Spring 2002 - Factor Nine News

The Coalition for Hemophilia B

Topics In Hemophilia

• TT Virus
• EMEA Clinical Trials - Benefix
• World Federation new Variant CJD Study
• Lawrence Madeiros
• Aventis Behring Quality of Life Patient Grant

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TT Virus
TT Virus: A Recently Identified Virus Contaminating Recombinant and Plasma-Derived Clotting Factor Concentrates Is probably not a Cause for Concern.

In 1997, medical researchers in Japan identified a virus in the blood of several patients who had contracted hepatitis apparently from transfusions of blood or blood products. Because the type of hepatitis afflicting these patients could not be identified as being caused by any of the known hepatitis viruses, the researchers were left with the question of whether it was caused by this new virus. The virus was named Transfusion-Transmitted Virus and is commonly referred to as TT Virus or TTV. TTV was soon identified as being the first known human circovirus. Other members of the circovirus family cause disease in livestock and birds.

Until the development of improved blood screening tests and processing methods to inactivate or remove viruses, hepatitis, was a common risk of blood transfusion and plasma product usage. Hepatitis can be a very dangerous disease. In addition to causing acute or immediate severe sickness, over the long term it can also lead to cirrhosis or to liver cancer, both eventually fatal. Most hepatitis cases are caused by a handful of known viruses, or by exposure to toxic chemicals. However, there are still some cases each year for which the cause is unknown. Therefore, the identification of a possible new hepatitis virus is a significant event that can immediately spur intense research. The story of the research on TTV provides an interesting demonstration of how scientists approach such a problem. It also demonstrates the dangers of jumping to conclusions before all the facts are known.

As an aside, when scientists talk about a “new” virus they usually mean a virus that has recently been discovered. Most often, the virus has been around for a long time but no one had ever noticed it. New viruses such as HIV, the AIDS virus, do appear from time to time, but there are thousands, if not millions, of viruses in nature that have existed for eons but just have never been identified.

A number of early studies appeared to show a strong correlation between the presence of TTV and the occurrence of hepatitis. The studies would typically find a much higher prevalence of TTV infection in patients with hepatitis compared to the prevalence of TTV in the general population. Alarmingly, other studies showed that clotting factor concentrates are often contaminated with TTV. One study even showed that recombinant clotting factor VIII concentrates were also contaminated with TTV. This was distressing because the recombinant products are usually considered to be free of the risk of transmitting viral diseases. These results raised great concern that here was yet another risk for people with hemophilia and others who are treated with blood and plasma products.

However, scientists are rigorously trained not to jump to conclusions. Just because something looks like it is happening, and even if it seems to make sense that it should be happening, that does not prove that it is happening. A correlation only means that two things are happening at the same time; it never proves that one causes the other. It takes much more study to provide enough evidence to show that one thing causes another. Thus, just because some patients with unexplained cases of hepatitis seemed to also have high levels of TTV, that does not prove a thing.

As it has turned out, TTV probably does not cause hepatitis or any other serious human disease. As more was learned about the virus, it was discovered that it has a large number of subtypes. That is, TTV can occur in various forms that have slightly different characteristics. Variation is the rule of nature. Except for identical twins, very few organisms, from humans all the way down to bacteria and viruses, are exactly alike. To help understand how this was a problem for research on TTV, think about what would happen if a team of alien scientists from another planet were studying the earth and discovered the human being. From that one discovery they might decide that humans have two arms, two legs and brown hair. If they went looking for more organisms that fit that criteria, they could miss a lot of humans that did not have brown hair.

That is essentially what happened with TTV. Before they realized that there could be a large variation in TTV, researchers only looked for viruses that had the same exact characteristics as the first TT viruses that had been discovered. Obviously, they missed a lot. Once they realized that they should be looking for TT viruses that fit a much broader range of characteristics, they discovered that most people in the general population are infected with TTV. TTV apparently is just something that most people pick up as they move through life. Since the general population does not appear to be afflicted with an TTV-caused disease, the current view is that infection with TTV is probably harmless. The reason that blood and plasma products are so often contaminated with TTV is because most blood and plasma donors are infected. Some recombinate products are also contaminated because all of the first-generation recombinant products contain albumin as a stabilizer and albumin is derived from plasma.

Thus the TTV story turned out to have a happy ending. However, it also demonstrates a dilemma that medical science has to deal with all of the time. Until you have enough information, how do you decide how to react to something like the news of a new, possibly dangerous virus that appears to contaminate most clotting factor concentrates? Everyone wants to choose the safest course of action, but it is not always clear what that is. As we will discuss in a future issue, the potential for harm exists no matter what you do. Striking the right balance in the absence of complete information is a real challenge, one that we must keep watching.

“A correlation only means two things are happening at the same time; it never proves that one causes the other”

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NEW CLINICAL TRIALS FOR BENEFIX
The European equivalent of the FDA called the CPMP ha required Wyeth-Genetics Institute to run more trials on Benefix. Although this could be seen as a negative for this product, we feel that it should be seen as not threatening to users of Benefix. Some of the issues involved are bureaucratic, as the previous trials done in many countries were not done quite right, but some of the issues are familiar to those who use Benefix. They involve the dosing levels that are necessary to get the results we all want. The Europeans will be getting much more data on the issue of dosing. What the Europeans learn will be of great interest to us all. With this information we will all know more about the effectiveness of Benefix than we know now.

Here at the Coalition, we see this as a good thing because knowledge of this product and its effectiveness is what we all want. Benefix is not a question here. It is a good product, but it might not be effective for everyone who has a Factor IX deficiency. This should all help us make better decisions on what product to use, and how much of it we should use.

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NEW ONLINE HEMOPHILIA SITE
Please note that the Hemophilia Site has moved. To subscribe please send email to Hemophilia-Support-Subscribe@lists.boygenius.com. Once subscribed you can post messages by sending an email to Hemophilia-Support@lists.boygenius.com Please remember to always add a subject matter and to hit the “Reply ALL” button when responding to an email.

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THE WORLD FEDERATION HAS COMPLETED A STUDY ON NEW VARIANT CJD (vCJD) IN EUROPE
A very rare condition called Creutzfeldt-Jacob disease (CJD) has existed in the world for many years. The agent, which transmits this disease, called a prion, has not been controlled in the blood collection process, and it is likely that the blood supply has been contaminated for many years. Although this has been very worrisome, the study points out that its impact has probably been zero. No cases have ever been diagnosed with CJD being passed through blood transfusions. Recent laboratory studies have also shown that CJD has not been transmitted through blood. This is what the government had expected to find and we can be happy at this time the analysis seems to be 100% correct.

However, Mad Cow Disease that developed in England during the 1980’s, which is a related disease, has proven to be more transmittable. The Mad Cow disease is a form of CJD and is closely related to Scrapie, a disease carried by sheep. This disease jumped from sheep to cattle in England because, for many years, the cattle were fed meal, which contained ground sheep carcasses to add protein. Mad Cow infected almost 200,000 cattle and was passed onto humans, presumably through their consumption of meat from infected cattle. The human form of this disease has been called new variant CJD or vCJD. The WFH study indicates that vCJD is transmittable through the blood supply. This would mean that the blood supply in a country with an incidence of vCJD sufferers would be contaminated. There is then a risk that this disease would be transferred to blood product recipients.

The various European countries have different risk profiles, which this study describes, but there are many assumptions that are not yet certain. Although it is clear that products developed from European plasma have a certain risk attached, the study goes on to point out that Factor IX products - and other hemophilia products - are cleared of the vast majority of the prions, which carry the disease. This clearing process is nothing more than the standard purification process that these products follow.

In the case of Factor IX it seems that the purification clears “7 log” of the CJD prions or All but 1 in every 10 million prions. There are some assumptions and we would not say that this means that there is no problem with these products. The blood safety groups and the FDA agree that there is risk, as no one can be sure.

We would be happy to send you a summary of these findings published by the WFH, just call us up and we will mail them to you.

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AVENTIS BEHRING…
Announced the launch of the Aventis Behring Choice Quality of Life Patient Grant Program, a pilot program designed to help relieve the financial burden of families affected by bleeding disorders. For more information please visit the website www.aventisbehring.com or call Kim Cayz (610) 878-4822, kim.cayz@aventis.com

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LAWRENCE MADEIROS
Larry Madeiros passed away on September 28, 2001 from an infection and liver complications. Larry was co-founder of Positudes, Inc. Larry was a nationally recognized community advocate. He was a member of the NHF, Hemophilia Federation of America, NHF Upper Hudson Valley Chapter, and a member of the Genetics Institute Advisory Board.

Larry and his wife Carol, became the first couple in the United States to succeed in securing a safe path toward parenthood where HIV is present, resulting in the births of two healthy children, Ashley and Taylor.

Larry was a wonderful person, he was always smiling and telling jokes. A very special person that will be missed by all. Carol urges people to please consider organ donation by telling your next of kin. Also if you knew Larry and have not already, please write a little something about Larry typewritten or hand-printed form. It can be funny, a picture, an anecdote, an impression, how he inspired you, who he was, so it may be preserved and shared with the kids when they are older. Carol continues to work with couples with HIV who would like to become parents and is active in Positudes, Inc. Tel: (518)863-2668.

In one of the stars I shall be living,
In one of them I shall be laughing
And so it will be
As if all the stars are laughing
When you look at the sky at night
And when your sorrow has lifted
You will be content that you have known me…

The Little Prince–Antoine deSaint Exupery