Summer 2002 - Factor Nine News

The Coalition for Hemophilia B

RESEARCH SURVEY

TNS Intersearch, a healthcare marketing research firm in Philadelphia is conducting a study on healthcare issues pertaining to people with bleeding disorders and would like to include your opinions. Your participation in this research will help pharmaceutical companies in their endeavor to research and develop quality pharmaceutical therapies that will have a direct impact on the quality of life of people with bleeding disorders.

The on-line survey will be available in mid-August and will take approximately 20 minutes to complete. A follow-up letter will be mailed to you prior to the survey to remind you of the survey. (The letter will also contain the Internet link and a password, which you’ll need to complete the survey.) All questions are strictly for research purposes and no sales are involved. Your answers are strictly confidential.

For your participation, TNS Intersearch has given an educational grant to The Coalition for Hemophilia B to support some families to attend the NHF meeting in Orlando. (see page 8, right column, if you wish to apply for a grant)

AVENTIS BEHRING CHOICE

Offers Quality of Life Grants

Belsito & Company, a Public Relations firm for Aventis Behring, has asked us to inform you of grants available for families who may need Quality of Life financial assistance.

Aventis Behring supplies $50,000 of initial funding for a first of its kind grant program. This Quality of Life Program is a pilot program designed to help relieve the financial burden of families affected by bleeding disorders. The program can provide at least 100 grants of up to $500 each to help families pay for quality of life items associated with managing a bleeding disorder that are not covered by insurance. Quality of life items intended for coverage under the program may include childcare, travel, dental and medical services.

To protect the confidentiality of the applicants, Aventis Behring has contracted with Patient Services Inc. (PSI), an independent not-for-profit organization that helps people with chronic illnesses deal with insurance and other financial issues. PSI will review applications and administer the grants. Grants are awarded based upon financial need, which will be determined through PSI’s nationally-recognized system of screening and qualifying people with chronic illness for financial assistance.

To receive a Quality of Life Patient Grant Program Application, please call the Aventis Behring Choice Member Support Center at 1-888-508-6978. Kim Phelan at the Coalition can help you fill out the forms if you wish.

ROBERT KELLER, MD

Hemophilia Federation of America Meeting

April 13, 2002; Speaker: Robert H. Keller, MD, ACP, Medical and Research Director, Biodoron and Immune Balance Technologies, Florida

The following information is drawn from notes taken at Dr. Keller’s seminar, and reviewed by Dr. Keller. I was impressed with his presentation. He had an interesting viewpoint and a lot of aggressive, innovative ideas. At the Coalition for Hemophilia B, we believe that you should listen to new ideas and try to evaluate them. We like these and hope that you find them of value too. It makes sense that you should properly balance your body before starting a Hepatitis C or HIV regimen. We know that Dr. Keller’s viewpoints may differ from those of other doctor’s, but we think they are worth listening to. In any case, we share them with you. Kim Phelan

Regardless of what the problem, Hepatitis C, HIV, or any other affliction, we need to deal with the body as a whole, first.

The first four things Dr. Keller looks at are:

• DHEA - low levels can tell if you are predestined to heart failure and if your immune system is working
• Testosterone - low levels cause depression
• Thyroid and Adrenal levels - low levels or high levels are a problem.

These four readings should be balanced before doing anything else. Dr. Keller stresses the importance of balancing the body before starting treatment for Hepatitis C.

Next, it is important to have good nutritional supplements. Dr Keller feels that the most important supplement to anyone’s diet is selenomethionine, a very powerful antioxidant.

The enzyme 23DPG determines the ease in which oxygen is delivered to the red blood cells. This enzyme is found in your blood.

Dr Keller says your platelets are a problem if they go under 10,000. Until they fall below 10,000 it is usually not a problem, however, in people with hemophilia it is better to keep them above 20,000. If you have low platelets, Dr. Keller recommends WINROW. It can triple the platelets in one infusion. Some insurance companies will tell you to go on COX 1 (which can cause gastrointestinal (GI) bleeds). Be persistent with your insurance company and tell them that COX 1 has this serious negative side effect, which will hurt you and cost them more money. This should make them change their mind.

For sleeping problems, Dr. Keller feels that the key is to get to delta wave sleep and Benzodiazapines lock the door to delta wave sleep. Non benzos are better, he feels that Ambien is good if you sleep straight through for 6 hours. Sonota is better if you tend to wake up in the middle of the night to go to the bathroom. His strategy is to take one pill when you go to sleep and another after you have gone to the bathroom as dosage lasts about 3 hours. Dr. Keller pointed out that sleeping raises endorphins, so it is important to get the right sleep, and that is delta wave sleep.

In answer to a question, Dr. Keller came down on the pro-biopsy side. The American Liver Disease Organization has now suggested that anyone with Hepatitis C should have a biopsy. When getting a biopsy, the direct approach is the easiest way to get a bigger core of the liver to see what is going on.

Putting this all together, he said that before starting the Pegulated Inteferon/Ribaviran treatment to treat Hepatitis C, you should start your nutritional diet and exercise program, as these are key elements to success. Here are the steps:

• See a good nutritionist, to get the proper nutritional supplements.
• Start an exercise program. Swimming is the best exercise for people with hemophilia.
• Be fully committed:
• Have the support of your family
• Be open and honest with your doctor
• Have a Positive Mental Attitude
• Find a hobby you enjoy
• Get outside of yourself - start and do it!

Most people are worried about depression when starting this treatment. As Dr. Keller suggests, low testosterone causes depression, so if you take care of yourself and get balanced before you start treatment, the likelihood of depression decreases. Yes, you will feel like “CRAP” for a little while, but you should not have depression.

“A Positive Mental Attitude, nutritional diet and exercise are key elements to success.”

Dr. Keller says that the success rate of this combination is 50% to 55%, but if you do all the other things beforehand, that the rate increases.

25% of people on the combination treatment will develop anemia, and you will need to be checked once a week for the first few months. If you develop anemia you need to have B12 shots, iron injections, folic acid and Procrit.

Dr. Keller pointed out that iron is a problem as it is actually dangerous for people with Hepatitis C because it is harmful every time it passes through the liver, which causes the liver work too hard. Injections work better.

Another question concerned bridging fibrosis. Some doctors will not treat you if you have a bridging fibrosis as the odds of success are lower, but it is still worth effort according to Keller.. Find the doctor who will take you. Remember that it is your life. Vote with your feet and walk away if you’re not satisfied.

Dr. Keller is in business of course. Here is how you can contact him. He sells nutritional supplements at 1-888-IMMUNE1, and is taking on new patients.

Dr. Keller is based in Hollywood, Florida
email: Rhk@IBTUSA.com
Telephone (954) 981-9400

PROF. INGA MARIE NILSSON

The Grand Dame of Hemophilia

Professor Inga Marie Nilsson gave this interview just a few months before her death in October 1999. In her lifetime she made extraordinary personal and professional contributions to the study and treatment of hemophilia and other coagulation-related disorders.

She is the uncrowned queen of coagulation. Even today, at age 76, Professor Inga Marie Nilsson carries herself regally as she greets a reporter and photographer at the front door at her home in Limhamn, a suburb of Malmo in southern Sweden.

She wears a bright, floral-patterned silk dress and her face is carefully made up. Her abundant white hair encircles a face that is nearly always smiling. Her blue eyes glint as she settles herself on a sofa and recalls with a natural storyteller’s enthusiasm the early days of her work in the treatment of hemophilia- that “fascinating, pioneering” time, as she describes it. “I was twenty-four years old when, as a young doctor, I began to work with bleeding problems with Professor Jan Waldenstrom at Malmo General Hospital, an internationally known expert in internal medicine and hematology,” says Inga Marie. “I had no idea that this would become my life’s work.”

Starting with her first patient in 1949, Inga Marie Nilsson became fascinated with the lack of coagulation in blood, the problem which plagued patients with hemophilia. Her first patient was a woman who had been in the hospital’s clinic for bleeding disorders for seven or eight years; the doctors had not been able to determine the source of her constant bleedings. Quite quickly Inga Marie understood that the woman carried antibodies against Factor VIII, an important coagulation factor in the blood. “I knew nothing about coagulation at the time. I read what little there was and drew conclusions from that,” explains Inga Marie, who insists that she never intended to move into research. Her Professor sent her to Oslo to learn to perform clotting test and upon her return, she began to do research full-time and together they traveled around the country in Blomback’s old unreliable car to map the genetic spread of von Willebrand disease, a type of hemophilia. They took blood tests at the patient’s homes, often surrounded by most of the villagers. Many small communities they visited had no local doctor, and the two women were often asked to investigate a whole range of ailments.

Inga Marie’s cooperation with both Margareta and Birger Blombeck led to the important discovery in 1956 of fraction 1-0, the first product that could be used effectively to stop the bleeding of hemophiliacs and normalize bleeding time. Inga Marie used it for the very first time on a young female patient named Birgitta Carlsson. “I knew it was her only chance, but it was a daring thing to do, since it had never been tested on a human being before. It was one of the moments in your life that you never forget. Time just disappears.” When the young patient’s bleeding stopped, Inga Marie knew her life’s work had only just begun.

In 1964, Kabi, as Pharmacia & Upjohn was known at the time, took over production of the fraction, which eventually was further refined into today’s highly purified Factor VIII and Factor IX.

Early on, Inga Marie Nilsson understood that it wasn’t enough to simply stop the bleeding in time. In 1958 she started devising a strategy for giving children with hemophilia Factor VIII prophylaxis. But because of shortages of plasma the technology to fractionate blood components had not yet reached its modern-day potential, children in Sweden could not be offered regular prophylactic treatment until early 1970s.

“The introduction of prophylaxis is one of the best things I’ve ever done in my life, “says Inga Marie. When she began her research, the average life expectancy for a person with severe hemophilia was 16 years. She pulls out a series of slides of some of these early patients. Their suffering is painfully evident. Many died as children or suffered serious damage from bleeding in the joints. Most were confined to wheelchairs. Few survived their 20th birthdays. The most common cause of death was cerebral hemorrhage.

Today children with hemophilia can live a normal life and play like other children. Inga Marie Nilsson has been telling her story without pause when she ushers us into her dining room where she has prepared tiny Swedish sandwiches of herring and meat pate`, a pot of tea, and glasses of light beer for lunch.

As we relax and talk, her eyes light up with memories of all the patients she has helped achieve a normal life. She called them “my boys.”

But suddenly she falls silent. She still has trouble talking about the great catastrophe that occurred when her patients received products with HIV-infected blood. It wasn’t until 1985 that methods existed to test all those with hemophilia in Sweden. The results were sobering. A third of the patients were found to be HIV positive. About 100 hemophiliacs were affected. Of these 40 were treated by Inga Marie. Twenty-two of them died of AIDS. “The alarm report about AIDS hit me hard. I saw how my whole life work would come crashing down. For a while I thought all my patients would die,” she recalls quietly.

Thanks to super-pure factor concentrates available today, the risk for hepatitis and HIV transmission from blood plasma products is practically non-existent.*

But Inga Marie Nilsson’s vision for the future is to see a cure for hemophilia through gene therapy.

“It’s just a question of time,” she says, the glint back in her eye. It is not difficult to be persuaded of her vision of a world in which children born with hemophilia today can look forward to a cure in their lifetime.~

There have been no reported hepatitis C or HIV cases transmitted through the Factor IX product, Mononine since it came out in 1992. For a list of highly purified factor IX products see the Coalition for Hemophilia B, Spring 1999 Newsletter (available on the web at http://www.coalitionforhemophiliab.org)

Special thanks to biovitrum AB, Stockhom Sweden, for permission to reprint this article in the Factor Nine Newsletter.

ADIRONDACK SPINTACULAR

Saturday, September 21, 2002

Larry Madeiros was a severe factor IX hemophiliac, infected with HIV and Hepatitis C through tainted blood products. Larry was a well-known patient advocate and co-founder of Positudes, Inc. the first non-profit bleeding disorder organization of its kind.

On September 28, 2001, Larry Madeiros became one of the sixteen people who die each day while waiting for an organ transplant. Larry would want people to know that it is possible for a single donor to save as many as 100 lives, and that most organ recipients are in their late 30’s. These are young people in the prime of their lives; most of them mommies and daddies, like him.

In Larry’s memory, the first annual “Adirondack Spintacular”, a six mile bike-a-thon, is scheduled for Saturday, September 21, 2002, at 10:00 a.m.Co-sponsored by Positudes, Inc. and the Center for Donation and Transplant, (a non-profit organ procurement organization in Albany, NY), the purpose is to raise Hemophilia and Organ Donation awareness, and raise money in Larry’s memory for a scholarship fund which will be awarded to graduating seniors continuing their education at an accredited college or technical school.

The course is a scenic 6-mile route amidst the Adirondack Mountains, and along the Great Sacandaga Lake in Mayfield, NY.

To register and join in this important event, to donate to the scholarship fund, or to learn more about the Adirondack Spintacular, please call Lisa or Carol at (518) 863-2668, or email us at LAMSPINTACULAR@aol.com.

Adults and children are invited to safely participate as walkers, cyclists, or passengers.

A separate one mile course is available for walkers and wheelchairs.

Awards are presented to the top finishes in biking, running, walking and wheelchair categories. All children will receive a certificate of participation.

Registration is $15.00 per participant, $20.00 if received after August 21, 2002 deadline. Individual registration fee waived with $50.00 in sponsor donations. (attach sponsorship sheet with checks for total of sponsor donations) Special Family registration $50.00 per family (immediate family members only). Please make checks payable to Positudes Inc. - Lawrence Madeiros Scholarship Fund: Attn: Adirondack Spintacular, 563 Mountain Rd, Mayfield NY 12117.

Highlights - (BBQ) catered lunch and dinner, silent auction, volleyball, horseshoes, etc, kids bounce house, DJ, karioke, BYOB (soda, lemonade, iced tea and coffee provided), information on hemophilia and organ donation.

SPONTANEOUS MUTATIONS

by Dr. David Clark

Our genes are the blueprints that determine how our bodies look and work. Genes tell our cells how to make proteins which are the molecules that form the structure of our bodies and which do the work that makes our bodies function. Each cell contains an identical copy of our genes in its center compartment called the nucleus. Genes are molecules made of DNA, and they are arranged on chromosomes, which are essentially racks to hold the genes in the correct positions. Humans have 46 chromosomes, 23 inherited from our father and 23 inherited from our mother.

Factor IX, one of the many proteins involved in the blood clotting process, is an enzyme, a protein that causes a chemical reaction. It is made by cells in the liver according to the blueprint of the Factor IX gene. Hemophilia B is caused by a mutation, a mistake in the body’s Factor IX genes, which cause it to make defective Factor IX molecules.

“Genes can now be sequenced fairly easily to determine the actual “blueprint” they contain.”

The Factor IX gene is located on the X chromosome, one of the two sex chromosomes that determine whether we are male or female. The other sex chromosome is the Y chromosome; men have an X and a Y chromosome, and women have two X chromosomes. The names come from the chromosome’s shapes, the X chromosome has four arms like an X, and the Y chromosome only has three arms like a Y. This explains why hemophilia appears almost exclusively in men while woman are “carriers” of the disease. Since woman have two X chromosomes, they have two copies of the Factor IX gene in each cell, one inherited from their Father and one inherited from their Mother. Even if they have a defective Factor IX gene on one X chromosome, it is very likely that the other one is all right. The one good gene could make enough Factor IX to prevent any clotting problems. However, since a man only has one X chromosome, and thus only one Factor IX gene, if that one is defective, all of his Factor IX is defective.

Since men always inherit their X chromosome from their mother, they necessarily also inherit hemophilia from their mother. Thus women are carriers of hemophilia, but are rarely afflicted with the disease. Hemophilia does occur in women, but it is extremely rare. To have hemophilia, a woman would have to inherit defective Factor IX genes from both parents, a father who is a hemophiliac and a mother who is a carrier.

There are many ways in which the Factor IX gene can mutate and similarly many types of possible defects in the Factor IX protein. However, in general, the result is a Factor IX protein that is less active but still somewhat functional, one that is completely non-functional, or one that is missing entirely. A somewhat functional molecule can cause mild or moderate hemophilia, while a non-functional or missing molecule causes severe hemophilia.

Where do these gene mutations come from and what causes them? Scientists have only had the ability to study gene mutations in detail for about the last twenty years. Genes can now be sequenced fairly easily to determine the actual “blueprint” they contain. This is the process that was used in the Human Genome Project to determine the sequence of all of the genes in the human body, but it can also be used on a smaller scale to look at the sequence of individual genes. Hemophilia B and the Factor IX gene have been studied extensively because they have a number of characteristics that make them good models for understanding human gene mutations in general.

Gene mutations are constantly happening in our bodies and are, in fact, a normal biological process. Mutations can be caused by damage to our genes by outside sources such as certain chemicals or by exposure to radiation. However, it appears that the majority of mutations actually occur because of natural processes happening inside our bodies.

Some mutations affect us directly. For instance, some types of cancer are a result of gene mutations. However, other mutations like those that cause hemophilia are only passed on to our children.

Many organisms, including humans, have mechanisms for repairing damage to genes, but it seems that nature has programmed us to allow some mutations to slip through un-repaired. This allows organisms to gradually, over generations, adapt to changes in their environment. Not all mutations are harmful; some improve the functioning of the organism. This can be seen more easily in organisms such as bacteria that reproduce very frequently. For instance, bacteria develop resistance to antibiotics via gene mutation. Random mutations eventually produce bacteria that have a gene for antibiotic resistance. Those bacteria and their offspring then have a genetic advantage that allows them to proliferate while bacteria that are not resistant may die off. Through this process the entire population of bacteria can eventually become resistant to the antibiotic. Of course, other random mutations will not be advantageous, and families of bacteria with those mutations will tend to die out. The same kinds of processes are constantly happening in humans. Unfortunately, hemophilia is the result of non-advantageous mutations. Historically, hemophiliacs tended to have severely shortened life spans and fewer children. Thus their gene mutation would tend to die out and not be passed on through a large number of generations. It is only because of the advances in modern healthcare and especially the availability of Factor IX concentrates that hemophiliacs today can live full productive lives.

National Hemophilia Federation 2ndAnnual Gala
Honoring Dr. Harold R. Roberts

Saturday, June 8, 2002

Dr. Roberts was honored for his internationally recognized contributions to coagulation research and dedication to improving the lives of people with bleeding disorders.

New York, Tavern on the Green; Over 300 people gathered for this special gala event hosted by The National Hemophilia Foundation, to honor the distinguished Dr. Harold R. Roberts.

Harold Roberts, born in Four Oaks, NC, became interested in science during his early school years. His third grade teacher recognized his interest and encouraged him to develop a relationship with his hometown general practitioner, Dr. John Dotterer. These early interactions set Roberts off on a path that led him to the University of North Carolina (UNC) where he graduated Phi Beta Kappa. He then went on to medical school at UNC. One of his professors, Dr. Kenneth M. Brinkhous, recognized the talented young student and introduced him to the hemostasis field. Following fellowships in Pathology, Neurology, and Hematology, Dr. Roberts returned to the University of North Carolina and to Brinkhous as an instructor in Pathology. He rose through the ranks in both medicine and pathology to become Professor in 1970. He served as Chief of the Division of Hematology from 1968 to 1994. Roberts also served as Director of the Clinical Coagulation Laboratory from 1977 until its incorporation into laboratory medicine in 1984. During that time he transformed the Coagulation Laboratory into one of the premier clinical hemostasis laboratories in the world. He was also the founding Director of the world renowned UNC Center for Thrombosis and Hemostasis. Under his direction, the center has grown into the second largest Center at UNC with over 45 scientists and clinicians focused on coagulation research.. He is presently the Sarah Graham Kenan Distinguished Professor of Medicine and Pathology at UNC.

Dr. Roberts has so many qualities that make him stand apart. His gentle and calm nature strikes one first, but his willingness to take time listening, questioning, and understanding is even more impressive. From him, you can always count on a reasoned and intellectually astute analysis, tempered with genuine care and humanity.

This is only half the story, as behind his kind Southern demeanor lurks a fiercely honest and unyielding warrior who sets out high standards and goals for our community-one that he leads by example. Quoting Dr. Roberts as support in a debate is always comforting and usually enough to win the point. His intellectual rigor influences all who know him. It is not by chance that Chapel Hill stands for excellence in hemophilia research and its graduates have made contributions that expand its reach around the world.

The Coalition for Hemophilia B would like to thank him for his past achievements and for what we know he will achieve in the years ahead.

- John R. Taylor, Jr.

AIR TRAVEL IN THE NEW ERA

Information By Carl Weixler, Community Resource Coordinator for Apex Therapeutic CareThe events of September 11th have forever changed our world. The changes in our society are far reaching. Of particular interest to the clotting disorder community is air travel and carrying factor with supplies. When I first heard the airport securities around the country were confiscating finger nail clippers, etc., I thought “What about the needles a person with hemophilia has to carry?” “Would they take them away from me or make me put them in my checked baggage and hope it will not get lost?”

Due to National Security, I was unable to get a written copy of the FAA’s security guidelines. However, I am able to quote Steve Clay, Manager of Delta Airlines in Lexington, KY who quoted to me the FAA Security Directive, Section 8 as follows:

“Needles & Syringes are allowed into the sterile concourse beyond checkpoint, provided the passenger can demonstrate the medical need for the needles and syringes. Proof of medical need, which would consist of a professionally printed label identifying the medication, manufacturer’s name, pharmaceutical label or prescription.

Mr. Clay did state however, that these guidelines are interpreted by each airline and airport, so there may be some differences. In this instance it would be advisable to have a letter from your physician stating the importance of carrying your medical supplies.

Here is a sample letter you should have from your physician:

To Whom It May Concern:

John Doe has severe hemophilia factor IX deficiency and must carry his/her coagulation supplies with him when traveling. The factor concentrate (bottles of white powder) is administered via syringe and needle and could be life threatening if not given immediately when needed.

Sincerely,
Jane Smith, M.D.

When traveling through Airports in the United States you will need the following in order to be permitted to “carry on” your factor:

1. Current Photo ID
2. Proof of Medical Necessity (this can be your Medic Alert emblem and/or letter from your doctor)
3. There must be a manufacturer’s label on the bottles
4. A prescription label (this can be from one of the boxes, bags or whatever your factor comes in)

Most airport security looks at the x-ray machine funny when they see my bag content. I just tell them it is medical supplies.

National Hemophilia Foundation Conference

Family Funding Form

We are pleased to offer a lotto drawing to fund some families in the USA to attend the National Hemophilia Foundation Meeting, October 31- November 2. Kindly fill out the form below and send to:

Marie Currim, c/o FX Concepts, 225 West 34th St.,
Suite 710, New York, NY 10122

Applications will be held strictly confidential. Drawing will be held on September 4th. Winners of this lotto drawing will be notified by telephone.

[Friendly web developer note, form omitted, no point in spending the time for an event long over.]