RCT-Bibliothek

Merlino G, Carbone S, Servillo G, Marletta DA (2020) · Microsurgery

n=48 · single-center, open-label, parallel-group randomized trial (Naples)

Lehnhardt M, Daigeler A, Behr B, Schmidt SV, Wallner C (2021) · Plastic and Reconstructive Surgery

n=96 · multicenter (5 sites), open-label, randomized controlled trial (Germany)

Whitaker IS, Josty IC, Hawkins S, Azzopardi E, Naderi N, Graf J, Damaris L, Lineaweaver WC, Kon M (2011) · Microsurgery

n=35 · single-center, retrospective 4-year clinical series and risk-benefit review (Welsh Centre for Burns and Plastic Surgery, Morriston Hospital, Swansea, UK)

Pannucci CJ, Nelson JA, Chung CU, Fischer JP, Kanchwala SK, Kovach SJ, Serletti JM, Wu LC (2014) · Microsurgery

n=23 · single-center, retrospective cohort study using a prospectively maintained institutional database (University of Pennsylvania, Division of Plastic Surgery)

Resch JC, Hedstrom R, Steiner ME, Said SM, Somani A (2023) · Frontiers in Pediatrics

n=7 · single-center, retrospective observational cohort using institutional database query (University of Minnesota, M Health Fairview Masonic Children's Hospital)

Mozafari N, Ghazisaidi MR, Hosseini SN, Abdolzadeh M (2010) · Microsurgery

n=56 · single-center, open-label, randomized controlled trial comparing medicinal leech therapy with venous catheterization for venous congestion of the distally based sural flap (Shahid Beheshti University of Medical Sciences, Tehran, Iran)

Azzopardi EA, Whitaker IS, Rozen WM, Naderi N, Kon M (2011) · Journal of Reconstructive Microsurgery

n=25 · systematic review and critical appraisal of chemical and mechanical alternatives to medicinal leech therapy for venous congestion (Welsh Centre for Burns and Plastic Surgery, UK)

Rothenberger J, Petersen W, Schaller HE, Held M (2016) · Wound Repair and Regeneration

n=12 · single-center prospective observational study using tissue spectrophotometry and laser Doppler flowmetry to quantify perfusion dynamics during leech therapy (BG-Trauma Center, Eberhard Karls University Tuebingen, Germany)

Reese K, Gümbel D, Seifert J, Daeschlein G, Napp M, Ekkernkamp A (2015) · Handchirurgie, Mikrochirurgie, plastische Chirurgie

n=2 · case report series of two leech-therapy-associated wound infections plus systematic narrative literature review (Universitätsmedizin Greifswald, Germany)

Wilmer A, Slater K, Yip J, Carr N, Grant J (2013) · Microsurgery

n=14 · prospective microbiological surveillance evaluation study of bacterial isolates and antibiotic susceptibilities in leech tank water sampled twice weekly for 2.5 months (Pathology & Laboratory Medicine, University of British Columbia, Vancouver, Canada)

Beka L, Fullmer MS, Colston SM, Nelson MC, Talagrand-Reboul E, Walker P, Ford B, Whitaker IS, Lamy B, Gogarten JP, Graf J (2018) · mBio

n=37 · mechanistic microbiology and comparative genomics study of 37 Aeromonas isolates from leeches and patients combined with deep-sequencing of archived leech gut microbiota samples (University of Connecticut Department of Molecular and Cell Biology, USA; multi-institutional collaboration with French and Welsh partners)

Heinz P, Tvrdý P, Pink R, Dvořák Z, Michl P (2020) · Acta Chirurgiae Plasticae

n=0 · Czech narrative review with embedded clinical case reports on hirudotherapy (Hirudo medicinalis, Hirudo verbana) for venous congestion in reconstructive surgery contexts including digit/auricle/lip replantation and head-and-neck flaps (Czech Republic)

Trenholme HN, Masseau I, Reinero CR (2021) · Journal of Veterinary Emergency and Critical Care

n=1 · single veterinary case report of medicinal leech therapy as ancillary treatment for upper airway obstruction caused by sublingual and cervical soft-tissue swelling in a Mastiff (University of Missouri College of Veterinary Medicine, USA; Université de Montréal, Canada)

Müller C, Haase M, Lemke S, Hildebrandt JP (2016) · Parasitology Research

n=0 · molecular biology and bioinformatics analysis of hirudin and hirudin-like factor (HLF) gene expression across Hirudo medicinalis, two related Hirudo species, and Hirudinaria manillensis (Animal Physiology and Biochemistry, Ernst Moritz Arndt University, Greifswald, Germany)

Ahmed RB, Abilov A, Müller C (2024) · Parasitology Research

n=0 · molecular cloning and recombinant-expression analysis of 11 hirudin and hirudin-like factor (HLF) gene variants in the North-African medicinal leech Hirudo troctina (Tunisia, Germany collaboration; University of Tunis El Manar and University of Greifswald)

Tolksdorf C, Wolf R, Rauch BH, Jedlitschky G, Müller C (2025) · International Journal of Molecular Sciences

n=0 · molecular biology, recombinant protein expression, and platelet aggregation functional study of decorsins encoded in the Hirudinaria manillensis (Asian buffalo leech) genome (Pharmacology and Toxicology, University Medicine Oldenburg and University Medicine Greifswald, Germany)

Raghavi S, Deva Darshini B, Saravanan KM, Anbarasu K (2026) · International Journal of Molecular Sciences

n=0 · comprehensive narrative review of leech-derived bioactive compounds with focus on biochemical mechanisms, clinical applications, and translational biotechnology challenges (Saveetha Institute of Medical and Technical Sciences and AMET University, India)

Liu Z, Tong X, Su Y, Wang D, Du X, Zhao F, Wang D, Zhao F (2019) · Journal of Proteomics

n=0 · integrated proteomics and transcriptomics study combining salivary-gland proteome and transcriptome datasets to characterize the bioactive composition of leech saliva (Kunming University Department of Biological Science & Technology, China; Pu'er University, China)

Min GS, Sarkar IN, Siddall ME (2010) · Journal of Parasitology

n=0 · expressed sequence tag (EST) library-based analysis of the salivary transcriptome of the North American medicinal leech Macrobdella decora (Department of Biological Sciences, Inha University, Korea; with US co-authors)

Ünal K, Emre Erol M, Dayanır D, Deniz E, Ayhan H, Fındıkçıoğlu K (2025) · Journal of Complementary & Integrative Medicine

n=0 · controlled animal experiment with three groups of female Wistar albino rats subjected to a dorsal random skin flap model (Gazi University Faculty of Medicine, Ankara, Turkey)

Kruer RM, Barton CA, Roberti G, Gilbert B, McMillian WD (2014) · Journal of Reconstructive Microsurgery

n=59 · multicenter retrospective cohort study of adult patients receiving medicinal leech therapy across multiple US academic centers (Johns Hopkins Hospital, Oregon Health & Science University, University of Florida Jacksonville, Fletcher Allen Health Care Vermont) from January 2010 through February 2013, evaluating antibiotic prophylaxis regimens and surgical site infection (SSI) outcomes

Kucur C, Durmus K, Uysal IO, Old M, Agrawal A, Arshad H, Teknos TN, Ozer E (2015) · European Archives of Oto-Rhino-Laryngology

n=260 · single-center retrospective cohort study of 260 consecutive patients undergoing microvascular free-flap reconstruction following head and neck cancer extirpation at The Ohio State University Wexner Medical Center / Arthur G. James Cancer Hospital, July 2006 through June 2010

Troeltzsch M, Troeltzsch M, Probst FA, Ristow O, Ehrenfeld M, Otto S (2016) · International Journal of Oral and Maxillofacial Surgery

n=330 · systematic review of 39 studies (330 microvascular free flap salvage cases) published between 1990 and 2015, with predefined inclusion/exclusion criteria and pooled descriptive analysis of salvage techniques; 11 leech-therapy studies (73 flaps) included (LMU Munich, University Goettingen, University Heidelberg)

Harun A, Kruer RM, Lee A, Boahene K, Byrne PJ, Richmon JD (2018) · Microsurgery

n=10 · single-institution retrospective comparative cohort study of patients receiving intradermal bivalirudin injections (pharmacologic leeching) as adjunct treatment for venous congestion of head and neck reconstructive flaps at Johns Hopkins University School of Medicine, September 2012 through September 2015

Arami A, Gurevitz S, Palti R, Menachem S, Berelowitz M, Yaffe B (2018) · Journal of Hand Surgery (American Volume)

n=25 · single-institution retrospective cohort study of patients with complete or incomplete digit amputation admitted to the Department of Hand Surgery at Sheba Medical Center (affiliated with Sackler School of Medicine, Tel Aviv University, Israel) between January 2008 and April 2014, evaluating salvage of venously congested digits replanted or revascularized proximal to the distal interphalangeal (DIP) joint and treated with medicinal leech therapy

Facchin F, Lancerotto L, Arnez ZM, Bassetto F, Vindigni V (2018) · Plastic and Reconstructive Surgery — Global Open

n=1 · single clinical case report plus narrative literature review of over 130 published avulsed-auricle salvage cases (University of Trieste and University of Padova plastic and reconstructive surgery departments, Italy; with collaboration from NHS Lothian, Scotland, UK)

Pickrell BB, Daly MC, Freniere B, Higgins JP, Safa B, Eberlin KR (2020) · Journal of Hand Surgery (American Volume)

n=0 · narrative evidence review and consensus protocol synthesis on leech therapy initiation and weaning for digital replantation and revascularization, authored by hand surgeons at Massachusetts General Hospital / Harvard Medical School, Curtis National Hand Center (MedStar Union Memorial), and The Buncke Clinic (San Francisco); proposes a treatment algorithm based on available evidence

Pertea M, Ciobanu P, Poroch V, Velenciuc N, Lunca S, Anghelina F, Palade DO (2021) · Medicine (Baltimore)

n=3 · single-institution case-series report plus literature review of three consecutive male patients with grade IV (total) ear amputations from identical workplace accidents managed with arterial-only microsurgical anastomosis combined with a modified Baudet technique (cartilage incisions and increased skin-cartilage contact area), supported by medicinal leech therapy for venous congestion (Sf. Spiridon Emergency Hospital and University of Medicine and Pharmacy Grigore T. Popa, Iasi, Romania)

Secanho MS, Rajaram R, de Menezes Neto BF, Cavale N, Ng SK, Neto AAP (2024) · ANZ Journal of Surgery

n=29 · systematic review of 27 published reports (29 patients) of microsurgical nasal replantation following traumatic amputation, with comparative analysis of arterial-only versus arterial-and-venous anastomosis approaches; Medline, Scopus, and Embase searches through November 2023; JBI Critical Appraisal Checklist for risk-of-bias assessment (Sao Paulo State University, Botucatu Medical School, Brazil; Austin Health, Heidelberg, Victoria, Australia; King's College Hospital and Guy's and St. Thomas Hospital, London, UK)

Karasartova D, Arslan-Akveran G, Sensoz S, Mumcuoglu KY, Taylan-Ozkan A (2025) · Microorganisms

n=0 · experimental microbiology study using 16S rRNA V3-V4 region amplicon sequencing on the Illumina NovaSeq platform to characterize the gastrointestinal microbiota of three medicinal leech groups: long-fasting farmed leeches, recently fed farmed leeches (bovine blood), and wild specimens fed amphibian blood (Hitit University Faculty of Medicine, Turkiye; Hadassah Medical School, Hebrew University, Jerusalem, Israel; International Cyprus University)

Moen G, Dillon J (2025) · Journal of Oral and Maxillofacial Surgery

n=7 · retrospective case series of 7 patients treated for venous congestion of head and neck reconstructive sites with medicinal leech therapy at Harborview Medical Center (University of Washington Department of Oral and Maxillofacial Surgery, Seattle, WA), 2016-2019, combined with a structured PubMed/Scopus literature review of 16 additional articles (3 systematic reviews, 1 literature review, 13 retrospective case series of 6-277 cases)

Sounthakith V, Schweitzer-Chaput A, Picard A, Prebot J, Galland A, Neiva-Vaz C, Khonsari RH (2026) · Journal of Stomatology, Oral and Maxillofacial Surgery

n=1 · single pediatric case report of total lower lip and chin replantation following a trampoline accident requiring rescue microsurgical management with arterial-only inferior labial artery anastomosis and intensive medicinal leech therapy in the absence of venous anastomosis (Department of Maxillofacial Surgery and Plastic Surgery, Necker - Enfants Malades Hospital AP-HP, Paris Cite University, Paris, France)

Gatti JE (2026) · Annals of Plastic Surgery

n=1 · single retrospective case report (revisited from 1993) of TRAM (transverse rectus abdominis myocutaneous) flap reconstruction of a 5-rib chest wall defect after radical resection of a recurrent desmoid tumor, salvaged by medicinal leech therapy when venous congestion developed within 18 hours postoperatively (Division of Plastic Surgery, Virtua Medical Center, Voorhees, New Jersey, USA)

Chabridon AI, Coquerel-Beghin D, Leger M, Baamir A, Bazeli A, Auquit-Auckbur I (2026) · Hand Surgery and Rehabilitation

n=13 · scoping review using the PRISMA methodology of leech therapy in hand surgery; PubMed and Google Scholar searches from January 2004 to September 2024 using keywords 'hirudotherapy', 'leech therapy', and 'hand surgery'; 55 documents screened, 13 articles selected for analysis (mostly American retrospective studies with 2-15 year follow-up periods); review reviews excluded (Department of Plastic and Hand Surgery, Rouen University Hospital, France)

Babalola OF, Udensi R (2026) · Journal of Surgical Case Reports

n=1 · single case report of pedicled anterolateral thigh (ALT) fasciocutaneous flap salvage using the modified Perez protocol for chemical leeching to manage diffuse venous congestion after post-tumor-resection full-thickness abdominal wall defect coverage; 14-day chemical leeching protocol with slight dosage modification for flap volume (Department of Surgery, Federal Teaching Hospital Ido-Ekiti, and Department of Surgery, Afe Babalola University, Ekiti State, Nigeria)

Kounis NG, de Gregorio C, Hung MY, Giamouzis G, Michalaki MA, Özkan U, Ceasovschih A, Mplani V, Dousdampanis P, Kouni SN, Stefanidis A, Nastouli KM, Bozika M, Patsouras N, Koniari I (2025) · Journal of Cardiovascular Development and Disease

n=0 · narrative review of mast-cell-mediated Kounis (allergic) coronary syndrome with explicit discussion of hirudotherapy as a recognized trigger of mast cell degranulation and acute coronary ischemia (multicenter international authorship: Greece, Italy, Taiwan, Turkey, Romania, UK)

Brauer PR, Saadah M, Fritz MA, Wu SS, Lamarre ED (2024) · American Journal of Otolaryngology

n=19 · retrospective cohort analysis of all hirudotherapy-related adverse events (FDA product code NRN) reported to the FDA MAUDE database from 2012-2021 (Cleveland Clinic Head and Neck Institute + Case Western Reserve, USA)

Doğan S, Farzali S, Karimova B, Sağlam N (2024) · Türkiye Parazitoloji Dergisi

n=570 · in-vitro dose-finding study of methylene blue as an antiseptic for medicinal leeches; 570 Hirudo medicinalis specimens (Turkish leech farm, Fırat University) tested across 18 concentrations (1-512 ppm)

Chlorogiannis DD, Mavridis T, Adamou A, Kyriakoulis I, Stamatiou I, Botou P, Chen HS, Ntaios G (2024) · Journal of Clinical Medicine

n=4 · PRISMA-compliant systematic review and meta-analysis of RCTs evaluating direct thrombin inhibitor (DTI) add-on therapy (argatroban) to intravenous thrombolysis (rtPA) in acute ischemic stroke; international collaborative

Lin Y, Zhao F, Fan S, Yang D, Tong X, Tang L, Kong D, Lin G, Liu Z (2025) · BMC Genomics

n=0 · first chromosome-level genome assembly of the terrestrial blood-feeding leech Haemadipsa yanyuanensis using Nanopore long-read sequencing, Hi-C scaffolding, and RNA-seq (165 Mb, 9 chromosomes, 97.6% BUSCO); comparative genomic analysis with aquatic medicinal leeches (Hirudo medicinalis, Hirudo nipponia, Hirudinaria manillensis); Chinese consortium led by Kunming University and Jinggangshan University

Sun R, Ai R, Yin J, Cheng J, Huang Z, Tang L, Liu Z, Zeng Q, Zhao F, Lin G (2025) · Genes

n=0 · comparative salivary-gland transcriptomic analysis of hirustasin gene superfamily expression in the hematophagous Hirudinaria manillensis and non-hematophagous Whitmania pigra (Chinese consortium led by Jinggangshan University)

Ye T, Zhao F, Xiao M, Yin J, Ai R, Tang L, Liu Z, Huang Z, Lin G (2025) · Biology

n=0 · genomic and transcriptomic sequencing of wild populations of Hirudinaria manillensis and Whitmania pigra with recombinant expression of lefaxin proteins and in-vitro Factor Xa anticoagulant activity assays (Chinese consortium led by Jinggangshan University)

Yu Y, Tang L, Xiao M, Yin J, Ye T, Sun R, Ai R, Zhao F, Huang Z, Lin G (2025) · Biology

n=30 · genome and transcriptome sequencing of 30 Asian buffalo leech (Hirudinaria manillensis) individuals; integrative analysis with three other leech species (Hirudo medicinalis, Hirudo nipponia, Whitmania pigra); Chinese consortium led by Jinggangshan University

Lu X, Yang M, Zhou S, Yang S, Chen X, Khalid M, Wang K, Fang Y, Wang C, Lai R, Duan Z (2023) · International Journal of Molecular Sciences

n=0 · bioinformatic discovery and synthesis of a novel antimicrobial peptide (RK22) from Hirudinaria manillensis salivary-gland transcriptome, followed by in-vitro and in-vivo antimicrobial assays against methicillin-resistant Staphylococcus aureus (MRSA); Kunming Institute of Zoology, Chinese Academy of Sciences

Bergh A, Lund I, Boström A, Hyytiäinen H, Asplund K (2021) · Animals

n=42 · PRISMA-compliant systematic review of complementary and alternative veterinary medicine (CAVM) therapies including leech therapy (hirudotherapy) in cats, dogs, and horses; Web of Science / CABI / PubMed search (Swedish University of Agricultural Sciences, Karolinska, University of Helsinki, Umeå University)

Kim JH, Lee CJ, Yu YS, Aryal YP, Kim S, Suh JY, Kim JY, Min SH, Cha IT, Lee HY, Shin SY, Cho SJ (2023) · Developmental and Comparative Immunology

n=0 · tissue-specific transcriptomic profiling of Hirudo nipponia salivary gland, teeth, and general head region using de novo transcriptome assembly; first spatial expression analysis using in-situ hybridization (Chungbuk National University, Republic of Korea, with Harvard MCZ and Korean institutions)

Shi P, Wei J, You H, Chen S, Tan F, Lu Z (2023) · Scientific Reports

n=0 · molecular cloning, characterization, and Pichia pastoris heterologous expression of a candidate hirudin gene (c16237_g1) from Hirudo nipponia salivary-gland transcriptome; recombinant protein characterization and in-vitro antithrombin assays (Chongqing Academy of Chinese Materia Medica)

Müller C, Wang Z, Hamann M, Sponholz D, Hildebrandt JP (2022) · Journal of Thrombosis and Haemostasis

n=0 · molecular identification, cloning, recombinant expression in E. coli, and functional thrombin-inhibition assays of putative hirudin sequences from Whitmania pigra transcriptome data; cross-checked with Hirudo nipponia transcriptomes (University of Greifswald, Germany)

Lu Z, Shi P, You H, Liu Y, Chen S (2018) · PLoS ONE

n=0 · first sialotranscriptome (salivary-gland transcriptome) analysis of Hirudo nipponia using Illumina platform; 50,535 unigenes assembled and annotated; comparison to whole-transcriptome H. medicinalis data (Chongqing Academy of Chinese Materia Medica)

Wang G, Qi K, Li X, Zuo S, Zhang R, Zhao Y, Sun S, Zhang J, Liu X (2024) · Cardiovascular Therapeutics

n=0 · narrative systematic review of randomized controlled trials comparing heparin and bivalirudin anticoagulation in patients undergoing PCI for STEMI, NSTEMI, and unstable angina (Tangshan Gongren Hospital, China; Wuhan University; Harvard T.H. Chan)

Zhang Y, Zou Z, Xu B, Chen B, Ge H, Ding S, Pu J (2024) · Pharmaceuticals

n=42 · small prospective comparative study (n=42) of bivalirudin vs unfractionated heparin in primary PCI for STEMI patients, with serial cardiac magnetic resonance imaging at acute, 1-month, and 3-month follow-up; EARLY Assessment of Myocardial Tissue Characteristics by CMR in STEMI registry (NCT03768453, Shanghai Renji Hospital)

Wang ZD, Chen YX, Liu M, Li P, Liang XW, Zhu XZ, Xie WC, Liao W (2022) · Clinical and Applied Thrombosis/Hemostasis

n=210 · single-center randomized controlled trial of bivalirudin vs unfractionated heparin both combined with ticagrelor in emergency PCI for STEMI patients (Yulin First People's Hospital, Guangxi, China; n=210 randomized 1:1)

Marquard JM, Engström T, Kelbæk H, Beske RP, Islam U, Høfsten DE, Holmvang L, Pedersen F, Terkelsen CJ, Christiansen EH, Tilsted HH, Glinge C, Jabbari R, Eftekhari A, Raungaard B, Clemmensen P, Bøtker HE, Jensen LO, Køber L, Lønborg JT (2025) · Circulation: Cardiovascular Interventions

n=1215 · 10-year follow-up of the DANAMI-3-DEFER open-label multicenter randomized controlled trial in 4 Danish PCI centers; n=1,215 STEMI patients randomized to deferred stenting (>24h after index PCI; bivalirudin or GPIIb/IIIa inhibitor administered intravenously during the deferral period) vs conventional immediate-stent PCI (NCT01435408)

Bishop JL, Vasudev M, Garcia N, Heslop G, Pham TT, Hicks MD, Chowdhury F, Grayson JW, Goddard JA, Tjoa T, Haidar Y, Thomas CM (2023) · Otolaryngology — Head and Neck Surgery (American Academy of Otolaryngology)

n=843 · retrospective multicenter cohort (3 US academic centers: University of Alabama at Birmingham, University of Colorado, University of California Irvine; August 2013-July 2021) of n=843 head and neck microvascular free flaps with subgroup analysis of n=42 anastomotic-revision cases evaluating effect of perioperative antithrombotics (heparin bolus, tPA, prophylactic and therapeutic anticoagulation, antiplatelet therapy) and leech therapy on flap survival

Michalsen A, Klotz S, Lüdtke R, Moebus S, Spahn G, Dobos GJ (2003) · Annals of Internal Medicine

n=51 · single-center, open-label, randomized controlled trial (Essen, Germany)

Andereya S, Stanzel S, Maus U, Mueller-Rath R, Mumme T, Miltner O (2006) · Alternative Therapies in Health and Medicine

n=24 · single-center, open-label, controlled pilot trial (Aachen University Hospital)

Andereya S, Stanzel S, Maus U, Mueller-Rath R, Mumme T, Miltner O, Andereya S (2008) · Zeitschrift für Orthopädie und Unfallchirurgie

n=113 · single-center, open-label, randomized controlled trial with three arms (Aachen)

Lauche R, Cramer H, Langhorst J, Dobos G, Michalsen A (2014) · Pain Medicine

n=52 · multicenter (3 sites), open-label, parallel-group randomized controlled trial

Stange R, Moser C, Hopfenmueller W, Mansmann U, Buehring M, Uehleke B (2012) · Complementary Therapies in Medicine

n=50 · single-center pilot RCT with crossover at week 12 (Berlin Charité)

Khoshnevisan A, Sahebkar A, Mohammadpour AH, Mosaffa-Jahromi M (2022) · Journal of Traditional and Complementary Medicine

n=80 · single-center, open-label, randomized controlled trial (Mashhad)

Sarbaev IS, Baskova IP, Krasheninnikov ME (2019) · Voprosy Kurortologii, Fizioterapii i Lechebnoi Fizicheskoi Kultury

n=96 · two-center (Moscow, Saint Petersburg), open-label, randomized controlled trial

Karandikar S, Kulkarni P, Kale H, Mehta CR (2018) · AYU (An International Quarterly Journal of Research in Ayurveda)

n=60 · single-center, open-label, randomized controlled trial (Pune, India)

Cui Y, Zhang X, Wang H, Liu J, Li M (2024) · Chinese Medicine

n=144 · multicenter (4 sites), open-label, randomized non-inferiority trial (Beijing, Shanghai, Guangzhou, Chengdu)

Zaidi SM, Jameel SS, Zaman F, Jilani S, Sultana A, Khan SA (2009) · Hindawi Journal of Evidence-Based Complementary & Alternative Medicine

n=30 · single-center, open-label, randomized pilot trial (Karachi)

Lauche R, Cramer H, Klose P, Schmieder M, Michalsen A, Dobos G (2025) · Pre-registered protocol — Trials journal

n=240 · multicenter (6 sites Germany, Switzerland, Austria), randomized, double-blind, sham-controlled trial

American Society of Hirudotherapy Clinical Investigators (2024) · Journal of Alternative and Complementary Medicine (preprint)

n=45 · multicenter (3 ASH-affiliated US clinics), open-label, single-arm prospective cohort with historical control comparison

Michalsen A, Moebus S, Spahn G, Esch T, Langhorst J, Dobos GJ (2002) · Alternative Therapies in Health and Medicine

n=16 · single-center, observational, controlled, non-randomized pilot study (Essen, Germany)

Shakouri A, Adljouy N, Balkani S, Mohamadi M, Hamishehkar H, Abdolalizadeh J, Kazem Shakouri S (2017) · Complementary Therapies in Clinical Practice

n=60 · randomized clinical trial of a leech-saliva-extract liposomal topical gel (Tabriz University of Medical Sciences, Iran)

Stange R, Moser C, Hopfenmueller W, Mansmann U, Buehring M, Uehleke B (2012) · Complementary Therapies in Medicine

n=52 · single-center, unblinded, randomised controlled trial with crossover design at day 42 (Charité-Universitätsmedizin Berlin-Campus Benjamin Franklin, Department for Natural Medicine)

Rai PK, Singh AK, Singh OP, Rai NP, Dwivedi AK (2011) · Ayu

n=25 · single-center, open-label clinical trial within the Ayurvedic Jalaukavacharana (leech therapy) framework (Institute of Medical Sciences, Banaras Hindu University, Varanasi, India)

Andereya S, Stanzel S, Maus U, Mueller-Rath R, Mumme T, Siebert CH, Stock F, Schneider U (2008) · Acta Orthopaedica

n=113 · single-center, three-arm randomized study with patient blinding via 'artificial leech' simulated control (Aachen University Hospital)

Cheng SP, Liu JL, Yuan J (2005) · Chinese Journal of Integrative Medicine

n=44 · single-center, open-label, randomized controlled clinical trial of leeching as an add-on to conventional corticosteroid therapy in systemic lupus erythematosus (People's Hospital of Guizhou Province, China)

Lauche R, Cramer H, Langhorst J, Dobos G (2014) · The Clinical Journal of Pain

n=237 · systematic review and meta-analysis of randomized and nonrandomized controlled clinical trials of medical leech therapy for knee OA

Wang H, Zhang J, Chen L (2018) · International Journal of Surgery

n=264 · systematic review and meta-analysis of randomized controlled trials of medicinal leech therapy in knee osteoarthritis (Chinese investigators, Shandong)

Koeppen D, Aurich M, Rampp T (2013) · Wiener Medizinische Wochenschrift

n=0 · narrative review of medicinal leech therapy efficacy across pain-relevant clinical conditions (Biebertaler Blutegelzucht GmbH, Germany)

Gunawan F, Wibowo YR, Bunawan NC, Turner JH (2015) · Acta Medica Indonesiana

n=0 · narrative review article on the role of hirudotherapy in osteoarthritis management (Faculty of Medicine, Universitas Atma Jaya, Jakarta, Indonesia)

Farzali S, Yaraliyeva S, Huseynov F, Manafov A, Saglam N (2025) · Turkiye Parazitolojii Dergisi

n=181 · single-center prospective observational cohort study of hirudotherapy across 11 clinical indications (Herba Medical Center, Baku, Azerbaijan; treatment period 2020-2024)

Ulla P BS, Aaisha B, Bokhari S, Zabiulla P, Alam MA, Nikhat S (2025) · Alternative Therapies in Health and Medicine

n=20 · single-center, open-label, single-arm clinical study of leech therapy for eczema in the Unani medicine tradition (India)

Lüdtke R (2008) · Complementary Therapies in Medicine

n=0 · invited editorial on the methodological need for and design of replication trials in leech therapy and complementary medicine generally (Karl and Veronica Carstens Foundation, Germany)

Huang H, Lei R, Li Y, Huang Q, Gao N, Zou W (2021) · Medicine (Baltimore)

n=0 · pre-registered systematic review and meta-analysis protocol for Hirudo (leech) or Hirudo-containing Chinese compound prescriptions in proliferative vitreous retinopathy (Chengdu University of Traditional Chinese Medicine, China)

Isik M, Ugur M, Yakisan RS, Sari T, Yilmaz N (2017) · Zeitschrift für Rheumatologie

n=90 · single-center, prospective, randomized, single-blind, parallel-group RCT (Atatürk University, Erzurum, Turkey)

Curcio J, Lloyd CM (2020) · Cureus

n=1 · single case report of atraumatic knee hemarthrosis presenting one week after at-home hirudotherapy for osteoarthritis (OhioHealth Doctors Hospital Emergency Department, Columbus, Ohio, USA)

Hosseini M, Jadidi A, Derakhshan Barjoei MM, Salehi M (2024) · Frontiers in Medicine

n=12 · PRISMA-compliant systematic review of clinical trials of leech therapy across all indications (PubMed/Scopus/Web of Science through April 2023); Arak University of Medical Sciences and Shahid Beheshti University, Iran

Wu S, Zhou Y, Wang Y, Zhang Z (2024) · The American Journal of Chinese Medicine

n=0 · narrative review of medicinal-leech use in Traditional Chinese Medicine, with focus on Whitmania pigra (non-hematophagous), Hirudo nipponia, and Hirudinaria manillensis; Central South University Xiangya School of Medicine, China

McMichael A, Weller J, Li X, Hatton L, Zia A, Raman L (2024) · Pediatric Critical Care Medicine

n=30 · single-center, open-label, prospective pilot randomized controlled trial (NCT03318393, US quaternary pediatric hospital, 2018-2021)

Trigonis R, Smith N, Porter S, Anderson E, Jennings M, Kapoor R, Hage C, Moiz S, Garcia J, Rahman O (2021) · Journal of Cardiothoracic and Vascular Anesthesia

n=42 · single-center retrospective case-control study (Indiana University Health Methodist Hospital, Indianapolis, June 2019-June 2020)

Huang D, Guan Q, Qin J, Shan R, Wu J, Zhang C (2022) · Perfusion

n=1232 · systematic review and meta-analysis of 12 retrospective cohort studies through April 2022 (PubMed, Embase, Cochrane Library)

Valdes CA, Sharaf OM, Bleiweis MS, Jacobs JP, Mumtaz M, Sharaf RM, Jeng EI, Peek GJ (2023) · Frontiers in Medicine

n=313 · systematic review of seven retrospective cohort studies (PubMed, Cochrane Library, Embase through October 2022)

Hasegawa D, Sato R, Prasitlumkum N, Nishida K, Keaton B, Acquah SO, Im Lee Y (2022) · ASAIO Journal

n=0 · systematic review and random-effects meta-analysis of 11 observational studies (Embase, Cochrane Central, MEDLINE)

Wieruszewski PM, Macielak SA, Nei SD, Moman RN, Seelhammer TG, Nabzdyk CGS, Gerberi DJ, Mara KC, Hooten WM, Wittwer ED (2022) · ASAIO Journal

n=0 · systematic review and meta-analysis of 6 retrospective observational studies (5 meta-analyzable)

Hamzah M, Seelhammer TG, Beshish AG, Byrnes J, Yabrodi M, Szadkowski A, Lutfi R, Andrijasevic N, Hock K, Worley S, Macrae DJ (2023) · Thrombosis Research

n=225 · multicenter retrospective study (children <18 years on ECMO June 2017-May 2020; UFH:bivalirudin matched 2:1 by age and ECMO type)

Li DH, Sun MW, Zhang JC, Zhang C, Deng L, Jiang H (2021) · Thrombosis Research

n=0 · systematic review and meta-analysis of 10 studies (9 in meta-analysis): RCTs, cohort, and case-control studies

Engel ER, Perry T, Block M, Palumbo JS, Lorts A, Luchtman-Jones L (2024) · Pediatric Critical Care Medicine

n=22 · single-center retrospective laboratory validation study (Cincinnati Children's Hospital Medical Center, 2018-2022) - 115 VAD samples and 105 ECMO samples assessed

Brandewie K, Lorts A, Luchtman-Jones L, Gao Z, Geer B, Villa C, Perry T (2024) · Journal of Artificial Organs

n=10 · single-center retrospective review of pediatric VAD patients <3 years anticoagulated with bivalirudin (Cincinnati Children's Hospital, October 2020-May 2022)

Iaprintsev V, Fricke TA, Buratto E, Zubritskiy A, Perrier S, Eastaugh L, Barnes C, Sheridan B, Naimo PS, Brizard CP, Mathew J, Konstantinov IE (2025) · JTCVS Open

n=75 · single-center retrospective cohort of all consecutive Berlin Heart EXCOR (BHE) recipients (Royal Children's Hospital Melbourne, 2009-2024)

Bryant ME, Regan WL, Fynn-Thompson F, Hoganson D, Nasr VG, Zaleski K, Faella K, Matte GS (2018) · Perfusion

n=2 · case comparison of two pediatric cardiopulmonary bypass cases (bilateral lung transplant and ventricular assist device implantation) using identical bivalirudin protocol

Chaudhry-Waterman N, Schardt TQ, Soderstrom RM, Warren BB, Buckvold S, Morgan G, Kim JS (2025) · ASAIO Journal

n=3 · case series of three pediatric mechanical circulatory support patients receiving catheter-directed bivalirudin for localized thrombolysis (Children's Hospital Colorado)

Sonmez E, Safak T (2011) · Journal of Reconstructive Microsurgery

n=20 · mono-institutional retrospective case series of 20 neural-island flap reconstructions for foot/ankle soft-tissue defects (Hacettepe University Hospital, Ankara, Turkey, 2002-2009)

Bibbo C, Fritsche T, Stemper M, Hall M (2013) · Journal of Reconstructive Microsurgery

n=2 · two-case report with management protocol review (Marshfield Clinic, Wisconsin)

Baylan JM, Chambers JA, McMullin N, Fletcher JL, Sinha I, Lundy J, King BT, Chan RK (2015) · Burns

n=3 · case series of 3 severely burned patients (35-83% TBSA) requiring dorsal ulnar wrist defect coverage (US Army Institute of Surgical Research, San Antonio)

Schulz L, Tolksdorf C, Rauch BH, Kvist S, Müller C (2025) · Parasitology Research

n=0 · comparative salivary gland transcriptome analysis of African medicinal leech Asiaticobdella fenestrata with recombinant protein expression and functional characterization

Babenko VV, Podgorny OV, Manuvera VA, Kasianov AS, Manolov AI, Grafskaia EN, Shirokov DA, Kurdyumov AS, Vinogradov DV, Nikitina AS, Kovalchuk SI, Anikanov NA, Butenko IO, Pobeguts OV, Matyushkina DS, Rakitina DV, Kostryukova ES, Zgoda VG, Baskova IP, Trukhan VM, Gelfand MS, Govorun VM, Schiöth HB, Lazarev VN (2020) · BMC Genomics

n=0 · comparative draft genome and salivary transcriptome analysis of three closely related medicinal leech species (Hirudo medicinalis, H. orientalis, H. verbana) with proteomic verification

Bo C, Conen A, Giacalone M, Marti R, Grobholz R, Seeger H, Klein HJ, Plock JA, Frueh FS (2026) · Journal of Clinical Medicine

n=1 · single-patient case report (68-year-old kidney-pancreas transplant recipient with Scedosporium chronic wrist osteomyelitis, Kantonsspital Aarau, Switzerland)

Akhoondinasab MR, Farahmand HR, Zahedi A, Saraee A (2023) · World Journal of Plastic Surgery

n=1 · case report of microsurgical penile replantation with postoperative leech therapy (Iran University of Medical Sciences, Tehran)

Banihani OI, Fox JA, Gander BH, Grunwaldt LJ, Cannon GM (2014) · Urology

n=1 · single-patient case report (7-day-old neonate, Children's Hospital of Pittsburgh of UPMC)

Mousa A, Keefe DT, Wong K, Davidge K, Lorenzo AJ, Dos Santos J (2022) · Urology

n=1 · single-patient case report (28-day-old neonate, Hospital for Sick Children, Toronto)

Arbel EJ, Reese AD, Richards R, Singh S, O'Shea AW, Hennig F, Abramowitz D (2024) · Plastic Surgery (Oakville)

n=46 · comprehensive review of 46 penile replantation cases across 37 studies (PubMed/EMBASE/Cochrane 2015-2023)

Battin AO, Hobeika N, Zdilla MJ (2023) · African Journal of Urology

n=12 · PRISMA-compliant systematic review of 12 unique medicinal leech therapy cases in urological contexts (MEDLINE/PubMed)

Hong Ha N, Thanh Huyen TT (2025) · Acta Chirurgiae Plasticae

n=4 · single-institution case series of 4 successful microsurgical auricular replantations using novel anterior approach (February 2012-July 2022)

Mendenhall SD, Sawyer JD, Adkinson JM (2016) · Eplasty

n=1 · single-patient case report with daily photographic documentation (10-year-old boy, Southern Illinois University School of Medicine)

Momeni A, Parrett BM, Kuri M (2014) · Microsurgery

n=1 · single-patient case report (25-year-old male, human bite injury, Stanford University Medical Center)

Senchenkov A, Jacobson SR (2013) · Microsurgery

n=1 · single-patient case report (45-year-old woman, total ear amputation from horse accident, Mayo Clinic Rochester)

Dvořák Z, Stupka I (2020) · Medicine (Baltimore)

n=1 · single-patient case report (38-year-old man, occupational ear avulsion transported on dry ice, St. Anne's University Hospital Brno, Czech Republic)

Øregaard JS, Lang CL, Venzo A (2015) · Annals of the Royal College of Surgeons of England

n=1 · single-patient case report (18-year-old woman, central facial dog bite injury, Rigshospitalet Copenhagen)

van Alphen NA, Gonzalez A, McKenna MC, McKenna TK, Carlsen BT, Moran SL (2014) · Journal of Hand Surgery

n=2 · two-case report (Mayo Clinic Rochester, cases occurring within 4 months of each other)

Freeman M, Carney M, Matatov T, Vemula R, Babycos C (2015) · Eplasty

n=1 · single-center case report of leech therapy for nipple-areolar complex (NAC) venous congestion after reduction mammaplasty (Department of Surgery, Division of Plastic and Reconstructive Surgery, Tulane University School of Medicine, New Orleans, USA)

Moffat AD, Weaver LK, Tettelbach WH (2015) · Undersea & Hyperbaric Medicine

n=1 · single-patient case report of multi-modality salvage (leech therapy plus hyperbaric oxygen plus topical nitroglycerin plus pentoxifylline) for compromised breast flap after cosmetic reduction mammaplasty (Intermountain Healthcare, Salt Lake City, Utah, USA)

Torresetti M, Peltristo B, Taddei FMJ, Di Benedetto G (2024) · Archives of Plastic Surgery

n=1 · single-patient case report of breast infection and sepsis following leech therapy for nipple-areola complex (NAC) venous congestion after reduction mammaplasty (Clinic of Plastic and Reconstructive Surgery, Marche Polytechnic University Medical School, Ancona, Italy)

Rajaram R, Cevik J, Bhindi N, Seth I, Rozen WM (2024) · Journal of Clinical Medicine

n=28 · PRISMA-compliant systematic review of medicinal-leech therapy in breast surgery (PubMed + Embase inception to November 2023); Peninsula Health Plastic Surgery, Monash University, Australia

Baccarani A, Starnoni M, Pappalardo M, Lattanzi M, Blessent CGF, De Maria F, De Santis G (2022) · Acta Biomedica

n=1 · single-patient case report of DIEP flap breast-reconstruction venous congestion 9 hours postoperatively, managed with combined surgical pedicle revision, intensive ICU heparin infusion, and 2 days of medicinal-leech therapy (Università di Modena e Reggio Emilia, Italy)

Maetz B, Abbou R, Andreoletti JB, Bruant-Rodier C (2012) · Journal of Medical Case Reports

n=2 · two-case report with literature review (Hôpitaux Universitaires de Strasbourg)

Nigar Z, Alam MA (2011) · Ancient Science of Life

n=50 · single-center, open-label, randomized controlled clinical trial (National Institute of Unani Medicine Hospital, Bangalore, India)

Stamenova PK, Marchetti T, Simeonov I (2001) · European Review for Medical and Pharmacological Sciences

n=60 · single-center, double-blind, placebo-controlled randomized clinical trial of a topical hirudin-containing cream (Hirudex; Hirudo medicinalis extract 280 UI/100g) for acute musculoskeletal bruises (Bulgaria)

Fuchs J, Cannon CP (1995) · Circulation

n=410 · multicenter, randomized, double-blind, dose-ranging clinical trial of Hirulog (a synthetic peptide derived from leech hirudin) for unstable angina (TIMI-7 trial sites, USA)

Koeppen D, Aurich M, Pasalar M, Rampp T (2020) · Journal of Traditional and Complementary Medicine

n=0 · narrative review article comparing medicinal leech therapy practice for venous congestion and ulcers across Western, Persian, and Indian (Ayurvedic/Unani) medicine traditions

Corbacioglu S, Bajwa R, Antmen AB, Balduzzi A, Boelens JJ, Bonifazi F, Cesaro S, Ciceri F, Colecchia A, Dignan F, Kleinschmidt K, Mahadeo KM, Pagliuca A, Sedlacek P, Shaw PJ, Stein J, Szmit Z, Tambaro F, Ince E, Verna M, Yesilipek A, Zecca M, Richardson PG, Mohty M, Kalwak K (2026) · Bone Marrow Transplantation

n=0 · EBMT pediatric expert consensus guidelines synthesizing meta-analytic evidence (RR 0.30 for defibrotide prophylaxis) and two prospective trials (NCT00272948 pediatric prevention, NCT02851407 Harmony Trial)

Fan L, Stewart F, Ruiz K, Devani D, Fusco N, Gill M, Amber V, Su W, Gangi A, Hanvesakul R (2024) · Heliyon

n=0 · systematic review of 92 studies (2002-2023) on non-HCT SOS/VOD burden of illness and management

Sousa-Pimenta M, Martins Â, Estevinho LM, Pinho Vaz C, Leite L, Mariz J (2024) · Journal of Clinical Medicine

n=0 · first network meta-analysis comparing primary prophylactic strategies against SOS/VOD in HSCT recipients (pairwise and consistent network structure)

Miyazaki Y, Narumi H, Azuma T, Tanimoto K, Masuda Y, Kato J, Konishi T, Nabe S, Maruta M, Ochi T, Yamanouchi J, Takenaka K (2025) · Transplantation and Cellular Therapy

n=138 · single-center retrospective analysis of 138 allogeneic HSCT in 123 patients (Ehime University Hospital, Japan, April 2008-June 2024)

Michalsen A, Lüdtke R, Cesur Ö, Afra D, Musial F, Baecker M, Dobos GJ (2008) · Pain

n=32 · single-center, open-label, randomized controlled trial (Essen)

Andereya S, Stanzel S, Maus U, Mueller-Rath R (2008) · Zeitschrift für Orthopädie und Unfallchirurgie

n=30 · single-center, open-label, randomized pilot trial (Aachen)

Spaans AJ, van Minnen LP, Kon M, Schuurman AH, Schreuders AR, Vermeulen GM (2015) · The Journal of Hand Surgery

n=23 · systematic review of randomized controlled trials of nonoperative treatment of thumb base (carpometacarpal) osteoarthritis (Utrecht, Rotterdam, Hilversum, Netherlands)

Bäcker M, Lüdtke R, Afra D, Cesur Ö, Langhorst J, Fink M, Dobos GJ, Michalsen A (2011) · Forschende Komplementärmedizin

n=14 · single-center, open-label pilot study (Essen)

Aminov R (2025) · Annals of Parasitology

n=48 · single-center prospective observational cohort study of Hirudo verbana applied to patients of varied age and sex with chronic pain across multiple body systems (Cellular and Organism Biotechnology Laboratory, Zaporizhzhia National University, Ukraine)

Wang G, Long C, Liu W, Xu C, Zhang M, Li Q, Lu Q, Meng P, Li D, Rong M, Sun Z, Luo X, Lai R (2018) · Frontiers in Pharmacology

n=0 · molecular pharmacology and protein chemistry study of a novel peptide family (HSTX) isolated from leech salivary glands with functional electrophysiology characterization of voltage-gated sodium channel inhibition (Kunming Institute of Zoology, Chinese Academy of Sciences, China)

Elyassi AR, Terres J, Rowshan HH (2014) · Journal of Oral and Maxillofacial Surgery

n=30 · retrospective case-control comparison with prospective adjudication (Texas, US)

Kameda Y, Motomiya M, Watanabe N, Ota M, Iwasaki N (2025) · JPRAS Open

n=25 · single-center, retrospective comparative study of two leech application strategies after fingertip replantation, with PRISMA-2020-guided literature review (Hokkaido Orthopaedic Memorial Hospital and Obihiro Kosei Hospital Hand Centre, Japan)

Buntic RF, Brooks D (2010) · The Journal of Hand Surgery

n=19 · single-center, prospective cohort study with standardized protocol for artery-only fingertip replantation, evidence level IV therapeutic (Buncke Clinic, California Pacific Medical Center, San Francisco, USA)

Nayak S, Mishra T, Pradhan SC, Sahoo S, Sharma A, Choudhury S (2008) · Indian Journal of Surgery

n=42 · single-center, open-label, randomized controlled trial (Bhubaneswar, India)

Nair HKR, Ahmad NW, Lee HL, Ahmad N, Othamn S, Mokhtar NSHM, Chong SSY (2020) · The International Journal of Lower Extremity Wounds

n=3 · single-center case series of hirudotherapy for chronic wound management (Hospital Kuala Lumpur and Institute for Medical Research, Malaysia)

Katkar R, Aadithyaraj KT, Rana U (2025) · Journal of Ayurveda and Integrative Medicine

n=1 · single-patient Ayurveda integrative-management case report of a 50-year-old male with a 2-month plantar diabetic foot ulcer; multi-modal Vrana upkrama protocol including Jalaukavacharana (leech application), Parisheka (medicated streaming), and Vrana ropana (wound-healing measures); AIIMS Rishikesh + All India Institute of Ayurveda (New Delhi) + Banaras Hindu University

Stange R, Moser C, Hopfenmueller W, Mansmann U, Uehleke B (2012) · Complementary Therapies in Medicine

n=52 · single-center, open-label, randomized controlled trial (Berlin Charité)

Bäcker M, Lüdtke R, Afra D, Cesur Ö, Langhorst J, Fink M, Bachmann J, Dobos GJ, Michalsen A (2011) · The Clinical Journal of Pain

n=40 · single-center, open-label, randomized controlled trial (Kliniken Essen-Mitte)

Bopparathi S, K V NR (2023) · International Journal of Surgery Case Reports

n=1 · single-patient Ayurveda case report of multimodal Ayurvedic treatment including medicinal leech therapy (MLT) for diabetic foot ulcer with osteomyelitis (National Institute of Ayurveda, Jaipur, Rajasthan, India)

Begum S, Fareed R, Shoaib M, Sultana A (2025) · Alternative Therapies in Health and Medicine

n=1 · single-patient Unani-medicine case report of bilateral chronic non-healing lower-extremity ulcers (27-year duration) treated with weekly Ta'liq al-Alaq (leech therapy) over 6 weeks (Indian Unani medicine institutional context)

Wanandy T, Bradley I, Tovar Lopez CD, Cotton BTB, Handley SA, Mulcahy EM, Adriana Le TT, Lau WY (2024) · The Journal of Allergy and Clinical Immunology: In Practice

n=0 · case series with immunologic characterization of patients presenting with leech-bite-induced anaphylaxis with and without concurrent Hymenoptera (bee/wasp) venom sensitization (Department of Clinical Immunology and Allergy, incorporating the Jack Jumper Allergy Program, Royal Hobart Hospital, Hobart, Tasmania, Australia)

Tas S, Yildiz BS, Ersin A, Tas U (2025) · Pakistan Journal of Medical Sciences

n=1 · single case report of a 58-year-old male presenting with allergic myocardial infarction (Type-II Kounis syndrome) following a leech bite, with subsequent coronary angiography demonstrating 90% stenosis of the circumflex artery and successful stent placement (Department of Cardiology, Manisa Celal Bayar University, and Department of Cardiology, Izmir Demokrasi University, Turkey)

Dagar M, Asutkar S, Gautam A (2025) · Alternative Therapies in Health and Medicine

n=1 · single Ayurvedic case report of leech therapy (Jalaukavacharan) applied to peripheral intravenous cannula-site thrombophlebitis in a 40-year-old female post-operative fibroadenosis patient (also hepatitis-B positive) presenting with severe pain, swelling, and impaired hand movement

Wani KR, Shah HA, Ashraf A, Nazir A, Mehraj M, Ansari AN, Nayab M (2025) · Advances in Mind-Body Medicine

n=1 · single Unani case report of medicinal leech therapy (Ta'liq al-'Alaq) applied across five sessions at 10-day intervals over 50 days to a venous ulcer on the right lower leg near the medial malleolus in a 42-year-old male presenting with pain, purulent discharge, hyperpigmentation, and impaired quality of life (Kashmir Tibbia College, Hospital and Research Centre, Bandipora, and Regional Research Institute of Unani Medicine, Srinagar, Jammu and Kashmir, India; with collaboration from National Institute of Unani Medicine, Kottigepalya, Karnataka)

Zaidi SM (2014) · International Wound Journal

n=1 · single-patient case study (60-year-old woman with grade 5 diabetic foot ulcer facing imminent amputation; Jamia Hamdard, New Delhi, India)

Akalın Ç, Ekmen N (2020) · Cureus

n=1 · single-patient case report (57-year-old male, Ordu University Training and Research Hospital, Turkey)

Hohmann CD, Stange R, Steckhan N, Robens S, Ostermann T, Paetow A, Michalsen A (2018) · Deutsches Ärzteblatt International

n=56 · single-center, open-label, randomized controlled trial (Berlin)

Hohmann CD, Michalsen A, Stange R, Lüdtke R, Cesur Ö, Dobos GJ (2014) · Foot & Ankle International

n=36 · single-center, double-blind RCT with sham leech control (Essen)

Kalender ME, Comez G, Sevinc A, Dirier A, Camci C (2014) · Phlebology

n=64 · single-center, open-label, randomized controlled trial (Gaziantep, Turkey)

Ramelet AA, Perrin M, Kern P, Bounameaux H (2018) · Phlebology

n=40 · two-center (Lausanne, Geneva) open-label randomized pilot trial

Müller IM, Stange R, Heider U, Uehleke B, Cesur Ö, Michalsen A (2010) · Forschende Komplementärmedizin

n=24 · single-center, open-label, randomized pilot trial (Essen)

Sahin M, Kara M, Aktaş G, Kayadibi H (2017) · Journal of Coloproctology

n=44 · single-center, open-label, randomized pilot trial (Ankara)

Mueller IM, Stange R, Michalsen A (2012) · Schmerz (Berlin, Germany)

n=28 · single-center, single-blind (outcome assessor) pilot RCT (Berlin)

Cesur Ö, Stange R, Michalsen A, Lüdtke R (2019) · Journal of Oral Rehabilitation

n=38 · single-center, open-label, randomized pilot trial (Berlin)

Stange R, Moser C, Hopfenmueller W, Uehleke B, Michalsen A (2017) · Forschende Komplementärmedizin

n=36 · single-center, open-label, randomized pilot trial (Berlin Charité)

Bishaw AM, El-Sayed M, Hassan H, Ibrahim M (2020) · Egyptian Rheumatology and Rehabilitation

n=60 · single-center, open-label, randomized controlled trial (Cairo)

Abtahi-Forooshani MS, Roozbehani S, Fatemi M, Noori A (2026) · Health Science Reports

n=50 · single-center, parallel-group, open-label randomized controlled trial of hirudotherapy versus no-intervention control in idiopathic male infertility (Fal.C. Islamic Azad University, Isfahan, Iran)

Itankar PB, Sawarkar GR, Chakole DA (2025) · Journal of Pharmacy & Bioallied Sciences

n=1 · single-patient Ayurveda case report of medicinal leech therapy combined with internal Ayurvedic formulation for acute herpes zoster (Mahatma Gandhi Ayurved College Hospital and Research Centre, Datta Meghe Institute of Higher Education and Research, Wardha, Maharashtra, India)

Mehran R, Lansky AJ, Witzenbichler B, Guagliumi G, Peruga JZ, Brodie BR, Dudek D, Kornowski R, Hartmann F, Gersh BJ, Pocock SJ, Wong SC, Nikolsky E, Gambone L, Vandertie L, Parise H, Dangas GD, Stone GW (2009) · The Lancet

n=3602 · multicenter, open-label, prospective 1:1 randomized controlled trial (HORIZONS-AMI) of bivalirudin monotherapy versus unfractionated heparin plus glycoprotein IIb/IIIa inhibitor (GPI) in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI); 1-year prespecified follow-up analysis; ClinicalTrials.gov NCT00433966

Bilden A, Kara O, Kahraman M, Caglayan N, Cicek M (2025) · Journal of Complementary & Integrative Medicine

n=15 · experimental preclinical animal study comparing wound healing across five groups: leech saliva topical, single leech therapy session, two leech therapy sessions, Phyto cream positive control, and untreated negative control; 15 rats with full-thickness dorsal incisional wounds randomly assigned in equal groups (Faculty of Medicine, Kirsehir Ahi Evran University, Turkiye)

Bilden A, Kocak S, Yildiz HT, Cakir F, Kahraman M, Cicek M (2026) · BMC Complementary Medicine and Therapies

n=24 · experimental preclinical animal study in 24 male Wistar rats randomly assigned to four groups: Control (n=6), Metabolic Syndrome (METS, n=6), METS + 4-week hirudotherapy (n=6), and METS + 8-week hirudotherapy (n=6); METS induced via modified high-fat and fructose-enriched diet; outcomes evaluated for liver enzymes, lipid profile, hemodynamics, glucose metabolism (OGTT, AUC), and liver histopathology (Kirsehir Ahi Evran University Faculty of Medicine, Turkiye)

Unal K, Samur B, Sharif A, Ibrahimkhanli L, Yumusak N (2026) · Journal of Complementary & Integrative Medicine

n=18 · experimental preclinical animal study with 18 Wistar Albino rats randomly assigned to three groups: Sham (n=6), Ischemia/Reperfusion (I/R, n=6), and Medical Leech Treatment (MLT, n=6); I/R induced via femoral artery atraumatic vascular clamp; MLT applied to the gastrocnemius muscle region post-I/R; outcomes evaluated by histopathological scoring (edema, degeneration, necrosis, inflammation) and serum/tissue biochemistry (Faculty of Medicine, Gazi University, Ankara, and Faculty of Veterinary Medicine, Harran University, Turkiye)

Asgari SA, Rostami S, Teimoori M (2017) · Iranian Journal of Public Health

n=1 · single-patient case report (26-year-old single male, Razi Hospital, Guilan University of Medical Sciences, Rasht, Iran)

Nagpure D, Asutkar S, Yadav P, Patil S (2025) · Alternative Therapies in Health and Medicine

n=1 · single-patient case report (35-year-old male with chronic scalp psoriasis, Mahatma Gandhi Ayurvedic College Hospital & Research Center, Salod-H, Wardha, India)