Links:
Emergency Reversal of Anticoagulation
General Principle: “HASHTI”
- Hold further doses of anticoagulant
- Consider Antidote
- Supportive treatment: volume resuscitation, inotropes, etc.
- Local or surgical Hemostatic measures: topical agents (aminocaproic acid, tranexamic acid)
- Transfusion (red cells, platelets, FFP as indicated)
- Investigate for bleeding source
Anticoagulant Reversal Agents:
| Agent | Dose | Comments |
| Vitamin K | 1-10 mg IV/PO, not SQ or IM | • Infusion reactions rare; administer over 20-30 min
• Takes 6 (IV) to 24 (PO) hours to reverse warfarin • Large doses can cause warfarin resistance on resumption |
| Protamine Sulfate | 10-100 mg IV | • Full reversal of unfractionated heparin
• 60%-80% reversal of LMWH • No reversal of fondaparinux |
| DDAVP/Desmopressin | 0.3 mcg/kg | • Consider use for antiplatelet medication reversal
|
| Blood Products
Platelets
Fresh frozen plasma (FFP)
Cryoprecipitate
|
1 apheresis unit, 4-6 whole blood units, 1 acrodose unit 10-15 mL/kg (1 unit: ~ 250 mL) 1-2 “pools” (5-10 units) (10 units pooled: ~100 mL) |
• Raise platelet count by 30-60 x 109/L • Goal platelet count 50 – 100 x 109/L (indication dependent) • Use for antiplatelet agent reversal • Replaces all factors, but cannot fully correct ° Hemostasis usually requires factor levels ~30% ° Factor IX may only reach 20% • May need repeat dose after 6 hours • Large volume, takes ~45 minutes to thaw and prepare • Replacement for fibrinogen, factor VIII, factor XIII, von Willebrand factor • Takes ~45 minutes to thaw and prepare |
| Prothrombin complex concentrates (PCCs)
Kcentra (“Four Factor PCC”)
FEIBA (Factor Eight Inhibitor Bypassing Activity) |
25-50 Units/kg (see back) 75 Units/kg |
• Kcentra is specific antidote for warfarin (small volume infusion over 10-30 minutes) • FEIBA can be used for reversal of Xa inhibitors but must be used with caution • Risk of thrombosis 1.4% • Contraindicated with history of HIT NOTE: PCC may partially correct PT/aPTT but will not affect anti-factor Xa activity and will not increase drug clearance; correlation of shortening PT/aPTT with reduction in bleeding risk is unknown |
| Recombinant Factor VIIa
(rFVIIa, NovoSeven) |
90 mcg/kg | • Risk of thrombosis 5-10%
• May need repeat dose after 2 hours |
| Reversal Agents for Oral Thrombin Inhibitors
Idarucizumab (Praxbind) |
5 g IV |
• Effect on bleeding not immediate! Median time from administration to bleeding cessation may be as long as 11 hours
• Will likely correct aPTT but correlation of improved lab results with clinical outcomes is not established • Plasma dabigatran concentrations may increase 12-24 hours following reversal due to re-distribution from extravascular space • Risks and benefits of repeat administration are not known |
Definitions Used for Reversal Situations
Non-urgent: Reversal is elective (procedures >7 days away)
Urgent (without bleeding): Reversal needed within hours
Urgent (with bleeding): Emergency reversal
REVERSAL SUGGESTIONS (UMCNO GUIDELINES – may not apply to other institutions):
| Drug to Reverse | Non-Urgent | Urgent (without bleeding) | Urgent (with bleeding) | ||||||||
| Antiplatelet Agents
Aspirin, Dipyridamole (Persantine/Aggrenox), Clopidogrel (Plavix), Ticlopidine (Ticlid), Prasugrel (Effient), Ticagrelor (Brilinta) |
• Discontinue agent 5-10 days prior to procedure | • Consider platelet transfusion prior to high risk bleeding procedures | • HASHTI
• Platelet transfusion • Desmopressin (0.3 mcg/kg) |
||||||||
| Warfarin (Coumadin) | • Hold warfarin until INR in therapeutic range | • Hold warfarin
• Consider Vitamin K 2.5 mg PO or 1-2 mg IV infusion if rapid reversal required |
• HASHTI
• Give Vitamin K 10 mg IV infusion over 30 minutes • Give Kcentra if life-threatening bleeding or intracranial hemorrhage INR 1.5-3.9: 25 units/kg (max 2500 units) INR 4.0-6.0: 35 units/kg (max 3500 units) INR >6.0: 50 units/kg (max 5000 units) (FFP if Kcentra not available) • If second dose considered, contact Anticoagulation Attending @ 2-3482 for approval |
||||||||
| Heparin (UFH) |
|
||||||||||
| Low-Molecular-Weight Heparins
Enoxaparin (Lovenox), Dalteparin (Fragmin), Tinzaparin (Innohep) |
• Hold day of procedure
• Once-daily regimens: ½ dose day prior • Twice-daily regimens: Hold evening dose day prior |
|
|||||||||
| Fondaparinux (Arixtra) | • Hold day of procedure
• Once-daily regimens: ½ dose day prior • Twice-daily regimens: Hold evening dose day prior |
• Wait 12-24 hours if possible | • HASHTI
• Consider rVIIa (90 mcg/kg) •If rVIIa considered, contact Anticoagulation Attending @ 2-3482 for approval |
||||||||
| Direct Thrombin Inhibitors
Argatroban, Bivalirudin (Angiomax), Lepirudin |
• Delay next dose or discontinue DTI | • HASHTI
• FFP |
• HASHTI
• FFP • If life-threatening bleeding or ICH, consider PCC; consult Anticoagulation Attending at 2-3482 |
||||||||
| Direct Thrombin Inhibitor with specific reversal reagents
Dabigatran (Pradaxa) |
• Delay next dose or discontinue inhibitor |
|
|||||||||
| Direct Xa Inhibitors
Edoxaban (Savasya), Rivaroxaban (Xarelto), Apixaban (Eliquis) |
• Delay next dose or discontinue inhibitor |
|
|||||||||