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Leech hirudin made recombinantly — the direct thrombin inhibitor with the highest thrombin affinity of its class, now discontinued.
Also known as: Refludan · HBW-023 · [Leu1, Thr2]-63-desulfohirudin · recombinant hirudin
Part of the Foundational & therapeutic peptides cluster
Overview
Lepirudin (Refludan) is a 65-residue recombinant hirudin, the anticoagulant peptide from leech saliva, differing from native hirudin by leucine at position 1 (for isoleucine) and the absence of a sulfate on tyrosine 63. C287H440N80O111S6, about 6,979 Da. A direct thrombin inhibitor approved by the FDA in 1998 for heparin-induced thrombocytopenia, it has been discontinued and is no longer marketed in the United States; bivalirudin and argatroban remain in the class.
Source & context
Biological / chemical source: Recombinant form of hirudin, the leech salivary anticoagulant, with Leu1 for Ile and no sulfate on Tyr63
Primary research or clinical context: Formerly approved (FDA 1998) as an anticoagulant for heparin-induced thrombocytopenia; discontinued (not withdrawn) and no longer marketed in the United States
What lepirudin is
Lepirudin is a recombinant form of hirudin, the anticoagulant found in the saliva of the medicinal leech (UniProt P01050), with two differences from the natural peptide: leucine replaces isoleucine at position 1, and tyrosine 63 carries no sulfate group (IUPHAR record). It is a 65-residue peptide — C287H440N80O111S6, about 6,979 Da by PubChem — whose six cysteines form the three disulfides of the compact hirudin fold. Marketed as Refludan, it was approved by the FDA in 1998 and is now discontinued, a status IUPHAR distinguishes from withdrawal; LactMed records that it is no longer marketed in the United States.
Mechanism: direct thrombin inhibition
Direct thrombin inhibitors interact with thrombin itself and block its catalytic activity on a wide range of substrates, in contrast to heparins, which act through antithrombin, and warfarin-type drugs, which interfere with synthesis of clotting-factor precursors (Kaplan & Francis, Seminars in Hematology 2002). Lepirudin binds thrombin and blocks its ability to cleave fibrinogen, preventing initiation of the clotting cascade (IUPHAR mechanism record). Among marketed direct thrombin inhibitors its affinity for thrombin is the highest, above bivalirudin (intermediate) and argatroban (lowest), which helps explain how strongly each interferes with functional clotting assays (Warkentin et al., Thrombosis and Haemostasis 2008).
Clinical role: heparin-induced thrombocytopenia
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug effect in which antibodies against complexes of platelet factor 4 and heparin activate platelets, producing hypercoagulability and a high risk of venous and arterial thrombosis, typically 5–10 days after starting heparin (Warkentin, Hematology/Oncology Clinics of North America 2007; Thiele et al., Der Internist 2010). Because heparin must be stopped, a non-heparin anticoagulant is needed, and direct thrombin inhibitors — lepirudin, bivalirudin and argatroban were the three approved for clinical use in the early 2000s — filled that role (Kaplan & Francis, 2002; Lee & Ansell, British Journal of Clinical Pharmacology 2011). The 2012 American College of Chest Physicians guideline addresses treatment and prevention of HIT, including platelet-count monitoring every 2–3 days from day 4 to day 14 when the risk exceeds 1% (Linkins et al., Chest 2012).
Laboratory monitoring
Ecarin-based coagulation tests, which use a viper-venom enzyme to activate prothrombin to meizothrombin, were initially described for assessing direct thrombin inhibitors such as bivalirudin, lepirudin and argatroban, are unaffected by heparins, and were long restricted to reference laboratories before the direct oral anticoagulants revived interest in them (Gosselin & Douxfils, American Journal of Hematology 2020). Lepirudin's high thrombin affinity means it interferes with functional clotting assays more than the other agents in its class (Warkentin et al., 2008).
Status as of September 2026
Lepirudin is discontinued and no longer marketed in the United States; the IUPHAR record is explicit that this is discontinuation, not a safety withdrawal. LactMed notes that limited information indicates very low milk levels at doses up to 100 mg daily and that, because of its size, infant absorption would not be expected. ClinicalTrials.gov returns a handful of unrelated or registry-type entries for the search term, including a retrospective registry of patients with acute HIT; no active lepirudin development exists. Bivalirudin, on this site, and argatroban remain the parenteral direct thrombin inhibitors in use.
How it relates to other peptides on this site
Bivalirudin is a 20-residue synthetic peptide designed from hirudin's two thrombin-binding regions, with the shortest half-life in the class (about 25 minutes) and predominant non-organ elimination (Warkentin et al., 2008); lepirudin is the full-length recombinant parent molecule. Desirudin is another recombinant hirudin. The thrombin-inhibiting peptides form a natural cluster with the antiplatelet cyclic peptides eptifibatide and bevifibatide, which act on platelets rather than the coagulation cascade.
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
- Hirudin variant from Hirudo medicinalis, recombinant; I1L substitution and desulfated Tyr63
- 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
L-V-Y-T-D-C-T-E-S-G-Q-N-L-C-L-C-E-G-S-N-V-C-G-Q-G-N-K-C-I-L-G-S-D-G-E-K-N-Q-C-V-T-G-E-G-T-P-K-P-Q-S-H-N-D-G-D-F-E-E-I-P-E-E-Y-L-Q (65 residues; three disulfides among the six cysteines)
- Molecular formula
- C287H440N80O111S6
- Average reference mass
- ≈ 6,979
- Receptors
- Enzyme target: thrombin (direct, bivalent inhibitor) — not a receptor ligand
- Backbone
- Hirudin variant from Hirudo medicinalis, recombinant; I1L substitution and desulfated Tyr63
- Status
- Discontinued (not withdrawn); formerly FDA-approved (1998). No longer marketed in the US
Leu1 replaces Ile1 at the N-terminus; Tyr63 lacks the sulfate group present in natural hirudin
- PubChem CID: 118856773
- IUPHAR ligand: 6469
- CAS RN: 138068-37-8
- UNII: Y43GF64R34
Chemistry values: curated profile, PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 9 registered studies with “Lepirudin” as an intervention (snapshot 2026-09-07). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT05847205 | Study Evaluation of Recombinant Hirudin in Prophylaxis of Post-Operative Deep Vein Thrombosis | Phase 4 | unknown | 2023-05-06 |
| NCT04593147 | Phase II Growth and Safety Study of an Infant Formula for Healthy Term Infants | Not applicable | completed | 2021-11-15 |
| NCT03331276 | Growth and Safety Study of an Infant Formula for Healthy Term Infants | Not applicable | completed | 2020-10-19 |
| NCT00603824 | Fondaparinux in Patients With Acute Heparin-Induced Thrombocytopenia (HIT) | Phase 4 | withdrawn | 2019-08-13 |
| NCT01304238 | Retrospective Registry of Patients With Acute Heparin-induced Thrombocytopenia Type II | — | completed | 2017-07-06 |
| NCT00003726 | Lepirudin in Treating Patients With Recurrent or Advanced Small Cell Lung Cancer | Phase 2 | terminated | 2016-08-08 |
Lepirudin — 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: Hirudin variant from Hirudo medicinalis, recombinant; I1L substitution and desulfated Tyr63Average reference mass: 6,979 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.
- IdentifiersCross-linked to IUPHAR ligand 6469 and PubChem CID 118856773.
- TrialsClinicalTrials.gov snapshot added: 9 registered studies, highest phase 4.
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Lepirudin
What is Lepirudin?+
Lepirudin (Refludan) is a 65-residue recombinant hirudin, the anticoagulant peptide from leech saliva, differing from native hirudin by leucine at position 1 (for isoleucine) and the absence of a sulfate on tyrosine 63. C287H440N80O111S6, about 6,979 Da. A direct thrombin inhibitor approved by the FDA in 1998 for heparin-induced thrombocytopenia, it has been discontinued and is no longer marketed in the United States; bivalirudin and argatroban remain in the class.
What Canadian product status is recorded for Lepirudin?+
Canadian product status for Lepirudin 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 Lepirudin?+
Lepirudin is commonly described as approximately 65 amino acids (Recombinant hirudin (direct thrombin inhibitor)).
What is lepirudin?+
A 65-residue recombinant hirudin (Refludan), the leech anticoagulant peptide, with Leu1 for Ile and an unsulfated Tyr63. It is a direct thrombin inhibitor formerly used for heparin-induced thrombocytopenia.
Is lepirudin still available?+
No. It has been discontinued (not withdrawn for safety) and is no longer marketed in the United States.
How does lepirudin work?+
It binds thrombin directly and blocks its cleavage of fibrinogen, halting clot formation — independently of antithrombin, unlike heparin.
How does lepirudin compare with bivalirudin?+
Lepirudin has the highest thrombin affinity in the class; bivalirudin is a 20-residue synthetic hirudin fragment with an intermediate affinity, a half-life of about 25 minutes, and remains in use.
What is the sequence of lepirudin?+
LVYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQSHNDGDFEEIPEEYLQ — 65 residues with three disulfides; formula C287H440N80O111S6, about 6,979 Da.
Related peptides
References & further reading
- 1.Warkentin TE et al. (2008). Bivalirudin. Thromb Haemost
- 2.Kaplan KL, Francis CW (2002). Direct thrombin inhibitors. Semin Hematol
- 3.Lee CJ, Ansell JE (2011). Direct thrombin inhibitors. Br J Clin Pharmacol
- 4.Warkentin TE (2007). Heparin-induced thrombocytopenia. Hematol Oncol Clin North Am
- 5.Linkins LA et al. (2012). Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: ACCP Evidence-Based Clinical Practice Guidelines. Chest
- 6.Gosselin RC, Douxfils J (2020). Ecarin based coagulation testing. Am J Hematol
- 7.Drugs and Lactation Database (LactMed) — Lepirudin
- 8.PubChem — compound summary for Lepirudin (CID 118856773)