Alternatively, for patients at high risk of thrombosis (i.e. valves), omit 1-2 doses and use FFP 2 units IV – DO NOT use Vitamin K
INR ≥ 9 No significant bleeding AND/OR Low-moderate risk of bleeding	Hold warfarin therapy Give FFP 2 units IV Give Vitamin K (2.5-5 mg po) In patients with prosthetic heart valves, give FFP 2 units IV and lower dose of Vitamin K (1-2.5mg po)

Reference:

Tomaselli GF, Mahaffey KW, Cuker A, Dobesh PP, Doherty JU, Eikelboom JW, Florido R, Hucker W, Mehran R, Messé SR, Pollack CV Jr., Rodriguez F, Sarode R, Siegel D, Wiggins BS. 2017 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. 2017 Dec 19;70(24):3042-3067.

Medical Letter. JAMA. 2018;320(4):399-400

Share this:

Like this:

Related

Leave a Reply Cancel reply