The Effects Of Other Substances In The Leech Saliva

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It has been estimated that there are about 60,000 miles or more blood vessels within a human body where blood, gases and nutrients are being circulated. [1] Any blockage of these vessels will cause blood congestion and thus give rise to various vascular diseases. For instance, a congested coronary artery will cause heart attacks, and a congested carotid artery will cause strokes. Other common examples are inflammatory reactions, haematomas, deep vein thrombosis, and so on. Hirudotherapy, also known as the leech therapy, is an ancient remedy now being revived and evaluated scientifically, hoping that it could be a one cure for all these diseases and provide a much more effective yet safer treatment.

So, how a leech can cure and is it really more effective over currently prescribed drugs in treating vascular congestion and related diseases?

The mechanism behind hirudotherapy can be simplified as such: when a medicinal leech (hirudo medicinalis) bites a target, the patient will not feel much pain because its saliva contains special anaesthetics. It then starts its active feeding by sucking the blood. At the same time, the saliva also contains various components that prevent the formation of blood clot at the wound and allow blood to ooze out continuously for hours even after the leech has been removed. This situation is known as passive bleeding.

Figure 1: Anatomy of a hirudo leech. <>

Figure 2: Medicinal leech saliva contents and their effects. [2] 

I have classified the leech treatment into 3 common types based on these effects of saliva contents and their applications.

Type 1: Hirudin as an anticoagulant

It has been recognised that the acute coronary syndromes involving the atherosclerotic plaques or thrombus have direct connection to the thrombin in the blood. Thrombin triggers platelet aggregation and gives rise to fibrin clot formation. Intravenous heparin, aspirin, and anti-ischemic medications are the standard treatments provided by hospitals. On the other hand, hirudin appears to have more advantages over heparin. It can act independently while heparin works indirectly with anti-thrombin III as its cofactor. As a result of this, heparin is not effective when it comes to the fibrin clot that already has thrombin bounded to it.

In addition, platelet factor 4 or plasma proteins might neutralise the effect of heparin. Some patients might even develop thrombocytopenia, which affects 5 to 15 percent of the patient population. In such cases, hirudin is highly selective for thrombin and is not affected by peptides and enzymes in the blood. It binds with thrombin to form an inactive hirudin-thrombin complex and halts the conversion of fibrinogen into fibrin. Another highlight of hirudin would be its stability as its form can remain unchanged when it is removed from the body through urination.

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Figure 3: Different attack points of hirudin and hementin in preventing blood clot formation. [3] 

In a research, patients with acute coronary syndromes were randomly given either intravenous heparin and hirudin placebo or hidurin extract and heparin placebo and follow-ups on a double blind basis. This led to the possibility of comparing the effect of hirudin and heparin in treating coronary syndromes and preventing deaths.

Figure 4: Estimate on probability of death or MI after hours of randomisation. [4] 

The outcome results showed that hirudin had significantly decreased the risk of death or myocardial infarction (MI) over hours of study compared to heparin.

Figure 5: Estimate on probability of death or MI in all patients.

The graph illustrated that over a long period of study, hirudin was still able to display significant advantage over heparin.

Type 2: Removal of blood via active feeding and passive bleeding

Detached body tissues or limbs can be reattached, transferred or transplanted through modern reconstructive surgeries. Microsurgical techniques are being used to restore the blood vessels supplying blood and oxygen to the connecting tissues or limbs to ensure their survival. However, often we see that after a complicated plastic or reconstructive surgery, venous congestion occurs at the connecting tissues due to the formation of blood clot after a venous outflow. Thus, the blood cannot be circulated and the tissue flap will eventually die off and is lost if the congestion prolonged.

It is then vital to remove excess blood accumulated at the site so that risk of cell death can be minimised. Moreover, it provides time for the ingrowth of new venous outflow from the surrounding normal tissues or the reconnection of veins. Surgical revision is rarely possible or successful to fix the problem.

When a tissue flap encounters venous congestion, live medicinal leeches (Hirudo medicinalis) are placed on it to expel the stagnant blood. This method is reportedly to have a great effect in restoring blood flow and salvaging tissues. [5] The oozing of blood from the wound also has the effect of cleansing the wound and reducing the risk of infection. Leeches are applied continuously until a new vascular circuit develops and replaces the old one.

Type 3: Effects of other substances in the leech saliva

As the leech saliva also contains anti-inflammatory and anaesthetics substances, the patient will feel no pain being bitten. This special effect attributes towards the treatment of diseases such as arthritis of the joint.

Although arthritis belongs to immunological disorder, the inflammation around the joints causes pain to the patients. Therefore, leech therapy might be useful in soothing the pain suffered. A study designed by researchers from Germany's Academic Teaching Hospital by applying living leeches at the pain site on randomly chosen patients described that 'one application of leeches can reduce pain 60%' for more than 2 months and it is even more effective than Diclofenac, a group of drugs which is commonly used to treat pain or inflammation caused by arthritis by reducing the hormones causing such symptoms. [6] 

Figure 6: Both leech and Diclofenac treatments compared by the total pain score.

The result had backed up a previous study on leech therapy for treating knee osteoarthritis.

Figure 7: Both groups in the study course compared by pain score.

Not known by many, an interesting study reported that the use of recombinant leech-derived tryptase inhibitor (LDTI) had successfully blocked the replication of HIV-1 virus in host cells. Such cases are the motivators that drive scientists to continue their studies as the potential of leech therapy for the better life quality is indeed worthy.


Recombinant Hirudin

A leech's saliva contains limited amount of natural hirudin, so the idea of mass hirudin extraction for treatments is almost impractical as this will multiply the cost. What can be done? One possible solution to this is to synthesise a similar substance. Scientists have previously cloned the cDNA for hirudin and it is expressed in yeast. However, the resulting recombinant protein was found unsulfated, having at least 10 times lower affinity for thrombin than natural hirudin.

Nevertheless, recombinant hirudin has been approved by United States' FDA to be produced and applied commercially. It can be an alternative when living leeches are not available and the patient seems to develop intolerance against heparin. A surgeon must always consider the following advantages and disadvantages when conducting treatments.



Recombinant Hirudin


Led to a very consistent anticoagulant effect over time, independently of the use of thrombolytic therapy

Inexpensive, performed well as an anti-thrombin agent in the studies and should still be regarded as the standard therapy

Demonstrable and consistent effect, especially on the rate of reinfarction


Excessive usage will increase bleeding risk, no known antidote

Might cause serious thrombotic complications such as thrombocytopenia

Small clinical effect

Table 1: Comparison between hirudin, heparin, and recombinant hirudin by means of advantages and disadvantages [7] 


Hementin is a unique secretion in the saliva of Amazon Giant Leech (Haementeria ghilianii). As shown in Figure 3, it inhibits the coagulation of blood by breaking down the fibrinogen. Because Haementeria ghilianii does not belong to the order of Arhynchobdellida but Rhynchobdellida, therefore it was not recognised as medicinal leech. However, Professor Maurice Moloney from Canada's University of Calgary discovered that while hirudin prevents clot formation, hementin breaks down clots formed more effectively than conventionally used drugs like streptokinase and urokinase.

Mechanical Leech

Increases in blood loss volumes from congested tissue flaps may improve postoperative blood perfusion, ensuring tissue flap viability and survival. However, passive blood loss from a single leech bite is not sufficient to decongest an impaired tissue flap. So, is there a way of boosting blood lost volumes? The idea increasing the tissue viability with mechanical devices was thus provoked.


Figure 8: Simplified design for mechanical leech device. [8] 

(1) A leech-bite alike cut is produced by the device and heparin is dripped onto the wound.

(2) Blood irrigant removed from device chamber by suction pressure produced.

(3) Bubble turbulence created by room air prevents thrombosis on skin surface.

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Figure 9: Prototype of mechanical device experimented and used to decongest tissue flap. [9] 


Figure 10: Use of mechanical device significantly increased blood retrieval relative to passive bleeding alone.

Ethical Implication

The studies have raised several ethical issues to be concerned. If leech therapy is proven to be more effective than all of the current treatments, it would be unfair for those patients being rejected for receiving better treatments. However, before leech therapy was proven to be safe, the studies had actually risked the patients' lives. Another concern is whether the doctors' practices are keeping pace with current research in providing leech treatment with best promising results. Continuous studies have been providing the latest found methods but despite being recommended through several publications, a number of doctors were discovered to be unaware of them, hence the common complications of leech treatment remain to be unsolved. Therefore, it is important for a leech therapist to frequently update themselves thoroughly with the latest information and equip themselves with better skills through practicals.

Social Implication

A spokesperson of the Australian Society of Plastic Surgeons, Mr Randall Sach estimated that one thirds of patients will feel fearful having slimy and wriggling leeches on their body. [10] This might leave traumatic experience on patients. However, most surgeons commented that when the conditions are critical, patients will normally regard leeches as their life savers and cooperate with their doctors. Moreover, development of mechanical leeches might be a solution to this, as patients would feel more confident to scientific devices. In future, we might see more mechanical leech devices being invented and commercialised, providing affordable yet effective treatment.


I have gone through several prestigious medical journals and books related to leech therapy. One of the sources I referred to is an article "A Comparison of Recombinant Hirudin with Heparin for the Treatment of Acute Coronary Syndromes" published in The New England Journal of Medicine, a peer-reviewed, oldest continuously published weekly medical journal in the world. I believe the result is reliable as similar results can be reproduced by other research teams. Besides that, it also involved a large sample of 12,142 patients in total, conducted at 373 hospitals in 13 countries. Furthermore, the aim of the study is intended to cure, not for financial interests. All these are directly credited to its reliability.

Another source would be an article "Effectiveness of Leech Therapy in Osteoarthritis of the Knee" published in Annals of Internal Medicine, one of the most-cited general clinical medical journals in the world. It stated that leech therapy had successfully surpassed conventional drugs in relieving pain. The result was later backed up by a similar study and result published in Pain, another prestigious medical journal, despite both results might be affected by anti-thrombolytic, antinociceptive (pain fighting) effects, counter irritation or placebo effect. [11] 


Vogel, S. & Calvert, R.A. (1993), Vital Circuits: On pumps, pipes, and the workings of circulatory systems, Oxford University Press, US

Michalsen A., Roth M., Dobos G.J., & Aurich M. (2007), Medicinal Leech Therapy, Thieme Medical Publishers, Germany