A vampire bat.Credit: Wikimedia Commons
NIAID researchers have identified a novel anticoagulant—a substance that prevents blood clotting—from vampire bat saliva. The anticoagulant prevented clot formation in the arteries of mice at doses that did not promote bleeding. The findings, published in the December 12, 2013, issue of Blood, could lead to the development of new, safer anti-clotting drugs.
Coagulation is the process by which blood forms clots. When a blood vessel is injured, small blood components called platelets gather at the wound site. At the same time, enzymes called clotting factors respond in a series of catalytic reactions to form fibrin, a sticky protein that binds the platelets and other cells together, resulting in clot formation.
Excessive fibrin production may lead to thrombosis, the formation of a clot inside a blood vessel. Thrombosis can obstruct blood flow, potentially leading to serious complications such as stroke and heart attack. Doctors use anticoagulant drugs to prevent and treat thrombosis. The major side effect of these medications is increased risk of bleeding.
Since the early 1930s, scientists have known that the saliva of vampire bats, which feed on the blood of mammals or birds, has anticoagulant and clot-dissolving properties. During the past 80 years, however, researchers have characterized only one clot-dissolving molecule from the bat’s saliva—an enzyme that is currently being tested in clinical trials for stroke treatment. In early 2013, scientists from NIAID's Laboratory of Malaria and Vector Research (LMVR) reported findings from a detailed analysis of vampire bat salivary glands, which revealed several molecules that affect blood vessels, including potential anticoagulants.
In the current study, research led by Dongying Ma, Ph.D., and Ivo Francischetti, M.D., Ph.D., of LMVR identified the bat saliva protein Desmolaris as an inhibitor of factor XIa, an enzyme that plays a key role in blood clot formation.
The scientists found that treating mice with Desmolaris prevents chemically induced blood clot formation in the carotid artery, which supplies blood to the brain. Desmolaris treatment did not increase bleeding from small cuts in the animals' tails. Mice given Desmolaris at concentrations needed to block thrombosis did not bleed more than mice that did not receive the anticoagulant. Very high doses of Desmolaris, however, did promote bleeding.
The results suggest that Desmolaris could be used as an anticoagulant or as a prototype for the development of new therapies to prevent and treat thrombosis. The protein may be particularly useful in conditions such as arterial blood clots, stroke, and ischemia-reperfusion injury—damage caused when blood returns to tissues after a period of oxygen deprivation. Compared to other factor XIa inhibitors, Desmolaris is fast-acting and effective at lower concentrations.
In addition, the finding that Desmolaris does not promote bleeding at concentrations needed to prevent clotting suggests that Desmolaris-based therapies may be safer than current anticoagulant drugs, which carry a high risk of bleeding.
The scientists plan to study how the body reacts to Desmolaris and evaluate its potential toxicities and side effects. In collaboration with other researchers, they hope to test Desmolaris in models of stroke and ischemia-reperfusion injury.
Ma D, Mizurini DM, Assumpção TCF, Li Y, Qi Y, Kotsyfakis M, Ribeiro JMC, Monteiro RQ, Francischetti IMB. Desmolaris, a novel Factor Xia anticoagulant from the salivary gland of the vampire bat (Desmodus rotundus) inhibits inflammation and thrombosis in vivo. Blood (2013)
Last Updated December 17, 2013