review
Wien Med Wochenschr
DOI 10.1007/s10354-015-0382-5
Medical leech therapy in plastic reconstructive
surgery
Khosrow S. Houschyar · Arash Momeni · Zeshaan N. Maan · Malcolm N. Pyles · Olivia S. Jew ·
Marion Strathe · Andreas Michalsen
Received: 30 April 2015 / Accepted: 4 August 2015
© Springer-Verlag Wien 2015
Summary  The use of Hirudo medicinalis in clinical prac-
tice has increased in recent years. The primary indication
in plastic surgery has traditionally been venous conges-
tion. However, other reported clinical applications were
in varicose veins, thrombophlebitis, and osteoarthritis.
In this review, we summarize recent data elucidating
the role that medicinal leeches play in the field of plastic
surgery.
Keywords  Leech · Venous congestion · Reconstruction
Blutegeltherapie in der plastischen
rekonstruktiven Chirurgie
Zusammenfassung  Die Verwendung von Hirudo medi-
cinalis in der klinischen Praxis hat in den letzten Jahren
zugenommen. Die primäre Indikation in der plastischen
Chirurgie ist traditionell die venöse Stauung. Darüber
hinaus sind weitere klinische Anwendungen bei Krampf-
adern, Thrombophlebitis, und Osteoarthritis bekannt. In
dieser Übersicht fassen wir die jüngsten Daten zusam-
K. S. Houschyar, MD () · A. Momeni, MD · Z. N. Maan, MBBS,
MRCS · M. N. Pyles · O. S. Jew · M. Strathe
Division of Plastic and Reconstructive Surgery, Department of
Surgery, Stanford School of Medicine,
Stanford, USA
e-mail: Khosrow.Houschyar@Bergmannstrost.com
K. S. Houschyar, MD
Clinic for Plastic and Reconstructive Surgery,
Bergmannstrost Halle,
Merseburger Str. 165,
06112 Halle, Germany
A. Michalsen, MD
Department of Internal and Complementary Medicine,
Immanuel Hospital Berlin,
Berlin, Germany
13
men und erläutern die Rolle, die die medizinischen Blut-
egel auf dem Gebiet der plastischen Chirurgie spielen.
Schlüsselwörter  Blutegel  · Venöse Stauung  · Rekonst-
ruktion
Introduction
Medicinal leeches (Hirudo medicinalis, Hirudi verbana)
have been used in medicine for thousands of years to treat
a variety of ailments. The popularity of leech therapy has
varied throughout history, reaching a peak in early nine-
teenth century Europe, during that time leech supplies
were regularly exhausted. During the latter half of the
nineteenth century, their use fell out of favor, as a new
paradigm of medical practice began to emerge [1]. In the
1970s and 1980s, leech therapy was revived as an adjunct
to plastic, reconstructive, and trauma surgery. In the 1980s,
French microsurgeons began using leeches to assist with
distal digital replantation involving arterial repairs [2].
Currently, medicinal leeches are used successfully for only
a few medical conditions, most notably venous conges-
tion and arthritic pain. This former condition is a serious
complication following microsurgical procedures such as
free flap transfer or replantation [3]. If surgical correction
of venous congestion is not feasible or fails, then medici-
nal leeches are used to provide drainage of the affected tis-
sues until new vessels develop to prevent sequelae such as
necrosis [4]. In the following sections, we present a sum-
mation of data describing the utility of medicinal leeches,
particularly in plastic and reconstructive surgery.
Basic biology of leeches and agents
Leeches belong to the phylum Annelida, class Hirudinea.
H. medicinalis/H. verbena is the species that inflicts the
Medical leech therapy in plastic reconstructive surgery   1
 review

Fig. 1  Medicinal leech mor-

phology. a Hirudo medicinalis
attached to the skin. b After
attaching its head sucker to
the skin, the leech uses its
three jaws with razor-sharp
teeth to make a neat Y-
shaped cut. Salivary ductules
between the teeth secrete
several pharmacologically
active substances, including
a local anesthetic and the
potent anticoagulant hirudin

deepest bite and the most prolonged post-bite extrava- Table 1  Components and effects of medicinal leech saliva
sation in its class [2]. H. medicinalis, while applied, can
Components of
grow to approximately 10  cm in length, with its resting
leech saliva
length being approximately one third of its maximal
length. The leech crawls using a large posterior sucker. Hirudin
On its posterior end, the leech has three jaws arranged Calin
in a tri-radiate configuration that can attach to and bite
through human skin, while the smaller anterior sucker is
utilized for feeding (Fig. 1). Medicinal leeches have two Hirustasin
different mechanisms of bloodletting. The first mecha-
Hyaluronidase
nism is through passive bleeding after each bite: this
accounts for the majority of the average blood meal vol- Eglins
ume for a leech [5]. This temporarily increases tissue per-
fusion by actively drawing off blood within the congested Destabilize
tissue, as demonstrated by Laser Doppler analysis [6]. Bdellins
Moreover, as the leech bite continues, it reduces conges- Factor Xa inhibitor
tion due to the anticoagulant effect of leech saliva, which
contains the potent thrombin inhibitor hirudin, apyrase, Complement
collagenase, hyaluronidase, factor Xa inhibitor, and fibri- inhibitors
nase I and II (Table 1). Leech saliva contains several sub- Histamine-like
stances that make their alimentary behavior possible: (1) substances
an anesthetic compound that makes the leech bite pain- Tryptase inhibitor
less, (2) a histamine-like vasodilator that increases blood Carboxypeptidase A
flow to the area of feeding, and (3) the most important inhibitor
component of leech saliva, hirudin (a selective throm- Acetylcholine
bin inhibitor). Hirudin is stabilized by three disulfide Anesthetic sub-
bridges. Its three-dimensional structure reveals three stance
distinct regions: a central core, a “finger”, and a loop. Collagenase
Recombinant biotechnology has been used to produce Apyrase
recombinant hirudin (r-hirudin), which, unlike natural
hirudin, lacks the sulfate group at Tyr-63 [7].
Effect on host
Inhibits blood coagulation by binding to thrombin
Inhibits blood coagulation and collagen-mediated
platelet aggregation by blocking the binding of von
Willebrand factor to collagen
Inhibits kallikrein, neutrophilic cathepsin G, trypsin,
chymotrypsin
Increases interstitial viscosity, antibiotic effects
Anti-inflammatory, inhibits the activity of chymotryp-
sin, subtilisin, cathepsin G, chymase, elastase
Dissolves fibrin
Anti-inflammatory, inhibits plasmin, acrosin, trypsin
Inhibits the activity of coagulation factor Xa by form-
ing complexes
Replace natural complement inhibitors in case of
deficiency
Vasodilator, increases the inflow of blood at the bite
site
Inhibits proteolytic enzymes of host mast cells
Increases the inflow of blood at the bite site
Vasodilator
Anesthetic
Faciliates tissue penetration
Inhibitor of platelet aggregation by inhibition of
adenosine triphosphate

for 1–2 days prior to therapy. The leech can be directed to

Practical considerations
Patients should be informed about the possible risks and
benefits of medicinal leech therapy and written consent
should be obtained before therapy is initiated. Patient
education is critical for effective use of medicinal leech
therapy. In particular, the patient should keep the pro-
posed site of application free of fragrances and chemicals
a precise target tissue using a small plastic tube, which is
of particular benefit when used intra-orally [8]. To pre-
vent aberrant leech biting of medical providers, medi-
cal gloves should be worn at all times during treatment
or handling of the leeches. Interestingly, leeches do not
attach to and feed from devitalized tissue. Therefore,
when presented with tissue of questionable viability, the

2   Medical leech therapy in plastic reconstructive surgery 13


absence of leech feeding behavior may serve as an indi-
cation for debridement.
Leeches should be obtained from reputable medical
leech producing companies where they are maintained
appropriately in farms and kept alive through artificial
animal blood feedings. Leeches obtained from the natu-
ral environment should not be used for hirudotherapy.
Prior to use in therapy, leeches should be starved suffi-
ciently to ensure adequate blood draw.
The actual volume of blood drawn by a single leech
is minimal, approximately 2–20  mL per feeding. The
amount of active and passive blood loss during a single
leech bite varies and is related to the length of leech star-
vation, leech size, and concentration of secretions. The
secretions from a single leech have been found to pre-
vent in vitro coagulation of 50–100 mL of human blood.
The presence of hirudin in the leech saliva ensures sus-
tained oozing from the leeching site even after the leech
has detached, allowing therapy sessions to be spaced
up to 6–8 h apart [9]. Because the leech bite site on the
host may continue to ooze blood for as long as 24–48 h,
the benefit from leech phlebotomy is thought to far
exceed the individual meal volume [10]. Indeed, when
leech therapy is utilized for retained hematomas, there
is continued drainage of dark nonclotted blood from
leech attachment sites for some time after leech detach-
ment [2]. Leeches will detach spontaneously after they
are maximally engorged. At this point, they should be
removed and disposed of as biohazardous waste follow-
ing sacrifice in 70 % alcohol or by freezing.
Coagulation cascade
The hemostatic system maintains blood in a fluid state
under normal conditions and responds to vessel injury
by the rapid formation of a clot. Once a platelet plug has
formed (primary hemostasis), the products of the coagu-
lation pathway (secondary hemostasis) strengthen the
plug [11]. Coagulation can be initiated from within the
circulation (intrinsic) or outside the circulation (extrin-
sic). It involves a cascade of protein activation leading to
the conversion of fibrinogen to fibrin via generation of
thrombin. The factors required for coagulation are nor-
mally found in the circulation as proenzymes or cofactors.
The secondary hemostatic response is initiated by tissue
factor (TF), a glycoprotein expressed on the subendothe-
lium of damaged vessels and the surface of nonvascular
cells, such as monocytes, after tissue injury or inflamma-
tion [12]. Activation of the coagulation cascade by TF is
known as the “extrinsic” pathway because the circula-
tion is not normally exposed to TF. TF activates and then
forms a complex with FVIIa to produce a complex that
activates both FX and FIX. In the presence of the cofactor
FVa and calcium ions, FXa forms the “prothrombinase”
complex, which activates prothrombin (FII), converting
it to thrombin (FIIa) [13]. By stopping thrombus forma-
tion, hirudin is essential to the process of venous decon-
gestion by permitting the leech to feed on blood for an
13
review
extended period of time without clotting the blood source
[14]. Thrombin activity is neutralized by hirudin in stoi-
chiometric amounts at extremely low concentrations
of both reactants. This makes hirudin the most known
potent and specific inhibitor of thrombin. Effective inhi-
bition of thrombin by antithrombin and heparin cofactor
II requires the catalytic actions of heparin (Fig. 2). In con-
trast, hirudin effectively inhibits thrombin independently
of any cofactor, forming noncovalent but irreversible 1:1
complexes with thrombin. Hirudin binds to at least two
sites on thrombin, and therefore is classified as a bivalent
direct thrombin inhibitor (DTI). Additionally, hirudin
inhibits both free and clot-bound thrombin, as well as
thrombin bound to fibrin split products [7]. In contrast,
heparin-antithrombin complexes are relatively poor at
accessing and inactivating clot-bound thrombin. This
could explain why hirudin is more effective than heparin
in promoting dissolution of mural thrombi in experimen-
tal models [15]. Another important difference is that hiru-
din shows virtually no interaction with plasma proteins,
whereas binding characteristics of heparin to plasma
proteins is the major explanation for its many limitations,
including its unpredictable dose–response relationship,
the potential for heparin “resistance”, and the induction
of neo-antigens after binding to PF4 (resulting in hepa-
rin-induced thrombocytopenia [HIT]) [16]. Lepirudin,
a recombinant hirudin, is a direct irreversible thrombin
inhibitor, binding to both free and clot-bound thrombin.
Lepirudin has been investigated extensively in controlled
clinical trials for acute coronary syndrome (ACS), includ-
ing myocardial infarction (MI) and unstable angina pec-
toris; and in pilot studies for prophylaxis and treatment
of deep-vein thrombosis (DVT) [17]. Lepirudin has also
been studied for anticoagulation in other clinical settings
such as hemodialysis and cardiac surgery utilizing the
cardiopulmonary bypass (CPB). Hirudins are approved
for only two indications: HIT complicated by thrombo-
sis (lepirudin) as well as thrombosis prophylaxis after
major orthopedic surgery, a clinical situation in which
desirudin has been studied systematically [18]. However,
despite this approval, the use of desirudin for postopera-
tive thromboprophylaxis is negligible (primarily due to
high cost) [7] and will not be discussed further. Recently,
additional antithrombotic compounds have been identi-
fied in leech oral secretions. A prostanoid fraction of leech
saliva and the enzyme destabilase have both been shown
to inhibit adenosine diphosphate-induced platelet aggre-
gation. Calin, another protein isolated from leech saliva,
has been shown to prevent wound closure after leech bite.
Calin inhibits collagen-mediated platelet adhesion and
activation through its interference with both direct plate-
let-collagen aggregation and as well as inhibition of von
Willebrand factor-dependent platelet adhesion to colla-
gen in vessel walls [19]. Together this is the biochemical
basis of prolonged bleeding from the leech bite, which
normally persists for 12 h. This prolonged bleeding is the-
orized to preserve the host by allowing for an outflow of
blood that cleanses the wound bed, thereby preventing a
potentially lethal sepsis.
Medical leech therapy in plastic reconstructive surgery   3
 review
Fig. 2  The hirudin-thrombin complex. a Thrombin is a coagu-
lation protein that has many effects in the coagulation cas-
cade. It is a serine protease that alters soluble fibrinogen into
insoluble strands of fibrin, as well as catalyzes many other
coagulation-related reactions. Hirudin acts as a direct inhibi-
tor of thrombin to stop coagulation at its source, unlike other
well-known drugs such as Coumadin (warfarin) and hepa-
rin. Hirudin is an anticoagulant peptide that directly inhibits
thrombin and can possibly replace the current drug warfarin
to help prevent strokes and heart attacks due to clotting. War-
farin affects the blood coagulation mechanisms by inhibiting
the vitamin K functions, which plays an essential role in the
synthesis of several blood coagulation factors. Since hirudin
directly inhibits thrombin, as a drug, it will not have the nega-
Treatment options with leeches
Medicinal leeches have been used throughout the ages to
treat a myriad of diseases and conditions with and with-
out objective proof of their benefit or understanding of
their mechanism of action. The use of leeches has been
expanded to treat disease entities other than those char-
acterized by venous congestion [20]. Leeches have been
used successfully to treat purpura fulminans, sublingual
hematoma, and infectious ear pathologies (otitis media
and otitis externa) [21]. In cases of macroglossia second-
ary to traumatic giant lingual hematoma, leeches have
been proved effective in decreasing the time to extuba-
tion by bringing about a rapid resolution of lingual swell-
ing. The mechanism of action for leech therapy in these
clinical scenarios is not well understood [22].
The application of medicinal leeches increases blood
flow within congested tissue. Due to the presence of anti-
inflammatory substances in their saliva, leech therapy has
also been used in recent times to treat localized inflam-
4   Medical leech therapy in plastic reconstructive surgery
tive side effects of possible hemorrhaging that warfarin has.
Other studies on hirudin have also pointed to the possibility of
its therapeutic applications toward osteoarthritis, specifically
on the knee joint, as well as its ability to greatly reduce the
unsightly appearance of varicose veins. b Hirudin chemical
structure: Full length hirudin consists of 65 amino acids. These
amino acids are organized into a compact N-terminal domain
containing three disulfide bonds and a C-terminal domain that
is completely disordered when the protein is denatured in so-
lution. The C-terminal domain forms numerous electrostatic
interactions with an anion-binding exosite of thrombin, while
the last five residues form a helical loop that constructs many
hydrophobic contacts
mation and pain. Michalsen et al. [23], recently published
several randomized controlled trials that demonstrated
significantly better pain relief among patients with osteo-
arthritis of the knee, rhizarthrosis, and chronic lateral epi-
condylitis [24] treated with leech therapy compared with
topical diclofenac therapy. Meanwhile, the use of leeches
in this area is supported by a further randomized con-
trolled trial (RCT) and a meta-analysis [25]. A well-known
entity in urologic trauma, penile amputation poses a dif-
ficult surgical problem. The current approach to penile
replantation involves reapproximation of the urethra
and corporal bodies with microsurgical anastomosis of
the dorsal artery and vein. Adequacy of postoperative
venous outflow is critical to the success of replantation.
Prior to the common use of microvascular techniques,
nonmicrosurgical penile replantations were plagued by
skin loss, urethral strictures and fistulae, loss of the glans
penis, and sensory deficits. Anecdotal evidence suggests
that the success of nonmicrosurgical replantation may be
augmented with the adjunctive use of leech therapy.
13
 review

Leeches in plastic surgery

The successful use of leeches, specifically of H. medici-

nalis, for treating poor circulation in skin flaps in plastic
surgery has long been recognized [26]. The focus of leech
therapy is still on the postoperative treatment of the local,
pedicled or microsurgical flap to treat a hemodynamic
imbalance or venous insufficiency [27]. The venous con-
gestion of a skin flap with consecutive thrombosis and
decreased perfusion dreaded complication [28]. In addi-
tion, there is necrosis of the corresponding skin or tissue
area with subsequent infection and risk of sepsis, resulting
in the loss or partial loss of the flap and undesirable con- Fig. 3  The relative number of publications reporting the use of
sequences by released necrotoxins [29]. Most commonly, leeches in plastic and reconstructive surgery over time
the initial approach to venous congestion is surgical explo-
ration and examination of the venous pedicle to alleviate
venous insufficiency [2]. Only when venous compromise
is determined to be surgically irreparable or if surgery is
contraindicated leech therapy should be considered [30].
Therapy with leeches initially aggravates the venous insuf-
ficiency before later producing a visible improvement in
graft perfusion, with success rates of > 80 % reported in the
literature [31]. The number of leeches and frequency of
treatment are quite variable and are determined by a mul-
titude of factors. In 1960, Derganc and Zdravic reported a
series of 20 pedicled flaps compromised by notable venous
engorgement [32]. Using 3–6 leeches at a time on the most
congested portion of the flap, and repeating this 2–3 times
over an unspecified period, they were able to completely
salvage 70 % of their flaps [32]. In a case series and meta-
analysis, de Chalain reviewed 108 cases in which leeches
were applied to replants, free-tissue transfers, and pedicle
flaps for an average of 4.2 days for venous congestion. The
survival rate was 83 % in 89 uninfected cases [33].
Vascular congestion poses a significant challenge in
reconstructive surgery. Traumatic injury with extensive Fig. 4  Use of medicinal leeches in different types of tissue
soft tissue loss and/or the need for replantation constitute
an important indication for medicinal leeching. Clinical
signs that should prompt consideration of leech ther- case series, 51 case reports, and 7 randomized controlled
apy in these settings include the development of tissue trials (Fig.  3). Interestingly, the greatest increase in the
edema, purple discoloration, and warmth of the recon- number of studies was seen from the short period of 2011–
structed/replanted tissue, which all suggest ongoing 2013. Free flaps (22.11 %) were the most common indica-
venous congestion in the presence of preserved arterial tion for leech therapy in this series, followed by pedicled
inflow. Leech use has also been described in distal digital flaps (16.84 %), ear replantations (11.58 %), digital replan-
replantation when venous repair was technically impossi- tations (10.53 %), lip replantations (9.47 %), penile recon-
ble. Foucher and Norris reported on their series of digital structions (8.42 %), nipple congestions (5.26 %), scalp
replantations distal to flexor digitorum superficialis inser- replantations (4.21 %), degloving injuries (2.11 %), and
tion and found a 68.1 % survival rate in digits performed ring avulsions (2.11 %) (Fig. 4).
without vein repair [33]. In 2004, Tuncali et al. reported
on two cases of class IIC ring avulsion injury (arterial sup-
ply intact, venous drainage disrupted) in which they were Complications and contraindications
unable to perform a venous repair. Both patients received
4–6 leeches per day for 7–10 days and both recovered Besides the positive effects of leech therapy, there are a
“excellent” function of the replanted fingers [33]. variety of complications involved, with the most common
A hand search was conducted including all issues of being anemia, localized infection, and sepsis. The inci-
PubMed for the years between 1970 and 2013. Parameters dence of anemia increases with prolonged duration of
of interest included the use of medicinal leeches in differ- leech therapy and with high quantities of leeches used [6].
ent fields of plastic surgery worldwide. Of the 95 included Aside from these more serious complications, patients are
papers published between 1970 and 2013, there were 37

13 Medical leech therapy in plastic reconstructive surgery   5

 review
also at risk for local pain and itching during the treatment
as well as episodic hypotension from bleeding.
The reported incidence of infection ranges from 2
to 20 % [34]. Local infections range from cellulitis and
abscess formation to myonecrosis. Aeromonas species
(e.g., Aeromonas hydrophila), Pseudomonas fluorescens,
and other glucose-nonfermenting gram-negative rods
have been isolated from H. medicinales. Aeromonas spe-
cies are the prominent bacterial flora in the leech gut and
are essential for digestion of blood. This species also has
a high affinity for muscle tissue, which makes deep tis-
sue infections associated with gas production more likely
[35]. Sepsis due to systemic infection with A. hydrophila
has been repeatedly observed after leech application in
reconstructive surgery indications, but not in any of the
other relevant fields of use. This supports the conclusion
that the risk of A. hydrophila sepsis is increased in patients
with severe underlying diseases or immunosuppression,
which often applies to patients after severe trauma and
surgery [36]. The potential risk of infection and its associ-
ated morbidity should be taken into account when con-
sidering leech therapy. Additionally, although it has not
been recorded in literature, leeches may have the poten-
tial to serve as vectors for infection and should not be
reused. Prophylactic antibiotics that are effective against
both leech surface and gut flora are recommended in
conjunction with leech therapy. Aeromonas species are
sensitive to second- and third-generation cephalospo-
rins, fluoroquinolones, sulfamethoxazole-trimethoprim,
tetracycline, and aminoglycosides, while Aeromonas is
resistant to penicillin, ampicillin, first-generation cepha-
losporins, and erythromycin [36, 37]. Regular surveil-
lance of medical leeches should be conducted to ensure
that resistance against antibiotics has not occurred. A
study involving surveillance of gut cultures in Aeromonas
showed that 71.4 % of 21 isolates of Aeromonas species
were ciprofloxacin susceptible, whereas all were suscep-
tible to sulfamethoxazole-trimethoprim [38].
Other complications include excessive blood loss
requiring transfusion, scarring from leech bites, local
hypersensitivity reaction, and anaphylaxis [32]. Rela-
tive contraindications for leech therapy include arterial
insufficiency, hemophilia, immunosuppression, oppo-
sition to blood transfusion, hypotension, sepsis, prior
allergic reaction to leeches, and the inability to cooperate
with leech therapy for psychological reasons.
Conclusion
Modern leech therapy utilizing H. medicinalis is based
on sound scientific principles and has resulted in impor-
tant enhancement of patient care. Leech therapy is most
often used in the settings of localized venous conges-
tion associated with flap reconstruction and surgical
replantation in the field of plastic and reconstructive sur-
gery. With minimization of infectious complications by
obtaining leeches from appropriate commercial sources
6   Medical leech therapy in plastic reconstructive surgery
and the utilization of effective antibiotic prophylaxis,
leech therapy represents an attractive treatment option
for flap salvage.
Acknowledgments
The study was supported by a grant from the Karl and
Veronica Carstens Foundation, Essen, Germany.
Ethical approval 
Ethical approval was not required for this study.
Conflict of interest 
No potential conflicts of interest were disclosed.
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