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Direct Thrombin Inhibitor (Parenterally Administered Anticoagulant)

Argatroban Monohydrate

Brand names: Exembol, Novastan

Adult dose

Dose: Heparin-induced thrombocytopenia (HIT): 2 micrograms/kg/min IV, adjusted to aPTT 1.5–3× normal; max 10 micrograms/kg/min. Hepatic impairment: start at 0.5 micrograms/kg/min
Route: Intravenous continuous infusion
Frequency: Continuous infusion; titrate to aPTT

Clinical pearls

  • Direct thrombin inhibitor — inhibits both free and clot-bound thrombin without requiring antithrombin as cofactor (unlike heparin)
  • Indicated when heparin is contraindicated, specifically HIT (heparin-induced thrombocytopenia with or without thrombosis)
  • No reversal agent available — manage bleeding with supportive care; half-life ~40–50 min
  • BSH HIT Guidelines: argatroban and bivalirudin are non-heparin anticoagulant alternatives for HIT; fondaparinux also used
  • Argatroban elevates INR — use chromogenic factor X assay (or target INR >4) when transitioning to warfarin
  • NICE does not have a specific TA — used per BSH/BCSH HIT guidelines and local formulary

Contraindications

  • Active major bleeding
  • Severe hepatic impairment (mainly hepatically eliminated — major dose reduction required)

Side effects

  • Haemorrhage (dose-dependent — most serious)
  • Fever
  • Nausea
  • Hypotension
  • Elevated LFTs

Interactions

  • Other anticoagulants — additive bleeding risk; avoid concomitant use
  • Warfarin transition: argatroban prolongs PT/INR — use a chromogenic factor X assay or specialist protocol for warfarin transition
  • Thrombolytics — additive bleeding risk

Monitoring

  • aPTT every 2 hours until stable, then every 4–6 hours
  • Platelet count (monitoring for HIT resolution)
  • Signs of thrombosis or haemorrhage
  • LFTs (hepatic elimination — dose-adjust in hepatic impairment)
  • INR (if warfarin overlap — see pearl above)

Reference: BNF; BSH Guidelines on diagnosis and management of HIT (2012 updated 2019); BCSH argatroban guidelines; https://bnf.nice.org.uk/drugs/argatroban-monohydrate/. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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