Reversal agent · Blood product
4F-PCC (Kcentra)
Also called Kcentra, prothrombin complex
Watch the explainer
Heparin vs Warfarin: aPTT vs INR, HIT, Bridging, Antidotes and DOAC Reversal
Indications
- Urgent warfarin reversal in adults with acute major bleeding, given with IV vitamin K (label)
- Warfarin reversal before urgent surgery or an invasive procedure (label)
- Warfarin-associated intracranial hemorrhage, instead of plasma
- Bleeding on apixaban, rivaroxaban or edoxaban (off-label), the US choice since andexanet's withdrawal
- Dabigatran bleeding when idarucizumab is unavailable (off-label)
- Bleeding after cardiopulmonary bypass (off-label; FARES-II 2025)
Dosing
| Where | Dose |
|---|---|
| Reversal and antidotes | 4F-PCC (Kcentra): 25–50 units/kg by INR (max 5,000 units) with vitamin K 10 mg |
On the quick cards
Mechanism of action
Four-factor prothrombin complex concentrate (4F-PCC) holds the vitamin K-dependent factors II, VII, IX and X, purified from pooled human plasma. It replaces the factors warfarin depletes at about 25 times their plasma concentration, restoring thrombin generation within minutes in a small volume. It also carries proteins C and S, plus a little heparin and antithrombin to keep the factors from activating in the vial. For factor Xa inhibitors it removes no drug; extra prothrombin and factor X raise thrombin generation enough to overcome partial inhibition.
Pharmacology
- Hematologic: median INR fell from above 3 to 1.2 by 30 min (label); INR 1.3 or less at 30 min in 62% vs 10% with plasma (Sarode 2013)
- Hematologic: effective hemostasis 72% vs 65% with plasma in major bleeding, 90% vs 75% before procedures (label)
- Hematologic: factor VII fades first (half-life 5 h), so the INR rebounds unless vitamin K is given
- Cardiovascular: a small volume avoids plasma's load: fluid overload 4.7% vs 12.7% (label)
Pharmacokinetics
| Onset | Minutes; INR corrected by 30 min (label) |
|---|---|
| Duration | Factors decay at their own rates; vitamin K sustains the effect |
| Half-life | Factor VII 5 h, X 32 h, IX 42 h, II 60 h; proteins C and S about 50 h (label) |
| Distribution | Intravascular; each unit/kg raises most factors about 2 units/dL (label) |
| Elimination | Consumed in clotting or catabolized like native plasma proteins |
| Routes | IV only, through a separate line, at 0.12 mL/kg/min, max 8.4 mL/min (label) |
| Repeat dosing | Not established and not recommended (label) |
Chemistry
- Kcentra: from pooled US source plasma; potency in factor IX units
- Per 500-unit vial (label): factors II 380–800, VII 200–500, IX 400–620 and X 500–1,020 units; proteins C 420–820 and S 240–680 units; heparin 8–40 and antithrombin 4–30 units; albumin
- Virus safety: donor testing, heat treatment at 60 °C for 10 h and two 20 nm virus filters
- Lyophilized; 20–31 units/mL in sterile water; store at 2–25 °C, use within 4 h and mix with nothing (label)
- Not interchangeable with 3-factor PCC (little factor VII) or activated PCC (FEIBA)
Adverse effects and cautions
In the one-pagers
- Bleeding, Reversal, HIT and DICReversing anticoagulants in major bleeding: Warfarin: 4F-PCC plus vitamin K 10 mg IV (slow): PCC 25–50 units/kg by INR; FFP only if no PCC
- Blood Products and TransfusionProducts at a glance: 4F-PCC: Factors II, VII, IX, X; proteins C and S: Fast warfarin reversal, small volume
- Neuro: ICP and StrokeHemorrhagic stroke (ICH): Warfarin, INR 2 or more: 4F-PCC (not FFP) plus IV vitamin K
- Subarachnoid HemorrhageUntil the aneurysm is secured: Reverse anticoagulants now: warfarin, 4F-PCC plus IV vitamin K; dabigatran, idarucizumab; factor Xa inhibitors, 4F-PCC; heparin, protamine.
- LVAD BasicsComplications: bleeding, stroke, infection, RV failure: Hemorrhagic stroke: No supratherapeutic INR, control MAP: Reverse warfarin (4F-PCC, vitamin K); neurosurgery
In the algorithms
Other reversal agent drugs
Sources
- FDA label: Kcentra (2023)
- Sarode 2013 (Circulation)
- Bouzat 2023 (PROCOAG, JAMA)
- Karkouti 2025 (FARES-II, JAMA)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow the order, the label and your institution's protocols.