S e r v i n g t h e B l e e d i n gD i s o r d e r s C o m m u n i t y

S p r i n g 2 0 0 4 V o l 3 9 N o 1

Hem philiaTODAY

PASSP RTto well-being

empowering people with bleeding disorders to maximize their quality of life

LAUNCHEDw w w . h e m o p h i l i a . c a

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 42

T his issue of Hemophilia Today that you’re holding is particularly chock-full. The subjects coveredare as varied as they are interesting, especially the Passport to Well-Being Program, which is thespecial feature. And justly so, since this initiative, financed by Baxter and initiated during the

CHS Annual General Meeting held in Toronto last May 29, promises to be highly enriching for anyonewho participates. The four modules that make up the passport are at the heart of the lives of peopleliving with a bleeding disorder. In fact, home care, along with adequate follow-up, a personalizedphysical exercise program and healthy management of pain make up a winning recipe that allowspeople with a bleeding problem to optimise their quality of life. I highly encourage you to get apassport, take part in the training workshops that will let you gain knowledge, aptitudes and strategiesin these four categories… and get your visas stamped.

The second Canadian Conference on Hepatitis C, held from April 27 to 30, 2004, also catches ourattention. Under the theme New Knowledge, New Hope, over 700 people from across Canada—healthprofessionals and social workers as well as people infected with the disease—gathered in Vancouver.As a representative from the Quebec Chapter, I was among the CHS delegation. It was no surprisewhen experts confirmed that the treatment with peg-interferon and ribavarin is the current treatmentof choice for chronic carriers of the virus, including people co-infected with HIV. We did learn,however, that we’ll still have to wait five to ten years for the creation of an effective vaccine.Researchers are, in fact, still confronted with a number of challenges. Since hepatitis C is a chronicdisease and has numerous forms (many genotypes), it’s difficult to find an adequate cellular host and a distinct antigen to properly block the replication of the virus. Moreover, non-human models reactdifferently to the disease. A bit farther on in these pages, you can read the announcement of theHealth Canada Research, Support and Prevention of Hepatitis C Program, including the renewal offunding, that was made at the opening of the Conference.

I want to remind you that the World Federation of Hemophilia (WFH) Hemophilia 2004 WorldCongress will take place in Bangkok, Thailand, from October 17 to 21. There’s still time to register byvisiting the WFH website at www.wfh.org or by requesting a registration form at (514) 875-7944.

I can’t end this column without talking about the departure of Daniel Lapointe, now formerExecutive Director of the CHS. During his tenure, from July 1999 to April 2004, the organizationmade major progress in a number of fields, due to his good judgement, his leadership, his dedicationto the cause and his helpful experience. Supported by volunteers and by the rest of the staff, he made a major contribution to raising the level of awareness in the Canadian public about hereditarycoagulation problems (von Willebrand Disease, in particular) thanks to the Bleeding DisordersInitiative campaign. He also worked to improve relations between the provincial chapters and thenational level, as well as those with our pharmaceutical industry partners. These are only a few of hisachievements. As well as wishing all the best to Daniel in his new position as the Executive Director ofthe Canadian Institute of Actuaries, I’d also like to welcome the new Executive Director, StéphaneBordeleau, to our organization.

SPRING 2004 • VOL 39 • NO 1

Hemophilia Today625 President Kennedy Avenue, Suite 505

Montreal, Quebec H3A 1K2www.hemophilia.ca

Phone: (514) 848-0503Fax: (514) 848-9661

Toll Free: 1(800)668-2686

Hemophilia Today is the official publication of the CanadianHemophilia Society (CHS) and appears three times yearly.

The Canadian Hemophilia Society exists to improve the quality of lifefor all persons with hemophilia and other inherited bleeding disorders

and to find a cure.

The purpose of Hemophilia Today is to inform the hemophilia andbleeding disorders community about current news and relevant issues.

Publications and speakers may freely use the information containedherein, provided a credit line including the volume number of the

issue is given. Opinions expressed are those of the writers and do notnecessarily reflect the views of the CHS.

The CHS consults medical professionals before distributing any med-ical information. However, the CHS does not practice medicine and inno circumstances recommends particular treatments for specific indi-

viduals. In all cases, it is recommended that individuals consult aphysician before pursuing any course of treatment.

Brand names of treatment products are provided for information only.They are not an endorsement of a particular product or company by

the writers or editors.

Hem hiliaTODAY S e r v i n g t h e B l e e d i n g

D i s o r d e r s C o m m u n i t y

IN THIS ISSUE

EDITORFrançois Laroche

PRESIDENTEric Stolte

EXECUTIVE DIRECTORStéphane Bordeleau

EDITORIAL COMMITTEEHélène Bourgaize

Clare CecchiniFrançois Laroche

David PagePatricia Stewart

CONTRIBUTING WRITERSTom Alloway, Ph.D.

Claudine Amesse, R.N.Frank Bott

Maureen Brownlow, RSWClare Cecchini

Suzanne ChampouxKaren Creighton

Kim and Stacy CullenFaye Katzman

Sylvie Lacroix, R.NFrançois Laroche

Peter Leung, M.D.Josh McCormack

David PageGeorges-Etienne Rivard, M.D.

Julie SerradorMary Jane Steele, BScPT

Bob SteffensPatricia Stewart

Eric StolteCandace TerpstraStacey Westman

PRODUCTION COORDINATORDavid Page

PRODUCTION ASSISTANT AND FRENCH VERSION COORDINATOR

Hélène Bourgaize

GRAPHIC DESIGNPaul Rosenbaum

TRANSLATORSNormand Latulippe

Lise MaloMarie PréfontainePatricia Stewart

PRINTINGHouston Press

WORDFROM THE EDITOR-IN-CHIEF François Laroche

EDITOR’S KEYBOARD ................................................2

PRESIDENTS’ MESSAGES ..........................................3

IN MEMORIAM ......................................................4

NEWS UPDATE ........................................................5

CHAPTER SPOTLIGHT ................................................9

FOCUS ON INHIBITORS• Immune tolerance, an historical overview..............11• Profile: The Quebec Reference Centre for the

Treatment of Patients with Coagulation Inhibitors ..12• Families in Touch: The Circle of Care Workshop ....14

FOCUS ON HEPATITIS C• New booklet on symptoms of hepatitis C ..............15• New treatments on the horizon ..........................15

MEDICAL NEWS• Pain – The Fifth Vital Sign: Effective use of opioid

and non-opioid analgesic ....................................17

THE BLOOD FACTOR• rAHF-PFM: Baxter’s third-generation recombinant

factor VIII under review by Health Canada ............19• Bayer devotes research energies to a

‘new, improved’ factor VIII ..................................21

THE FEMALE FACTOR• What if you’re a carrier? ....................................22

THE GLOBAL PERSPECTIVE• Jordan and TCOR twinning – the first year! ..........23

Cover: (clockwise from top left): Pam Wilton, CHSVice-President, Programs; Martin Kulczyk, QuebecChapter; Clare Cecchini, CHS Program Coordinator;Eric Stolte, CHS President; Mike Hamilton, BaxterBioscience, Vice-President of Bioscience andTransfusion Therapies.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 3

T he past three years have been a busy and rewarding time for I’ve hadthe opportunity to visit most CHS chapters and meet a substantialproportion of our members from coast to coast. I particularly treasure

my memories of family weekends and annual meetings in Saskatchewan,Manitoba, Ontario, the Maritimes, and Newfoundland. Meeting andtalking to people at these get-togethers has impressed me with both thediversity of our membership and the extent to which, despite the diversity,we share the same issues when it comes to the management of ourinherited bleeding disorders.

During my time as President, I have striven to increase the inclusivenessof the CHS by making it a more welcoming organization to individuals ofboth sexes and to the families of Canadians with all inherited bleedingdisorders. As part of this effort, we have completed the von WillebrandDisease Awareness Program and launched a new “brand” that we call theBleeding Disorders Initiative. As part of these programmes, we have notonly updated our informational material on factor VIII and factor IXhemophilia but also created and disseminated some of the mostcomprehensive information to be found anywhere in the world on vonWillebrand Disease and other inherited bleeding disorders. We can all beproud of the pamphlets and informational brochures that we havepublished and of our web site (www.hemophilia.ca) which contains perhapsthe most encyclopaedic information to be found anywhere on rare bleedingdisorders. These programmes and educational materials have helpedthousands of Canadians to understand their bleeding disorders more fullyand greatly increased the number of people who are being diagnosed withvon Willebrand Disease and other bleeding disorders.

A major challenge that began in the recent past and which we must facemore effectively in the years to come is assuring the financial future of theCHS. During the tainted blood crisis of the 1980s, the CHS for the firsttime obtained substantial government funding to assist us with ourprogrammes for people who had been infected with HIV and hepatitis C.In the 1990s, before and during the Krever Inquiry, heightened publicawareness of the CHS enabled the organization to launch successful direct-mail and telemarketing campaigns. Our sources of government funding arenow “drying up,” and the public is less and less aware of the CHS’s vigilantrole as a guardian of the Canadian blood system. These circumstancesmean that we must either find new ways of funding the CHS or facesubstantial reductions in the services which the CHS, both nationally andlocally, will be able to offer. During the past several years, the decrease ingovernment funding has to a degree been offset by increases in fundingfrom the pharmaceutical industry. We greatly appreciate the help that ourpharmaceutical partners have provided; however, in order to maintain ourability to be independent commentators on the blood system and on thesafety and efficacy of treatments offered people with bleeding disorders,the CHS cannot afford to be seen as too dependent on pharmaceuticalfunding. To a large extent, the future funding of the CHS and its chaptersis going to have to depend upon the community of people with inheritedbleeding disorders. They and their families are the principal beneficiaries ofthe programmes that the CHS and its chapters provide. If we are notwilling to give to the CHS, who will?

In closing, I want to thank each and every one of you who has offeredme your support, your encouragement, and your friendship. This summer,the CHS will have a new President and a new Executive Director. I amconfident that you will give them the support that they will need to movethe organization forward.

OUTGOING PRESIDENT’SMESSAGETom Alloway, Ph.D.

If we are not willing to give tothe CHS, who will?

Same Journey, New Phase

PRESIDENT’SMESSAGEEric Stolte

T he CHS has been on a 51-year journey to find a cure forhemophilia. Along that journey, we have improved the quality oflife for thousands of people with hemophilia. Recently, we have

engaged the entire bleeding disorder community in our journey and arenow traveling together. Until a cure is found, our journey will be one ofvigilance in ensuring an ever improving, quality of life for all peoplewith bleeding disorders.

As the new CHS President, I have the privilegeand responsibility to give volunteer leadership tothis journey. But it is truly a journey we traveltogether, each one of us playing an importantrole. No single role is all-encompassing. Idesperately need the contribution of each one inour society, from the “least” to the “greatest”, ifour journey together is to be one of progressand not regress.

Right now, a critical challenge to this progress is our ability toacquire sufficient public funding for our mission. Our industrypartners are to be congratulated for their contribution of resources.But raising public funding is like swimming upstream. If you look atthe current alone, you think you’re making progress. But if you’re notswimming vigorously enough, when you look at the shore line, you seethat you’re actually losing ground. This is our situation. The currentdecrease in public funding threatens our missional strength. This, inturn, threatens the level of quality services we’ve been able to achieve.Ultimately, this can even threaten not only quality of life, but lifeexpectancy itself.

Although we’re far from this threat at the moment, we must generatenew energy and momentum in the development of resources so that asituation of compromised care never becomes our reality. We can onlydo this as one strong organization whose regional, provincial andnational levels pull in the same direction. Then we can tap in to theenormous abundance of as yet untapped philanthropic dollars that areavailable in Canada.

The CHS’s energy to effect change in response to vast threats in thepast resulted in a changed blood system in Canada. Now, not in responsebut with proactive action, we can change our funding future. We can bringabout a new day of coordinated effort to take advantage of opportunitieswhich now lie beyond our grasp. Opportunities which are not onlyfunding based, but program based as well. Opportunities which will bringus along this next leg of our journey together to a place of quality care andmaybe even a cure!

I deeply believe in the power of all members of our society in helpingto find our way forward to this new day of increased public funding. Wewill be launching a national effort to ensure as many members as possiblecan make their contributions to a national public funding strategy. I lookforward to seeing many of you in this process and devoting my efforts tosee that this comes to pass in a way that will ensure a confident resourcedevelopment future.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 44

E M E R Y M A R T I N

After a courageous battle, Emery Martin passed away on March 18th, 2004. Those who knew Emery wellwill remember him as a person with strong convictions and a warm, fun-loving man who had a great sense ofhumour. He loved to spend time with his family and friends, and that time was often spent laughing andtelling some hilarious stories of his youth; he had a great way of looking at life.

Although he did not have a bleeding disorder, Emery worked energetically for the British ColumbiaChapter of the Canadian Hemophilia Society. For 10 years, Emery was the Chapter’s vice-president and thepublisher/creator of their award-winning newsletter. He generously spent many hours every week handling allthe details that needed attending to. At times, he almost single-handedly ensured the survival of the Chapter. For many years healso served on the National Board of Directors that required travel and time away from his family. His friends at the chapter willalways be grateful for his contributions and we will miss his presence profoundly.

Emery will be especially missed by his wife Julianna and his 2 daughters, Julia and Judith, who loved and respected him deeply.

I N M E M O R I A M

P E T E R W A C H T E R

The hemophilia community was saddened to learn in May of the passing of Peter Wachter of Montreal.Rich with his years of experience as a financial analyst at Bell Canada Enterprises, Peter joined the Quebec

Chapter Board in 1985 and became CHS Treasurer in 1986, when the organization’s serious financialdifficulties demanded his considerable skills.

Peter was a stalwart member of the Compensation Task Force lobbying the federal government in the late1980s and a member of the CHS negotiating team in Ottawa. With Peter in the room, there was little danger thefederal government would succeed in discrediting CHS actuarial projections of the financial impact of HIV!

Peter became CHS President in 1990, a difficult time when attempts to complete the drive for fair compensation had to becarried out in ten provincial capitals. During Peter’s term, national programming to support those with HIV was increasedconsiderably. The Women Helping Women Network was established. An international conference on recombinant factor VIIIwas hosted by CHS, which laid the groundwork for its introduction in 1993. He and his wife, Jackie Marin, were instrumental in securing Opening Nights of The Phantom of the Opera, with significant benefits coming to the CHS.

Later in the 1990s, Peter remained active within the CHS as a strong supporter of fundraising efforts and as a trustee of theMillion Dollar Club. In all of his volunteer efforts with the CHS, Peter demanded the integrity and dedication of those heworked with. He was even more demanding of himself.

K A R R T I K S H A H

Karttik Shah died on March 18th, 2004 after a valiant year-long battle with cancer. He is survived by hisparents, Fulchand and Amrit Shah, his sister Minashi and her husband Ravi Varma, his niece Sohum andnephew Akshay Varma.

Karttik first developed visibility within the CHS in 1995, when he was appointed Chair of the HemophiliaOntario Youth Committee. With characteristic dedication and drive, he called monthly meetings resulting in ayouth retreat, publication of the Youth News, and an annual canoe trip, initiatives recognized with a ChapterRecognition Award by the Canadian Hemophilia Society. A weekend symposium was organized in 1997, underHemophilia Ontario auspices with CHS funding, for young people with hemophilia and von Willebrand Disease.Within a few years, Karttik was also heading up youth committees at national and international levels.

By 2000, he was serving on regional, provincial, and national boards of directors and committees within the CanadianHemophilia Society. By then, he had enlarged his scope to also embrace AIDS and hepatitis C concerns, international projects,and blood safety issues, most notably with regards to the latter appearing as a panelist on the CHS Consumer Forum on Safety,CJD and Blood Products in Toronto (1999). He was actively involved in the organization of Hemophilia 2000 in Montreal,including an international youth retreat prior to the Congress, as well as Chair of one of the sessions at the symposium. In 2001Karttik became President of the Toronto & Central Ontario Regional Hemophilia Society (TCOR), a position he held until hisdeath, fulfilling his responsibilities, at times, from his hospital bed. During his presidency, he further broadened his internationalvision, promoting twinning between TCOR and the Kingdom of Jordan. In September 2002, he and Candace Terpstra met withthe Jordanian Hemophilia Society (JHS) to inaugurate the twinning relationship. By the time of the second visit a year later, hewas no longer able to travel and Candace has very capably carried on his work. A tribute to Karttik personally and to the region,TCOR and the JHS were recognized with the WFH Twins of the Year Award for 2003.

This is the legacy that Karttik Shah has left in the few years he was with us. While the recitation of these achievementstouches on his energy, drive, and dedication, it does not do justice to the spirit, personality, and intellect of this remarkableyoung man who did more in his shortened years on behalf of people with bleeding disorders than many do in a lifetime.

This tribute is abstracted from an article by the author written for the Spring 2004 edition of the TCOR Community News.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 5

� NEW EXECUTIVEDIRECTOR AT CHS

T he CHS Board of Directorsannounced on May

25 the arrival ofStéphane Bordeleau asthe organization’s newExecutive Director.Stéphane, a bilingualMontrealer, begins hisnew duties on June 14.

Stéphane comes to the CHS with more thanten years of experience in the not-for-profitsector. Most recently, he served for five years asExecutive Director of the Quebec Chapter of theParkinson’s Society of Canada. He has alsoworked in a fundraising capacity with Leucan,the University of Montreal and the CanadianRed Cross.

On behalf of the entire bleedingdisorder community, welcome toStéphane!

Mr. Bordeleau succeeds Daniel Lapointe whoannounced his resignation in April to take on anew challenge with the Canadian ActuariesAssociation in Ottawa. During his five-year tenureat the CHS, working with two Presidents, ErmaChapman and Tom Alloway, Daniel workedextremely hard to broaden the scope of CHSactivities to include services for people with alltypes of bleeding disorders, in addition tohemophilia A and B. The organization launchedthe von Willebrand Disease Awareness Programand held a world-class medical symposium onVWD. It also adopted a new brand, the BleedingDisorders Initiative, to reflect its expanded focus.Under Daniel’s wise guidance, the CHS solidifiedits role as the principal community voice in theblood system, placing members on all majorblood system committeesand producing two reportcards on progress inimplementing the KreverCommission recommen-dations. In an era whenfunds from bothgovernment and thegeneral public are harderand harder to find, he hasleft the CHS with someroads forward to a more solid financialfoundation. In addition, thanks to hisprofessionalism, the organization is betteradministered than ever before.

All those who have worked with Daniel since1999 wish him the best in his new endeavours.

n e w s u p d a t e

NEWS UpdateRepresentatives from Baxter BioScience (L-R):Mike Hamilton, Vice President of BioScience andTransfusion Therapies, Barb Dawson, Director ofCommunications, Wendy Liu, Marketing Manager,Serge Messerlian, Business Unit Manager.

� PASSPORT TO WELL-BEING PROGRAM LAUNCHED !

The Canadian Hemophilia Society and BaxterBioscience have launched an exciting newprogram aimed at empowering people withbleeding disorders, at all stages of their lives,to maximize their quality of life. The newprogram was officially presented to thebleeding disorders community at a receptionheld on May 29th at the Toronto AirportRenaissance Hotel. Attending the launch weremembers of the CHS Board of Directors and other keyvolunteers as well as representatives from Baxter.

The Passport to Well-Being Program has been designed around4 modules:

Charting Your Course – promoting accurate patient record keepingand monitoring of product usageDestination Fitness – promoting the benefits of physical activity,fitness and sports Home Care: the Road to Independence – helping patients takegreater control of their disease through home treatment.Roadmap for Managing Pain – raising awareness of ways to managepain

Key messages relating to these themes will be communicatedthrough educational booklets, newsletters and workshopstargeted at children, adults and caregivers of people withbleeding disorders. Participants in the program will eachreceive a personal passport which they will have stamped witha visa when they take part in a workshop or related activity.For more information about how to get involved in thePassport to Well-Being Program please see the special bulletinincluded with this issue of Hemophilia Today.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 46 n e w s u p d a t e

Mary Jane Steele, BScPT, South Western OntarioRegional Hemophilia Program

Fourteen physiotherapists from acrossCanada, affiliated with HemophiliaTreatment Centres (HTC), had an

active, yet highly productive weekend April 23 – 25, 2004. With the generoussupport of Baxter Corporation, BayerHealthcare, the Canadian HemophiliaSociety (CHS) Physiotherapy Group wasable to meet in Edmonton, Alberta inconjunction with the Association ofHemophilia Clinic Directors of Canada

� CHS PHYSIOTHERAPY GROUP UPDATE

Fourteen physiotherapists from across Canada involved in the treatment of people with bleeding disorders met in Edmonton April23-25, 2004 to share their knowledge and expertise. Back row: Betty Hale, Kathy Mulder, JoAnn Nilson, Andrea Hahn; Middlerow: Nick Zourikian, Danielle Levac, Greig Blamey, Brenda Elliott, Catherine van Neste; Front row: Mary Jane Steele, CathyWalker, Pam Hilliard, Jenny Aikenhead; Missing: Nicole Graham.

(AHCDC) and the Canadian Associationof Nurses in Hemophilia Care (CANHC)annual general meetings. Most HTCphysiotherapists have very limited clinicaltime dedicated to the care of individualsaffected by inherited bleeding disorders.Therefore, the opportunity to get togetherto share experiences, exchange informationand to promote best practices in acollaborative way is highly valued andgreatly appreciated.

Topics of discussion at the meetingincluded an update from Dr. B. Feldmanon the Canadian Hemophilia ProphylaxisStudy, as well as an update from P. Hilliardand N. Zourikian, members of thephysiotherapy group, regarding theongoing refinement of an internationalphysiotherapy assessment tool. There was consensus among the CanadianHemophilia Physiotherapy Group to worktoward integrating the current Canadianassessment tool with the internationalguidelines. The ultimate goal is toincorporate findings from regularphysiotherapy clinic assessments into theCanadian Hemophilia AssessmentResource Management System (CHARMS),

in a nationally consistent manner. This willin turn provide access to important datafor research and clinical managementpurposes. For this reason, the groupreceived an orientation to the datagathering possibilities of CHARMS. Thegroup intends to investigate efficient andeffective methods of data collection, andplans to provide hands-on orientation toall clinic physiotherapists to ensureconsistency in assessment techniques anddata entry across the country.

Other topics of discussion included:review of the Physiotherapy ResourceBinder and other recently publishedresource materials; a proposed physio-therapy link from the CHS website;individual therapists’ experience with theWFH twinning program; and upcomingeducational opportunities, including theXXVI International Congress of the WorldFederation of Hemophilia, Bangkok,Thailand from October17-21, 2004.Members of the group had the opportunityto present challenging case studies forconsideration on Sunday morning. Thisprovided the opportunity for someextremely helpful exchanges of clinicalinformation.

Of course, physiotherapists do like toengage in physical activities. Saturdayevening, members of our group proved tobe leaders on the dance floor.

The group unanimously andappreciatively agreed to continue workingunder the leadership of K. Mulder, P.Hilliard, and N. Zourikian. There wasconsensus that these meetings areextremely important to furthering clinicalcompetence and expertise. Meeting inconjunction with the AHCDC andCANHC helps to foster an increased senseof collegiality and comprehensive care.The Physiotherapy Group intends to workdiligently to ensure that these meetingscontinue on an annual basis.

� DECENTRALIZATION OF BUDGETSFOR BLOOD AND BLOODPRODUCTS IN QUEBEC

A threat to the quality of careoffered to people with bleedingdisorders

François Laroche, Past-President,Quebec Chapter

O ver the past 12 months, the QuebecChapter (CHSQ) has been workingto find a solution to problems posed

by a Quebec Minister of Health and SocialServices (MSSSQ) plan to decentralizebudgets for blood and blood productsfrom the supplier, Héma-Québec, to the 99 hospitals in the province. The MSSSQ’sinitiative, which has been planned sincethe creation of Héma-Québec in 1998, isbeing closely watched by other provinces.It originates in recommendations 15 and16 of the Krever Inquiry on the bloodsupply in Canada, calling on the bloodservice to charge hospitals for bloodproducts, thereby encouraging morerational use. According to Krever, thiswould also lead to the establishment ofan independent relation between thegovernment and the national bloodservice, helping to reinforce the ability ofthe supplier to quickly introduce safetymeasures.

The CHSQ, however, considers thisproject a threat to the quality of care givento people with bleeding disorders. While itisn’t opposed to the transfer of budgets forfresh components (blood, red blood cells,platelets, plasma) from Héma-Québec tohospitals, the CHSQ is greatly concernedabout the transfer to regional hospitals ofbudgets for clotting factor concentrates.In reality, blood banks in these outlyinghospitals serve as mere drop-off points for the delivery of home care products.Physicians there have no expertise intreating bleeding disorders nor experiencewith these rare and valuable products, butwould nevertheless become accountablefor the concentrates prescribed byphysicians in Quebec’s four hemophiliatreatment centres. This would bring abouta confusing sharing of responsibilities(prescription vs. distribution and funding)that is undesirable. What’s more, thesystem favoured by the MSSSQ foresees

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 7

budgets based on consumption in theprevious year. If utilization surpasses thislevel, adjustments at the end of the yearare possible only if rational utilization can be demonstrated by the distributinghospitals. In the case of clotting factorconcentrates, such justification will beimpossible for those hospitals whichmerely act as depots. In our opinion,this is not a sensible and efficient way tomanage these products. After having sent‘virtual’ bills to hospitals for their use ofblood and blood products in 2003 and2004, Héma-Québec will implement thebilling system in April 2005, afterharmonizing computer programs withhospitals.

The CHSQ, with the support of thedirectors of the hemophilia treatmentcentres, proposes instead the creation ofan integrated hemostasis program thatwould unite the four existing treatmentcentres (which would become satellitecentres), in addition to the QuebecReference Centre for the Study of Patientswith Inhibitors. The recommendationsinclude:

Williams and the opposition critic forhealth, Ms. Louise Harel), this proposalwas not accepted. And this, despite the factthe Minister of Health, Philippe Couillard,during a meeting in January, admitted thatthe CHSQ case, notably concerning theneed to recognize the expertise existing inthe hemophilia treatment centres and toreinforce their mandate for theprescription of products and theirresponsibility to ensure adequatetraceability, made great sense.

The CHSQ is developing a strategy toshow that its proposed solution is best forpatients, does not create a precedent inthis field and that the system beingimplemented by the MSSSQ risksencountering serious problems.Discussions are ongoing with the principleactors involved. The National Assemblycommittees on the study of healthexpenditures, being held this spring, arebeing closely followed.

Supported by the CHS, the CHSQ isdevoted to doing everything possible toreach an adequate solution for allconcerned. It has no intention of giving up.

n e w s u p d a t e

Front row: Susan Anderson, Tom Alloway, Heather Carlson, Mylène D’Fana, Pam Wilton, Martin Kulczyk. Middle row: Bruce Ritchie MD, StéphaneBordeleau, CHS Executive Director, Roxanne Nadeau, Betty Anne Hines, Tony Niksic, Sheila Comerford, Christine Keilback, Clara Penner, Mike Beck.Back row: Eric Stolte, Craig Upshaw, Norman Locke, James Kreppner, John Plater, Brian Whitehead, Steven Bardini, Bob Steffens. Missing from photo:Normand Landry.

� CHS BOARD OF DIRECTORS 2004-2005

• That a medical director with expertisein hemostasis and the treatment ofpatients with coagulation inhibitors benamed as head of the program;

• That the budget for clotting factorconcentrates be associated with thehospital managing the program and thatthe latter have the mandate to ensure the proper distribution and inventorymanagement of products, as well as theirtracing in the case of a recall.

• That the necessary financial resourcesbe provided to the program to cover thecosts for the proper management ofclotting factor concentrates.

• That a special budget, distinct fromeach hospital budget, be affected to theprogram, in order to cover the costs ofhuman and physical resources necessaryfor the running of the satellite centres andthat this budget reflect the recent increasein clientele and services offered.

Unfortunately, following numerousmeetings and discussions with the MSSSQ,the Quebec Blood System Secretariat, thedirectors of hemophilia clinics andprovincial deputies (notably Mr. Russell

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 48 n e w s u p d a t e

Eric StolteChair, CHS National Awards Committee

As in any group of Olympic calibre athletes, certain ones stand out for theirextraordinary achievements and so it is with our people. CHS people tend to be“Olympic calibre”; that’s why I’ve always counted it a privilege to volunteer with the

CHS and a special honour to chair the awards committee this past year. At the November2003 Awards Banquet, the CHS recognized a group of dedicated volunteers, health careproviders and staff who had made a significant contribution to the bleeding disorderscommunity during the preceding year(s).

Chapter Recognition AwardsThis award is designed to recognize chapters who have demonstrated an achievementover the preceding year in a specific area such as fundraising, patient services, education,or chapter/regional development.• Ottawa and Eastern Ontario Chapter– for outstanding efforts in fundraising at the regional level.

Award of AppreciationThis award honours individuals who have demonstrated outstanding service to the careof persons with inherited bleeding disorders.• Maureen Brownlow, RSW, Social Worker, Halifax, Nova Scotia • Julia Sek, R.N., Past Nurse Coordinator, Hamilton, Ontario

Dr. Cecil Harris AwardThis award honours distinguished contributions in the areas of hemophilia-relatedresearch or the advancement of the care of patients with hemophilia or other inheritedbleeding disorders. It is named after the late Dr. Cecil Harris, in recognition of hiscontribution as one of the pioneers in the care and treatment of hemophiliacs in Canada.• Dr. Mohan Pai, Past Clinic Director, Hamilton, Ontario• Dr. Robert Card, Clinic Director, Saskatoon, Saskatchewan

Pierre Latreille AwardThis award for excellence is given to a staff member of the CHS working at either thenational, chapter or regional level who demonstrates outstanding qualities of devotionand support for volunteers and other staff members.• Robert St-Pierre, Past CHS Hepatitis C Program Coordinator

Frank Schnabel AwardThis award was initiated to honour the outstanding service of Frank Schnabel, thefounder of the Canadian Hemophilia Society. The award is presented in his name tohonour a volunteer who, over a number of years, has rendered distinguished services andnoteworthy contributions to the mission and objectives of the Canadian HemophiliaSociety.• Bill Mindell, North York, Ontario

Honorary Life Membership AwardThis award recognizes exceptional leadership and devotion to the CHS over many years.The award is given to an individual who has merited special recognition for continuingefforts, particularly at the CHS Board level, to further the growth and development of themission and objectives of the CHS and the development of public recognition of the CHSand its goals at the National and Chapter level.• Frank Bott, Etobicoke, Ontario

Maybe you know of more “hidden heroes” – people sacrificing their own time and energy for the greater good of improving the quality of life for ALL people with bleedingdisorders. If you do and would like to nominate them for an award, we’re requestingpeople forward nominations to CHS for 2003 by June 30th. The awards package isavailable on the CHS website at www.hemophilia.ca. We’re eager to read yournominations and honour a new group of volunteers this year.

MaureenBrownlow, left,receiving herAward ofAppreciationfrom CHS Past-President, ErmaChapman.

Dr. Robert Card,right, receivingthe Cecil HarrisAward from Eric Stolte at theSaskatchewanChapter AGM

Robert St-Pierre,left, receiving thePierre LatreilleAward fromCHS Vice-President,James Kreppner.

Frank Bott, left,receiving hisHonorary LifeMembershipAward fromCHS President,Tom Alloway.

Bill Mindell,right, receivingthe FrankSchnabel Awardfrom CHS Vice-President,John Plater.

� CHS 2003 AWARDS BANQUETCongratulationsTO ALL

AWARDRECIPIENTS

TO ALLAWARD

RECIPIENTS

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 9

MANITOBAGala Evening ofCulinary Inspirations

Stacey Westman, Gala Dinner CommitteeChairperson, Canadian Hemophilia Society,Manitoba Chapter

Hemophilia Manitoba’s “GalaEvening of Culinary Inspirations”was held on February 21, 2004 in

honour of Jim Love, Manitoba ChapterPresident, who passed away in September.Our energetic committee worked hard forsix months to plan a dinner that was unlikeany other Fundraising Dinner. What setours apart was that we had four ofWinnipeg’s top Executive Chefs eachprepare one of their specialties. Theevening began with samples of chocolatemartinis for all our guests; the elegancecontinued on throughout the evening. Themeal consisted of an appetizer, soup, mainentrée and dessert. We also secured fourwine distributor representatives who pairedwine/liqueurs for each course and offeredfree tastings to each of our dinner guests.Once the wine was sampled, it wasavailable for purchase by those who wishedto have more.

While each course was being served theExecutive Chefs took stage and wereinterviewed on their culinary secrets by ourspecial guest M.C., local celebrity, and radioand TV personality, Mr. Lee Major of 99.1Cool FM. The wine reps also took theirturn on stage educating us on the particularwine they had paired with each course.

Our goal for the evening was not onlythat everyone have an amazing meal, butalso that they feel they had just had an“Outstanding Culinary Experience.” Basedon the rave feedback we received, we weremore than successful in achieving our goals.We were also successful in raising over$12,000 for our chapter. We were able toachieve this by having an almost sold-outevent, generous sponsors, and by havingmost of the food donated by localcompanies and distributors. The Chefs andwine reps also donated their time. A silentauction sale added to the success of thenight as well.

Stacey Westman, Erma Chapman and daughter,Charlotte, at the Gala Evening of CulinaryInspirations held in honour of Jim Love.

Delta Winnipeg’s Executive Chef Jason Gower and Chef Kelly Andreastogether with guest MC, Mr. Lee Major of 99.1 CoolFM.

As the charity of choice, HemophiliaSaskatchewan was this year’srecipient of the proceeds of the HighVoltage Classic, organized annuallyby the engineering students at theUniversity of Saskatchewan. Over$22,000 was raised through pledgesfor a marathon of street hockeygames. Thanks to Sid Katzman forhelping to make this possible.

C h a p t e r S p o t l i g h t 9

CHAPTER

SASKATCHEWAN FUNDRAISER

The Gala Dinner really helped to raisepublic awareness about the ManitobaChapter of the Canadian HemophiliaSociety and presented a positive reflectionof the membership. The evening was asmashing success and we are looking forward to ensuring next year’s event isequally successful.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 410

The Reids at the Just the Guys Getawaynear Kitchener, Ontario.

C h a p t e r S p o t l i g h t

The second annual Just the Guys Getaway, formerly known as the Father and SonWeekend, was held October 24-26 at Camp Ki-Way-Y near Kitchener. The cloudyskies just wouldn’t break, and the rain came on and off all weekend long, but that

didn’t stop the 37 soggy participants from the Central Western Ontario Region (CWOR)and the South Western Ontario Region (SWOR) from having a great time. All of the guyshad a chance to try for a bulls eye during archery, swing like Tarzan on the low ropescourse, and balance across the beam that was strung high up in the trees. We builtbirdhouses, played board games, built shelters, carved pumpkins and even had a costumeparty. Fortunately, the rain stopped long enough each night for everyone to relax around thecampfire. The action-packed weekend also included two education sessions. Dr. Pai, PediatricHematologist from the Central West Hemophilia Program, spoke about current treatmentpractices and gene therapy research. Julia Sek and Lori Laudenbach, our Hemophilia Nursesfor the weekend, spoke about parenting practices and risk assessment of activities. Bothsessions were very interactive and informative. This joint event between CWOR and SWORwas made possible through the generous support of Bayer.

JUST THE GUYS GETAWAY JUST THE GUYS GETAWAY

CWOR and SWOR

Once again this spring, one hundredand eighty-five members of theQuebec Chapter attended our

annual family weekend and AGM at theCentre de Plein Aire Matawinie, about twohours north-east of Montreal. One workshopdealt with hemophilia through the ages, withthree hemophiliacs aged 21, 35 and 45 talkingabout their personal experiences with ableeding disorder as they grew up and astreatment changed. Parents had lots ofquestions and were impressed by the positiveattitudes of these men, despite their physicalproblems. Other workshops included the“Demystification of inhibitors” given by Dr. Jean St-Louis, “Dealing with fatigue fromhepatitis C” given by Dr. Bernard Willems, anart therapy workshop and a session that hasbecome a tradition: “A Coffee Klatch” whereboth newly diagnosed and experiencedparents share information and talk abouteveryday living with hemophilia in thefamily. The Infusion workshop, part of thePassport to Well-Being Program, was a

QUEBEC Chapter Annual Family Weekendchance for parents to learn and try infusionon themselves or on one another and toquestion older parents about their tips andtechniques. Saturday night was dance nightand almost everyone was up on the dancefloor. There was also a special news team withyoungsters from 8 to 13 years of age whoworked on a newsletter with photos andarticles about the weekend. This familyweekend is the one occasion when allmembers of the hemophilia community,both children and adults, meet and shareinformation and also have a good time.It’s a real family gathering.

CHAPTER

Patricia Stewartreceives the Quebec

ChapterVolunteer of the the

Year award fromFrançois Laroche,

President.

One of the weekend's many workshops.

Saturday: Dancing the night away.

The Society's young journalists.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 11F o c u s o n I n h i b i t o r s

In the wake of the National Inhibitor Weekend, entitled the Circle of Care Workshop, held last October at Mont-Gabriel, Quebec,Hemophilia Today thought it would be interesting to do a profile of

a program that is unique in the world: The Quebec Reference Centrefor the Treatment of Patients with Coagulation Inhibitors.

It is well known that the appearance of an inhibitor is a seriouscomplication in hemophilia. It requires even more specializedtreatment for a condition that already calls for specialists. Thoughrelatively rare, an inhibitor affects about 30% of hemophilia A patientsat some point in their lives. What’s more, about 10% of severehemophilia A and about 2% of severe hemophilia B patients arechronically affected. In factor IX deficiency, however, the diagnosis ofan inhibitor is more serious, at times even leading to an allergicreaction and anaphylactic shock, and is even more difficult to treat. Itis estimated that of the 850 Canadians with severe hemophilia A, 80are affected by a persistent, that is, chronic inhibitor, of whom 20 livein Quebec.

The coagulation factor inhibitor can also occur in people who don’t have a hereditary coagulation problem. This is called acquiredhemophilia, an extremely rare autoimmune disease (1 case in 1 millionpeople per year, about 7 per year in Quebec and 30 in Canada) thatmainly affects the elderly. Acquired hemophilia is particularly harmfulsince is it usually detected when the crisis is at its peak (life-threatening) in a person who knows nothing about his condition andwho has never managed bleeds in the past. It is associated with a fairlyhigh mortality rate (20%).

The creation of the programIn March of 2000, in order to offer proper care to people with

inhibitors, the Quebec Health and Social Services Ministry (MSSSQ)created the Quebec Reference Centre for the Treatment of Patientswith Coagulation Inhibitors in Montreal. The purpose of designatingthis ultraspecialized centre to care for a serious, complex and expensivecondition was to improve the treatment and quality of services for thisclientele through the development and maintenance of state-of-the-artexpertise and to optimize the use of resources.

For one of the co-directors of the program, Dr. Georges-EtienneRivard, this meant the realization of a long-held dream. “The treatmentof people with this condition had to be centralized in order to offerthem proper care. At times, it annoyed me to hear some of mycolleagues’ anecdotes when they asked my advice. They talked about a‘special case’ instead of the people affected by this problem who weregoing through a hard time. Dr. Jean St-Louis and I had been thinkingabout it for a while. The meetings of the Gélineau Committee on thesupply, management and distribution of blood in Quebec gave us thechance to present the idea of a single centre for the treatment of thiscondition. The Committee even included this recommendation in itspreliminary report. The MSSSQ then asked us to present a documentspecifically dealing with the centre’s operation. Ste-Justine officiallyreceived the designation on March 23, 2000.”

The principal playersBecause Ste-Justine Hospital is a pediatric centre, Dr. Rivard sees

only the children. Sacré-Cœur Hospital, its affiliated centre, receivedjoint designation to treat adults under the supervision of the secondco-director, Dr. Jean St-Louis. Today, adults are seen by Dr. St-Louis atMaisonneuve-Rosemount Hospital. But in reality, the treatment of

patients is not done in isolation. The twodoctors consult each other frequently to discussa particular situation. What’s more, a strongworking relationship exists between the twomen. “We make a good team. This is the key tosuccess when problems with inhibitors occurand require special expertise. But the linchpinof our team, without a doubt, is Sylvie Lacroix,the nurse coordinator for the program,who manages it all,” says Dr. St-Louis. Dr. Rivard feels the same.“We give a lot of credit to Sylvie for the success of this program.She’s an exceptional person as well as a great nurse. Very independent,she quickly understands what’s at stake when a situation arises. She’svery dedicated to the cause and is always available.”

ServicesLet’s talk about availability. Among the services offered by the

Centre, besides consultations, is a 24-hour-a-day, 7-day-a-weektelephone line. If no one answers immediately, one leaves a messageand is called back within ten minutes in the case of an emergency.Most of the time it is Sylvie Lacroix who takes care of this, bringingher pager with her wherever she goes. But the physicians are alsoinvolved. Dr. Rivard, along with his pager, carries both a NorthAmerican and an International telephone. If you can’t reach him,it’s probably because his batteries are dead! He often does telephoneconsultations and answers calls from all over Quebec, Canada, andfrom around the world. He mentioned the case of an adult with mildhemophilia and an inhibitor referred by Dr. Man Chiu Poon fromCalgary. “This was a hemophiliac who was bleeding in his tongue andhis larynx. He was intubated for intensive care with the smallest tubepossible to allow him to breathe. He needed a plasmapheresistreatment with immuno-absorption to remove the coagulation factorantibodies present in his blood. But, there are only three machines ofthis kind in Canada: one in Vancouver, one in Toronto and another atSte-Justine. We transferred the patient from Calgary to Montreal. Notonly did he survive, but he responded well to treatment and nowleads a normal life. It’s at times like these that you feel greatsatisfaction… and we tell ourselves that transfers like this can happenanywhere in Quebec!”

This machine has saved more than one life. Dr. Rivard also told the story of the 8- or 9-month-old baby with a factor IX inhibitorsuffering from a central nervous system hemorrhage who had anallergic reaction, and that of a child with FXIII inhibitors. “Thesepeople mustn’t go through Emergency. As soon as a problem arises,and if the child can get to the hospital, Sylvie, Jean or I go to meetthem. Of course, this means that we have to be available at all times,because this condition often requires immediate care. Sometimes wedo consultations from home and even, on one occasion, whiledriving!” adds Dr. Rivard, passionate about this topic.

Fortunately, such situations are exceptional. In general, in the caseof a person with a congenital coagulation factor deficit, as soon as hedevelops an inhibitor, he is systematically referred to the InhibitorCentre by his treatment centre. Patients with acquired hemophilia arereferred by Héma-Québec, the organization responsible for the supplyof blood products. “In the case of acquired hemophilia, you have togive credit to Héma-Québec, especially to its CEO, Dr. Francine

Dr. Jean St-Louis

PROFILE

The Quebec Reference Centre for the Treatment of Patients with Coagulation Inhibitors

by François Laroche

continued on p13

Table 2: The Malmö protocolTREATMENT TIME

Extracorporal immunoabsorption Day 1 and day 2

Cyclophosphamide 12-15 mg/kg I.V. Day 1 and day 2

Cyclophosphamide 2-3 mg/kg po Day 3 for eight to ten daysOnce a day

FVIII to obtain a 40 to 100% FVIII level, Day 3 and thereafter until the then FVIII administered every eight to inhibitor is no longer detectabletwelve hours to maintain a FVIII level of 30 to 80%

IVIG 0.4 g/kg/day Days 4 – 8

FVIII 30 u/kg/day two or three days/week Once the inhibitor is undetectable

A three-phase treatment (Table 3) has been used with eleven children (median age of two years) with severe hemophilia and hightitre inhibitors. These are the results:

• the average durations of the first and second phases are six andfourteen weeks respectively; phase two is initiated when theinhibitor is undetectable (with Bethesda measurement);• phase three is then initiated when the half-life of the FVIII ismeasured at more than five or six hours;• finally, in phase three, prophylaxis is resumed.

Table 3: Three-phase treatmentPHASE TREATMENT

1 FVIII 200 u/kg/day

2 FVIII 100 u/kg/day when the inhibitor level is less than one Bethesda unit

3 FVIII 50 u/kg in prophylaxis until the inhibitor is eliminated and thehalf-life of the FVIII is five to six hours

A protocol using low doses of concentrate was used by theVan Creveld clinic in Holland and recommended the adminis-tration of low doses of concentrate: 25 u/kg on alternate days,reduced to 10-15 u/kg three times a week when FVIII recoverymeasured 30%. The success rate reported using this method is87% of the group of patients treated, but 100% in subjects withan inhibitor level under 40 Bethesda units, compared to 75% inpatients with an inhibitor level over 40 Bethesda units. An aver-age of twelve months is reported to obtain tolerance. The lengthof treatment is directly proportional to the maximum inhibitorlevel and inversely proportional to the age when the inhibitordeveloped.

Finally, as mentioned at the beginning of this text, treatersadjust the protocols described according to their practice and tothe specific needs of their clientele. Since 1993, the NorthAmerican Immune Tolerance Registry collates data from 168hemophilia treatment centres in North America. Approximately50% of the centres use 100-200 u/kg/day of FVIII to induceimmune tolerance. In general, the duration of the treatment isshorter when higher doses of concentrate are used. The highestrates of success are found in patients with a maximum inhibitortitre of less than 50 Bethesda units.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 412 F o c u s o n I n h i b i t o r s

• Is immune tolerance a new approach in the treatmentof inhibitors?No, it’s not a new approach. In 1974, Brackman and Gromsen

discovered and described the phenomena of immune tolerance. Allthese protocols are intended to eliminate the inhibitor and, ideally,restore the normal FVIII recovery kinetics.

• Are all protocols similar? No, there are some differences among the various protocols.

The goal is always the same, but the ‘recipe’ changes. Certainprotocols use a combination of immunosuppressant drugs (drugsthat try to slow or lessen the system’s immune response) such as,for example, cyclophosphamide and prednisone. Others useimmunomodulators (that modulate/modify the immune system)such as extracorporal immunoabsorption. These drugs/treatmentscause certain secondary effects that must be explained anddiscussed with each person to be treated, making sure to carefullyweigh the advantages and inconveniences of each. What’s more,the addition of immunoglobulin that causes an immuno-modulator effect through an anti-idotypical mechanism(antibody) has been reported.

• What are the most frequently used protocols?There are a number of individual recipes or specific

adjustments adapted to each patient’s condition, but the greatestsources of inspiration can be resumed as follows.

First of all, in the Bonn protocol (study by Brackman et al.),high doses of FVIII are used in order to induce immune tolerance(Table 1). A résumé of the results obtained with this protocolshows that in 22 patients with high response inhibitors, the averageduration of treatment to obtain an inhibitor of less than oneBethesda unit is seven months with normal FVIII kinetic recovery,an average of fifteen months being required to complete theprocedure.

Table 1: The Bonn protocolTREATMENT

FVIII 100-150 u/kg twice a day until the inhibitor is no longerdetectable and the FVIII recovery and half-life are normal; theseresults must be measured three times over a six- to eight-week period.

A 10% reduction in the FVIII dosage every two to four weeks.

Final tolerance evaluation: after a two- or three-day period withouttreatment, recovery and half-life are maintained with prophylactic oron-demand treatment.

The Malmö protocol, initially described in 1988, consists of inject-ing high doses of immunoglobulin used as immunomodulatorsand immunosuppressors (Table 2). Up to 1996, 20 pediatric andadult patients had received this treatment. The success rate report-ed was 80%. The average duration of the treatment is 28 days, therapid response being attributed to the lowering of the productionof inhibitors in response to the presence of high levels of FVIII orFIX in this treatment.

Immune tolerance,an historical overview

Sylvie Lacroix, R.N., Georges-Etienne Rivard, M.D.,Quebec Reference Centre for the Treatment of Patients with Inhibitors

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 13F o c u s o n I n h i b i t o r s

the other hand, in certain cases, if the inhibitor titer (the proportionit occupies in the blood calculated in Bethesda units) isn’t too high, itcan be annihilated with immune tolerance techniques. “Massive dosesof FVIII are given to the child in order to accustom his immunesystem to it. The antibodies are overwhelmed and can no longerneutralize the coagulation factor. The chances of this techniqueworking are better if the inhibitor has been present for less than oneyear and if the titer is lowered to between 5 and 10 Bethesda units atthe start of treatment,” adds Dr. St-Louis.

“The main difficulty with immune tolerance resides in venousaccess,” adds Sylvie. “This treatment calls for injections at least threetimes a week and, often, every day. More often than not, a central linehas to be installed, a PICC-line (Peripheric Intraveinous CentralCatheter) and this, despite the possibility of infection. I’m alwaysimpressed, however, by the attitude of the children and their parents,their perseverance, their strength. The treatment of hemophilia withinhibitors requires frequent trips to the hospital and a very particulartreatment regimen for parents. We ask for a great deal of involvementbecause the treatment necessitates so much time and good adherence.”

“As for acquired hemophilia,” according to Dr. St-Louis, “whenpatients with this condition consult us, they’re often very ill, to thepoint that their lives are in danger. But, at the same time, it seems thatit’s easier to eliminate their inhibitor. Immune tolerance treatment isvery effective for people dealing with acquired hemophilia. Massivedoses of cortisone or cyclophosphamide are administered to patientsand most of the time they manage to get rid of their inhibitor.”

PredispositionThere’s still a lot of work to do to identify what causes a coagulationfactor inhibitor. “As far as acquired hemophilia is concerned, it’s justabout impossible to foresee the occurrence of an inhibitor. We have toconcentrate our research in order to find out how bleeding occurs inthese patients. What we know is that they bleed differently fromclassic hemophiliacs,” says Dr. St-Louis. For Dr. Rivard, the factorsthat seem to influence the appearance of an inhibitor in ahemophiliac are race, the severity of the factor, other hereditaryparameters, the time when replacement factor is introduced, breast-feeding, vaccination, and more. “We have to get a betterunderstanding of the the molecular genetics of people with inhibitorsin order to to better foresee the prevalence of this condition,” he adds.

Future perspectivesWhat challenges does the future offer? Dr. St-Louis feels that we haveto be able to better identify patients who are at greater risk ofdeveloping an inhibitor in order to prevent its appearance. Treatmentand techniques will also improve with time, according to him. Thisopinion is shared by Dr. Rivard, for whom the prevention of thiscondition is essential. “We have to know more about the biologicalenvironment of this condition to better counteract it. One of theindications we have is the time when replacement factor isintroduced. Perhaps treating with rFVIIa during the first years so as todelay exposure to FVIII, or treating with a product containing a largequantity of von Willebrand factor are possible roads to a solution, butthis remains to be seen. But the limited number of cases complicatesresearch in this field. In order to study 100 people, almost all thepeople affected in North America have to be included!” he concludes.

As for Sylvie, her dream is for every patient she treats to have acomputer equipped with a webcam, and a laptop for her. “That way, Icould get a good idea of their condition in real-time on my computerand I would be able to act more rapidly and more efficiently inrelation to the symptoms that I see on the screen.” Reality or fiction?The message is out there, only time will tell if there’s an answer…

Thanks to Sylvie Lacroix and to Drs. Georges-Etienne Rivard and JeanSt-Louis for their availability and their medical review of this article.

• What about patients with a FIX inhibitor?Some hemophilia patients with a FIX inhibitor are successful

in obtaining immune tolerance using protocols like those men-tioned above; however, experience in this field is more limited.Complications related to a nephrotic syndrome are mentioned,but allergic reactions are reported more frequently.

• Anything to add?In conclusion, one could say that for over twenty-five years

immune tolerance has been recognized as a treatment to eradicateinhibitors in people with hemophilia. A lot of questions remainunanswered. Many approaches are effective; however, the perfectimmune tolerance program is yet to be defined. Researchers haveinitiated an international research protocol in this field with thisin mind. It is imperative that data from a large group of patientsbe collated in order to come to pertinent conclusions that mayhelp to determine the best mode of intervention. Inhibitors arerare, but their impact is very serious with major repercussions forpatients and their families.

During the inhibitor family weekend organized by theCanadian Hemophilia Society, the great generosity of these fami-lies in regards to their participation in research could be seen.Everyone present recognized its importance and demonstratedtheir desire to contribute to the advancement of science. Thisaltruistic attitude is worthy of mention.

Décary, who immediately understood the necessity to act quickly inthese situations,” says Dr. Rivard. “As soon as Héma-Québec receives arequest, it refers the call to us and we can immediately talk to thehematologist who saw the patient. If possible, the patient istransferred to Maisonneuve-Rosemont. This means there’s no delay,no inadequate treatment and no product is wasted.”

The diagnosis of inhibitors is done on a regular basis; children aretested twice a year, while tests on older hemophiliacs are done once ayear. The Inhibitor Centre then designs a treatment plan that can befollowed up by the person’s own Hemophilia Treatment Centre(HTC). A check-up is done at least once a year and a report is alwayssent to the HTC. Along with the two doctors and the nursecoordinator, the program includes a lab technician specialized in thisfield and, as consultants, a physiotherapist, whose time is divided withthe HTC, a social worker and a psychologist. The nurse coordinatorhas her own office. As for the others, the Centre shares space with theSte-Justine HTC.

The Inhibitor Centre produces a quarterly bulletin, L’Idée fixe, thatis distributed by mail to all patients and all hemophilia treatmentcentres in Quebec and Canada. Sylvie Lacroix is responsible forgathering the information and experiences of interest that appear inthis periodical. For more details about this publication, you cancommunicate with the Quebec Reference Centre for the Treatment ofPatients with Inhibitors at 514-345-2360 or by e-mail atsylvie_lacroix@ssss.gouv.qc.ca.

TreatmentTreatment for hemophilia with inhibitors can be very demanding.

“Products available to treat this condition are substitutes for FVIII:FEIBA, porcine FVIII and recombinant FVIIa. In the case of rFVIIa,this is an effective product, but expensive, and must be used with caresince it carries the risk of thrombosis,” according to Dr. Rivard. On

The Quebec Reference Centre continued from p11

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 414

THE CULLEN FAMILY AT THE CIRCLE OF CARE WORKSHOP

We were so excited when we heard we wereaccepted to go to Montreal. The trip wasto be a real adventure as my husband

and boys had never flown. Grandma was alllined up to look after the baby.

Our son Randy has hemophilia A with aninhibitor so a weekend completely focused on

inhibitors was wonderful. We went to Montreala day early so we could meet with Dr. Rivard and his

team at the Sainte-Justine Hospital.Stacy and I were very surprised and pleased to

hear Randy didn’t need a port for us to startimmune tolerance. Dr. Rivard said Randywould be a good candidate for immunetolerance. We were excited; now we hadsomething to hope for in the area of Randy’smedical treatment.

During the weekend, we learned so muchabout how inhibitor treatment (immune

tolerance) works – past, present and future.We also learned how inhibitors develop. There

were nurses and physiotherapists speaking ontreatment. It was wonderful! Randy enjoyed the Tai

Chi and his brother Gene made friends. Stacy and Ireally appreciated the fact that there is support from other

families going through similar problems.We are now well into home infusion doing the immune toler-

ance program. We still have a way to go as far as how and when todo blood tests for inhibitors. Communication is getting much bet-ter. The Montreal weekend was a real boost in getting us started. Weare very grateful for having had the privilege to be chosen to attend.

Kim and Stacy CullenRegina, Saskatchewan

Ihave been involved in our community for alittle over ten years and I can rememberwhen there were very few opportunities

for families to get together and offer the spe-cial support and kinship that we call ourown. It thrills me to take note of theincreasing number of events planned andmade available to individuals and familiesacross the country. Families of childrenwith inhibitors gathered last fall to share,learn, support and have fun with eachother. Circle of Care, the second CHSNational Inhibitor Family Weekend, tookplace in Montreal on October 24-26, 2003.The workshop was again made possible thanksto an educational grant from Novo Nordisk.It was a huge success.

Twenty-two families came from across Canada to par-ticipate in this program. The hardships and isolation felt by familiescoping with inhibitors were eased for all through family camaraderie,presentations, discussions and learning opportunities. Providing fam-ilies, especially the children, with the opportunity to connect, toshare, to unburden, to recharge and to hope, continues to be thedriving force behind our ability to support each other. This year fam-ilies from outside of Quebec were given the unique opportunity fortheir children to have a consultation with Dr. Georges Rivard,Medical Director of the Quebec Reference Centre for the Study ofPatients with Inhibitors. This weekend also enabled families withinhibitors to meet and discuss currenttreatment options and future trendswith health care providers fromHemophilia Treatment Centres whohave developed expertise in this area.Especially for families who do nothave regular access to a large team ofhemophilia experts, this opportunitywas invaluable.

Families left with the sense theycould handle their challenges.Children and parents exchangedemail addresses and some even wenthome to try new protocols such ashome infusion. Attendees were reju-venated—perhaps a little emotionallydrained, but definitely betterinformed—and emotionallyrecharged. The stories below describethe impact the weekend had on twoof the families who attended. Onceagain the power of families in touchhas helped all who participated!

As always, keep in touchand be safe.

D

k

M

-

z

w

Karen Creighton

families inTOUCHCIRCLE OF CARE WORKSHOP2nd CHS National Inhibitor Family Weekend

My name is Josh McCormack. I am 12 years old and I live in Carlisle,Ontario. I have hemophilia B and an inhibitor. Having hemophilia is alot of work, and it can be very painful. On the other hand, there are

some benefits, such as the chance to spend a wonderful weekend at Mont-Gabriel where the CHS organized a weekend for families with inhibitors. I hadalready attended one three years earlier and I was excited about seeing myfriends again.

We drove from Carlisle to Quebec. On Friday, I had an appointment with Dr. Rivard and histeam at the inhibitor centre, and I think he felt I was doing pretty well. In the evening we met allthe families who were participating. It was great to see my friends, Tony and John. It was like wehad never been apart.

The organizers planned a complete day of activities for us while our parents were busylearning more about inhibitors. I really liked the Saturday evening dance. I noticed that even ifmany of the kids had hemophilia and an inhibitor, it didn’t stop them from having a good time…even at the risk of hurting their knees. We were all happy and able to have fun.

I consider myself lucky that my family and I were invited to participate in this family weekend.I realized that I wasn’t alone with my inhibitor. Others have to face the same pain and the samechallenges. I think knowing that helps a lot.

Josh’s testimonial first appeared in L’idée fixe, le journal des inhibiteurs, published by the QuebecReference Centre for the Treatment of Patients with Inhibitors, now also available in English. Thosewishing to subscribe may do so by calling Sylvie Lacroix at 514-345-2360 or by writing to her atsylvie_lacroix@ssss.gouv.qc.ca.

F o c u s o n I n h i b i t o r s

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 15

The 16-page booklet is divided into tensections. The first seven deal with liverfunction, a description of hepatitis, thenatural history of infection, commonsymptoms, other organs affected by HCV,cirrhosis and end-state liver disease, andcommon side effects of hepatitis Ctreatment. The final sections of the bookletoutline financial options, tips on findinghelpful health information, and communityand government contacts.

The booklet provides information oncommon symptoms of HCV, includingdepression, and lack of energy. Some peoplefind that they can’t focus, their memory isunreliable, and they have difficulty seeing atask through from beginning to end. TheCHS hopes that the booklet will be a usefultool when applying for sickness benefits.

People who are on HCV medicationmay experience a range of side effects.Some people may experience mildersymptoms, while others may become

Faye Katzman

In March 2004, the CanadianHemophilia Society, with funding fromHealth Canada, published a new

educational resource entitled Hepatitis C:Common Disabling Symptoms andTreatment Side Effects. Jeff Rice,Coordinator of Regional Resources andHepatitis C Programs with the CHS,coordinated the project. Both HTML andPDF versions are available on the CHSwebsite at www.hemophilia.ca.

In plain language, this bilingualpamphlet addresses the range of symptomsthat someone infected with HCV mightexperience. The booklet also describes thecontinuum of side-effects—from mild tosevere—that someone on hepatitis Cmedication could encounter. It is intendednot only for people infected and theirfamilies, but also for health care providers,employers and insurers.

New treatmentson the horizonSuzanne Champoux

There is no perfect treatment forhepatitis C; thus research is ongoing.While there’s no revolution on the

horizon, interesting molecules are beingstudied in humans.

The first molecule that could bemarketed is on which modulates theimmune system, thymosine, by theSiClone company (Zadaxin®). Two PhaseIII studies including a total of 1000participants are ongoing in the UnitedStates. Subjects randomly receive acombination peginterferon plusthymosine or peginterferon plus a placebofor one year. Results should be available atthe end of 2005.

Viramidine®, manufactured by ValeantPharmaceuticals, has recently started phaseII studies. The goal here is to replaceribavirin. This requires what is called aprodrug, a molecule that has to betransformed in the body to become anactive drug. Viramidine® is a ribavirinprodrug that offers the advantage of beingspecifically transformed by the liver cellswhich should diminish the normal toxicityof ribavirin on blood cells. The two phase

HEPATITIS C:COMMON DISABLING SYMPTOMSAND TREATMENT SIDE EFFECTS

totally—even if temporarily—disabled.Some people on treatment may have tostop working. Knowing what to expect interms of symptoms may help people tocope better.

The booklet also aims to help people bebetter informed so they can explore theirfinancial options, both public and private,including Human Resources DevelopmentCanada (HRDC), employment insurance(EI), Canada Pension Plan (CPP) andQuebec Pension Plan (QPP), disabilitypensions and provincial-territorial socialassistance.

Employee benefit packages, uniondisability plans and private insurancebenefits might also be available to somepeople who are HCV positive. The bookletgives tips on how to apply for benefits anddescribes various plans which may help payfor the cost of treatment.

To request a copy of this booklet or tohave more information on other hepatitis C initiatives, call Jeff Rice at 1-800-668-2686or write to him at jrice@hemophilia.ca .

New booklet on symptoms of hepatitis C

F o c u s o n h e p a t i t i s C

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 416

States. The molecule is offered to 40patients who already failed the firstpeginterferon and ribavirintreatment.

The Human Genome Sciencesfirm has used a technology that itdeveloped, albumin fusion, a bloodprotein that has a 20-day lifespan, inorder to increase the activity time ofinterferon. Studies show that thehalf-life of Albuferon® is 145 hours,that is, 6 days, compared to 40 to 80hours for peginterferon. (The half-life isthe time it takes for the concentration ofthe drug in the blood to be halved).

Vertex, on the other hand, is looking todevelop a drug that will inhibit an enzymein the body that the virus needs to multiplycells. Merimepodib® (VX-497) is aninosine monophosphate dehydrogenaseinhibitor (IMPDH). Behind thisintimidating name lies a mechanismsimilar to that of ribavirin; thus it works insynergy with the latter. First results inphase two studies in the United States on85 subjects show that after 24 weeks oftreatment, the addition of Merimepodib®has increased the response to treatmentfrom 33% (peginterferon + ribavirin +placebo) to 86% (peginterferon + ribavirin+ Merimepodib®). It remains to be seen ifthe virus reappears or not after treatmentis stopped. Vertex hopes to be able to starta phase III study in 2004.

Researchers have shown an interest inadding epöetine alfa, a molecule similar toEPO used illegally in the cycling world, totreat anemia associated with ribavirin. Thestudy carried out with 186 patients whodeveloped anemia under treatment withthe association of interferon and ribavirinshowed that EPO allowed these patients to

III studies will each include 1000 patients.Viramidine® will be compared to ribavirinin association with peginterferon.

Another molecule that is generatingsome hope is BILN 2061 from theGerman company Boehringer Ingelheim.This is a protease inhibitor, an enzymeessential to the multiplication of theHCV. The inhibition of the enzymeessential for replication of the virus is thebasis of the success reported fortreatment of HIV. This first HCVprotease inhibitor was discovered inCanada, at the Boehringer Ingelheimresearch and development centre locatedin Laval, Quebec. However, BILN 2061 isonly at the beginning of its road throughthe numerous clinical trial paths. It hasonly been tested on about twenty patientswho received it for two days.

For its part, the Isis Company isinterested in a very different approach.This involves the use of anti-sens, thisbeing a tiny piece of genetic material,which would stick to the genetic code ofthe virus to neutralize it. The Isis anti-senscarries the code name ISIS 14803. A phaseII study is being developed in the United

get higher doses of ribavirin whilemaintaining a good level of red blood cells.

For those who have heard aboutresearch with amantadine, an antiviral witha certain efficacy against the flu, anAmerican study carried out on 171 patientsreported no difference between those whoreceived amantadine with interferon andribavirin and those who received a placebo.

To keep up to date, the HIV andHepatitis website at this address:www.hivandhepatitis.com/index.html isyour best choice. In the hepatitis C-section, under ‘New stories’, there is awealth of choice.

A drug doesn’t arrive by chance on thepharmacy’s shelves. It is subject to a severeselection process. 5000 different moleculesin pre-clinical trials are tested (on cellcultures or on animals) in order to get 5that will be tested on humans. Of these 5molecules, only one will go through thethree clinical trial phases (phase I, II andIII) and be approved for marketing. Adrug that has already been sold may beremoved from the shelves because of aserious secondary effect, unknown untilthen, which has made its administrationtoo risky.

This article was originally published in thewinter issue of L’Echo du facteur, newsletterof the Quebec Chapter of the CHS.

Illusrations from Hepatitis C Common Disabling Symptoms and Treatment Side Effects by Darcia Labrosse

Colleen Barrett and Norman Locke, both of theNewfoundland and Labrador Chapter, and FayeKatzman of Hemophilia Saskatchewan, at the 2ndCanadian Hepatitis C Conference in Vancouver.

F o c u s o n h e p a t i t i s C

LIVER

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 17

PAIN - THE FIFTH VITAL SIGN

As people with bleeding disorders try to establisha range of strategies todeal with acute and/orchronic pain, they maybe reluctant to considerpain medication due toconcerns about sideeffects, the potential ofaddiction, possiblenegative interactionswith other medicationsor previous experienceswith using painmedication that “didn’twork”. The informationthat Dr. Peter Leungpresents in this article,the third in HemophiliaToday’s series on painmanagement, addressesthese topics, and willadd to people’s ability tocommunicate with theirphysicians withconfidence.Maureen Brownlow, Co-chair,CHS Pain Management Working Group

Peter Leung, M.D. Pain Management Service,St. Michael’s Hospital, Toronto

There are many useful medications forcontrolling pain. The type and route ofadministration must be tailored to the patient.Most importantly, the underlying problem mustbe managed by knowledgeable health careworkers.

What types of pain are experienced byhemophilia patients?Pain is usually of two types:Acute pain - due to bleeding, surgery ortrauma Chronic pain - due to damaged tissuesand/or altered brain and spinal cordfunctions.

The pain of acute bleeds is due to thebody’s perception of unpleasant stimuli onnerve endings. Ongoing chronic pain can beassociated with either joint degeneration orother hemophilia-related complications.

What are the treatment options for acutepain due to bleeds and/or surgery?

Most patients with acute pain can obtainrelief with the careful use of common drugssuch as acetaminophen (Tylenol®) or non-steroidal anti-inflammatory drugs (NSAID).The new COX-2 inhibitors (Celebrex®,Vioxx®) have less effect on platelet functionthan ibuprofen, which was often used forpatients as the NSAID of choice. Theaddition of opioids (see following list) canincrease the control of severe pain, dependingon the individual patient.

If oral medication is ineffective,intravenous (IV) therapy is an option.Opioids can be given by IV bolus, or bycontinuous administration for even morecontrol.

One option is the use of patient-controlledanalgesia (PCA). This is a form of computer-assisted self-administration of IV opioid painmedication. It is commonly called a “pump”. Itcan be used for acute bleeds or for post-operative pain control. The patient can press abutton for delivery of doses, limited by thecomputer to a safe level.

The drug doses can be adjusted on anindividual basis and the patient plays a role indetermining the effectiveness of treatment. APCA can be used with children as young asseven years.

Once pain is controlled, the IV opioidscan be stopped and the patient switched tooral medication.

Most hospitals provide PCA service and

have information pamphlets and even videosto help the patient learn to use the PCAeffectively.

There may be a tendency to minimize theseverity of acute pain and the benefits to thepatient of adequate acute pain relief. Somehealth care workers overestimate the risk ofthe stronger pain medications, even in thepost-operative period.

What are the treatment options for chronicpain?

The ideal chronic pain medication wouldbe predictable, easy to use, fast acting,effective with no side effects and no risk oftolerance.

Medications may be given by mouth orIV. The duration of the pain relief is variable.Physicians and patients must choose theindividual drug wisely, as well as the routeand the timing of administration.

What are the different medications?The following is a brief summary of some

of the available options in hemophilia useand is not exhaustive or to be treated asrecommendations.

NON-OPIOIDS

Celecoxib (Celebrex®)– Given by mouth

Rofecoxib (Vioxx®)– Given by mouth

Acetaminophen (Tylenol®)– Given by mouth

These are generally safe in normal doses forhemophilia patients.

OPIOIDS

The following is provided only as a roughguide in hemophilia use.

Codeine– Available as a single dose or combined with

acetaminophen and caffeine(Tylenol®#1,2,3)

– Can be prescribed in slow-release form(Codeine-contin®)

– Usually given by mouth– Ceiling effect, that is, there is no increase in

effect after the maximal dose is reached – InexpensiveMorphine – Can be prescribed in short-acting or slow-

release forms (MS-contin®)

M e d i c a l N E W S

Effective use of opioid and non-opioid analgesicMEDICALNEWS

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 418

Addiction is not the same as tolerance.When people use opioid pain medication,their bodies become accustomed to the dose.One may need to increase the amount to getthe desired effect. Changing to a differentmedication can sometimes avoid the increase.

Poorly treated pain is detrimental topatients. Poor pain management producesabnormal pain behaviour and may even causepatients to seek out street drugs because theyare afraid of not being able to manage severepain.

What are adjuvant medications? Why arethey useful?

Adjuvant analgesics are a diverse group ofdrugs used to enhance pain control in specificcircumstances. They do sometimes reducepain levels by themselves but often are bestused in combination with pain killers.

What adjuvant medications can be used?

Anti-depressants

Amitriptylline (Elavil®)Nortrytilline (Aventyl®)Fluoxetine (Prozac®)

Anti-convulsants

Carbamazepine (Tegretol®)Phenytoin (Dilantin®)Valproic Acid (Depakote®)Clonazepam (Rivotril®)Gabapentin (Neurontin®)Pregabalin

The rational use of pain medications canbe based on the World HealthOrganization Analgesic Ladder.

Pain levels change. What adjustments can bemade for good days and bad days?

While slow-release forms are ideal formanaging day-to-day pain levels, mostdoctors will allow a certain amount ofshorter-acting breakthrough medications for

bad days and for acute bleeds. If thebreakthrough medications are being used too frequently, the doctor will re-assess thesituation, look for a cause and adjust themedication.

Does marijuana work for pain?Marijuana is probably better to reduce

nausea, improve appetite and promotesleeping. Its use must be individualized.For most patients it is not the magic drug.Legal access to marijuana is difficult.

Are there things to remember whentraveling?

When the patient is traveling, the doctorcan provide a specific letter detailing themedications and the amount needed. He/shemay even set out a suggested plan ofmedication for mild and severe bleeds. Thiswill help the doctor in another city managethe pain according to what the patient usuallyneeds, and avoid too much or too littlemedication. It will also provide evidence atborders that a person is authorized to carrythese medications.

Always keep the medication in theoriginal bottle so that there is no doubt as tothe kind of medication being carried. Do notmix different pills (blue, yellow, big, small,round, cylindrical…) into one bottle. Thiscan cause confusion and mistakes.

Why are some doctors reluctant to givestronger pain medicine?

There are many different answers to thisquestion. Some doctors do not have muchexperience treating pain. Others areconcerned about the professionalconsequences. Unfortunately, one of thebarriers to effective pain management is that

the governing body of doctors stillfrowns on the prescription of strongpain medicine, especially opioids.

There is also a lot of discussion asto whether doctors can ethicallyrefuse to prescribe effective opioidmedication for pain. If this happens,ask the doctor for a referral to a painclinic. Or try to find another doctorwho works well with the patient tomanage his pain. Good painmanagement does not always mean alot of medicine.

In conclusion, it is important toremember that there are many useful

medications for controlling pain. In all cases,the type of analgesic and the route ofadministration must be tailored to theindividual patient. What’s more, theunderlying health problem must be managedby knowledgeable health care workers.

– Can be given by mouth, subcutaneously(injected under the skin) or intravenously

– Special circumstances allow it to be givenclose to the spinal cord

– Inexpensive

OxycodonePercocet ® or Oxycocet® (Combination with acetaminophen)– Can be prescribed in slow-release form (Oxy-contin)– Inexpensive

HydromorphoneDilaudid®– Can be given by mouth, subcutaneously or

intravenously– Can be prescribed in slow-release form

(Hydromorph-contin)

Fentanyl– Very potent– Very short acting– 3-day Patch (Duragesic®) or lollipop form

for children– Expensive

PropoxypheneDarvon®– Not frequently used

PentazocineTalwin®– Not frequently usedCaution: may have an opposite effect if addedto other opioids

What are the common side effects of allopioids?– Nausea and vomiting– Sleepiness– Constipation– Itchiness– Tolerance– Respiratory Depression

What are the other concerns relatedto opioids?– Addiction– Abuse– Diversion (used by others or sold)

Are opioids addictive?There are no guarantees in

medicine. Physicians take all possibleprecautions and still there will bepatients who will use more thanneeded. On the other hand, who is to say howmuch is needed except the patient himself? Aslong as the amount used is for pain, then thechance of addiction is quite low. Short-termuse for surgery or acute bleeds is veryunlikely to lead to addiction.

M e d i c a l N E W S

Inadequate Relief

Inadequate Relief

Strong Opoid + Non-opoid

Adjuvant Agents+–

Weak Opoid + Non-opoid

Adjuvant Agents+–

Non-opoid Analgesics

Adjuvant Agents+–

WHO ANALGESIC LADDER

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 19

community for many years in the U.S.where safety has been a major issue, andthere have been recommendations todevelop new products like rAHF-PFM thatare free of these human and animalcomponents. This is something peoplehave been asking for.

Hemophilia Today: Whatare the similarities anddifferences betweenRecombinate and rAHF-PFM?

Dr. Ewenstein: The codingsequence for the factor VIIIgene is identical for bothRecombinate and rAHF-PFM. We also started withthe same cell line, which isa Chinese hamster ovary(CHO) cell line, andselected a clone for itsability to grow in a protein-free environment. So fromthe developmentstandpoint, this is one ofthe chief differences withRecombinate. Another bigdifference is that sugars,rather than albumin, areadded in the finalformulation. The last bigdifference is the addition ofa solvent detergent viral inactivation step.

Hemophilia Today: In the past, the celllines in which factor VIII was producedwere fed either bovine or human albumin.What is being used now?

Dr. Ewenstein: We succeeded in adaptingthe cell line to a ‘vegan diet’, eitherinorganic material or plant derivatives, theexact nature of which is proprietary. To myknowledge, there has never been a case oftransmission of human viral pathogensfrom plants. That’s the idea behind rAHF-PFM: to remove the risk of a human oranimal pathogen crossing the speciesbarrier.

Hemophilia Today: If Chinese hamsterovary cells are used to express humanfactor VIII, can it be said that rAHF-PFMcontains no animal proteins?

Dr. Ewenstein: It’s true that the CHO cellsare animal-derived but they have been in

culture for many years and are well-characterized. They are known to beinherently resistant to viruses and havebeen isolated from what’s happening in therest of the biosphere. So, yes, factor VIII isproduced in animal-derived cells. Nobodyknows how to produce factor VIII in a cell-

free environment—it’s nottechnically possible at thepresent time.

Hemophilia Today: Themonograph also mentionsthe presence of mouse antibody.

Dr. Ewenstein: Themonoclonal antibody isthe same well-characterizedantibody that is used in thepurification ofRecombinate with the onedifference that it is derivedfrom hybridoma cells thathave also been adapted to a‘vegan diet’.

Hemophilia Today: Is itfair to say there are traceamounts of mouseimmunoglobulin and CHO protein?

Dr. Ewenstein: Yes, thereare trace amounts that can be detected,virtually the same amounts that are presentin Recombinate, but those have never beenshown to be harmful in terms of allergicreactions.

Hemophilia Today: You mentioned theaddition of a solvent detergent viralinactivation step. If this product does nothave the potential to transmit human andanimal viruses, why is there a viralinactivation step?

Dr. Ewenstein: The answer is based, inpart, on regulatory considerations. InEurope there are EMEA recommendationsto have a dedicated viral inactivation stepagainst the major classes of virus in allsuch products. You could call it a ‘belt-and-suspenders’ approach. But from atheoretical point of view, it is not easy toimagine how a pathogen could get into theprocess; nevertheless, this step providesanother level of security.

B l o o d F a c t o r

rAHF-PFM: Baxter’s third-generation recombinant factor VIII under review by Health Canada

In the spring 2002 issue of HemophiliaToday, this column reported on a new, third-generation, recombinant factor VIII calledrAHF-PFM, in development by BaxterBioscience since 1997. It received regulatoryapproval from the Food and DrugAdministration (FDA) in the U.S. in July2003, and from the European MedicinalEvaluation Agency (EMEA), responsible forthe European Union in early 2004. Thetherapy is currently being marketed byBaxter in those jurisdictions under the nameof Advate®. The company has submitted thedrug for approval by Health Canada and thereview is underway.

Baxter Bioscience has plans to phase outits current recombinant factor VIII product,Recombinate®. The exact schedule of thephase-out, however, has not beenannounced. It will depend on the timing ofthe new drug’s approval, production andplanning at Baxter, and ongoing discussionswith the Canadian Blood Services andHéma-Québec.

In May, Hemophilia Today interviewedBruce Ewenstein, M.D., Ph.D., GlobalMedical Director for Hemophilia Therapyfor Baxter Bioscience. Dr. Ewenstein workedfor 17 years as a director of an adult andpediatric hemophilia centre in Boston untiljoining Baxter two years ago.

Hemophilia Today: Baxter already has arecombinant factor VIII—Recombinate—on the market. What led to thedevelopment of this new therapy?

Dr. Ewenstein: We started with the premisethat Recombinate was a great drug. It hasbeen around almost 15 years and has anexcellent safety and efficacy record. Onepotential drawback, however, is thepresence of human and animal proteins. Ihave been involved in the hemophilia

BLOODTHE

FACTORDavid Page, CHS Blood Safety Coordinator

I have been involvedin the hemophilia

community for manyyears in the U.S.where safety has

been a major issue,and there have been

recommendations to develop new

products like rAHF-PFM that are free of

these human andanimal components.This is somethingpeople have been

asking for.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 420

Hemophilia Today: Is there any evidencethat Recombinate, the current Baxterproduct in Canada, has transmitted humanor animal pathogens?

Dr. Ewenstein: No, we do not have anyevidence of transmission so this is alltheoretical. But I don’t think you have towait for the next emerging pathogen tocause harm before takingpreventive action. Ourfeeling is that viruses areconstantly emerging orbeing discovered; they arecreated from other viruses.So the best approach, notknowing what nature has instore, is to do whatever youcan to isolate your systemfrom what may happen outthere.

Hemophilia Today:Recombinate containsalbumin in both the cellculture and in the finalformulation as a stabilizer.Is there any evidence thatalbumin has resulted inpathogen transmission?

Dr. Ewenstein: Albuminhas an excellent safety record over the past50 years and Recombinate has proven to bean effective and safe product. But there arenew kinds of pathogens, such as prionsresponsible for variant Creutzfeldt-JakobDisease (vCJD), that have emerged. Whilethese prions are eliminated to a certainextent in the preparation of albumin, thereis no way to test for them in a large-scaleway. At the same time, it is important toemphasize that there has been no evidenceof transmission of vCJD through factorconcentrates, either plasma-derived orrecombinant. There is evidence now,however, that it can be transmitted throughblood. So the best approach is to removethe risk to the extent technology is able.

Hemophilia Today:What has beenCanada’s involvement in clinical trials?

Dr. Ewenstein: Canada has made asignificant contribution to thedevelopment of Advate. The Hospital forSick Children in Toronto is playing anongoing role in the pediatric study. Thetreatment centres in Edmonton and

Hamilton were involved in the surgicalstudy. And a Canadian physician serves onthe Global Data Safety MonitoringCommittee that reviews all Advate studies.As the clinical program continues to rollout after licensure, additional Canadiancentres will be involved. So Canada hashelped get us to where we are and I wouldlike to extend my thanks.

Hemophilia Today: Whathave clinical trials revealedabout the efficacy of rAHF-PFM?

Dr. Ewenstein: A directcomparison withRecombinate was madethrough pharmacokineticstudies and demonstratedthat it is biologicallyequivalent. After the pre-clinical studies in animals,human clinical trials beganat the end of 2000. In thepivotal study, rAHF-PFMwas studied in 108 patientsover the age of 10 who hadhad at least 150 priorexposure days to factorVIII, and demonstrated thesame level of efficacy that

we saw with Recombinate. One or twoinfusions were needed to treat a bleed inthe vast majority (94%) of cases. We alsolooked at the breakthrough bleed rate inthese older patients on prophylaxis; theaverage number was 4 events per yearamong patients who were reasonablyadherent to the protocol.

There is a separate surgery study, includingmajor surgery, minor surgery and dentalprocedures, which is not yet completed. Inan interim analysis of 41 patients treated,there was a very high degree of hemostaticefficacy in the operating room and duringthe post-operative period.

Finally, there is an ongoing pediatric studyin children less than 6 years of age whohave had some exposure to factor VIII (atleast 50 infusions). Again, the efficacy hasproven to be excellent, essentially the sameas in the pivotal study of older patients.

Hemophilia Today: Is rAHF-PFM licensedfor children under 6 years of age?

Dr. Ewenstein: It is licensed in the U.S. forchildren under 6 years of age based on dataobtained on the first 14 patients. Now thatwe have data on more than 40 patients, weare submitting a larger interim report toboth the EMEA and Health Canada.

Hemophilia Today: Let’s look at the safetyside. What have clinical trials revealedabout adverse reactions, in particular,inhibitors?

Dr. Ewenstein: The good news is that inthe entire clinical program, in all studies todate, there have been no high-titerinhibitors. We did see one low-titerinhibitor that showed up throughlaboratory testing, not because of lack ofefficacy. By the time we re-tested, it haddisappeared. So that makes one low-titer,non-persistent inhibitor in over 200patients. There have been no reports ofinhibitors through pharmacovigilance inthe first 9 months post-launch.

Hemophilia Today: What about otherreactions to the therapy?

Dr. Ewenstein: During the clinical trials,when reactions are rigorously reported, wehave had no serious adverse events thatwere judged to be related to rAHF-PFM.Among the non-serious events, reactionsare divided into “mild”, “moderate” and“severe”. Several were considered by theirphysicians as severe, including one highfever, which was not related to rAHF-PFM.

Since marketing, we have had a verypositive experience. When compared withRecombinate for the same time afterintroduction, we have seen about half thenumber of adverse reactions reported withtwice the number of units distributed. Wehave had ten adverse events reported inthe first 9 months post-launch and most ofthese were mild. There was a single seriousadverse event, a severe allergic reaction in apatient who appears to react to all FVIIIproducts. It’s been a very reassuringintroduction.

Hemophilia Today: What is the currentsituation with Health Canada?

Dr. Ewenstein: We are still in activeconversations with Health Canada toprovide them with the latest informationon our clinical trials and would hope for apositive decision by the end of this year.

B l o o d F a c t o r

The good news is that inthe entire clinical program,in all studies to date, there

have been no high-titerinhibitors. We did see one

low-titer inhibitor thatshowed up through

laboratory testing, notbecause of lack of efficacy. By the time we re-tested,it had disappeared. So thatmakes one low-titer, non-

persistent inhibitor in over200 patients. There have

been no reports ofinhibitors through pharma-

covigilance in the first 9 months post-launch.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 21

Bayer devotes researchenergies to a ‘new,improved’ factor VIII

David Page, CHS Blood Safety Coordinator

Following news that a scientificpresentation by Bayer Biological Products(BP) was recognized as the second-bestabstract presented at the recent Society for Thrombosis and Hemostasis meeting inGermany, Hemophilia Today interviewedthree Bayer scientists familiar with thisresearch into the development of a longer-lasting recombinant factor VIII molecule.They are: Michael Fournel, Senior VicePresident, Research and Development; Dr.Peter Larson, Director of Global ClinicalStrategy; and Dr. Peter Radtke, SeniorStaff Scientist.

M any readers will know that Bayeralready has a second-generationrecombinant factor VIII product

on the market in Canada. Kogenate FS®,which uses no animal or human proteins asstabilizers in the final formulation, wasapproved for use in Canada in 2001. Bayer isalso in the process of launching a needlelessreconstitution device—called BIO-SET—which will reduce the number ofreconstitution steps for Kogenate andinvolve only one ‘sharp’, the needle that goesinto the vein.

Hemophilia Today, however, was especiallyinterested in the research to develop a ‘new,improved’ factor VIII molecule. MichaelFournel explains Bayer’s decision to foregodevelopment of a ‘third-generation’ factorVIII (See rAHF-PFM: Baxter’s third-generation recombinant factor VIII underreview by Health Canada on page 19).

“We made a decision to market asecond-generation product because ofwhat we thought were safety concerns withthe albumin present in the stabilizer. Wefelt that eliminating this significantamount of human protein in the finalcontainer would achieve a significantbenefit. Our decision to skip the third-generation product was made inconsultation with the hemophiliacommunity, scientists and opinion leaders.They told us it made more sense to investour research dollars in something that wouldoffer a substantial benefit to the patient

rather than the incremental differencebetween second-and third-generationproducts.”

Peter Radtke described the work forwhich Bayer and collaborators from theScripps Research Institute in La Jolla,California received the award. “The work ispart of a larger project here at Bayer to lookat different ways to improve the factor VIIImolecule itself, and ways to improvefeatures such as ease of administration. Theparticular work that was recognized was fora factor VIII molecule that, once activated,stays activated for a longerperiod than normal factorVIII. So the molecule we’redesigning has a higherstability once activated. Agenetically engineeredmolecular bridge holds vitalparts of the activated factorVIII together. This factorVIII doesn’t fall apart asquickly so it can participatein clot formation for alonger time. A personwouldn’t need as muchfactor VIII.”

Other strategies underinvestigation includelooking to increase the half-life of the non-activatedfactor VIII and, by makingmodifications at the surfaceof the molecule, to preventit from being cleared asquickly as the wild-typemolecule. This would bedone by identifying residueswhich are involved in the binding to aclearance receptor so that the binding isinterrupted. Michael Fournel describesanother approach to modify the moleculeby changing certain amino acids whichwould influence the pharmacokinetics orthe half-life once in circulation. “We’retrying to modify the structure of factor VIIIby mutating certain amino-acid residuesand replacing them with other amino acidswhich achieve our goals—true geneticengineering.”

He went on to explain the motivationbehind the research.“Our goal is to reduce thefrequency of administration to avoidbreakthrough bleeding with prophylaxistherapy. We’d like to take three-times-a-weekprophylaxis and be able to cut it down to oncea week. That’s the order of magnitude. Ideally,

we’d like to do even better than that.”While those who dream of the day when

gene therapy might reduce the frequency oftreatments to once a year or less may findthis unimpressive, Peter Larson says that thebenefits would be critical. “We received areally strong message from pediatricians ofthe real need to lower the number ofinfusions required to achieve effectiveprophylaxis. There are many benefits to this:better adherence to treatment protocolswhich are so difficult for younger children,and reduction in the use of central venous

access devices with theirattendant risks of infectionand thrombosis.”

The specter of increasedantigenicity—thedevelopment ofinhibitors—is always raisedwhen molecules are beingmodified from their naturalform. “We’re paying closeattention to the problem ofantigenicity,” says PeterRadtke. “We’re building thebridges that stabilize factorVIII between the sub-domains in the molecules inplaces where the antibodiesare not able to see them.There should be noincreased risk of inhibitors.”

Another area of research,according to MichaelFournel, is to look atdifferent non-vascularroutes for administration offactor VIII. “Getting the

drug into circulation would be via animplant or an absorption mechanism ratherthan infusion into a vein.”

Hemophilia Today asked the obviousquestion: How long will it take before someof this research is translated into marketedproducts? “Going for the home run,” saysMichael Fournel, “is a challenging task. Ittakes a long time to get there. The normaltime line for drug development can be aslong as eight years. Some of the approacheswe have underway are building on theexisting molecule and could come soonerthan that.”

Peter Larson adds, “We’re committed toworking on these developments that wouldreally change the quality of life for peoplewith hemophilia.”

B l o o d F a c t o r

Hemophilia Todayasked the obvious

question: How long will it takebefore some of this

research is translatedinto marketed products?

“Going for the homerun,” says Michael

Fournel, “is a challengingtask. It takes a long timeto get there. The normal

time line for drugdevelopment can be as

long as eight years.Some of the approacheswe have underway arebuilding on the existing

molecule and could comesooner than that.”

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 422

WHAT IF YOU’RE ACARRIER?

Claudine Amesse, R.N., Nurse Coordinator,Hemophilia Treatment Centre, Ste-JustineHospital

F or the past three years, a geneticstudy led by Dr. David Lillicrap,hematologist at Queen’s

University in Kingston, Ontario, hasbeen carried out to identify allmutations responsible for severehemophilia A and B in Canada. It hasmade it possible for the majority ofsevere factor VIII or IX hemophiliacsto know the exact mutationresponsible for their condition.

All female members of these familieshave free access to a moleculardiagnosis, allowing them to establishwith certitude whether or not they arecarriers of hemophilia. The moleculartests used in this study are sophisticatedand expensive; most of these tests arenot available elsewhere in Canada.

For 50% of severe factor VIIIhemophiliacs, it is relatively easy to identifytheir mutation in a regular molecularbiology laboratory. In these cases, a part ofthe gene responsible for the factor VIIIdeficiency (intron 22) is inversed. It’s as if anose were upside-down on a face. It’s easyto understand that this organ can’t work.It’s what’s referred to as the intron 22inversion or the flip.

In order to find out if a woman is acarrier in these families, one simply looksfor the flip on a blood sample. It’s a testthat’s fairly simple, and only requires a fewweeks delay. For the other half of the severeFactor VIII deficiencies, and all factor IXdeficiencies, the identification techniquefor the mutation can be very complex. This

technique sometimes requires manymonths of work, despite state-of-the-artequipment and a highly qualified team ofprofessionals.

In order to identify the mutation in apotential carrier, it first has to be identifiedin the hemophiliac. Ideally, all bloodspecimens from the family should be sentat the same time. The technicians can lookfor the corresponding mutation in theother members of the family. Of course, allresults are kept on file. People who may becarriers and who haven’t been testedshould take advantage of this study bycommunicating with the treatment centreof their choice.

The nurse, using the family tree collatedat the time of diagnosis of the first hemo-philiac in the family, will verify that theperson is actually at risk of being a carrier.

Why is it so important to know yourstatus as a carrier? The first reason is thatdiagnosis as a carrier of severe hemophiliaimplies a 25% possibility of having a child

with severe hemophilia. If a woman shouldbecome pregnant, couples must choosebetween two separate options. She cancarry the pregnancy to term and know thediagnosis only when the child is born. Byknowing the carrier status of the womanright from the start, the obstetrician,working with the team from thehemophilia treatment centre, can provideproper care during pregnancy, and plan forthe birth of the child under safeconditions.

The couple can also opt for prenataldiagnosis and termination of the pregnancyin the case of a foetus with hemophilia. It isessential that the diagnosis be establishedearly on in the pregnancy so as to avoid the

F e m a l e F a c t o r

This section is related specifically to womenwith bleeding disorders and their families. Allarticles are reviewed by physicians to ensuremedical accuracy. If you have any questions, comments or ideas,feel free to contact me, Patricia Stewart, at thefollowing addresses: Phone & Fax: 418-884-2208 or e-mail:stewart.page@globetrotter.ca or simply put pento paper and mail to: 389, R.R. # 4, La Durantaye,Quebec G0R 1W0

FEMALE FACTORTH

E

Patricia Stewart

patient having to go through theinconvenience of a late abortion. Thus it’simperative to advise hemophilia treatmentcentre personnel as soon as the pregnancyis confirmed, usually around the 5th or 6th

week. This allows the molecular biologylaboratory staff to gather the materialneeded to identify the specific gene for thisfamily during chorionic villus biopsy(taking cell samples from the placentathrough the vaginal passage). This isplanned by the genetic and gynecology-obstetrics team at the 11th week ofpregnancy. Results are available at aroundthe 13th week.

To meet this objective, the patient’scarrier status must be known at the start ofpregnancy, as well as the specific mutation.Otherwise, while it is possible to acceleratethe process by requesting a priority forgenetic analysis, it will be a challenge tohave the results in time for the 11th week ofpregnancy.

Amniocentesis (punction ofamniotic liquid through theabdomen) between the 14th and 16th

week of gestation is the secondalternative. It takes four weeks afterthe test to get the results, whichwould imply an abortion at the 18th

to 20th week of pregnancy. All thesedelays can be avoided with aninvestigation carried out at thehemophilia centre before pregnancy.

The second reason why it’simportant for carriers to know theirstatus is the possibility that they aresymptomatic carriers. Since carriershave only one gene that functionsproperly compared to two in non-carrier women, they can have a lowlevel of factor VIII or IX. Some maypresent with coagulation problemslike mild hemophilia. In women,these symptoms are: heavy menstrual

bleeding, frequent bruising, andimportant bleeding following surgery orserious injury. All these inconveniencescan be controlled or prevented byestablishing a diagnostic and individualtreatment plan at a hemophilia centre.

I suggest that all hemophiliacs andthose related to a hemophiliac contact allthe females in the family likely to becarriers (cousins, aunts, granddaughtersof hemophiliacs) to share the contents ofthis article with them. If they don’t knowtheir status, I encourage you to convincethem to contact your hemophilia centre.Thus you can avoid many problems andallow them to make an enlighteneddecision in a timely manner.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 4 23

President, National MemberOrganizations, addressed issues of thesafety and supply of blood products.

The second session focused onorthopedic problems, with a presentationon the management of orthopedic problemsby Dr. Jerome Wiedel, orthopedic surgeonand Co-chair of the WFH MusculoskeletalCommittee, Mountain States RegionalHemophilia and Thrombosis Centre,Colorado. This was followed by a verythorough review of the benefits ofphysiotherapy in the management ofhemophilia by Kathy Mulder,physiotherapist from the Winnipeg HealthSciences Centre and the second Co-chair ofthe WFH Musculo-skeletal Committee. In acountry like Jordan where treatment is notalways available, physiotherapy takes on anew meaning in the form of identifying ableed, using RICE (Rest, Ice, Compressionand Elevation). I remember thinking it waslike going back to basics – basics we coulduse right here in Canada.

On Saturday and Sunday, orthopedicworkshops were conducted at each of twohospitals with excellent results and over 50

THEGLOBAL PERSPECTIVEEric Stolte Chair, International Projects Committee

By Candace Terpstra

T COR is now part of something muchlarger than itself. We are part of aglobal plan to improve the quality of

life for people with hemophilia around theworld and, in particular, for approximately500 people with hemophilia in the countryof Jordan. By working together with theJordanian Hemophilia Society to educatepeople with hemophilia, their families andmedical personnel while strengthening themembership and building the capacity ofthe organization for fund-raising andlobbying, we can improve care andtreatment for all people with inheritedbleeding disorders.

Our most recent visit to Jordan tookplace in September 2003. The highlight was a three-day medical conference whichattracted over 80 participants from allthree levels of care within the country:the royal military hospital, the university(private) hospital and the public hospital.

Dr. Bernadette Garvey, Co-Director ofSt. Michael’s Hospital HemophiliaProgram, addressed the basics in herexcellent presentation on clinical care andtreatment of hemophilia which included

Jordan and TCOR twinning – the first year!

Close to 100 health care providers gathered inAmman, Jordan to take in the orthopedic and physical therapy presentations by Dr. JeromeWiedel and physiotherapist Kathy Mulder.

the diagnosis of Hemophilia Aand B, and its treatment usingblood components such asplasma, cryoprecipitate andconcentrates, as well asdesmopressin and anti-fibrinolytic agents. Also includedwas a review of thecomplications of hemophilia anda discussion of inhibitors andtheir management. Last but notleast was a description of thecomprehensive care model oftreatment which we use here inCanada.

David Page, World Federationof Hemophilia (WFH) Vice-

people in attendance at each.Dr. Wiedel and Kathy Mulderparticipated in workshops withdoctors and physiotherapists in avery practical way. JordanianHemophilia Society membersvolunteered their joints to beexamined by both the surgeonand the physiotherapist. Physio-therapists were taught how toidentify bleeds, as well as whenand how to begin movement aftera bleed. Dr. Wiedel then spokeabout the physiology of the joint,explaining hemarthrosis andvarious kinds of surgicalcorrections.

G l o b a l P e r s p e c t i v e

TCOR is now partof something muchlarger than itself.We are part of a

global plan toimprove the qualityof life for peoplewith hemophilia

around the worldand, in particular,for approximately500 people withhemophilia in thecountry of Jordan.

H E M O P H I L I A T O D A Y S P R I N G 2 0 0 424

The patients’ meeting was held onSaturday afternoon with over 75 membersassembled to hear short presentations by theJordanian Hemophilia Society President,Arafat Awajan, Dr. Dhowari, Dr. Wiedel,Kathy Mulder, David Page and me.Members enjoyed the opportunity toaddress their questions directly to theexperts, a trait hemophilia society membershave in common the world over.

In addition to the three days of theconference, there were several otherimportant meetings. Dr. Garvey met withkey physicians providing hemophilia care ateach of the three levels of care within thecountry. Meetings were held withgovernment officials to promote the WFHGlobal Alliance for Progress (GAP)program, which has recently receivedJordanian Ministry of Health approval.This WFH program will bring resources tobear, not the least of which is the Ministryapproval required to establish a medicalcentre twinning. David Page had anopportunity to tour the National BloodBank, meet the Director, and discussvarious aspects of blood safety.

In summary, this first year has been a hugesuccess. The Jordanian Hemophilia

Dr. Jerome Wiedel examines a young Jordanian boy with severe synovitis in a knee.

G l o b a l P e r s p e c t i v e

Society has been highly successful ineducating its members through meetingsand the patients’ conference, newsletters,a one-hour television show, and the firstArabic brochure on hemophilia in theMiddle East region. The first HemophiliaConference was very well received andattended by medical professionals from allthree levels of care. And this was all made

possible through the Twinning Programand the collaboration of the WFHvolunteers and staff with the financialassistance from the WFH, the CHS, TCORand the JHS. In the words of JordanianHemophilia Society President, ArafatAwajan, “Twinning provides the foundationupon which everything is built.”