Kcentra: coumadin reversal in acute major bleeding or need for urgent surgery:
- Pretreatment INR: 2 to <4: Administer 25 units/kg; maximum dose: 2,500 units
- Pretreatment INR: 4 to 6: Administer 35 units/kg; maximum dose: 3,500 units
- Pretreatment INR: >6: Administer 50 units/kg; maximum dose: 5,000 units
*Dosage expressed in units of factor IX activity
*give concurrent vitamin K
*Repeat dosing is not recommended (has not been studied).
Life-threatening hemorrhage with DOACs: (off label)
Optimal dosing not established
European Heart Rhythm Association, 50 units/kg (+25 units/kg if clinically necessary) recommended based on limited evidence in healthy volunteers
ICH due to various antithrombotic agents (NCS/SCCM [Frontera 2016]):
- apixaban, edoxaban, rivaroxaban:
- 50 units/kg if ICH within 3 to 5 terminal half-lives of drug exposure or when liver failure co-exists.
- argatroban, dabigatran [if idarucizumab unavailable], bivalirudin, desirudin:
- 50 units/kg if administered within 3 to 5 half-lives prior and no renal failure or there is renal impairment leading to drug exposure beyond 3 to 5 half-lives
FIXED vs. VARIABLE DOSE
Advantages of fixed dose KCentra:
- eliminates need for dose calculation based on patient-specific variables
- earlier start of hemostasis – limits hematoma enlargement?
- easier administration, no complex tables, reduction of door-to-needle time
- ?better clinical outcome
Retrospective study from Netherlands – fixed dose 1000 IU fIX PCC, ffd by 500 IU if INR>1.5, used Cofact (Sanquin BV) which contains FII FVII FIX FX and PrC and PrS, no activated factors or heparin. CONCLUSION: that fixed dose required further dose/s to achieve target INR. Door-to-needle time shorter, but not significant. ?clinical outcome unknown.
Bottom line: For now, calculate dose based on weight and INR.
“Prothrombin complex concentrate, 4-factor, unactivated, from human plasma”. Uptodate.com. Accessed 13 Dec. 2016.
Kcentra product insert.
Abdoellakhan, Rahat Amadkhan et al. “Fixed Versus Variable Dosing Of Prothrombin Complex Concentrate In Vitamin K Antagonist-Related Intracranial Hemorrhage: A Retrospective Analysis”. Neurocritical Care 26.1 (2016): 64-69.