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Twenty residues, two thrombin-binding ends, and a 25-minute half-life that ends when thrombin itself cuts the peptide.
Also known as: Angiomax · Angiox · Hirulog · BG-8967
Part of the Foundational & therapeutic peptides cluster
Overview
Bivalirudin is a synthetic 20-residue peptide (FPRPGGGGNGDFEEIPEEYL) modelled on the leech anticoagulant hirudin. It binds thrombin at both the active site and the fibrinogen-recognition exosite, is cleared mainly by proteolysis rather than by an organ, and has the shortest half-life of the marketed direct thrombin inhibitors, about 25 minutes (Warkentin et al., Thrombosis and Haemostasis 2008). It is an approved anticoagulant for percutaneous coronary intervention.
Source & context
Biological / chemical source: Synthetic 20-amino-acid analog of hirudin
Primary research or clinical context: Approved anticoagulant (FDA) for percutaneous coronary intervention, including patients with or at risk of heparin-induced thrombocytopenia; studied off-label in ECMO
What bivalirudin is
Bivalirudin is a synthetic peptide congener of hirudin, the anticoagulant in the saliva of the medicinal leech Hirudo medicinalis. Twenty residues long, it was designed to reproduce hirudin's two-site grip on thrombin in a molecule small enough to synthesise chemically: an N-terminal D-Phe-Pro-Arg-Pro that occupies thrombin's catalytic site, a four-glycine linker, and a C-terminal dodecapeptide copied from hirudin's tail that binds the enzyme's fibrinogen-recognition exosite. It is a competitive, reversible inhibitor of thrombin; blocking thrombin interrupts the conversion of fibrinogen to fibrin and prevents clot formation. It is marketed as Angiomax in North America and Angiox in Europe.
Mechanism and what makes it unusual
Among the marketed direct thrombin inhibitors, bivalirudin has a unique profile: it is eliminated predominantly by proteolysis rather than by the kidney or liver, and it has the shortest half-life, about 25 minutes (Warkentin et al., Thrombosis and Haemostasis 2008). Thrombin itself slowly cleaves the Arg-Pro bond in the bound peptide, so inhibition is self-limiting — the enzyme escapes as the inhibitor is consumed. Its thrombin affinity sits between lepirudin's (highest) and argatroban's (lowest), which explains why it prolongs functional clotting assays such as the PT/INR to an intermediate degree (Warkentin et al., 2008).
Approved uses
Bivalirudin's first FDA-approved indication was anticoagulation during percutaneous transluminal coronary angioplasty; it is also indicated for PCI with provisional glycoprotein IIb/IIIa antagonist use, and for patients with, or at risk of, heparin-induced thrombocytopenia undergoing PCI (Warkentin et al., 2008). Assays to monitor it, including activated clotting time and dilute thrombin time, are reviewed by Davidson (Methods in Molecular Biology 2023). Its role in acute coronary syndromes remains debated: it reduces bleeding compared with unfractionated heparin but several randomised trials showed more acute stent thrombosis, a risk that a full-dose infusion continued after PCI appears to mitigate (Galli et al., Expert Review of Cardiovascular Therapy 2023).
ECMO and other off-label settings
Bivalirudin is increasingly used for anticoagulation during extracorporeal membrane oxygenation, especially in children who fail heparin. Single-centre studies describe less blood-product transfusion and lower cost with similar outcomes in paediatric ECMO patients switched from heparin, with aPTT the usual but limited monitoring test (Ryerson and McMichael, Current Opinion in Pediatrics 2022). In a single-centre randomised pilot in neonates and children on ECMO, 16 patients received bivalirudin and 14 heparin; there was no difference in time at goal anticoagulation, haemorrhagic complications were similar, and thrombotic complications were higher with bivalirudin, with six of 16 needing one or more circuit changes (McMichael et al., Pediatric Critical Care Medicine 2025). Larger randomised ECMO trials are recruiting.
| Setting | Finding | Source |
|---|---|---|
| Pharmacology | Half-life ≈ 25 min; proteolytic elimination; intermediate thrombin affinity | Warkentin et al., 2008 |
| ACS / PCI | Less bleeding than heparin; more acute stent thrombosis unless full-dose post-PCI infusion | Galli et al., 2023 |
| Paediatric ECMO pilot RCT (n=30) | No difference in time at goal; more thrombotic complications with bivalirudin | McMichael et al., 2025 |
| Registered studies | 92, including phase 2 ECMO trials | ClinicalTrials.gov snapshot |
Pharmacokinetics
The 25-minute half-life and non-organ clearance are the defining features (Warkentin et al., 2008). Because elimination is mostly proteolytic, kidney impairment lengthens the half-life less than it does for renally cleared anticoagulants, though dose adjustment is still described in clinical references (Berlioz et al., StatPearls 2026). The short half-life is why the drug is given as an intravenous bolus plus infusion during procedures and why anticoagulant effect wanes quickly after the infusion stops — an advantage in the catheterisation laboratory and a liability if thrombus protection is needed after the sheath is removed.
Regulatory status as of September 2026
Bivalirudin is an approved prescription anticoagulant in the United States (Angiomax) and Europe (Angiox), with generic versions available, and is catalogued by IUPHAR as an approved peptide. Its ECMO use is off-label and under active study. It has no grey-market presence of note; it is a hospital drug.
Bivalirudin vs hirudin, lepirudin and desirudin
Lepirudin and desirudin are recombinant 65-residue hirudins — full-length proteins with the highest thrombin affinity and renal clearance. Bivalirudin is the synthetic 20-residue distillation of hirudin's two binding motifs, trading affinity and duration for a short, self-limiting action that suits procedures. Lepirudin has since been withdrawn; desirudin was approved for thrombosis prophylaxis. The profiles for those two, and the leech hirudin they derive from, sit alongside this one as a case study in shrinking a natural protein into a synthetic peptide drug.
Sequence
One-letter sequence commonly cited for Bivalirudin (educational; isoforms and modifications may differ):
FPRPGGGGNGDFEEIPEEYL
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- 20 residues: D-Phe-Pro-Arg-Pro (active-site segment) – Gly4 linker – Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu (exosite segment from hirudin's C-terminus)
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Not specified
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
- Molecular formula
- C98H138N24O33
- Average reference mass
- ≈ 2,180.3
- Plasma half-life
- ≈ 25 min (predominantly non-organ elimination by proteolysis)
- Receptors
- Thrombin (serine protease): competitive, reversible bivalent inhibition of the catalytic site and anion-binding exosite 1; affinity intermediate between lepirudin and argatroban
- Backbone
- 20 residues: D-Phe-Pro-Arg-Pro (active-site segment) – Gly4 linker – Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu (exosite segment from hirudin's C-terminus)
- Status
- Approved (FDA): anticoagulation in PCI, with provisional GP IIb/IIIa use, and in patients with or at risk of HIT (IUPHAR record; Warkentin et al., 2008)
- PubChem CID: 16129704
- IUPHAR ligand: 6470
- ChEMBL: CHEMBL2103749
- DrugBank: DB00006
- CAS RN: 128270-60-0
- UNII: TN9BEX005G
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology, PubChem · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 92 registered studies with “Bivalirudin” as an intervention (snapshot 2026-09-06). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT04278404 | Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children Per Stan | — | recruiting | 2026-08-21 |
| NCT06080074 | Multicenter Trial of ECMO in Children With Severe Cardiac Failure Using the Cardiohelp System | Phase 2 | recruiting | 2026-08-10 |
| NCT05959252 | BivaLirudin versUS Heparin in Extracorporeal Membrane Oxygenation | Phase 2 | recruiting | 2026-05-08 |
| NCT06275555 | Use of Bivalirudin for Anticoagulation in Patients With Extracorporeal Membrane Oxygenation | Not applicable | recruiting | 2026-04-06 |
| NCT07383155 | Bivalirudin Versus Heparin During PCI in High Bleeding Risk Patients With Acute Coronary Syndromes | Phase 4 | not yet recruiting | 2026-02-03 |
| NCT03537586 | A Single Center Diagnostic, Cross-sectional Study of Coronary Microvascular Dysfunction | Not applicable | active not recruiting | 2025-11-28 |
Bivalirudin — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: 20 residues: D-Phe-Pro-Arg-Pro (active-site segment) – Gly4 linker – Asn-Gly-Asp-Phe-Glu-Glu-Ile-Pro-Glu-Glu-Tyr-Leu (exosite segment from hirudin's C-terminus)Average reference mass: 2,180.3 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Bivalirudin
What is Bivalirudin?+
Bivalirudin is a synthetic 20-residue peptide (FPRPGGGGNGDFEEIPEEYL) modelled on the leech anticoagulant hirudin. It binds thrombin at both the active site and the fibrinogen-recognition exosite, is cleared mainly by proteolysis rather than by an organ, and has the shortest half-life of the marketed direct thrombin inhibitors, about 25 minutes (Warkentin et al., Thrombosis and Haemostasis 2008). It is an approved anticoagulant for percutaneous coronary intervention.
What Canadian product status is recorded for Bivalirudin?+
Canadian product status for Bivalirudin has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Bivalirudin?+
Bivalirudin is commonly described as approximately 20 amino acids (Direct thrombin inhibitor).
What is bivalirudin?+
A synthetic 20-residue peptide anticoagulant modelled on leech hirudin. It inhibits thrombin at two sites and is approved for anticoagulation during percutaneous coronary intervention.
How does bivalirudin work?+
Its N-terminal D-Phe-Pro-Arg-Pro blocks thrombin's active site while a hirudin-derived tail binds the fibrinogen-recognition exosite. Thrombin slowly cleaves the peptide, so inhibition is reversible and self-limiting.
What is bivalirudin's half-life?+
About 25 minutes, the shortest of the marketed direct thrombin inhibitors, with elimination mainly by proteolysis (Warkentin et al., 2008).
Bivalirudin vs heparin?+
In PCI it causes less bleeding than unfractionated heparin but has been associated with more acute stent thrombosis unless a full-dose infusion is continued after the procedure (Galli et al., 2023).
Is bivalirudin used in ECMO?+
Off-label, increasingly, especially in children. A 30-patient pilot RCT found no difference in time at goal anticoagulation and more thrombotic complications with bivalirudin (McMichael et al., 2025); larger trials are under way.
What is the sequence of bivalirudin?+
FPRPGGGGNGDFEEIPEEYL — with a D-phenylalanine at position 1.
Further reading
- PK conceptsWhy Peptides Have Short Half-Lives (And How Engineers Fix It)Proteases, renal clearance, DPP-4, PEGylation, lipidation, cyclization—educational guide to peptide pharmacokinetics concepts.
- ManufacturingPeptide Synthesis Basics for Non-ChemistsPlain-language introduction to solid-phase peptide synthesis (SPPS), purification, and why custom peptides cost what they cost.
- PharmacologyGLP-1 and Incretin Peptide Half-Lives Compared: From 2 Minutes to 8 DaysA sourced table of the plasma half-lives of native GLP-1, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, retatrutide, cagrilintide and the newer co-agonists — and the three engineering strategies (DPP-4 resistance, albumin binding, Fc fusion) that stretch minutes into a week.
Related peptides
References & further reading
- 1.Warkentin et al. (2008). Bivalirudin. Thromb Haemost
- 2.Davidson (2023). Assays to Monitor Bivalirudin. Methods Mol Biol
- 3.Warkentin et al. (2005). Bivalirudin: a review. Expert Opin Pharmacother
- 4.McMichael et al. (2025). Prospective Randomized Pilot Study Comparing Bivalirudin Versus Heparin in Neonatal and Pediatric Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med
- 5.Bittl (2017). Bivalirudin or heparin for radial access?. Catheter Cardiovasc Interv
- 6.Dunham et al. (2024). Bivalirudin in Extracorporeal Membrane Oxygenation. J Cardiovasc Pharmacol
- 7.Gilchrist (2019). Heparin, bivalirudin, or the best of both for STEMI interventions. Catheter Cardiovasc Interv
- 8.Ryerson et al. (2022). Bivalirudin in pediatric extracorporeal membrane oxygenation. Curr Opin Pediatr
- 9.Galli et al. (2023). Bivalirudin in acute coronary syndromes. Expert Review of Cardiovascular Therapy
- 10.Berlioz et al. (2026). Bivalirudin. StatPearls
- 11.Shammas (2005). Bivalirudin: pharmacology and clinical applications. Cardiovascular Drug Reviews