Warfarin, DOAC, heparin reversal - ACEM Fellowship Notes

#trauma #resus > [!references]- > - [LITFL prothrombinex](https://litfl.com/prothrombinex/) > - [Dunn's clotting factor replacement](x-devonthink-item://1BC22B6F-8634-47D6-8C7E-BE2827AD7DC9) > - [Reversal of anti-coagulation - Dunn’s](x-devonthink-item://DE95D41B-96AB-4334-A1B3-C00F70175AB4) > - [rosen medication-induced anticoagulation](x-devonthink-item://F3C647AF-B411-4C79-AA85-8C42F04A7DFC?page=11&istart=2855&ilength=33&search=Medication-Induced%20Anticoagulation) > - [Hayes' thrombolysis and heparin reversal](x-devonthink-item://B1217276-B3E7-4AD4-87E5-F5105CDA4546) > - EBM: Eastern Trauma 2024 [4F PCC non-inferior to andexant alfa for Xa reversal](https://journals.lww.com/jtrauma/fulltext/2024/10000/four_factor_prothrombin_complex_concentrate_is_not.8.aspx) See also: [[Prothrombinex]], [[FFP]], [[DOAC overdose]] > [!treatment] Warfarin reversal if unstable > - [[Prothrombinex]] 25-50 unit/kg > - [[FFP]] 1-2 units 150-300mL IV > - Vitamin K 5-10mg IV # Indications - invasive percutaneous procedures - joint tap INR <2.5, preferably <2 - [[TPA|thrombolysis]] for stroke - INR needs to be <1.7 - # treatment for supratherapeutic INR | INR | tx | | ---------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------- | | major life-threatening bleeding and INR ≥ 1.5 (intracranial, spine, other life-threatening) | - cease warfarin - vitamin K 10mg IV over 30 min - prothrombinex 50 units/kg max 5000 - 150-300 mL of FFP (15mL/kg if PCC not available) | | INR > 10 + bleeding | - vitamin K 10 mg - prothrombinx 50 u/kg | | INR > 10, no bleeding | - cease warfarin - vitamin K 5mg oral or IV - consider PCC 15-30 IU/kg if high risk bleed - rpt INR in 12-24 hours | | INR 4.5-10, no bleeding | - clease warfarin - if higher risk of bleeding or low chance VTE, consider vitamin K 1-2.5mg oral - repeat INR in 24 hours - admit SSU for this | | INR <4.5, no bleeding | - lower or omit next dose if >10% above therapeutic range | | minor haemorrhage | - omit warfarin - rpt INR in 24 hours and dose-adjust - 1 u [[FFP]] - vitamin K 1-2 mg orally or 0.5-1mg IV if INR > 4.5 or ongoing bleeding | **ProthrombineX dose for Warfarin reversal in major bleeding** - INR 2-4: 25 u/kg max 2500 units - INR 4-6: 35 u/kg max 2500 - INR >6: 50 u/kg max 5000 ## vitamin K - takes hours to take effect - IV solution is well-absorbed orally! - don't give IM ## FFP - 150-300mL IV generally the volume - usually 1-2 units of FFP IF also giving with [[Prothrombinex]] - 15mL/kg FFP (2-4 units) if PCC not available # heparin reversal - protamine 1mg per 100 units of heparin - do not exceed more than 50mg over 10 minutes, can lead to hypotension ## LMWH reversal protamine 0.5-1mg for every 1mg of LMWH 1mg if last given ≤ 8 hours ago 0.5 mg if > 8 hours ago # DOAC reversal see [[DOAC overdose]] | anticoagulant | reversal agent | | ----------------------- | --------------------------------------------------------------------------------------------------------------- | | dabigatran | - idarucizumab 5g IV - if unavailable, then prothrombinex 50 units/kg IV - can be dialysed within 4 hours | | apixaban rivaroxaban | - andexanet alfa - prothrombinex 25-50 units/kg IV or fixed dose of 2000 units IV | 4FCC 50 u/kg cap 5000 beriplex also for apixaban ## Andexanet alfa See: [Andexanet Alfa RMH guideline](x-devonthink-item://FF9A6497-374A-455E-B2E0-FFCABABCAE6C) **MOI**: Recombinant modified activated Factor X. Factor Xa inhibitors bind to andexanet alfa with the same affinity as to natural FXa. As a consequence, in the presence of andexanet alfa, natural FXa is partially freed, which can lead to effective haemostasis. ***Indications*** For patients on apixaban or rivaroxaban with intracranial haemorrhage or life-threatening GI bleed who meet the strict formulary approval criteria: ***Inclusion*** 1. Administration able to occur within 6 hours of ICH onset or 6 hours of waking with symptoms, **AND** 2. Last dose of apixaban or rivaroxaban within 15 hours - Life-threatening gastrointestinal (GI) haemorrhage with last dose of apixaban/rivaroxaban within 18 hours ***Exclusion*** 1. Patient with clear palliative care goals 2. Prior arterial thrombotic event within the last 2 weeks 3. GCS <7 4. Haematoma volume >60mL **Risks** - Reversal of anticoagulant therapy exposes patients to the thrombotic risk of their underlying disease. The use of andexanet alfa has been associated with a ==10.5% risk of thrombosis.== Resumption of anticoagulant therapy should be considered as soon as medically appropriate - No data in pregnant patients - Avoid using concomitantly with 4CC products - Common adverse effects(1-10%): Cerebrovascular accident, ischaemic stroke, acute myocardial infarction, deep vein thrombosis, pulmonary embolism, pyrexia, urinary tract infection, pneumoniae, delirium, hypotension, headache, hypertension, nausea, pneumonia aspiration, constipation # General reversal table | Scenario | Agent | Dose | Comments | Level of Evidence | | ------------------------------------------- | -------------------------------- | -------------------------------------- | -------------------------------------------------- | ----------------- | | Warfarin | FFP *or* | 15 mL/kg | Usually 4-6 U (200 mL) each are given | B | | | PCC (prothrombinex) *and* | 15-30 U/kg | Works faster than FFP but carries risk of DIC | B | | | IV Vitamin K | 10 mg | Can take up to 24 h to normalize INR | B | | Warfarin and emergency NSx intervention | Above plus rFVIIa | 20-80 μg/kg | Contraindicated in acute thromboembolic disease | C | | Unfractionated or LMWH | Protamine sulfate | 1 mg per 100 U heparin or 1mg LMWH | Can cause flushing, bradycardia, or hypotension | C | | Platelet dysfunction or thrombocytopaenia | Platelet transfusion *and/or* | 6U | Range, 4-8 U based on size; transfuse to > 100,000 | C | | | desmopressin (DDAVP) | 0.3 μg/kg | single dose required | C | | Thrombin inhibitors (Dabigatran) | Oral charcoal *plus* | 15-30 U/kg 20-80 μg/kg | If ingestion < 2 h Risk of DIC | C | | | PCC *plus* | | | | | | rFVIIa plus | | | | | | haemodialysis | | | | | Factor Xa inhibitors (apixaban, xarelto) | rFVIIa | 20-80 μg/kg | | C | ![[Pasted image 20240219135421.png]] ^ from [current management of spontaneous ICH bookends 2017](bookends://sonnysoftware.com/ref/DL/299170)