Anticoagulation agents
Warfarin: INR lags 48 h. Life-threatening bleed: vitamin K 5–10 mg IV + 4F-PCC. INR >10 no bleed: PO vitamin K 2.5–5 mg.
Warfarin
Warfarin is a vitamin K antagonist: it blocks gamma-carboxylation of factors II, VII, IX, X and proteins C and S (ASH: ; CHEST: ; AHA: ). Half-life ~40 hours and highly variable. CYP2C9 is the interaction highway. INR lags ~48 hours behind a dose change.
Overlapping a direct thrombin inhibitor: follow chromogenic factor Xa, goal 20–40% — not the INR.
| INR versus goal | Move (UW dosing nomogram) |
|---|---|
| Below goal | Increase weekly dose 5–15%, or a one-time booster |
| At goal | No change |
| 0.1–1.0 above goal | Decrease 5–15%; consider holding one dose |
| >1.0 above goal | Hold until back at goal, then restart 10–20% lower |
- To parenteral anticoagulation: start the drip without a bolus when INR <2.
Bleed
Life-threatening or intracranial
Vitamin K 5–10 mg IV over 10–20 min plus 4-factor PCC (Kcentra) over 10 min if INR >2 (≥1.5 in ICH). If PCC is unavailable, 2 units FFP by rapid infusion.
No bleed
Number only
INR >10: vitamin K PO 2.5–5 mg. INR 4.5–10: vitamin K PO 1–2.5 mg if bleeding risk is high. INR <4.5: hold warfarin, no reversal.
DOACs
Xa-inhibitor switching (J Thromb Thrombolysis 2016;41:206): to parenteral — start when the next DOAC dose is due. From LMWH/fondaparinux — start 0–2 h before the next dose. From UFH — start when the drip stops (edoxaban: 4 h later). DOAC-to-DOAC: start when the next dose would have been due.
| Agent | Mechanism / kinetics | Dosing that matters | Switch / reverse |
|---|---|---|---|
| Dabigatran | Direct thrombin (IIa) inhibitor. t½ 12–17 h. 80% renal. P-gp substrate. Dyspepsia; possible coronary signal | AF: 150 mg BID if GFR >30, 75 mg BID if 15–30 (, ); some use 100 mg BID if high bleed risk. VTE: 150 mg BID after 5 days UFH/LMWH (, ). Prophylaxis: 110 mg × 1 then 220 mg daily (RE-NOVATE II, ) | To parenteral: start 12 h after last dose (24 h if CrCl <30). From parenteral: start <2 h before the next dose. To warfarin: start warfarin 3 d before stopping if CrCl ≥50; 2 d if 31–50; 1 d if 15–30. From warfarin: start when INR <2. Reversal: idarucizumab 5 g (RE-VERSE, ). Hydrophilic — dialysis works |
| Rivaroxaban | Direct Xa. t½ 5–9 h (11–13 in elderly). ~66% renal. Avoid dual CYP3A4 and P-gp inhibitors. Take with food | AF: 20 mg daily if GFR >50, 15 mg if 15–50 (ROCKET AF, ). VTE: 15 mg BID × 21 d then 20 mg daily; after 6 months consider 10 mg daily if risk persists (; ; ). Prophylaxis 10 mg daily (). ASCVD: 2.5 mg BID + ASA () | Start when INR <3 coming off warfarin. Not dialyzable (protein-bound) |
| Apixaban | Direct Xa. t½ 12 h. Only ~25% renal — usable in ESRD | AF: 5 mg BID; 2.5 mg BID if 2 of 3: Cr ≥1.5, weight ≤60 kg, age ≥80. Some use 2.5 mg BID if CrCl 15–29 (). VTE: 10 mg BID × 7 d then 5 mg BID × 6 months; after 6 months consider 2.5 mg BID ( & 368:699). Prophylaxis 2.5 mg BID () | Start when INR <2 coming off warfarin |
| Edoxaban | Direct Xa. t½ 10–14 h. ~50% renal. P-gp substrate. Avoid if CrCl >95 or <15 | AF: 60 mg daily; 30 mg if CrCl 15–50 or weight ≤60 kg (). VTE: 60 mg daily after 5 days UFH/LMWH; 30 mg if CrCl 15–50, ≤60 kg, or on a P-gp inhibitor () | Start when INR ≤2.5 coming off warfarin. High CrCl → low levels → more ischemic stroke in ENGAGE |
- To warfarin from rivaroxaban/apixaban: stop the DOAC, start warfarin, and use a parenteral until INR is therapeutic. All Xa inhibitors raise INR, so do not 'read' it as warfarin effect while they are still on board.
- Edoxaban: cut the dose in half, start warfarin, stop edoxaban once INR ≥2.
Parenteral agents
| Agent | Dosing / monitor | Switching | Reversal and notes |
|---|---|---|---|
| UFH — binds ATIII, inactivates Xa and IIa. t½ 60–90 min | ACS: 60 U/kg then 12 U/kg/h, PTT 63–83 (assay-specific). VTE: 80 U/kg then 18 U/kg/h, PTT 70–100. Prophylaxis 5,000 U SC q8–12h. Anti-Xa 0.3–0.7 if baseline PTT is high or doses are large; ACT when doses are huge | To LMWH: give LMWH and stop UFH together. To warfarin: stop UFH once INR therapeutic ≥2 days | Protamine 1 mg per 100 U heparin (max 50 mg). Do not give FFP — it contains ATIII and potentiates heparin. Preferred in CrCl <30, peri-procedure, poor absorption, pregnancy |
| Enoxaparin (LMWH) — ATIII, Xa >> IIa. t½ 4.5–7 h | ACS/VTE: 1 mg/kg BID; daily if GFR <30. Prophylaxis 40 mg SC daily; 30 mg BID if high risk; increase ~30% if BMI ≥40; 30 mg daily if GFR <30. Anti-Xa not routine; if used, 4 h after the 4th dose, goal 0.5–1.0 | To UFH: start UFH without bolus 1–2 h before the LMWH dose is due. To warfarin: stop LMWH once INR therapeutic ≥2 days | Protamine ~60% reversal, best if last dose <8 h. Acute VTE: LMWH > UFH (Cochrane Rev 2017). Half-life prolongs in renal failure |
| Fondaparinux — ATIII, Xa only. t½ 17–21 h | VTE: <50 kg → 5 mg daily; 50–100 kg → 7.5 mg; >100 kg → 10 mg. Prophylaxis 2.5 mg daily. Contraindicated if CrCl <30. Anti-Xa at 4 h if you must | To warfarin: stop once INR therapeutic ≥2 days. To UFH: start UFH (no bolus) 1–2 h before due. From UFH: start 1 h after the drip stops | No reversal agent. Therapeutic doses raise aPTT. If CrCl 30–50, consider a different agent |
| Argatroban — direct thrombin inhibitor. t½ 45 min | HIT: 1–2 mcg/kg/min. PTT goal 1.5–3× baseline. Caution in critical illness, cardiac dysfunction, liver disease | To warfarin: stop once chromogenic factor Xa is 20–40% (argatroban raises INR) | No reversal agent. Hepatic clearance — the HIT drug in renal failure |
Factor XI/XII inhibitors are under investigation (): antisense oligonucleotides, antibodies (abelacimab, ; osocimab), and small molecules (milvexian). They are not ward drugs yet.