Biomedical Engineering Reference
In-Depth Information
12.3.1 Hirudin
Hirudin is a leech-derived anticoagulant that functions by directly inhibiting thrombin. A range
of blood-sucking animals contain substances in their saliva that specifi cally inhibit some element
of the blood coagulation system (Table 12.4).
A bite from any such parasite is characterized by prolonged host bleeding. This property led to
the documented use of leeches as an aid to blood-letting as far back as several hundred years BC.
The method was particularly fashionable in Europe at the beginning of the 19th century. Many
doctors at that time still believed that most illnesses were related in some way to blood composi-
tion, and blood-letting was a common, if ineffective, therapy. The Napoleonic Army surgeons, for
example, used leeches to withdraw blood from soldiers suffering from conditions as diverse as
infections and mental disease.
With the advent of modern medical principles, the medical usage of leeches waned somewhat.
In more recent years, however, they did stage a limited comeback. They were occasionally used to
drain blood from infl amed tissue, and in procedures associated with plastic surgery.
The presence of an anticoagulant in the saliva of the leech,
Hirudo medicinalis
, was fi rst de-
scribed in 1884. However, it was not until 1957 that the major anticoagulant activity present was
purifi ed and named hirudin. Hirudin is a short (65 amino acid) polypeptide, of molecular mass
7000 Da. The tyrosine residue at position 63 is unusual in that it contains a sulfate group. The
molecule appears to have two domains. The globular N-terminal domain is stabilized by three
disulfi de linkages, whereas the C-terminal domain is more elongated and exhibits a high content
of acidic amino acids.
Hirudin exhibits its anticoagulant effect by tightly binding thrombin, thus inactivating it. In
addition to its critical role in the production of a fi brin clot, thrombin displays several other (non-
enzymatic) biological activities important in sustaining haemostasis. These include:
•
it is a potent inducer of platelet activation and aggregation;
•
it functions as a chemoattractant for monocytes and neutrophils;
•
it stimulates endothelial transport.
Table 12.4
Some substances isolated from bloodsucking parasites which inhibit their host's haemostatic
mechanisms. All are polypeptides of relatively low molecular mass
Polypeptide
Molecular mass (Da)
Producer
Haemostatic effect disrupted
Hirudin
7 000
Hirudo medicinalis
Binds to and inhibits thrombin
Rhodniin
11 100
Rhodnius prolixus
Binds to and inhibits thrombin
Antistatin
15 000
Haementeria offi cinalis
Inhibits factor Xa
Tick anticoagulant
peptide (TAP)
6 800
Ornithodoros moubata
Inhibits factor Xa
Calin
55 000
Hirudo medicinalis
Inhibits platelet adhesion
Decorsin
4 400
Macrobdella decora
Inhibits platelet adhesion
Search WWH ::
Custom Search