Fall 1996 - Factor Nine News
The earliest written reference to hemophilia may be that found in the Mishneh, a second century compilation of Jewish law. There it states that if a mother has had two sons circumcised who both died as a result, then a third son must not be circumcised. Although it is not specifically stated that the deaths were due to bleeding, other sections of these writings do refer to “loose” blood.
Another early reference is the legend of the Curse of Tenna. In 1769 a judge in the small Swiss village of Tenna condemned an innocent man to death. The legend states that this act led to the inflicting of a curse upon the judge and his family. This curse was believed by the citizens of Tenna to be the cause of a serious bleeding disorder, sometimes leading to bleeding to death, which afflicted the family for generations.
This was, in fact, a family of hemophiliacs. Using detailed church and civil registers which have survived through the ages, modern investigators have complied a family tree covering 13 generations from 1600 to 1955. This is the oldest and largest family of hemophiliacs ever described comprising 3072 members of whom 55 were hemophiliacs. The first known bleeder of the family died in 1741 (28 years prior to the act which supposedly resulted in the curse being inflicted). Interestingly, the terms bleeders (”blutters” in German) for the affected hemophiiacs and carriers (”conductoren”) for women who transmit disease were created by the people of Tenna, not by physicians. Also of note is that the family disease turned out to be hemophilia B rather than the more common hemophilia A.
An early medical account published in 1803 correctly described the disease as one which affects males but is transmitted by females. Remarkably, this was a half century before Mendel discovered the laws of genetics and more than a century prior to the discovery that such diseases are carried by the X-chromosome. In 1937 the existence of an “antihemophilic globulin”, a component absent from the blood of hemophiliacs, was discovered.
However, it was not until the early 1950’s that the existence of the two separate forms of hemophilia was finally determined. This is not surprising since the clinical symptoms of the two diseases are essentially identical. Factor VIII and factor IX work together to activate factor X in the clotting process. A deficiency of either factor causes the process to stop at that step. In 1952 , researchers in Oxford, England described Christmas disease, “a condition previously mistaken for hemophilia.” Christmas was the family name of the patient they studies. At the same time researchers in San Francisco independently described PTC deficiency, “a new disease resembling hemophilia.” PTC referred to the newly-identified missing clotting factor Plasma Thromboplastin Component, now known as factor IX. In 1954, at the Paris Congress of the International Society of Hematology, the terms hemophilia A for factor VIII deficiency and hemophilia B for factor IX deficiency were officially adopted.
At this point the histories of the two diseases diverge as they follow the search for two different treatments. Around the turn of the century the transfusion of serum was determined to be effective in treating bleeding episodes. However, by the 1930’s this practice was being condemned as useless. The reason for this inconsistency is that the physicians of that day did not yet realize that they were dealing with two separate diseases. Serum is the liquid portion remaining after plasma has been allowed to clot. Factor IX remains active in serum while factor VIII is degraded and becomes inactive. Thus serum worked for the hemophilia B patients, but was not effective for the larger population of hemophilia A patients.
Until the late 1950’s serum, and later plasma, were the only treatments available for hemophilia B. Then in 1959 the first purified IX concentrate derived from plasma was developed in France. This was followed by the development of similar concentrates in Britain and the U.S. The first factor IX Complex products in the U.S. was licensed in 1969. These became known as Factor IX Complex concentrates. The word “complex” in the name refers to the fact that in addition to factor IX these products also contained several related clotting factors such as factor II, factor X, and in some cases factor VII. Because of the similar properties of these factors, it is difficult to purify factor IX away from the others.
The availability of Factor IX Complex and its effectiveness in treating bleeding episodes significantly improved the health and well-being of hemophilia B patients. The use of Factor IX Complex, however, soon became associated with thromboembolic complications, that is, unwanted, and potentially life-threatening internal clotting. This happened most often when the product was used in large amounts for extended periods of time, for instance in hemophilia B patients undergoing surgery. The reason for these complications is still unknown. One theory is that this unwanted clotting is due to overloading the patients blood with the other clotting factors in the complex. To eliminate this problem, more highly purified products containing only factor IX have recently been developed with the first one being licensed in the U.S. in 1990. Another important advance has been the development of better methods for inactivating or removing viruses from these products.
The wheels of history continue to turn today. This is an exciting time with advances in product purity and viral safety, development of genetically engineered factor concentrates, and new treatment methods such as prophylaxis and continuous delivery appearing rapidly. On the horizon is even the potential “cure for hemophilia by gene therapy.
The U.S. Food and Drug Administration licensed Alpha Therapeutic Corporation’s AlphaNine SD, Solvent Detergent Treated/Virus Filtered, Coagulation Factor IX (Human) Product for patients with Factor IX deficiency. AlphaNine SD Virus Filtered includes solvent detergent treatment and a nanofiltration process for removing viruses. For more information please call (800) 292-6118.
The testimonials of hemophilia patients clearly illustrate the rewards of prophylactic therapy. With this in mind, two panels have been assembled, each consisting of a patient, his parent(s), and the patient’s hemophilia physician, nurse, and social worker. This symposium is designed to provide the opportunity for candid discussion among the panel participants and the audience. The forum will address, from a “real-life” perspective, the issues, challenges, and rewards that result from prophylactic therapy.
Objectives
- To provide patients, family members and caregivers with a new, revealing perspective on prophylactic therapy.
- To promote further understanding and acceptance of prophylactic therapy by fostering candid discussions of the challenges and rewards associated with it.
| Moderator | Presenter |
| Craig M. Kessler, MD | W. Keith Hoots, MD |
| Professor of Medicine | Associate Professor of |
| George Washington University | Pediatrics and Internal Medicine |
| Medical Center | University of Texas Medical School at Houston |
| Director, | Associate Professor and Pediatrician |
| Hemophilia Comprehensive Care Ctr | University of Texas M.D. Anderson |
| Washington, D.C. | Cancer Center at Houston |
| Panel One | Panel Two |
| Marilyn J. Manco-Johnson, MD | Peter S. Smith, MD |
| Brenda K. Riske, RN, MSN, MBA | Joan M. Holden, RN, BSN |
| Ann C. Johnson, MSW, ACSW, LCSW | |
Note: The following panels will feature a patient accompanied by his parent(s)
Agenda Synopsis
The symposium will begin with a general overview of prophylaxis, covering such topics as the difference between primary and secondary prophylaxis, a review of US and European clinical experience, patient compliance, and economic issues. A video that follows the true stories of a patient, his family, and his treatment team will then be shown. The two separate panel discussions will come next, each, in turn, followed by an audience question and answer session.
To register for this symposium, please call the National Hemophilia Foundation at (212) 219-8180 (fax (212) 966-9247 (On-site registration is permitted)
Topics of discussion will be on educational and support programs, packaging, enhanced delivery systems, etc. Food will be served and a $60.00 (sixty dollars) honorarium will be offered to each participant. The discussion will be confidential and will not be used for any promotional purposes.
Three meeting times are offered, as listed below. The meetings will be held at the Town and Country Hotel in a small room or a suite, the number and location of which will be indicated to you at a later stage. Further details will be available at the Marketing Research Bureau’s exhibit booth.
1) Friday, October 18, from 7:30 a.m. to 9:00 a.m.
2) Friday, October 18, from 5:30 p.m. to 7:00 p.m.
3) Saturday, October 19, from 7:00 a.m. to 8:30 a.m.
If you are interested, or if you need further information, please call Patrick Robert at (800) 484-5147 Ext. 8855 or visit the Marketing Research Bureau’s exhibit booth during the NHF meeting.
GENETICS INSTITUTE
FOR THEIR KIND SUPPORT WHICH HELPS US TO HELP KEEP YOU BETTER INFORMED!!
For back issues of the Factor Nine Newsletter or for more information on research please call or write to Kim Phelan, 712 Fifth Avenue, 42nd Floor, New York, NY 10019, Telephone (212) 554-6823 Telefax (212) 554-6900. We are now on the Web - our web site number is http://www.coalitionforhemophiliab.org/
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You’re currently reading “Fall 1996 - Factor Nine News,” an entry on The Coalition for Hemophilia B
- Published:
- 09.01.96 / 6pm
- Category:
- Newsletter
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