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Deadly performance enhancer

Posted: Saturday, July 08, 2000

Life-saving human drug has been turned into life-threatening, illegal blood doping on the racetrack

Racing industry groups have launched investigations and research into abuse of the human drug Epogen to enhance performance in racehorses. The medication, whose benefits are questionable (see case study article), has proved deadly in some horses to which it was administered.

At its annual meeting in May, the Association of Racing Commissioners International (RCI) expressed concern over blood doping with Epogen, which stimulates red blood cell production and thereby increases stamina. Authorities are concerned not only because of the unfair advantage it affords in the short term but also because of the deadly consequences of its abuse. Veterinarians, horse trainers, and racing commissions worldwide have reported suspected cases of misuse of the drug to RCI.

Epogen, also marketed as Procrit, was developed by the research company Amgen Inc. to aid humans with severe anemia caused by acute kidney failure or cancer treatment. Anemia is a decrease in red blood cells, which carry oxygen from the lungs to the rest of the body. When red blood cells become depleted, extreme fatigue results because the body cannot function without adequate oxygen. Hold your breath while exercising, and you quickly get the idea.

Epogen is a genetically engineered form of the natural hormone erythopoietin (EPO), which is formed in the kidneys and causes bone marrow to produce red blood cells. Its use stimulates production of new red blood cells to alleviate anemia.

Enhanced performance

Heralded by the human medical community as a life-saving drug, Epogen has been turned into a life-threatening drug on the racetrack. While it is an effective performance enhancer, it also causes extreme disruption of the horse's blood chemistry-enough to cause death.

Red blood cells deliver oxygen to exercising muscles, and then the blood carries away lactic acid-the waste product left behind when oxygen is used by those muscles. Lactic acid causes the burning you feel when your muscles tire. Increase red blood cells and you increase oxygen to muscles and decrease exhaustion. In other words, anything that increases oxygen delivery to muscles enhances performance.

Kenneth McKeever, Ph.D., associate professor of equine exercise physiology at Rutgers University in New Jersey, is spearheading the research study there. He said the two most serious results of blood doping with Epogen are that it may cause the blood to thicken to a sludge, or it may cause the body to shut down its own natural production of red blood cells, causing severe anemia. "When you increase red blood cells, you increase aerobic capacity," said McKeever. "The bone marrow cranks out more red blood cells. The problem is that you can't turn off the effects of Epogen."

Given in low doses over a period of weeks, Epogen's effects are not noticeable until about three weeks into the course of treatment, said McKeever. There is no way of knowing how the dosage administered will affect an individual horse until it is too late to reverse the effects.

McKeever explained that the horse's spleen holds a large reservoir of packed red blood cells-a sort of natural blood-doping mechanism. The horse gets a jolt of adrenalin when it is startled, frightened, or pumped up for competition, and at the same time the spleen dumps a concentration of red blood cells into the circulatory system to enable the horse to run faster and longer. Simply, it is the chemical basis of the flight response.

"When the spleen contracts and sends red blood cells into a circulatory system that is already packed with red blood cells from administration of Epogen, the blood thickens and has the potential to start throwing clots," McKeever warned. "Another problem is that it causes blood pressure to go up and could cause bleeding (exercise-induced pulmonary hemorrhage, or EIPH)."

The more significant problem, and one that could be irreversible, is that the horse's body may develop antibodies to attack the synthetic EPO.

"These antibodies can't tell the difference between Epogen and the natural hormone EPO, so they destroy both, shutting down the body's production of red blood cells in bone marrow and causing severe anemia," McKeever said. "The drug has been used to treat dogs and cats, and about 30% have 'crashed.' These are anecdotal reports-not documented studies-but that's a large percentage of complications."

Difficult to detect

Epogen abuse cannot be detected by current post-race testing procedures because it is virtually impossible to distinguish it from the naturally produced hormone EPO.

"Epogen's half-life is minutes, although the red blood cells it produces last for 120 days," McKeever said. "And even if you could spot antibodies in the blood, you would not be able to determine when it was administered or point your finger at the current owner or trainer."

Through the joint backing of the National Thoroughbred Racing Association's (NTRA) Racing Integrity and Drug Testing Task Force, the Thoroughbred Horsemen's Association, and the RCI, McKeever will be able to take his study one step further to identify a specific marker left in the blood by Epogen use. "Plasma transferrin receptors float in blood plasma," explained McKeever. (Transferrin is a protein in blood serum that transfers iron through the body.) "When a horse is given Epogen, transferrin receptor levels go up and stay up. If we can detect elevated transferrin receptors in the blood, we can identify Epogen abuse."

"The RCI is very pleased to join with the NTRA in this first joint research effort of the regulatory and marketing branches of the racing industry," RCI President Tony Chamblin said. "Blood doping is a potentially serious problem in racing. We are hopeful that Dr. McKeever's research will provide the foundation for what eventually will lead to a confirmatory test for Epogen."

Epogen is not something a bottom-level trainer would be able to afford. Kenneth McKeever, Ph.D., associate professor of equine exercise physiology at Rutgers University and a leading researcher into Epogen abuse on the racetrack, said blood doping one horse with enough Epogen to get results would cost thousands of dollars, and that is just for the drug. Enlisting a veterinarian or medical doctor to put his license on the line to obtain the drug is another issue.

Although Epogen is not a controlled substance, it can only be obtained by a medical professional, said Ann Gresham, pharmacist for HDM Drug Co., an arm of Hagyard-Davidson-McGee equine hospital in Lexington.

"It's a human drug, so either a veterinarian would have to write a prescription for it or obtain it directly from a drug wholesaler," Gresham said. "The only other way to get it would be to have a human doctor supply it. "Epogen wouldn't be something someone could pick up on the street because it isn't something people generally abuse. There would be no reason for it." The dosage required to blood dope a horse is much greater than that required for a course of human treatment. Until a test is developed to identify horses that have been victims of this abuse, any volume purchase of Epogen by a medical professional should be a tip-off.

Last year, large quantity purchases of steroids caused the Ohio State Veterinary Licensing Board to lodge administrative charges against several Ohio-based veterinarians on the basis that giving steroids to a healthy horse was tantamount to abuse.

A large-volume purchase of Epogen should spark an investigation by regulatory agencies such as the United States Food and Drug Administration or the U.S. Department of Agriculture for the same reason.

-Denise Steffanus

A three-year-old Thoroughbred gelding was brought to an equine veterinarian for treatment of severe anemia. The gelding had 20 lifetime starts and was still a maiden. In the first six months of 1999, he had six starts and did not earn any purse money. His last start was two months prior to examination.

Initial evaluation: The gelding exhibited the classic signs and symptoms of severe anemia. Conversation with the trainer and groom indicated that the horse "had been off his feed for a while" and had possibly been treated with Epogen, although specifics regarding treatment were unavailable. A blood chemistry confirmed the diagnosis of anemia.

Treatment: A treatment plan consisting of a 12-liter blood transfusion followed by daily injections of dexamethasone (to control the tissue reaction resulting from rejection of the human hormone), iron, and B12 was initiated. Response and complications: The gelding exhibited a severe allergic reaction to the human hormone. Systemic swelling occurred with acute swelling of the head, nose, muzzle, and mucous membranes. Despite treatment, the gelding remained lethargic, had little appetite, and was extremely weak. A follow-up blood chemistry was not optimistic. Due to a drastic loss in weight, twice-daily tube feeding was initiated. Due to a low blood count, the gelding was unable to metabolize enough nutrients from the feed and continued to lose weight.

Outcome: The gelding was euthanized 30 days after the initial examination. At that time the gelding exhibited acute weakness, general swelling of the extremities with severe swelling of the head, nose, and mucous membranes. Additional symptoms included severe malnutrition; the estimated body weight at death was only 600 pounds.