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Report on anticoagulant factors found in nature Partial requirement for Independent Study on Blood Renae Bullock When damage occurs to our blood vessels, clotting is necessary to keep from losing too much blood. This hemostasis occurs in three stages. In the first stage, when a blood vessel is broken, pain receptors are stimulated and innervate blood vessels and cause them to restrict. Platelets send out pseudopods that adhere to the blood vessels and other platelets. These pseudopods contract and draw the walls of the vessels together. In the second stage, the platelets undergo degranulation which results in release of chemicals which increase vasoconstriction and increased platelet aggregation. And lastly, in a series of steps, from a prothrombin factor, thrombin is formed that chops up the blood protein fibrinogen to the sticky protein fibrin that blood cells and platelets stick to forming a clot. At the same time that the body is promoting hemostasis, it must also promote anticoagulation so that the blood does not clot when there isn’t vessel damage. Formation of anticoagulants must be balanced with formation of procoagulants. After tissue repair is completed, a clot has to be dissolved. Cells secrete Hageman factor which promotes catalyzes the formation of kallikrein that catalyzes the formation of plasmin which is the enzyme that dissolves clots. The small amount of thrombin that is found in the blood is normally diluted enough that it won’t promote the formation of clots. The anticoagulant antithrombin which is secreted by the liver deactivates thrombin, and heparin which is secreted by basophils and mast cells interferes with the formation of prothrombin activator, blocks the action of thrombin on fibrinogen and promotes the action of antithrombin. Interestingly enough, the clotting mechanism that is necessary to save us, also kills us by resulting in blood clotting in inappropriate times and leading to strokes and heart attacks. In an attempt to alleviate this possibility, anticoagulant medications are administered to patients that seem likely to be susceptible to blood clots. There are three categories of anticoagulant drugs; inhibitors of clotting factor synthesis, inhibitors of thrombin, and antiplatelet. (Ross-Flanigan, 2004) These medications don’t dissolve existing blood clots. They stop enlargement of existing clots and prevent new ones from developing by interfering with some of the steps involved in clotting. Some common anticoagulant medications are Coumadin and Heparin. Heparin inactivates thrombin and Coumadin inhibits the production of certain clotting factors in the liver. Misuse of these drugs can result in too much bleeding as manifested in easy bruising or severe bleeding. (Ross-Flanigan, 2004) There are a number of naturally occurring foods and supplements that have anticoagulant properties. Preliminary studies on ginger show that it may help in prevent clotting, garlic has been shown to prevent clotting with the chemical property allicin, Vitamin E which is found in foods such as almonds, sunflower seeds, and spinach prevents clotting, fish such as salmon and tuna that contain omega 3 fatty acid slows down the development of blood clots. There are some plants that contain anticoagulants: chamomile, gingko, ginseng. Caution is usually advised when using these foods and supplements when taking anticoagulant medications. (Lavie 2009) Acetylsalicylic acid is a derivative of salicylic acid found in aspirin. It is an antiplatelet drug called a COX inhibitor. Aspirin is an inhibitor of both prostaglandin synthesis, which coats the endothelium of the vessels and is a platelet repellent, and platelet aggregation, by inhibiting the formation thromboxane that promotes platelet aggregation, degranulation and vasoconstriction. (Buntic 2009) Insects that suck blood contain anticoagulants that allow the blood to flow freely as they feed. The saliva of bed bugs (Cimex letularius) inhibits the conversion of factor X to factor Xa. (Huntly 1999) The saliva of ticks (Ornithodoras moubata)contain a protein that inhibits the activity of factor Xa. (Waxman 1990) The saliva of mosquito contains Alboserpin an anticoagulant that also inhibits the activity of Xa. (Calvo 2011). The saliva of Rhodnius prolixus a carrier of Chagas disease contains Nitrophorin 2 which inhibits Factor VIII from activating Factor X. (Ribeiro, J.) Besides arthropods that contain anticoagulants that inhibit the formation of blood clots so the blood freely flows for them to feed, vampire bats and leeches. The saliva of vampire bats (Desmodus rotundus) contains a glycoprotein called draculin which is an anticoagulant that inhibits coagulation factors IX and X. This enzyme (Is it DSPA – desmoteplase) is more effective at treating clots and does not promote brain damage as the present FDA approved drug does. (Graham 2008) Leeches like (Hirudo medicinalis)are parasitic segmented worms that feed on blood. Their saliva contains an anticoagulant called hirudin. It is a polypeptide that prevents clotting by inhibiting thrombin. It is used to prevent thrombosis after hip replacements. Leeches are used medicinally to reattach organs by allowing blood to flow freely until new veins grow into the reattached organ and to removed clotted blood after surgery. (Saladin 2007). The venom of the Malayan pit viper (Calloselasma rhodostoma) has both coagulant and anticoagulant actions. (Graham 2008). The anticoagulant action is present at high concentration of venom. The anticoagulant is found in a substance call ancrod which works by reducing the level of fibrinogen in the blood. (American Heart Association 1999) This may be an alternative to the FDA approved treatment for acute strokes Tissue Plasminogen Activator. Reducing the level of fibrinogen to a target level, had advantageous results to patients recovering from a stroke, although there was also a higher risk of bleeding in the brain than with the TPA. In addition to the naturally occurring anticoagulants that can be accessed from animals, there is the possibility of obtaining anticoagulants by genetic engineering. Goats are being genetically engineered to produce antithrombin III, a naturally occurring human protein that acts as an anticoagulant. The process involves taking DNA from the genes of a human that codes for the antithrombin III, and injecting it into a fertilized goat embryo that is then implanted in a female goat. The result is an offspring which if a female, has the possibility of producing the desired protein in her milk. (Zim 2000) Bibliography: American Heart Association (1999, February 5). Experimental Drug Derived From Snake Venom Shows Promise In Reversing Effects Of Stroke. retrieved from http://biology.about.com/library/weekly/aa021199.htm Buntic, R.F. (2009). Microsurgery Atlas, Techniques and Principles. Retrieved from http://www.microsurgeon.org/anticoagulation.php?mode=print Calvo E., Mizurini D., Sa-Nunes A., Ribeiro J., Andersen J., Mans B., Monteiro R., … Francischetti, I., 2011. Alboserpin, a Factor Xa Inhibitor from the Mosquito Vector of Yellow Fever, Binds Heparin and Membrane Phospholipids and Exhibits Antithrombotic Activity. Journal of Biological Chemistry, retrieved from http://sciencestage.com/r/factor-xa-inhibition-alboserpin-cell-biology Graham, S. (2008). Vampire Bat Saliva Compound Could Help Treat Strokes. Scientific American retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7755571 Huntley, A.C. (1999). Bed Bugs. Dermatology Online Journal. Retrieved from http://dermatology.cdlib.org/ Lavie CJ et al. Omega-3 polyunsaturated fatty acids and cardiovascular diseases. J Am Coll Cardiol. 2009; 583-594. Retrieved from http://www.blood-thinners.org/pages/blood-thinners-diet/ Ribeiro, J., Schneider, M., Guimaraes, J., US National Library of Medicine National Institutes of Health Purification and characterization of prolixin S, the salivary anticoagulant of the blood-sucking bug Rhodnius prolixus retrieved from (www.ncbi/nlm/nih.gov/pmc/articles/PMC136869) Ross-Flanigan, Nancy; Uretsky, Sam. "Anticoagulant and Antiplatelet Drugs." Gale Encyclopedia of Surgery: A Guide for Patients and Caregivers. 2004. Retrieved June 29, 2013 from Encyclopedia.com: http://www.encyclopedia.com/doc/1G2-3406200037.html Waxman, L., Smith, D., Arcuri, K., Vlasuk, G. (1990) Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa. American Association for the Advancement of Science. Retrieved from http://www.readabstracts.com/Science-and-technology/Tick-anticoagulant-peptide-TAP-is-a-novelinhibitor-of-blood-coagulation-factor-Xa.html#ixzz2XeJ9S4cV Zim, A. (2000). Goats turned into medicine factories. In Bloomburg News. Retrieved from http://www.mult-sclerosis.org/news/Dec2000/GoatsMedicineFactories.html