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The Hamilton Case: A doctor explains blood doping

By Shannon Sovndal, M.D.

How times change. Just last week, EPO was the talk of the town. Now you can’t open the sports page without reading something about transfusion blood doping. Sport doping is going old school. Out with the new, in with the old.

Blood transfusions have long been used to enhance athletic performance. Transfusions are an extremely straightforward, simple, and effective method of increasing the blood’s oxygen carrying capacity. Physiologists believe that it is the rate at which hemoglobin delivers oxygen to the exercising muscle that limits muscle performance. Blood transfusions address this limitation by increasing the number of hemoglobin molecules carrying oxygen to the muscles.

The term “blood doping” refers to various techniques used to increase the oxygen carrying capacity of blood. Recently, recombinant human erythropoietin, more commonly known as “EPO”, has been the drug of choice. However, with the advent of more effective and inclusive testing, the use of EPO has become more difficult and complex.

Because of the increased risk of detection, there has been concern that athletes may turn to an older form of blood doping that, until recently, has been virtually undetectable. This basic performance enhancing use of blood transfusions is at the center of the recent doping controversy involving rider Tyler Hamilton.

Homologous versus autologous
There are two methods of doping through blood transfusions: autologous and homologous. With an autologous transfusion, an athlete receives his or her own blood. An athlete donates blood, stores it, and then receives the blood at a later point in time. The advantages of this technique are the avoidance of diseases such as HIV or hepatitis, the reduction of the risk of detection through testing, and the alleviation of potentially deadly transfusion reactions.

The downside of autologous doping is that it takes time for the body to recover from the loss of blood that occurs during donation. It would be hard to train effectively while having to donate a supply of blood sufficient to enhance performance. In a homologous transfusion, the blood comes from another person. The benefit of homologous transfusion is no decrease in performance during the donation period. However, the disadvantages are the risk of contracting blood born diseases, the risk of transfusion reactions, and increased transfusion sensitivity.

Homologous transfusion is now the focal point of the current doping controversy. All individuals have a specific and consistent genetically programmed blood type. Each blood cell in the body has markers or antigens that hang off the cells. These specific antigens determine an individual’s blood type. The major blood types are A, B, and O. The positive or negative value added to the ABO type refers to another antigen on the blood cell called Rh(d). If you have both the A antigen and the Rh(d) antigen, your blood type is A positive. In addition to these major antigens, there are numerous other “lesser” antigens that make up each person’s blood composition. It is possible to test not only for one’s major blood type (A+ or O-, for instance) but also for the lesser antigens on one’s blood cell. By this test, we can define even more specifically the makeup of an individual’s blood.

Researchers have now applied this test to the war on doping. A scientific paper written by Nelson, et al., and published in the journal Haematologica explains the new test in more detail. But, because of the subject matter, the article gets a bit technical. I will try to explain the test using as little medical jargon as possible.

Every red blood cell has a consistent and specific set of blood group antigens. When these antigens are tagged with fluorescent dyes, a machine known as a flow cytometer can differentiate cells with different sets of antigens. Based on the blood being tested, a certain set of antigens is marked, and the cells are placed in the flow cytometer.

A large number of cells, 50,000—60,000, are shuffled into a single-file line and moved through a detection tube. A laser illuminates the fluorescent tags and sensors sort the cells depending on which antigens light up. The machine produces a graphical picture of the findings, and for any individual person, a single spike representing their inherent antigen set appears on the paper. If a person has received even a small amount of homologous transfused blood, a second, smaller spike representing another antigen set also appears, and the test is “positive” for doping.

This procedure may sound complex and fraught with errors, but flow cytometry is nothing new to medicine or science and has been used for a long time with accurate results in many applications.

Does it work?
The research study mentioned above tested the process on 25 patients and was 100-percent accurate. Still, many question the validity and applicability of the test. Should the group of test subjects be larger? Should the test subjects be elite cyclists? Should a large sample of people not receiving transfusions be tested to look for false positives? (A false positive occurs when the test reads positive, but the athlete has not been doping.)

The answer to all these questions would seem to be yes. However, in defense of the test, flow cytometry does work. Hundreds of athletes have been tested using this technique and only a few positives have been found. It is also possible that additional research was completed internally by the drug testing organization prior to the test’s use. It would seem that at the very least, this test is a good screening test.

While a screening test is extremely good at catching all individuals doping, it does run the risk of having false positives. The next step in a thorough investigation would be a confirmatory test. This mirrors the procedure for HIV testing in the hospital. If the screening test is positive for HIV, a second, more specific test is completed to confirm the diagnosis.

The problem is, there is no easy confirmatory test. A first thought is to evaluate the blood sample for a DNA. Every person has a totally unique DNA program that can be differentiated from every other person. However, testing a blood sample with only a small fraction of homologous blood could be tricky. If, by chance, the sample used for the test didn’t contain the donated blood, the result would show only the DNA of the tested individual.

This is called preferential amplification. There are tests available that can avoid this problem, but they are complicated and pricey. Many of these methods have certainly been tested in the field of criminology, but as evidenced by the OJ Simpson case, a definitive and convincing answer is often elusive.

Before these tests could be used to prove doping occurred, research studies would need to be performed specifically addressing this situation. A simpler suggestion, but by no means foolproof, would be to repeat the flow cytometry test again at a later date. Red blood cells have a lifespan of 120 days. If the test is run at 60, 90, and 120 days, the transfused red blood cells should slowly disappear, leaving only the athlete’s cells on the test. The only way to keep these cells from diminishing would be to continue to transfuse the exact same blood supply the athlete previously received. It is plausible the athlete could do this, but it would be complicated, especially during the scrutiny of an investigation.

Athletes these days are often put through the ringer by the drug testing agencies. Their lives are disrupted frequently, even if they never test positive. Since a positive test will likely ruin an athlete’s career, there should be no doubt when delivering a positive test verdict. I have long been a fan of cycling, and am sorry to continually read about new doping scandals. I never thought I’d need my medical degree just to figure out the technology behind the latest and greatest doping techniques.

Over the years I have learned to trust the scientific method and analyze the research data with as little bias as possible. However, in this case, as a longtime fan of Tyler Hamilton, I hope the available data is incorrectly pointing to a conclusion that is ultimately untrue.

Nelson et. al “Proof of homologous blood transfusionthrough quantification of blood group antigens.” Haematologica,vol. 88(11): November 2003Cram, Scott. “Flow cytometry, an overview.” Methods in Cell Science, 24: 1-9: 2002Alvarez et. al “Relative sensitivity of direct antiglobulintest, antibody’s elution and flow cytometry in the serologic diagnosisof immune hemolytic transfusion reactions.” Haematologica, vol 85(2):February 2000
Dr. Shannon Sovndal is an emergency medicine physicianin Boulder, Colorado, where he lives with his wife and two boys. He attended medical school at Columbia University in New York and completedhis residency at Stanford University.  He was an avid and active bikeracer prior to entering his medical training.  He now works with athletesand individuals through his business Thrive Health Fitness Medicine. Dr.Sovndal is available for any questions or comments at