Anticoagulant · Direct thrombin inhibitor
Argatroban
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Heparin vs Warfarin: aPTT vs INR, HIT, Bridging, Antidotes and DOAC Reversal
Indications
- Prevention or treatment of thrombosis in suspected or confirmed HIT
- PCI in patients with or at risk of HIT
- HIT with kidney failure or CRRT, since the kidneys play no part in its clearance
- Circuit anticoagulation for CRRT or ECMO when heparin cannot be used (off-label)
Dosing
Argatroban drip card and mL/h converterStart: 2 mcg/kg/min; 0.5 mcg/kg/min with moderate or severe liver impairment (label); 0.5–1.2 with heart failure, multiorgan failure or after cardiac surgery (ACCP 2012)
Mechanism of action
Argatroban is a small synthetic direct thrombin inhibitor built on L-arginine. It binds reversibly to thrombin's catalytic site (Ki about 40 nM), its guanidino group sitting in the arginine-specific S1 pocket, and needs no antithrombin, so it inhibits free and clot-bound thrombin alike. That blocks fibrin formation, activation of factors V, VIII, XIII and protein C, and thrombin-induced platelet aggregation. It spares trypsin, Xa, plasmin and kallikrein and is not recognized by HIT antibodies.
Pharmacology
- Hematologic: dose-dependent rise in aPTT, ACT, PT/INR and thrombin time, reaching steady state in 1–3 h
- Hematologic: raises the INR more than other thrombin inhibitors, so warfarin overlap follows special INR rules
- Hepatic: clearance falls in liver dysfunction and with congestion or low flow (heart failure, shock, after cardiac surgery), so these patients start lower
Pharmacokinetics
| Onset | Immediate IV; check the aPTT 2 h after each change |
|---|---|
| Duration | aPTT back to baseline 2–4 h after stopping; longer in liver failure |
| Half-life | 39–51 min; about 3 h (181 min) in hepatic impairment |
| Distribution | Vd 174 mL/kg, mainly extracellular fluid |
| Protein binding | 54% (34% α1-acid glycoprotein, 20% albumin) |
| Metabolism | Liver: CYP3A4/5 hydroxylation and aromatization of the tetrahydroquinoline ring; the main metabolite is 3–5 times weaker |
| Clearance | 5.1 mL/kg/min; 1.9 in hepatic impairment, where the label starts at a quarter of the usual rate |
| Elimination | Feces via bile about 65%, urine about 22% (16% unchanged); no kidney adjustment |
| Dialysis | About 20% removed in 4 h of hemodialysis, too little to change dosing |
Chemistry
- Synthetic L-arginine derivative carrying a 3-methyl-tetrahydroquinoline sulfonyl group and a 4-methylpiperidine carboxylic acid; MW 508.6 (526.7 as the monohydrate)
- Three chiral centers are fixed; the fourth, C-21 on the tetrahydroquinoline, is a 65:35 R:S mixture given as is
- Zwitterion at pH 7.4 (protonated guanidino group, ionized carboxyl), modestly lipophilic (XLogP 1.3); limited water solubility explains the propylene glycol and ethanol vehicle and the brief haze on dilution
- The 250 mg/2.5 mL concentrate is diluted 100-fold to 1 mg/mL in NS, D5W or LR; ready-to-use 1 mg/mL also exists. Diluted drug keeps 24 h at room temperature, 96 h protected from light
Adverse effects and cautions
In the one-pagers
- Bleeding, Reversal, HIT and DICHeparin-induced thrombocytopenia (HIT): Start a non-heparin anticoagulant at once: argatroban (liver-cleared; good in kidney failure) or bivalirudin; fondaparinux or a DOAC when stable
- CRRT (Continuous Renal Replacement)Anticoagulation: Metabolic alkalosis usually means citrate overload (citrate becomes bicarbonate). In HIT, stop all heparin, including catheter locks, flushes and priming; use a non-heparin anticoagulant such as argatroban (liver-cleared, aPTT-monitored) per protocol.
- ECMO EssentialsMonitoring and anticoagulation: UFH is usual; bivalirudin or argatroban if HIT. High free Hb, bilirubin or lipids falsely lower anti-Xa. Follow your institution's protocols.
- Impella Heart PumpPurge system: HIT: stop all heparin, purge included. Use a bicarbonate-dextrose purge and IV argatroban or bivalirudin, per your institution's or agency's protocols.
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Sources
- FDA label: Argatroban, Fresenius Kabi (2025)
- PubChem: argatroban
- Garcia, ACCP Parenteral Anticoagulants (Chest 2012)
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.