Thursday, September 20, 2012

It's All About Blood

By Robin Parisotto
Robin Parisotto is a sports scientist based in Australia.  He was part of a group of Australian scientists who helped develop the first blood tests for detecting use of "blood doping" by athletes for the Sydney Olympics in 2000.  Currently his input is sought by sports federations on cases of suspected blood manipulation, biological passport abnormalities that, if confirmed, lead to the sanction of athletes for doping violations.  

The USADA(United States Anti-Doping Agency) case, where charges were brought against Lance Armstrong, his team manager, and team doctors and advisors has received a lot of attention.  Even more since Armstrong decided not to contest those charges before an arbitration panel, stating that he could not get a fair hearing in that forum.  The result being that USADA has levied sanctions commensurate with the violations listed in the charge letter.

UCI(cycling's governing body) are waiting for the details of the case file to be submitted to them before any action can be taken on the sanctions proposed by USADA, which include stripping Armstrong of his race results including his seven Tour de France victories from 1999-2005.

The following is an analysis Parisotto did recently using the blood  values cyclist Lance Armstrong posted on his website back in 2008-2009 during his comeback to competitive cycling for the 2009 Giro and Tour de France. This was not part of any official investigation into the data, but more as a matter of curiosity about available information on the case and what it can tell us.

Part of USADA’s charge letter that led to the sanctioning of Lance Armstrong(LA) and other "co-conspirators" was that there was strong evidence of blood manipulation(blood doping) in data examined by USADA. I can only presume that some/all of this data included information that Lance Armstrong had posted on a website some time ago where the UCI and USADA were referenced as the testing agencies. 

To better understand the basis for charges against Armstrong, it is worth remarking on some of this data.  The figures referenced in this article are from Armstrong's published blood values for 2008-2009.

The following graphic indicates a fairly regular and normal pattern of Hemoglobin (Hb) values until a significant drop on May 5, 2009, four days before the start of the Giro d'Italia(the Tour of Italy which was contested from May 9-31, 2009 and where Armstrong placed 12th). This is followed by a quite staggering increase on June 16, 2009 (further explained below), shortly before the Tour de France(which went from July 4, 2009 to July 25, 2009 and Armstrong placed third).

Fig.1 Hemoglobin values for LA October 2008 to July 2009

The graphic below is significant because while Hemoglobin appears to have been significantly disrupted, the reticulocytes (young red blood cells) have suddenly diminished and stabilized just before the Tour de France. This change is counter-intuitive (for reasons stated below).

Fig.1 Reticulocyte values for LA October 2008 to July 2009

The charts show a halving of the reticulocyte values in circumstances when the Hemoglobin has risen dramatically, which is not consistent with normal physiology. If one is making more red blood cells and increasing Hemoglobin then it is inconceivable to not have more immature red blood cells (reticulocytes) in the body of a normal healthy person.

The decrease in Hemoglobin  from April 30, 2009 to May 31, 2009 (149 – 130) in samples 10 to 13 is 15% however there is no expected increase in reticulocytes. In fact from October 16, 2008 the average reticulocyte levels are 1.1 but from May 18, 2009 the average reticulocyte levels are 0.6.

The sudden increase in Hb from sample May 31, 2009 to June 16, 2009 (130 – 160) in samples 13 to 15 is 23%, however the response in reticulocytes is again not consistent with normal physiology. Such a scenario is consistent with a deceleration in red blood cell production following auto-bleed and re-infusion(i.e. removal of blood to store for later re-infusion, otherwise know as blood doping). 

The subsequent low reticulocyte values are consistent with re-infusion of blood and continued micro-doses of rhuEPO(recombinant erythropoietin) to ‘stabilize’ and therefore mask the expected response in reticulocytes.

A Cycling News article of July 13, 2012 noted that if USADA were to present evidence such as this during a legal hearing of the charges, this evidence of doping would be challenged by Armstrong lawyers “by summoning medical experts who would say that a person's hematocrit score could conceivably jump 7.5 percentage points in 16 days because of external influences like changes in altitude and heavy perspiration.” Reportedly Armstrong was in Aspen, Colorado at nearly 8000 feet above sea level between the two above-mentioned tests. 

There any number of studies that refute the hypothesis that such a large increase in Hemoglobin is merely a response to altitude exposure.  To suggest that a 23% increase in Hemoglobin and a 50% decrease in reticulocytes was the result of time spent at altitude is stretching the bounds of the known and documented physiological responses to altitude exposure. For example, the Ashenden et al study in 2003 demonstrated that in no less than 7 study groups either at natural or simulated altitudes (above 2600 metres – about 8500 feet) that even after 4 weeks of exposure the increase in Hb was, at best, muted.

The largest increase in Hemoglobin was 9.5% in a group of elite cyclists returning from living and training in Toluca (Mexico) after 4 weeks. The Hemoglobin measures were taken 7 days after returning to sea level conditions. In all other study groups there was no increase or at best a 1-2% increase in Hemoglobin. Similar responses were noted with reticulocyte levels. Whatever way you cut it, Armstrong's blood values are undoubtedly indicative of blood manipulation. 

This is hard empirical evidence lending support to the charges filed by USADA.  If this profile had been submitted to me for review by me as a member of the Passport Panel(biological passports which are used by the UCI, cycling's governing body, and the IAAF),  it would have been assessed as an anti-doping rule violation particularly in view of the timing of the disturbances leading into the 2009 Tour.


Winter Warlock said...

Thanks for a very detailed and data focused report - but I do have a question. Just doing a quick look, there does appear to be other factors that can influence the reticulocyte count, including the lab equipment and calibrations used to analyze the sample. During that period of discrepancy, were all samples analyzed at the same lab?
Interestingly enough - WebMD lists five events that can affect the results - one does include transfusions, and it makes sense autologous transfusions are the same - but the other factors were...assuming we can rule out the fact that he may have been pregnant,the chemo and radiation therapy is of compelling interest to wonder if he was still being treated in some way?
Reasons you may not be able to have the test or why the results may not be helpful include:

--Taking certain medicines. Medicines that affect the results include ones used for Parkinson's disease, rheumatoid arthritis, fevers, malaria, and cancer chemotherapy.
--Getting radiation therapy.
--Taking sulfonamide antibiotics (such as Septra).
--Being pregnant.
--Having a recent blood transfusion.

jdf said...

The beauty of science, at least for lawyers, is that there are always variables that they can introduce to plant doubt. Even if the chances of one theory or another is statistically only a fraction of a percent. If there are several of them the lawyer can introduce more than one making it appear that there is legitimate doubt where there really isn't. The development of the biological passports and the blood profiling has gone through much scrutiny over the years, mainly from the legal perspective. Do the lawyers prosecuting doping cases believe that their data will stand up to attack? They have become comfortable enough with the decisions of the experts on the various panels who evaluate the data and make a determination--guilty or not. But it is a human system, where the people make the decisions, so nothing is ever absolutely certain. Thus it often degenerates into a public relations battle with each side trying to paint the other as evil. Rarely do you see a site on the internet or elsewhere where the probabilities of each possabililty are listed, but that is what those having to make the decisions of guilt or innocence use to determine their verdicts. What is the most probable explanation for the abnormal values? In this case it is Parisotto's opinion that it is blood doping. Also they are using more than one variable in this instance to reach that conclusion--both the hemoglobin measurement and the reticulocyte count are used, so the behavior of both factors into the decision, not just the retiuclocyte measurement. And you can probably find more things that impact hemoglobin measurement as well. The first question you asked about all the samples being tested in the same lab is easier to answer--highly doubtful--but also not as important as one might think as the WADA accredited labs tend to use very similar, if not the same, equipment and the variability of the tests they run is also known. So, that would be factored into the decisions made by the panels to determine if there was any possibility that the results of the testing could produce the abnormality that is noted in the testing.

Berzin said...

Armstrong has no legal recourse.

Sure, his lawyers could have challenged the readings of these results, but keep in mind he decided to forego the arbitration process, so where is he going to challenge these findings?

Nowhere, that's where.

deserthead said...
This comment has been removed by the author.
deserthead said...

The probability that Armstrong raced clean is about the same as the probability that Armstrong was pregnant.

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