Blood doping

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Blood doping is the practice of boosting the number of red blood cells (RBCs) in the circulation in order to enhance athletic performance. Because they carry oxygen from the lungs to the muscles, more RBCs in the blood can improve an athlete’s aerobic capacity (VO₂ max) and endurance.

Contents 1 Methods 1.1 Detection of Blood Doping 1.2 Detection of EPO Use 1.3 Detection of Blood Transfusions 1.4 Notable Blood Doping Cases 2 Preventative measures 3 Negative Effects 4 In Popular Culture 5 References

[edit] Methods

The term blood doping originally meant doping with blood, i.e. the transfusion of RBCs. RBCs are uniquely suited to this process because they can be concentrated, frozen and later thawed with little loss of viability or activity. There are two possible types of transfusion: homologous and autologous. In a homologous transfusion, RBCs from a compatible donor are harvested, concentrated and then transfused into the athlete’s circulation prior to endurance competitions. In an autologous transfusion, the athlete's own RBCs are harvested well in advance of competition and then re-introduced before a critical event. For some time after the harvesting the athlete may be anemic.

Both types of transfusion can be dangerous because of the risk of infection and the potential toxicity of improperly stored blood. Homologous transfusions present the additional risks of communication of infectious diseases and the possibility of a transfusion reaction. From a logistical standpoint, either type of transfusion requires the athlete to surreptitiously transport frozen RBCs, thaw and re-infuse them in a non-clinical setting and then dispose of the medical paraphernalia.

In the late 1980s an advance in medicine led to an entirely new form of blood doping involving the hormone erythropoietin (EPO). EPO is a naturally-occurring growth factor that stimulates the formation of RBCs. Recombinant DNA technology made it possible to produce EPO economically on a large scale and it was approved in US and Europe as a pharmaceutical product for the treatment of anemia resulting from renal failure or cancer chemotherapy. Easily injected under the skin, pharmaceutical EPO can boost hematocrit for six weeks or longer. The use of EPO is now believed by many to be widespread in endurance sports.

EPO is also not free of health hazards: excessive use of the hormone can cause polycythemia, a condition where the level of RBCs in the blood is abnormally high. This causes the blood to be more viscous than normal, a condition that strains the heart. Some elite athletes who died of heart failure—usually during sleep, when heart rate is naturally low—were found to have unnaturally high RBC concentrations in their blood^[1].

[edit] Detection of Blood Doping

A time-honored approach to the detection of doping is the random and often repeated search of athletes’ homes and team facilities for evidence of a banned substance or practice. Professional cyclists customarily submit to random drug testing and searches of their homes as an obligation of team membership and participation in the UCI ProTour. In 2004, British cyclist David Millar was stripped of his world time-trial championship after pharmaceutical EPO was found in his possession. Because athletes sometimes inject or infuse non-banned substances such as vitamin B or electrolytes, the possession of syringes or other medical equipment is not necessarily evidence of doping.

It has also been possible to link athletes to blood doping entirely through documentary evidence, even if no banned substance has been found and no athlete has failed a doping test. The Operación Puerto case is a recent example.

A more modern approach, which has been applied to blood doping with mixed success, is to test the blood or urine of an athlete for evidence of a banned substance or practice, usually EPO. This approach requires a well-documented chain of custody of the sample and a test method that can be relied upon to be accurate and reproducible. Athletes have, in many cases, claimed that the sample taken from them was misidentified, improperly stored or inadequately tested.

Yet another detection strategy has been to regard any apparently unnatural population of RBCs as evidence of blood doping. RBC population in the blood is usually reported as Hematocrit (HCT) or as the concentration of hemoglobin (Hb). HCT is the fraction of blood cells by volume that are RBCs. A normal HCT is 41-50% in adult men and 36-44% in adult women^[2]. Hemoglobin (Hb) is the iron-containing protein that binds oxygen in RBCs. Normal Hb levels are 14-17 g/dL of blood in men and 12-15 g/dL in women. For most healthy persons the two measurements are in close agreement.

There are two ways in which HCT and Hb measurements can suggest that the blood sample has been taken from a doping athlete. The first is simply an unusually high value for both. The Union Cycliste Internationale (UCI), for example, imposes a 15-day suspension from racing on any male athlete found to have an HCT above 50% and hemoglobin concentration above 17 grams per deciliter (g/dL). A few athletes naturally have high RBC concentrations (polycythemia), which they must demonstrate through a series of consistently high hematocrit and hemoglobin results over an extended period of time.

A recent, more sophisticated method of analysis, which has not yet reached the level of an official standard, is to compare the numbers of mature and immature RBCs in an athlete's circulation. If a high number of mature RBCs is not accompanied by a high number of immature RBCs--called reticulocytes--it suggests that the mature RBCs were artificially introduced by transfusion. EPO use can also lead to a similar RBC profile because a preponderance of mature RBCs tends to suppress the formation of reticulocytes. A measure known as the "stimulation index" or "off-score" has been proposed based on an equation involving hemoglobin and reticulocyte concentrations. A normal score is 85-95 and scores over 133 are considered evidence of doping. (The stimulation index is defined as Hb (g/L) minus sixty times the square root of the percentage of RBCs identified as reticulocytes.)

These threshold levels, and their specific numeric values are sources of controversy. Establishment of incorrect threshold values is one way that false positive test results can be produced by a doping control program.

[edit] Detection of EPO Use

Some success has also been realized in applying a specific test to detect EPO use. An inherent problem, however, is that whereas pharmaceutical EPO may be undetectable in the circulation a few days after administration, its effects may persist for several weeks. In 2000 a test developed by scientists at the French national anti-doping laboratory (LNDD) and endorsed by the World Anti-Doping Agency (WADA) was introduced to detect pharmaceutical EPO by distinguishing it from the nearly identical natural hormone normally present in an athlete’s urine. The test method relies on scientific techniques known as gel electrophoresis and isoelectric focusing. Although the test has been widely applied, especially among cyclists and triathletes, it is controversial and its accuracy has been called into question. The principal criticism has been the ability of the test to distinguish pharmaceutical EPO from other proteins that may normally be present in the urine of an athlete after strenuous exercise.

The validity of a doping conviction based on the EPO test method was first challenged successfully by Belgian triathelete Rutger Beke. Beke was suspended from competition for 18 months in March 2005 by the Flemish Disciplinary Commission after a positive urine test for EPO in September 2004. In August 2005 the Commission reversed its decision and exonerated him based on scientific and medical information presented by Beke. He asserted that his sample had become degraded as a result of bacterial contamination and that the substance identified by the laboratory as pharmaceutical EPO was, in fact, an unrelated protein indistinguishable from pharmaceutical EPO in the test method. He claimed, therefore, that the test had produced a false positive result in his case.

In May 2007 Bjarne Riis, Rolf Aldag, Erik Zabel and Brian Holm, all former members of the Telekom cycling team, admitted to using EPO during their cycling careers in the mid 1990s. Riis also relinquished his title as champion of the 1996 Tour de France. EPO was again a factor in the various doping scandals at the 2007 Tour de France, including the suspension of Spanish cyclist, Iban Mayo.

[edit] Detection of Blood Transfusions

In the case of detecting blood transfusions, a test for detecting homologous blood transfusions (from a donor to a doping athlete) has been in use since 2000. The test method is based on a technique known as fluorescent-activated cell sorting. By examining markers on the surface of blood cells, the method can determine whether blood from more than one person is present in an athlete’s circulation.

The American cyclist Tyler Hamilton failed this test during the 2004 Olympics but was allowed to keep his gold medal because the processing of his sample precluded conducting a second, confirmatory test. He appealed a second positive test for homologous transfusion from the 2004 Vuelta a España to the International Court of Arbitration for Sport but his appeal was denied. Hamilton's lawyers proposed Hamilton may be a genetic chimera or have had a 'vanishing twin' to explain the presence of RBCs from more than one person. While theoretically possible, these explanations were ruled to be of 'negligible probability'.^[3]

At present there is no accepted method for detecting autologous transfusions (that is, using the athlete’s own RBCs) but research is in progress and the World Anti-Doping Agency (WADA) has promised that a test will eventually be introduced. The test method and its introduction date are to be kept secret in order to avoid tipping off doping athletes. The assay under development may be a measure of 2,3-bisphosphoglycerate (2,3-BPG) levels in an athlete's red blood cells. Because 2,3-BPG is degraded over time, the stored blood used in autologous transfusions will have less 2,3-BPG than fresh blood. A 2,3-BPG concentration lower than normal may therefore be an indication of autologous transfusion.

In 1993, U.S. Special Forces commanders at Fort Bragg started experimenting with blood doping, also known as blood loading. Special forces operators would provide two units of whole blood, from advantage over any potential adversary," Mr Forbes-Ewan said. "What we will have is a head-start."

In this study, over 50 performance enhancing drugs and techniques were rejected. The six approved were caffeine, ephedrine, energy drinks, modafinil, creatine and blood-loading. (REFERENCE; Canada's Secret Commandos, David Pugliese. ISBN 1-895896-18-5)

[edit] Notable Blood Doping Cases

Tour de France rider Alexander Vinokourov, of the Astana Team, tested positive for two different blood cell populations and thus for homologous transfusion, according to various news reports on July 24, 2007. Vinokourov was tested after his victory in the 13th stage time trial of the Tour on July 21, 2007. A doping test is not considered to be positive until a second sample is tested to confirm the first. Vinokourov's B sample has now tested positive, and he faces a possible suspension of 2 years and a fine equal to one year's salary.^[4] He also tested positive after stage 15.^[5][6]

Vinokourov's teammate Andrej Kashechkin also tested positive for homologous blood doping^[7] on August 1st, 2007, just a few days after the conclusion of the 2007 Tour de France (a race that had been dominated by doping scandals). His team withdrew after the revelation that Vinokourov had doped.

[edit] Preventative measures

It was revealed in autumn 2007, following another troubled year for professional cycling, that the sport's governing body (UCI) would introduce mandatory "blood passports" for all professional riders. The scheme, thought to be the the first of its type in any sport, involves using blood and urine samples to create a medical profile that could be compared to results of subsequent doping tests. Blood doping can be very effective but also very dangerous.

Former World Anti-Doping Agency (WADA) President Dick Pound has stated a belief that anti-doping passports will be in widespread use within three years, although not in time for the 2008 Olympic Games.^[8]

[edit] Negative Effects

There are many negative effects to blood doping. The simple act of increasing the number of RBCs in the blood stream makes blood thicker. This can also make it clot more readily. This has shown an increase in the chances of heart attack, stroke and pulmonary embolism. This has been seen in cases where there is too much blood reintroduced into the blood stream. Another problem that has been seen is if the blood in not properly stored and prepared. If they are prepared improperly the blood may become contaminated. This was seen in 1 in every 500,000 transfusions of RBC in 2002.^[9] This contamination can lead to sepsis or an infection that affects the whole body. This may seem like a small number but as blood doping becomes more popular among athletes, infections due to the procedure may increase. Also certain medications used to increased RBCs can reduce liver function and lead to liver failure, pituitary and increase cholesterol levels.^[10]

[edit] In Popular Culture

• In an episode of House M.D., a patient who is a professional cyclist was found to be blood-doping.

[edit] References