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# Parenteral direct thrombin inhibitors

Intravenous anticoagulants that block thrombin directly, without antithrombin. Key options in heparin-induced thrombocytopenia and coronary procedures.

Updated 2026-11-01

## What they are

Intravenous drugs that bind thrombin (factor IIa) itself: argatroban, a small synthetic molecule, and bivalirudin, a synthetic peptide modelled on hirudin from leeches. Dabigatran is the oral member of the same idea (DOAC page).

## Mechanism of action

Thrombin turns fibrinogen into fibrin, activates factors V, VIII and XIII and strongly activates platelets. Direct thrombin inhibitors bind the active site of thrombin (and, for bivalirudin, also exosite 1, the fibrinogen-binding groove), both free and inside clots, without needing antithrombin. They have no structural relation to heparin, so they do not trigger or worsen heparin-induced thrombocytopenia.

Target: Thrombin (coagulation factor IIa)

## Key points

- Argatroban is the classic anticoagulant for heparin-induced thrombocytopenia; it is cleared by the liver, so the regimen is reduced in liver impairment.
- Bivalirudin is used during percutaneous coronary intervention, including in HIT; it is cleared by the kidneys and by proteolysis.
- Both have short half-lives (under an hour) and are followed with the aPTT (argatroban) or the activated clotting time (bivalirudin).
- Argatroban raises the INR on its own, which complicates the switch to warfarin.
- There is no specific antidote; their short action is the safety net.

## Drugs in this class

- [**Argatroban** An intravenous anticoagulant that blocks thrombin directly. The usual choice when heparin-induced thrombocytopenia… Thrombin (coagulation factor IIa)](https://durgical.com/en/pharmacology/argatroban/)
- [**Bivalirudin** An intravenous peptide that blocks thrombin directly during coronary angioplasty. Its effect fades about an hour after… Thrombin (coagulation factor IIa)](https://durgical.com/en/pharmacology/bivalirudin/)

## Others in the class

- dabigatran (oral, DOAC page)
- desirudin
- lepirudin (withdrawn)

## Test yourself

Think of the answer, then tap the question to see it.

## Why are direct thrombin inhibitors used in heparin-induced thrombocytopenia?

They block thrombin directly and are unrelated to heparin, so they do not react with the heparin-platelet factor 4 antibodies that drive HIT.

## Which organ clears argatroban, and which clears bivalirudin?

Argatroban: the liver (biliary route). Bivalirudin: the kidneys, plus breakdown by proteases.

## Why can the INR look too high while argatroban and warfarin overlap?

Argatroban prolongs the prothrombin time and INR by itself, so the combined INR overstates warfarin's effect.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - ARGATROBAN injection, solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=629aee90-3bf3-4947-a978-21cbba2e1c41) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - BIVALIRUDIN injection, powder, lyophilized, for solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ce56f806-7845-429d-a1ce-c2dbf79b22eb) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=B01AE&showdescription=no) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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