Shock Syndromes II
iv.
Recommendations in a life-threatening hemorrhage:
| (a) | Phytonadione 10 mg intravenously and a 4F-PCC (dose is determined by patient weight |
|---|
and pretreatment INR; see Table 7) are preferred for most patients.
| (b) | Fixed dose 4F-PCC (e.g., 1000–1500 units) has been evaluated for warfarin reversal |
|---|
showing correction of the INR, but the lower dose may fail to correct the INR to goal,
necessitating additional treatment. The 2020 ACC guidelines consider fixed low dose
(1000 units for non-intracranial major bleed and 1500 units for intracerebral hemorrhage)
as an alternative to the package insert dosing, but this is off-label and has lower-quality
supporting evidence.
| (c) | In patients with a contraindication to 4F-PCC (e.g., a history of heparin-induced |
|---|
thrombocytopenia), fresh frozen plasma 10–15 mL/kg or non-heparin containing PCC
may replace 4F-PCC for reversal.
| (d) | Although the goal INR is controversial, the 2016 Neurocritical Care Society guidelines |
|---|
recommend trending an INR in patients with intracranial hemorrhage with repeat reversal
strategies until the INR is less than 1.4. Randomized controlled trials of 4F-PCC included
only patients with an INR of 2 or greater.
Direct oral anticoagulants (DOACs) – Dabigatran/apixaban/rivaroxaban/edoxaban:
Coagulation assays that have direct, linear relationships to the DOAC anticoagulation activity are
not available for clinical use (Table 6).
Therefore, the initial approach to reversal should be guided by clinical bleeding and the knowledge
of preexisting DOAC use rather than coagulation assays.
Given the relatively short DOAC half-life in patients with normal end-organ function, establishing
the time from the last dose is critical in determining whether the drug is contributing to bleeding.
In general, if it has been more than 3–5 half-lives since the last dose, reversal is probably not
indicated (Table 6).
Warfarin
Dabigatran
Apixaban
Rivaroxaban
Edoxaban
Action
Vitamin K
antagonist
Direct factor IIa
inhibitor
Direct factor Xa
inhibitor
Direct factor Xa
inhibitor
Direct factor Xa
inhibitor
Peak action
4–5 days
~2 hr
~2 hr
~2 hr
1–2 hr
Half-life (hr)
CrCl: > 80
CrCl: 50–79
CrCl: 30–49
CrCl < 30
> 48 hr
12–14
5–9
8–15
8.5
9.5
Clinical coagulation
monitoring
Protime/INR:
Quantitative
aPTT and TT:
Qualitative
ECT and
dilute TT:
Quantitative
Protime
Rivaroxaban, edoxaban: Qualitative, if validated
Apixaban: Insensitive
Chromogenic anti-Xa: Quantitative
Heparin or low-molecular-weight heparin assay:
Qualitative
anti-Xa = anti-factor Xa; CrCl = creatinine clearance reported as mL/min/1.73 m2; ECT = ecarin clotting time; TT = thrombin time.
| d. | Activated charcoal may be considered if the last dose was administered less than 2 hours previously. |
|---|
Given significant enterohepatic recirculation, charcoal can be given up to 6 hours after the last
apixaban dose.