Mechanisms of Leeching and their Clinical Correlatives

Compared to conventional pharmacological and interventional treatment modalities, leech therapy has a very broad range of uses in various fields of medicine. To understand why this is so, one must analyze the potential and known mechanisms of leech therapy. The efficacy of leeching is based on a combination of multiple effects resulting in hemodilution (venesection), modification of local tissue rheology, segmental (reflex) counterirritation, and antinociception. In other words, leech saliva contains a range of bioactive substances that exert manifold pharmacological effects.

When a leech bites, the bite wound immediately begins to bleed and continues to bleed for several hours. This prolonged bleeding is due to the presence of hirudin and other anticoagulant substances in leech saliva and it is the most relevant mechanism of leeching in plastic and reconstructive surgery. Leeching achieves extensive local venous drainage and improves the hemorheological characteristics of the blood to effectively counteract postoperative venous congestion and imminent tissue necrosis. Although the secretion of hirudin by the leech only represents a local tissue injection, systemic effects of hirudin are also presumed to occur. In a cohort of 23 patients, a reduction of viscoelasticity and aggregation tendency of the blood was observed four weeks after a single leech treatment in the lumbar region, while the hematocrit and plasma viscosity values remained unchanged. Considering the short plasma half-life of hirudin, the authors proposed that differential stimulation of erythropoiesis might be responsible for the long-term modulation of hemorheological parameters. However, such systemic effects of leeching are of little importance in surgical indications for leech therapy.
Leeching is no longer recommended for prevention and treatment of thrombosis. Modern drugs such as heparin and coumarin have reliably effective and controllable pharmacological effects and are now preferred for these indications.

A number of the known biochemicals in leech saliva exhibited analgesic and anti-inflammatory properties in experimental studies. Recent studies on hirudin and thrombin inhibitors have highlighted the direct anti-inflammatory effects of these substances in addition to their known anticoagulant effects. Experimental studies by researchers at the University of Lausanne have received much attention. The investigators first produced antigen-induced joint inflammation in experimental animals and then treated the animals with subcutaneous doses of recombinant PEG hirudin for 13 days. Significant scintigraphic reduction of inflammation and histological reduction of synovial thickening occurred within seven days. These findings suggest that the inhibitory effect of hirudin acts not only on the thrombin system, but also on inflammatory processes at the cellular level. Ir. another study, they showed that hirudin inhibits a number of proinflamma-tory cytokines in synovial fluid. In leech therapy, it is important to beai in mind that a leech bite represents only a single hirudin "injection" and that the half-life of natural hirudin is shorter than that of recombinant PEG hirudin. As already mentioned, hirudin normally works in combination witl many other anti-inflammatory substances in leech saliva. This additive effect is presumably very significant.

The jaws of the leech pierce the skin so that these potent biologically active substances can penetrate into the deeper tissues. Hyaluronidase (spreading factor), an enzyme in leech saliva, further facilitates the penetration and diffusion of these pharmacologically active substances into the tissues. Experimental research data on commonly used topical antiphlogistic drugs can be used to draw certain general conclusions about the accumulation of locally administered substances in body tissues. After topical application of diclofenac gel to the knees of patients with knee joint effusions, the drug could be detected in the deep periarticular tissues and body compartments. With the additive effect of hyaluronidase, it is highly probable that the antiphlogistic substances in leech saliva can penetrate deep enough to exert significant effects on periarticular myofascial structures and perhaps even on intra-articular structures. A recent study showed that peri-articular myofascial structures play an important role in the development of chronic joint pain and regional pain syndromes in patients with osteoarthritis. A systemic anti-inflammatory effect of leech therapy is less plausible, especially in light of the prolonged effect of a single leech bite.

As a rule, any treatment that causes irritation of the cutis and subcutis will trigger local antinociceptive and segmental effects. This is the rationale behind the use of specific antinociceptive substances such as capsaicin (Spanish pepper) in pain treatment. These mechanisms are also involved in acupuncture and in the skin stimulation techniques employed in traditional European medicine (Braunscheidt's technique, cupping, etc.). The extent to which a single leech bite activates such mechanisms is not known and is difficult to determine in experimental models. However, it would seem plausible that the antinociceptive effects of the leech bite might enhance the other primary mechanisms of leeching. The significance of segmental organization is often stressed in the historical literature. For example, one author states that leeches should be applied to the margins of the liver for treatment of hydropic liver congestion and to a defined connective tissue "headache zone" for treatment of migraines. For the unbiased researcher, these theories can be interesting and merit further investigation. At present, the available study findings are insufficient to reliably determine whether there are clinical indications for leeching based on these mechanisms.

In addition to the aforementioned pharmacological effects, some investigators postulate that leeching improves lymph flow. The available data on this subject is sparse and stems from older studies. Clinical experience with leech therapy in joint disease and pain management does not give any strong evidence in support of such an effect. There are no empirical reports of a specific effect of leech therapy on concomitant lymphedema. However, previous clinical studies have demonstrated the efficacy of leech therapy, even in patients without palpable tissue abnormalities or lymphedema. Likewise, some practitioners postulate that local leech therapy is especially effective in patients with so-called connective tissue zones. However, subanalyses of two large studies on leech therapy in the treatment of osteo-arthritis of the knee did not show any correlation between the extent of local connective tissue zones and the clinical efficacy of treatment. Based on the current state of knowledge, the effects of leech therapy on lymph flow and connective tissues seem to be of little relevance to pain management, but the stimulation of lymph flow might be more important in the treatment of symptomatic varicosis. Further clinical studies are needed for a reliable assessment of such effects.

A.Michalsen