Sala Horowitz, Ph.D.

L eeches have been used for medical purposes for millen-nia and in various applications in modern hospitals forat least the past 20 years. Recently, the U.S. Food and

Drug Administration (FDA) officially approved these blood-sucking invertebrates as medical devices. This article pro-vides detai ls of that approval process and reviews thehistorical and modern therapeutic applications of this age-oldremedy.

FDA Approval as Medical Devices

On June 28, 2004, the FDA gave clearance to Ricarimpex SAS, acompany based in Audenge, France, to market medicinal leech-es—specifically, Hirudo medicinalis—commercially as medicaldevices. Approved indications are such therapeutic applicationsas restoring circulation in blocked veins and aiding the healing ofskin grafts. During the approval process, the FDA reviewed thepublished literature on the medical use of leeches, data on safety,and information on the quality of their aquatic environment andtheir handling.

A “grandfather” clause allowed companies that had suppliedleeches prior to 1976 and American hospitals that already usedthem, to continue doing so. But the medical device clausepassed that year as part of the Food, Drug, and Cosmetic Actrequired newcomers to the field to seek FDA approval. This actdefines a medical device as “an article intended to diagnose,cure, treat, prevent, or mitigate a disease or condition, or toaffect a function or structure of the body, that does not achieveits primary effect through a chemical action, and is not metabo-lized.”1

According to Marie Bonazinga, the president of Leeches U.S.A.Ltd. (Westbury, New York), the company that serves as the U.S.distributor for Ricarimpex, “over the last decade, the use ofmedicinal leeches has again entered the mainstream of modernmedical practice”2 (see box entitled Resources). Such medical useof live organisms has been termed “biotherapy.”3

Species Description

The European medicinal leech is a dark-colored parasiticannelid with brown or reddish stripes on its cylindrical body anddark speckles on the vertical surface; its body is divided into 33or 34 segments. Belonging to the Hirudinidae family, this speciesinhabits freshwater habitats, such as marshes, streams, andponds.4 Distantly related to the earthworm, these creatures mea-sure from 5 to 10 centimeters in length at rest and up to twicethat length when swimming.

H. medicinalis have two muscular, disk-shaped suckers. Theone at the posterior end is used to attach itself while feeding—primarily on the blood of mammals (juveniles initially feed onfrogs). The smaller but more powerful sucker at the anteriorend encloses a mouth uniquely composed of three jaws; eachjaw has 60–100 teeth that produce a small, Y-shaped radialpuncture wound when the leech bites its host. Leeches canincrease their typical weight of 2–3 g up to 800 percent in onefeeding session and can remain satiated for as long as severalmonths.5

The H. medicinalis leech is endangered or extinct today in itsnative range. This range consists of parts of western and south-ern Europe to the Ural Mountains and countries bordering thenortheastern Mediterranean. The problem stems from overhar-vesting for medicinal use and as a result of habitat loss or pollu-tion.6

It should be noted that another leech species in the same fami-ly, Hirudinaria manillensis (the Asian medicinal leech), has beenfound to have similar properties of biomedical significance.However, this species has not been investigated or applied aswidely as H. medicinalis.7

Historical Background

The use of leeches dates back to ancient Egypt, where theywere used for bloodletting and as an alternative to amputation.In the many centuries since Galen, the second century AD physi-cian who first suggested that disease was caused by an imbalanceof hypothesized body humors, leeches were believed to restorebalance by drawing out “bad” blood. Because of the widespread

12

Medicinal Leeches in Modern Medicine An Age-Old Remedy Revived

medical use in the Middle Ages, “leech” became a synonym forAnglo-Saxon physicians, and medical writings of the period werecalled “leech books.”

Medicinal leeches reached their height of popularity in themid-nineteenth century. The influential French physician Fran-cois Broussais, M.D., routinely applied as many as 30 leeches tothe skin of his patients. Period illustrations also showed patientsapplying leeches for self-care. A contemporary physician notedthat the frequency of blood tests today in hospitals is reminiscentof this earlier type of bloodletting! After Dr. Broussais’ death in1838, enthusiasm for leeches for therapeutic purposes waned.Concomitantly, they became harder to obtain as their naturalhabitats were converted to other uses.5

However, medicinal leeches made a comeback in the twentiethcentury with the rise of commercial leech farms to replenishdwindling supplies for clinical and research purposes and forresearch into the properties of the animal’s saliva. This revival isdue, in large part, to Roy Sawyer, Ph.D., an American scientistwho established the first commercial leech farm—said to be theworld’s only such farm today—near Swansea, South Wales, Unit-ed Kingdom.8

Two surgeons in Ljubljana, Slovenia, were pioneers in the useof leeches in modern plastic and reconstructive surgery. In anow-classic 1960 paper, they described leech-assisted tissue flapsurgery. In this type of surgery, a flap of skin is freed or rotatedfrom an adjacent body part to cover an injury or defect. The twosurgeons attributed the inspiration for their work to a nineteenth-century French surgeon who wrote about using leeches to restorecirculation following the reconstruction of a nose.9

Medically Important Substances Produced by Leeches

It was well-known in earlier eras that bleeding may continuefor a prolonged period (up to about 48 hours) after leeches aredisengaged from the area of a bite. Therefore, instructions weregiven to stop hemorrhaging from a leech bite. It was discoveredin the late nineteenth century that this prolonged bleeding wascaused by an anticoagulant factor in leech saliva, which evolvedto enable the creature to feed on blood from its host. This factorwas named hirudin, after the animal’s order Hirudinea. Hirudin isa potent, highly specific thrombin inhibitor. Thrombin is a serineprotease that plays a key role in cardiovascular disease.10

The study of hirudin has contributed greatly to understandingof the mechanism of action of thrombin and the clotting system.The development of drugs such as heparin and warfarin to inhib-it platelet adhesion aggregation initially eclipsed the clinical useof hirudin.

However, hirudin from leeches has several well-recognizedadvantages over heparin, the most widely used drug. Relativelack of availability of the natural compound much in demand forbasic and clinical studies has led to the development of recombi-nant forms of hirudin (known as r-hirudins) and hirudin ana-logues as anticoagulants.11 In fact, hirudin is considered thestandard for designing these offshoot drugs to treat thromboem-bolic diseases.12

Additional biologically and pharmacologically active sub-stances were isolated from leech saliva later, including a collage-nase that appears to be the mediator that disrupts clot formation,hyaluronidase that enhances the absorption and dispersion ofsubstances in tissues, a local vasodilator, and a local anesthetic.5

Calin has been identified as the inhibitor of collagen-mediatedplatelet adhesion.13

Therapeutic Applications

Today, the applications of medicinal leeches are more speci-fically targeted than in the past, when they were used as a reme-dy for a wide range of ailments. Their anticoagulant propertieshave been the main reason for the revival of interest in medicinalleeches and “may lead to wider applications in the preventionand treatment of thromboembolic disease.”2,14

A recent survey of the 62 plastic and reconstructive surgeryunits in the United Kingdom and the Republic of Ireland indicat-ed that the majority of these units use leeches postoperativelyand that the average number of patients receiving leech therapywas 10 cases per unit annually. However, it was noted in thissurvey that a standard protocol for medicinal leech use has notyet been developed.15 No comparable survey could be locatedfor the United States or other countries.

ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2005 13

Central nervous system of the leech. A. The central nervous system ofthe leech. B. The nerve cord of the leech.

Graphic reprinted from Figure 1 in Blackshaw SE, Nicholls JG. Neuro-biology and development of the leech. J Neurobiol 1995;27:269. ©1995.Reprinted with permission of Wiley-Liss, Inc., a subsidiary of JohnWiley & Sons, Inc.

Reattachment Surgery

In complex plastic and reconstructive microsurgery thatattempts to reattach traumatically amputated body parts, suchas fingers and ears, leeches have been prescribed for nearly 2decades for cases in which damage to veins traps and stagnatesblood in target tissues that are at risk for turning blue anddying. “You use the leech when you have good arterial inflowbut when the blood can’t get out because the veins are dam-aged,” according to Fred Deleyiannis, M.D., assistant professorof plastic surgery at the University of Pittsburgh Medical Cen-ter in Pennsylvania.16 In a recent first-reported case of its kind,leeches were used in a penile reimplantation. Follow-up indi-cated that the patient was able to have normal sensation, void-ing, and erections.17

Leeches’ therapeutic benefit is derived from the phenomenonof extended local bleeding for 24–48 hours after the leech disen-gages as well as the amount of blood ingested (from 5 to 15 mL)during its feeding session (typically about 45 minutes). Inapproximately 30 minutes, a leech can ingest up to a half-ounceof blood.2

Leech therapy should be continued at the site of maximal con-gestion until new blood-vessel connections form sufficientlyaround the affected tissues so that they can begin effectivevenous drainage on their own. This may involve adjusting theuse of one or more leeches at a time for an average of 3–7 days.The attainment and maintenance of normal skin color after leech-induced venous oozing is a key indicator that such therapy canbe discontinued.2

In extolling the benefits of H. medicinalis, Matthew Concan-non, M.D., an associate professor of plastic and reconstructivesurgery and the director of hand and microsurgery at the Uni-versity of Missouri Hospital and Clinics in Columbia, statedin a 2000 article: “Though people associate them [leeches]with questionable medical procedures from centuries past,they apply the perfect amount of suction to get the blood

flowing after delicate reattachment surgery. If you can’t getthe blood out, it backs up, and this is just as bad as if youdidn’t have any blood coming in.” Getting blood to flow inthe veins is more of a challenge than in the arteries of thereattached part, and the consequence may be tissue deteriora-tion and death.18

Therefore, Dr. Concannon keeps dozens of leeches on standbyfor such emergency situations. But he only uses them after deter-mining that a patient is experiencing true venous congestion andas a last resort when other options have failed to reestablishblood flow.

Because leeches are not effective in cases of insufficient arterialflow, it is critical that venous congestion be accurately diagnosedprior to application (see box entitled Indicators for Leech Thera-py in Reconstructive Surgery). For example, in an early case ofsuccessful microsurgery in 1997 to reattach a child’s ear that wasbitten off by a dog, Dr. Concannon applied some 50 leeches in thecourse of a week to train the ear to redevelop its circulatory sys-tem.18

Case Example

A middle-age man suffered a complete severing of the uppertwo thirds of one of his ears. No veins were available for anasto-mosis, so the ear was reattached via microvascular anastomosisof a small artery anteriorly. Shortly after anastomosis, severevenous congestion was evident in the reimplanted ear, whichwas treated by medicinal leech therapy. At 48 hours postopera-tively, 3 leeches were applied every 8 hours, with improvementbeing noted after the initial application. At 72 hours postopera-tively, 3 leeches continued to be applied every 8 hours for peri-ods of 15–30 minutes.

Marked improvement in color with decreased swelling andcongestion was noted. At 6 days postoperatively, the reimplant-ed ear was viable and healing well. At a 2-month postoperativefollow-up, the complete survival of the patient’s reattached earwas noted.2

Skin Grafts

Leeches also help heal skin grafts by removing blood thatpools around the graft and by restoring blood circulation. Forinstance, venous congestion is a fairly common problem ingrafted neurocutaneous flaps for reconstructing compromisedsoft tissue in patients with diabetes or those with electricalburns. If partial or complete capillary perfusion is not reestab-

14 ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2005

ResourcesOrganization

Leeches U.S.A. Ltd.300 Shames DriveWestbury, NY 11590Phone: (516) 333-2570 or (800) 645-3569Fax: (516) 997-4948E-mail: info@leechesusa.comWeb site: www.leechesusa.comThis company is the U.S. supplier of leeches and leech storage and

maintenance products to physicians and hospitals for RicarimpexSAS, the French company that received approval from the Food andDrug Administration in June 2004 to market leeches as a medicaldevice.

BookThe Development of Medical Techniques and Treatments:

From Leeches to Heart SurgeryBy Martin Duke, M.D.Madison, CT: International Universities Press, Inc., 1991

Indicators for Leech Therapy in Reconstructive Surgery

• Venous congestion in skin grafts or reattached limbs or otherbody parts

• Patient history of problems with veins in the area of target surgery• Severe edema

From refs. 2, 7, and 21.

lished immediately, partial or complete tissue loss results.Leeches have been used successfully in microrevascularizationin such cases.19

In an experimental study of 11 pigs, leech therapy was com-pared to a mechanical device for treating venous congestion in 9x 7–cm fasciocutaneous flaps clamped for 15 hours. Leeches werefound to be equal to the mechanical device in terms of blood vol-ume removed, surface perfusion, and oxygen tension. However,there were significant differences in skin color change over the15-hour period, with the device promoting more global decon-gestion.20

Other Therapeutic UsesThe clinical policy bulletin of a major health insurance com-

pany noted that it considers medicinal leech therapy experi-mental and investigational for treating the pain of kneeosteoarthritis. However, the company also cited promisingresearch evaluating the effectiveness of H. medicinalis for thisindication.*

In a randomized, controlled study of outpatients at an integra-tive medicine department of an academic teaching hospital,patients (N = 51, mean age, 64 years old) received either a singletreatment with 4–6 locally applied leeches (intervention group)or a 28-day topical regimen of the nonsteroidal anti-inflammato-ry drug diclofenac (control group). At the primary endpoint atday 7, patients getting the leech therapy reported a significantreduction of pain compared to those treated with diclofenac.Although the differences between group pain scores were nolonger significant after 7 days, differences on standard measuresin stiffness, function, total reduction in symptoms, and quality oflife in favor of the leech therapy persisted until the end of thestudy.

An insurance company that was involved said, however, thatthese results needed further validation.21

Medicinal leeches have also been used in patients sufferingfrom ophthalmologic conditions such as periorbital hematomas,severe macroglossia (enlarged tongue), and puerpura fulminas (ahemorrhagic condition).22 The use of leeches in flaps used inbreast reconstruction was noted in one report,21 but no furtherreferences to this application could be located. The overall suc-cess rate of salvaging tissue with medicinal leeches has been esti-mated to be 70–80 percent.21

Risks and Patient Care

Leeches should not be prescribed for patients with HIV/AIDSor those taking immunosuppressive medications because of therisk of overwhelming bacterial sepsis.21 To prevent infectionfrom bacteria that medicinal leeches normally harbor in their gutflora, patients are routinely given antibiotics prophylactically tominimize risk. In countries in which leeches are obtained from

local habitats or markets, leeches can be treated with hydrochlo-ric acid to suppress bacteria without suppressing their desiredfunctioning.23

During the leech-induced bleeding period, a patient’shemoglobin levels must be monitored regularly to prevent themfrom falling too low and to check the clinical response of the tis-sue being treated. Any clots forming at the bite site should beremoved to encourage continued bleeding. Like used syringes,leeches full of blood are considered hazardous medical wasteand must be disposed of properly after a single use.2

Cases of contact dermatitis from the anticoagulant hirudin inthe saliva of medicinal leeches and products derived from it(such as creams), have been noted but are considered to berare.24 One case was reported of Aeromonas meningitis, a type ofbacterial infection, associated with leech therapy in attempting tosalvage a patient’s skin flap after surgery on the central nervoussystem.25

Another possible risk is the migration of leeches from a target-ed surgical site into body orifices or deeper into the wound itself.This risk can be prevented by affixing one end of a surgicalsuture to the leech and tying the free end to a dressing or otherfirm object.26

Patient Acceptance

The majority of patients are said to be much more concernedabout potentially losing functioning or a body part than beingsqueamish about the use of these much-maligned creatures.Moreover, the process is painless partly because the nerves in anaffected body part are already impaired and also because leechsalvia contains an anesthetic.18 Health care professionals’ atti-tudes can help make patients more receptive. However, for thosepatients who would be psychologically stressed by the thoughtof leeches on their bodies, the University of Wisconsin–Madisonannounced in December 2001 that it had developed a mechanicalleech. No follow-up reports could be located on the status or suc-cess of this device.3

Other Uses for Medicinal Leeches

H. medicinalis has widely been used in basic research on thecentral nervous system. Researchers in Russia have found thatcomponents in medicinal leeches’ salivary gland secretions stim-ulated growth of the neurites (outgrowths) of sensory neurons inin vitro tissue cultivation of the spinal ganglia from chickenembryos. Application of this identification of the stimulatingaction of these protease and protease inhibitors may lead to thedevelopment of new treatments for neurodegenerative dis-eases.27

Products made from the saliva of medicinal leeches are alsobeing marketed in skin care products by a sister company ofRicarimpex.16

Because of their sensitivity to aquatic environments andease of maintenance under laboratory conditions, medicinalleeches have been used in experiments on water-qualityassessment.28

ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2005 15

*The study referred to is Michalsen A, et al. Effectiveness of leech therapyin osteoarthritis of the knee: A randomized controlled trial. Ann InternMed 2003;139:724–730.

Conclusions

Medicinal leeches and humans have had a symbiotic relation-ship since antiquity. The bloodsucking characteristic of H.medicinalis has been long known as an aid to circulation. Inmodern surgery, such leeches are invaluable, cost-effective aidsto help restore blood circulation to impaired tissue in patientshaving appendages reattached or skin grafts.

Standardized protocols for leech use need to be developed.Studies identifying the specific chemical components in leechsaliva that act therapeutically have maintained clinical interestin leeches. Recent FDA approval will undoubtedly spur furtherresearch interest in leeches’ medicinal properties and widerclinical applications of this age-old remedy. ■

References1. U.S. Food and Drug Administration. FDA clears leeches for marketing[talk paper]. September 27, 2004. Online document at: www.fda.gov/bbs/topics/answers/2004/ANS01294.html2. Leeches U.S.A. Ltd., Medicinal leeches: General information. August 25,2004. Online document at: www.leechesusa.com Accessed September 9, 2004.3. Riverdeep Interactive Learning Ltd. Bug Medicine. March 4, 2002.Online document at: www.riverdeep.net/current/2002/03/030402_bugmedicine.jhtml4. Mann KH. Leeches (Hirudinea): Their Structure, Physiology, Ecologyand Embryology. [International series of monographs on pure andapplied biology, vol. 11]. New York: Pergamon Press, 1962.5. Duke M. The Development of Medical Techniques and Treatments:From Leeches to Heart Surgery. Madison, CT: International UniversitiesPress, 1991.6. Silverstein K. Hirudo medicinalis. Animal Diversity Web. September 27,2004. Online document at: http://animaldiversity.ummz.umich.edu/site/accounts/information/Hirudo_medicinalis.html Accessed Septem-ber 27, 2004.7. Electricwala A, et al. Isolation of thrombin inhibitor from the leechHirudinaria manillensis. Blood Coagul Fibrinolysis 1991;2:83–89.8. Sawyer RT. Biopharm Leeches Online: The Biting Edge of Science.February 15, 2002. Online document at: www.biopharm-leeches.comAccessed August 21, 2004.9. Derganc M, Zdravic F. Venous congestion of flaps treated by applica-tion of leeches. Br J Plast Surg 1960;13:187–192.10. Salzet M. Leech thrombin inhibitors. Curr Pharm Des 2002;8:493–503.11. Sohn JH, et al. Current status of the anticoagulant hirudin: Its biotech-nological production and clinical practice. Appl Microbiol Biotechnol2001;57:606–613.

12. Markwardt F. Hirudin as an alternate coagulant: A historical review.Semin Thromb Hemost 2002;28:405–414.13. Munro R, Jones CP, Sawyer RT. Calin: A platelet adhesion inhibitorfrom the saliva of the medicinal leech. Blood Coagul Fibrinolysis1991;2:179–184.14. Abdelgabar AM, Bhowmick BK. The return of the leech. Int J ClinPract 2003;57:103–105.15. Whitaker IS, Izadi D, Oliver IS, et al. Hirudo medicinalis and the plasticsurgeon. Br J Plast Surg 2004;57:348–353.16. Snowbeck C. That leech isn’t icky, it’s a medical device. PittsburghP o s t - G a z e t t e , J u l y 6 , 2 0 0 4 . O n l i n e d o c u m e n t a t : w w w . p o s t -gazette.com/pg/04188/342419.stm Accessed August 25, 2004.17. Mineo M, Jolley T, Rodriguez G. Leech therapy in penile reimplanta-tion: A case of recurrent penile self-amputation. Urology 2004;63:981–983.18. University of Missouri Health Care. Medicinal Leeches: Using an OldRemedy in a New Way. February 24, 2000. Online document at:www.muhealth.org/~news/LEECHES.shtml Accessed August 21, 2004.19. Gideroglu K, Yildirim S, Akan M, et al. Immediate use of medicinalleeches to salvage venous congested reverse pedicled neurocutaneousflaps. Scand J Plast Reconstr Surg Hand Surg 2003;37:277–282.20. Hartig GK, Connor NP, Heisey DM, et al. Comparing a mechanicaldevice with medicinal leeches for treating venous congestion. Otolaryn-gol Head Neck Surg 2003;129:556–564.21. Aetna. Medicinal Leech Therapy. Clinical Policy Bulletin [number0556]. Online document at: www.aetna.com/cpb/data/CPBA0556.htmlAccessed September 27, 2004.22. Whitaker IS, Rao J, Izadi D, et al. Historical article: Hirudo medicinalis.Ancient origins of, and trends in the use of medicinal leeches throughouthistory. Br J Oral Maxillofac Surg 2004;42:133–137.23. Aydin A, Nazik H, Kuvat SV. External decontamination of wild leech-es with hydrochloric acid. BMC Infect Dis 2004;4:28.24. Blaise S, Le Brun V, Sparsa A, et al. Contact dermatitis with Hirudomedicinalis. Ann Dermatol Venereol 2002;129:1380–1382 [French]. 25. Ouderkirk JP, Bekhor D, Turett GS, et al. Aeromonas meningitis com-plicating medicinal leech therapy. Clin Infect Dis 2004;38:e36–e37.26. Granzow JW, Armstrong MB, Panthaki ZJ. A simple method for thecontrol of medicinal leeches. J Reconstr Microsurg 2004;20:461–462. 27. Chalisova NI, PennijajnenVP, Baskova IP, et al. The neurite-stimulat-ing activity of components of the salivary gland secretion of the medici-nal leech in cultures of sensory neurons. Neurosci Behav Physiol2003;33:411–414.28. Petrauskiene L. The medicinal leech as a convenient tool for watertoxicity assessment. Environ Toxicol 2004;19:336–341.

To order reprints of this article, write to or call: Karen Ballen, ALTERNA-TIVE & COMPLEMENTARY THERAPIES, Mary Ann Liebert, Inc., 2Madison Avenue, Larchmont, NY 10538-1961, (914) 834-3100.

16 ALTERNATIVE & COMPLEMENTARY THERAPIES—FEBRUARY 2005