4-Factor Prothrombin Complex Concentrate
Kcentra · Octaplex · Beriplex
Prothrombin complex concentrate (factors II, VII, IX, X + proteins C/S)
Replaces the vitamin-K-dependent factors → rapid restoration of coagulation. Small volume, fast, no cross-match.
Indications
- •Urgent warfarin reversal (major bleed / emergent surgery)
- •Factor Xa inhibitor reversal (off-label; the US option since andexanet left the market in December 2025)
Dosing
| Context | Adult | Pediatric |
|---|---|---|
| Warfarin reversal (INR 2–4) | 25 units/kg IV (max 2500) + IV vitamin K 5–10 mg | — |
| INR 4–6 / ≥6 | 35 / 50 units/kg IV (max 3500 / 5000) | — |
Pharmacokinetics
Onset minutes — corrects INR within 30 min; factor VII shortest half-life so recheck/redose.
Side effects
- !Thrombotic events
- !Contains heparin (Kcentra) — avoid in HIT
- !DIC (relative)
Contraindications
- ×HIT (Kcentra contains heparin)
- ×DIC
Clinical pearls
- ★Preferred over FFP for urgent warfarin reversal — faster, small volume, no cross-match (guideline-preferred).
- ★ALWAYS co-administer IV vitamin K — PCC factors decay in hours, vitamin K sustains reversal.
- ★Kcentra contains heparin → contraindicated in HIT (use an alternative PCC).
Other drugs in Coagulation Related
- Heparin (unfractionated)
Activates antithrombin → inactivates IIa (thrombin) and Xa.
- Tranexamic Acid (TXA)
Reversibly binds plasminogen, blocking conversion to plasmin → preserves fibrin clot.
- Protamine Sulfate
Strongly basic (positive-charge) protein binds to highly acidic (negative-charge) heparin → inactive ionic complex → renal excretion. 1 mg protamine neutralizes ~100 units heparin.
- DDAVP (Desmopressin)
Selective V2 agonist (renal water retention + Factor VIII/vWF release from endothelial Weibel-Palade bodies). NO V1 vasopressor activity at therapeutic dose.
- Warfarin
Inhibits vitamin K epoxide reductase (VKORC1) → depletes reduced vitamin K → ↓ synthesis of factors II, VII, IX, X plus proteins C/S. Full effect takes days (waits for existing factor decay).
- Enoxaparin
Antithrombin-mediated inhibition, weighted toward factor Xa over IIa (~3.8:1). More predictable than UFH — no routine monitoring.
- Dalteparin
Antithrombin-mediated factor Xa > IIa inhibition. Similar profile to enoxaparin; preferred LMWH in cancer-associated VTE (CLOT trial).
Suggested reading
- •Miller's Anesthesia, 9e
- •FDA package insert