Etamsylate (sometimes spelled ethamsylate) is an antihemorrhagic agent which is believed to work by increasing resistance in the

endothelium The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...

capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

and promoting

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby i ...

adhesion. It also inhibits biosynthesis and action of those prostaglandins which cause platelet disaggregation,

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...

and increased capillary permeability.

Indications

Prophylaxis and control of haemorrhages from small blood vessels, neonatal intraventricular haemorrhage, capillary bleeding of different etiology, including: menorrhagia and metrorrhagia without organic pathology, after trans-urethral resection of the prostate, hematemesis, melena, hematuria, epistaxis; secondary bleeding due to thrombocytopenia or thrombocytopathia, hypocoagulation, prevention of periventricular hemorrhages in prematurely born children.

Mechanism of action

Etamsylate is a haemostatic agent; also promotes angioprotective and proaggregant action. It stimulates

thrombopoiesis Thrombopoiesis is the formation of thrombocytes (blood platelets) in the bone marrow. Thrombopoietin is the main regulator of thrombopoiesis. Thrombopoietin affects most aspects of the production of platelets. This includes self-renewal and expan ...

and their release from bone marrow. Haemostatic action is due to activation of thromboplastin formation on damaged sites of small blood vessels and decrease of PgI2 (

Prostacyclin Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprosten ...

) synthesis; it also facilitates platelet aggregation and

adhesion Adhesion is the tendency of dissimilar particles or surfaces to cling to one another ( cohesion refers to the tendency of similar or identical particles/surfaces to cling to one another). The forces that cause adhesion and cohesion can b ...

, that at last induce decrease and stop of hemorrhage. The precise mechanism of action of etamsylate is unknown. It has been shown to reduce bleeding time and blood loss from wounds. This appears to relate to increased platelet aggregation mediated by a thromboxane A2 or prostaglandin F2a dependent mechanism. It has also been associated with decreased concentrations of 6-oxoprostaglandin F1a, a stable metabolite of prostacyclin. Prostacyclin is a potent vasodilator, and may be implicated in reperfusion; it is also a disaggregator of platelets. Whereas prostaglandins themselves may have a role in regulating cerebral blood flow, etamsylate appears to have no effect on cerebral blood flow. Etamsylate was also thought to stabilise capillaries, reinforcing capillary membranes by polymerising hyaluronic acid. Etamsylate limits capillary bleeding through its action on hyaluronic acid and initial studies showed a reduction in intraventricular haemorrhage. Etamsylate may also have an effect on the microcirculation, encouraging platelet aggregation and vasoconstriction and therefore haemostasis. It also inhibits the effects of the prostaglandin mediated vasodilatation and increased capillary permeability, thereby reducing oedema secondary to capillary leakage. It is also possible that etamsylate would reduce reperfusion haemorrhage in ischaemic areas of the brain, preventing secondary damage. By inhibiting the effects of prostaglandins, etamsylate may exert an effect by closing the patent ductus and thereby increasing cerebral blood flow. Further, etamsylate has demonstrated interference with heparin, antagonizing its pro-hemorrhagic and anti-coagulant effects, without inhibiting its vasodilatory properties.

References

{{Vasoprotectives Benzenesulfonic acids Hydroquinones Antihemorrhagics