Blood doping

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

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 hormone 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 to twenty-four weeks, or longer. The use of EPO is now believed by many to be widespread in endurance sports.

EPO is not free of health hazards: Excessive use of the hormone can raise hematocrit above 70% which can cause polycythemia, a condition wherein 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.

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.

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 by volume occupied by red blood cells. A normal HCT is 41-50% in adult men and 36-44% in adult women. 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.

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 toward 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 triathlete 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. The IOC found that athletes were using a new version of EPO, a chronic kidney disease drug called MIRCERA, and three athletes tested positive for the substance in April 2009.

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.

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 test 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.

Military use
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 which red blood cells would be extracted, concentrated, and stored under cold temperatures. Twenty-four hours before a mission or battle, a small amount of red blood cells would be infused back into the soldier. Military scientists believe that the procedure increases the soldiers' endurance and alertness because of the increase in the blood's capability to carry oxygen.

In 1998, the Australian Defence Forces approved this technique for the Special Air Service Regiment. Senior nutritionist at the Australian Defence Science and Technology Organization Chris Forbes-Ewan is quoted as saying that, unlike in sport, "all's fair in love and war." "What we are trying to gain is an advantage over any potential adversary," 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 that were approved are caffeine, ephedrine, energy drinks, modafinil, creatine, and blood-loading.

Notable blood doping cases
Blood doping probably started in the 1970s but was not outlawed until 1986. While it was still legal, it was commonly used by middle and long-distance runners. The US cycling team at the 1984 Olympics also employed blood doping.

The Swedish cyclist Niklas Axelsson tested positive for EPO in 2000. The American cyclist Tyler Hamilton failed a fluorescent-activated cell sorting test for detecting homologous blood transfusions during the 2004 Olympics. He 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'.

The Operación Puerto case in 2006 involved allegations of doping and blood doping of hundreds of athletes in Spain.

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. He also tested positive after stage 15.

Vinokourov's teammate Andrej Kashechkin also tested positive for homologous blood doping on August 1, 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.

According to Russian investigators, 19-year-old New York Rangers prospect and Russian hockey player Alexei Cherepanov was engaged in blood doping for several months before he died on October 13, 2008, after collapsing on the bench during a game in Russia. He also had myocarditis.

The German speed skater and five-fold Olympic gold medalist Claudia Pechstein was banned for two years in 2009 for alleged blood doping, based on irregular levels of reticulocytes in her blood; these levels were always highest during competitions. This can be read in many newspapers. However, it is not true. Instead of, mean reticulocyte count of the ten years from 2000 to 2009 was 2.1% during top events like Olympic Games and during world championships. At world cup races the mean reticulocyte was 1.9% and during training phases 2.0%. The Court of Arbitration for Sport confirmed the ban in November 2009.

On May 20, 2011 Tyler Hamilton turned in his 2004 Olympic Gold Medal to the U.S. Anti-Doping Agency after admitting to doping in a 60 Minutes interview.

Preventive 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 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. Former World Anti-Doping Agency (WADA) President Dick Pound stated his belief that anti-doping passports would be in widespread use within three years.

Negative effects
The simple act of increasing the number of RBCs in blood raises its viscosity, which can cause it to clot or coagulate more readily. This increases the chances of heart attack, stroke, and pulmonary embolism, which has been seen in cases where there is too much blood reintroduced into the blood stream. Among factors that govern blood flow, however, viscosity is of relatively minor importance except in extreme circumstances or in patients with vascular disease. The Hagen–Poiseuille equation for blood flow states that any change in blood viscosity affects blood flow 16-fold less than a proportionate change in vessel radius, and therefore polycythemia is unlikely to be harmful except in certain circumstances.

Blood contamination during preparation or storage is another issue. Contamination was seen in 1 in every 500,000 transfusions of RBC in 2002. Blood contamination can lead to sepsis or an infection that affects the whole body.

Certain medications used to increase RBCs can reduce liver function and lead to liver failure, pituitary problems, and increases in cholesterol levels.