proceedings of the first annual congress of the european association for haemophilia and allied...

European Association for Haemophilia and Allied Disorders

Proceedings of the First Annual Congress of the EuropeanAssociation for Haemophilia and Allied Disorders

A. GATT and P. CHOWDARY

The Katharine Dormandy Haemophilia Centre & Thrombosis Unit, Royal Free Hospital, Pond Street, Hampstead,

London

Huge advances in haemophilia care have beenachieved over the last three decades, especially so inthe developed world, which includes many Europeancountries. However, it is clear that the standards ofhaemophilia care across the continent are not uni-form. This is because of a variety of reasons includingdifferences in percentage gross domestic productdedicated to health care, lack of haemophilia patientpressure groups, and paucity of trained specialisthaemostasis physicians, nurses, orthopaedic surgeonsand other members of the multidisciplinary team.Furthermore, there is an increasing need to coordinateclinical research in large numbers of individuals withhaemophilia. This situation has highlighted the needfor, and led to, the establishment of a new professionalassociation – the European Association for Haemo-philia and Allied Disorders (EAHAD) – that couldaddress similar challenges facing haemophilia care inEurope in the twenty-first century. Membership of theassociation is open to all who provide haemophiliaservices whether they be physicians, nurses, physio-therapists, social workers as well as laboratory-basedclinical scientists (see http://www.eahad.org). Thisnew association had its inaugural meeting on 7th June2007 in Vienna where a constitution was agreed andan Executive Committee was elected. The first Con-gress was in Amsterdam, Netherlands, on 14th and15th February 2008. Recordings of the presentationsare available at Eahad.org.

Scope and history behind EAHAD

Prof. Jørgen Ingerslev gave an appreciation in honourof Dr Hubert K. Hartl who recently passed away.

Dr Hartl was a public health physician from Austriawho helped found the European Haemophilia Con-sortium, a European haemophilia patients supportgroup. He was also pivitol in the discussions leadingup to the establishment of EAHAD.

Prof. Christopher Ludlam welcomed the largenumber of attendees at the historical De GrooteIndustrieele Club. He and the rest of the organizingcommittee were appreciative of the huge interestexpressed in this first congress meeting. He outlinedthree current challenges in haemophilia care that hadbeen identified in 2005 and addressed by the Inter-disciplinary Working Group (IDWG) [1]. These werefirst maintaining and improving standards of haemo-philia care; second, monitoring adverse events totherapy especially the development of inhibitors; andthird, promoting more trainee physicians in haemo-philia. The IDWG has published the European Prin-ciples of Haemophilia Care that outline and justify theessential components of comprehensive haemophiliacare [2]. To monitor adverse events, the EuropeanHaemophilia Safety Surveillance project has beenestablished (see next). To address the third topic,a European curriculum for trainee physicians inthrombosis and haemostasis has been formulated [3].

European Haemophilia Safety SurveillanceProject (EUHASS)

Pier Mannucci and Michael MakrisThe aim of this European Union DG SANCO

(Director General for public health and consumerprotection) and industry-funded project is long-termpharmacovigilance, especially for inhibitor develop-ment. Forty-five haemophilia centres across 26countries will contribute annonymized data and itis expected that more than 14 000 patients witheither haemopihilia A or B (including carriers) andvon Willebrand�s disease (VWD) will be followed upover a period of 3 years, starting later on in 2008.

Correspondence: A. Gatt, The Katharine Dormandy Haemophilia

Centre & Thrombosis Unit, Royal Free Hospital, Pond Street,

Hampstead, London NW3 2QG, United Kingdom.Tel.: +447733107537; fax: +442074726759;

e-mail: [email protected]

Accepted after revision 9 September 2008

Haemophilia (2009), 15, 329–336 DOI: 10.1111/j.1365-2516.2008.01911.x

� 2008 The Authors

Journal compilation � 2008 Blackwell Publishing Ltd 329

Apart from basic data like the number of patients percentre and type of treatment used, EUHASS willcollect data every 3 months on the incidence of newinhibitors, cancer, allergic reactions, thromboticevents, transfusion-transmitted infections, new car-diovascular events and causes of death. This data willbe supplemented every 12 months by details onconcentrate use in the same group of patients. Therewas particular emphasis on the need to have a simpledata collection tool to enable participation by busyclinicians.

EUHASS will be supported by the EuropeanHaemophilia Consortium, which will develop aregistry of all haemophilia centres in Europe andset up a rapid response system. UKHCDO Ltd. willprovide IT support, the University of Utrecht willperform statistical analysis while the University ofMilan will set up a concentrate registry. Furtherinformation can be obtained from [email protected].

Clinical Practice Symposium (1)

Problems with factor VIII concentrate (FVIII:C)assessment

Michael MakrisThe presentation focussed on two main aspects.

First was the performance of the FVIII assays. Themethods in use include the most commonly per-formed one-stage activated partial thromboplastintime-based assay, which is both simple to use andeasily automated; the more laborious two-stageassay that is not widely used in routine practiceand the chromogenic FVIII assay. There is wideinter-laboratory variation in the reported results asassessed by external quality exercises like UKNE-QAS. This is around 15–20% for the samples withan elevated FVIII. The assays are often insensitiveto very low FVIII levels making it difficult todistinguish between 0.5% and 1.5%.

Up to 13% of mild haemophilia A patients can bemissed if only a one-stage assay is used in routinediagnostic practice and a further 6% can have awrong diagnosis of mild haemophilia A, if a chro-mogenic or a two-stage assay is not performed. Thisrelates to the issue of discrepant FVIII results givenby the one- vs. two-stage or chromogenic assays.Dr Makris presented data, which suggest that two-stage assay results correlate better with the bleedingphenotype. This has not been the universal experi-ence as others have observed the opposite, i.e.�reverse discrepancy�. This notion was supported byProf. Oldenberg, who made a brief presentation,

with an emphasis on the mutations responsiblefor discrepant results and the mechanisms ofdiscrepancy.

How do I measure von Willebrand factor (VWF)?

Peter J. LentingVWF is a complex glycosylated protein that

contributes to a number of physiological processes.The laboratory diagnosis of this bleeding disorder ismade by a combination of these tests. However,routine assays like vWF:Ag have a coefficient ofvariation as high as 15%, making the diagnosisdifficult at times. New tests like the VWF propeptideassay could offer more insight into the pathogenesisof VWD, and need to be standardized beforeintroduction into routine clinical practice. There isa suggestion that the propeptide:vWF ratio is usuallyincreased in type I and acquired VWD. An ELISA testto measure anti-VWF antibodies is ideal in suspectedacquired VWD but one should aim to use recombi-nant VWF in order to avoid non-specific binding ofABO determinant recognizing antibodies. The colla-gen-binding assay is more sensitive to type II VWDbut this is subject to the type of collagen used.

Desmopressin (DDAVP) – When and how it shouldbe used?

Giancarlo CastamanDDAVP is the treatment of choice for patients with

mild haemophilia A and type 1 VWD. This drug hasbeen in clinical use for the last 30 years [4] and itsrole in reducing human immunodeficiency virus(HIV) spread among haemophilia A patients in Italyin the 1970s and 1980s was outlined. The risk oftransfusion-transmitted infection is almost non-exis-tent with modern viral inactivation procedures, but itis not completely abolished with �emerging� patho-gens like the agent causing variant Creutzfeld Jacobdisease. Exactly 3–13% of mild and moderatehaemophilia A patients develop inhibitors followingintensive therapy with FVIII concentrates. Hence,DDAVP could also be useful in avoiding inhibitordevelopment in similar patients as it can decrease theamount of FVIII concentrate used in similar patients[5]. In VWD, it is now clear that genotype can affectresponse to this drug [6]. Patients with mutations inD3 and A1–A3 domains of the VWF gene usuallyrespond less well than those with other geneticmutations.

The practical aspects of treatment with DDAVPare well known and include, the route of adminis-tration, time to peak response, magnitude of

330 A. GATT and P. CHOWDARY

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response, duration of response and the potential fortachyphylaxis. The response to treatment needs to beassessed in individual patients by performing aDDAVP tria [7], where FVIII and VWF levels arechecked before the infusion, and 1, 2 and 4 h later.Platelet counts should also be checked in certainsubgroups. This will not only select the respondersfrom the non-responders but also help in establishingthe frequency and adequacy of DDAVP administra-tion. In the absence of controlled trials, a postinfu-sion FVIII:C level of 30 IU dL)1 should suffice forminor bleeding or minor procedures and a level of50 IU dL)1 for major surgery. The drug can beadministered every 12–24 h for around 3 days and iscontraindicated in patients with asthma, coronaryvascular disease, hypertension, atherosclerosis, epi-lepsy and children less than 2 years old. DDAVP isprobably safe in early pregnancy and after umbilicalcord section but evidence is still lacking in thispatient group. In general, children tend to respondless well to this drug when compared with adults.The response tends to be conistent over time in anindividual and family.

How do I manage surgery in VWD?

Stefan LethagenA practical overview of the various modalities of

treatment avaliable to prevent bleeding in VWDpatients during surgery was presented. The impor-tance of performing a DDAVP trial on all type 1 andsome type 2 patients before any surgical interventionto assess response was reiterated. Patients unrespon-sive or poorly responsive to DDAVP, those requiringprolonged treatement or those in whom DDAVP iscontraindicated, should be covered with a VWF-containing factor concentrate. Several concentratesare available, which vary in the VWF:RCo/VWF:Agratio, VWF:RCo/FVIII:C ratio, viral inactivationsteps and publication of clinical studies. Variationsare also found in different batches of the sameproduct.

The need to calculate treatment doses based on thevWF:RCo activity of the concentrate, taking intoaccount the patients� baseline VWF level, and natureand severity of the procedure were also emphasized.A preoperative pharmacokinetic study can provideuseful information to individualize treatment [8] andoften replacement needs to be administered every12–24 h postoperatively. Treatment should ideallybe monitored by measuring levels of VWF:RCo andFVIII:C, although the latter is adequate after the firstfew days. Long-lasting FVIII:C levels above 1.5–2 IU dL)1 should be avoided owing to a risk of

thrombosis. During the discussion, Dr Federiciobserved that most of the high FVIII seen postoper-atively is probably endogenous and not related to theFVIII content of the concentrate infused. Antifibrin-olytic agents are important when procedures involvemucous membranes, and on occasion can be used inisolation.

How do I manage surgery in haemophilia?

Kathelijne PeerlinckDr Peerlinck stressed the importance of close

liaison between haematologists, anaesthetists andexperienced surgeons as well as the wide availabilityof a perioperative treatment plan.

Bolus infusions preoperatively should aim toachieve FVIII levels of 90–100% in severe haemo-philia A and 60–70% in severe haemophilia B. It isimportant to compensate for intraoperative bloodloss and a practical formula followed by the speakeris to administer an extra 1000 IU of concentrate forevery 500 mL blood loss. In the postoperativeperiod, for bolus infusions the trough levels shouldbe maintained greater than 50% for the first 3 daysand around 30–40% until wound healing. Oncontinuous infusion, the target levels are 80–100%for the first 3 days, followed by levels of 40–50%until wound healing. The role of preoperative phar-macokinetic studies was discussed with an emphasison differences found in the bleeding and normalstates. Bacterial filters should not be used for FVIIIconcentrate infusions as they could block the passageof FVIII into the patient. It is also important tore-evaluate the patient 6–8 weeks after surgery inorder to check wound healing and also to assess forinhibitor development.

European Research Groups

The second day started with an overview on theEAHAD Nurses Committee by Ms. H. Thykjaer.This committee is a fundamental part of EAHAD asthe nursing community represents the fulcrum ofmodern haemophilia care. Ms. Thykjaer envisagedthat there should be a �natural� cooperation betweenEAHAD and the World Federation of Haemophiliaas nurses are affiliated with both organizations.

PedNET (European Paediatric Network forHaemophilia Management)

Rolf LjungThe European Paediatric Network for Haemo-

philia Management is an exclusive association for

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� 2008 The AuthorsJournal compilation � 2008 Blackwell Publishing Ltd Haemophilia (2009), 15, 329–336

paediatric haematologists. The association started in1997, and holds annual meetings with lectures anddiscussions on clinical practice and research with theaim of improving the quality of care of children withhaemophilia. Contributions so far include the estab-lishment of a European magnetic resonance imaging(MRI) scoring system to assess haemophilic arthro-pathy in greater detail [9], the refinement of thepaediatric orthopaedic score, a PedNet glossary anda PedNet registry for all haemophilic boys born afterthe 1st January 2000. The latter is based in Utrecht.There have been two PEDNET surveys, one in 1998and the latest in 2003, for a snapshot of haemophiliacare among the participating centres. Findingsinclude a decrease in Port-a-Cath usage over time;no significant change in the relative usage ofrecombinant vs. plasma-derived factor IX (FIX)concentrates with the market still being equally split;an increase in FVIII usage as primary prophylaxis[10]. Several meeting proceedings have been pub-lished [11–13] and the association has its website athttp://www.pednet.nl.

EN – RBD (European Network of Rare Bleedingdisorders)

Jenny GoudemandRare bleeding disorders constitute 3–5% of all

inherited deficiencies. These include the followingfactors: FI, FII, FV, FV + FVIII, FVII, FX, FXI andFXIII but not the platelet disorders. An internationalregistry was created in 2005 (http://www.rbdd.org)to improve knowledge of these disorders and wasclosely followed by the development of an onlinewebsite (http://www.rbdd.eu) to register patients�data. This was prepared and funded by PHEA(Public Health Executive Agency) in 2006 andcurrently includes 10 participating centres. Thepossibility of downloading data from national data-bases like the UKHCDO and FranceCoag is beinginvestigated. It is hoped that once fully operational,this network would be accessible to all centres inEurope. The other aims of the group include stan-dardization of laboratory methods for assessment ofthe bleeding phenotype and genotype analysis andexchange of best medical practice.

HIV exposed but uninfected individuals withhaemophilia

A. McMichael, K. Shianna on behalf of Centre forHIV/AIDS Vaccine Immunology (CHAVI)

Prof. Andrew McMichael from the University ofOxford and K. Shianna from Duke University, USA,

briefed the audience on a new CHAVI initiative(http://www.chavi.org). CHAVI is a global enterprisewith the aim of developing new vaccine strategies forHIV. Some of the road blocks include a lack ofunderstanding of the correlates of protective immu-nity to HIV-1. Indeed, a significant minority ofhaemophilia patients were not infected with HIV-1despite a high probablity of exposure. It is knownthat a quarter of these uninfected individuals arehomozygous for the coreceptor mutation ofCCR5D32 allele [14,15]. The homozygous form ofthis allele is present in less than 1% of the generalpopulation [16]. CHAVI is conducting a wholegenome association study in HIV-1 exposed butuninfected individuals with moderate or severehaemophilia A, to identify genetic polymorphismsthat impart resistance to the HIV-1 virus. This hasbeen helped by modern chip technology that permitsthe detection of more than half-a-million singlenucleotide polymorphisms (SNP) using one chip[17]. It is calculated that around 1000 subjects needtesting in the CHAVI 014 Haemophilia Study in orderto achieve the desired study power. Patients withhaemophilia should have received FVIII concentratebetween 1979 and 1984. This study is currentlyrecruiting and the team is looking to various haemo-philia centres across the world for patient recruitment.A full study protocol can be found at http://www.chavi.org/modules/chavi_trials/index.php?id=1. Theinformation generated will be used to identify newtargets for HIV-1 vaccine design.

An observational research programme on immunetolerance induction (ITI) in patients with haemo-philia A and FVIII inhibitors (obsITI)

Carmen Escuriola-Ettingshausen presentation onbehalf of W. Kreuz

Around 25% of severe haemophilia A patientsdevelop inhibitory antibodies to FVIII and this isprobably the most serious complication of treatmentthat haemophilia treaters face in this day and age.Inhibitors can be eradicated by ITI regimens, severalof which are available with varying success. How-ever, little is known about the evolution of theinhibitors while on ITI therapy. Details of anobservational research programme on ITI in patientswith haemophilia A and inhibitors were presented.

The ITI regime recommended for this study is theBonn protocol and no immunosuppressive agents areused. ObsITI will document and evaluate patient-and therapy-related variables on ITI. It will alsostudy the utility of various laboratory tests to monitorITI, including new global assays of coagulation like



thrombin generation, the outcome with differentFVIII concentrates used in ITI and immunologicalmarkers like T-cell subsets, FVIII-specific B cells,inflammatory markers and identification of cell typesthat have endocytosed FVIII molecules.

von Willebrand Disease Prophylaxis Network(VWDPN)

Erik BerntorpAn important issue faced by haemostasiologists is

the role of prophylaxis in the management ofclinically severe VWD [18]. This is being addressedby the VWDPN [19], an international study groupwith contributing centres across Europe and UnitedStates, in the VWD International Prophylaxis (VIP)Study, with the goal of establishing optimal treatmentregimens for the most common bleeding indicationsthrough prospective data collection. VIP is a pro-spective, non-randomized study with dose escalationin eligible VWD patients who suffer from recurrentbleeding. Products used to treat study participantswill not be provided as part of the study. Afterenrolment, the subjects will be followed for 1 year. Itis planned to enrol 40–50 patients per bleeding site(gastrointestinal, joint, menorrhagia and epistaxis).Data on response to the various VWF-containingconcentrates available are included in the study. Theultimate aim is to identify an optimal prophylacticstrategy. VWDPN is also coordinating two retro-spective studies, one on patients who are already onprophylaxis and the other looking at the naturalhistory of gastrointestinal bleeding that can presentan unsurmountable clinical challenge.

Alloantibodies in type 3 VWD

Augusto B. FedericiType 3 VWD is a rare inherited bleeding disorder.

Its prevalence is estimated to be around 1 in300 000–500 000 individuals. This figure is derivedfrom sparse data available from different ethnicgroups (e.g. 5.3 per million in Arabs and 1.5 · 106 inEuropeans [20]). However, the true global preva-lence is still unknown. In patients with large genedeletions, alloantibodies to infused VWF may occuras in haemophilia patients. In these cases, treatmentwith similar concentrates becomes ineffective andpotentially dangerous owing to the risk of anaphy-laxis. Owing to its rare nature, patient characteristicslike genotype, type of alloantibodies and clinicalhistory have not been fully elucidated. In order toaddress these issues in a systematic fashion, thePMCMDM-AlloVWD3 project (levels <5 IU dL)1)

has been instituted, addressing the prevalence,molecular and clinical markers for diagnosis andmanagement of alloantibodies in type 3 VWD. Theaim is to establish a international registry to collectdata on bleeding history, FVIII levels and molecularmarkers of patients with alloantibodies. This initia-tive will also aim to standardize laborotary methodsfor testing of alloantibodies, by recommending stan-dard protocols for participating centres and perform-ing the more sophisticated tests in centralized labs.

Clinical Symposium (2)

The congress concluded with a symposium onimportant current topics ranging from prophylaxisand FVIII/FIX inhibitors to quality of life (QoL)issues.

Prophylaxis for severe haemophilia: where do westand and what answers do we need?

Kathelijn FischerDr Fischer presented the upcoming issues around

how to optimize prophylactic treatment in severehaemophilia. It is well established that prophylaxisprevents bleeds and arthropathy in young boys withsevere haemophilia, enabling a pratically normal life.She enumerated the major issues in this area thatinclude, first, the ideal age to start prophylaxis [21].It is still not established whether treating before orsoon after the first bleed offers significant long-termbenefits. Second, the optimum treatment regimenwith regards to dose, frequency (i.e. once a week vs.thrice a week vs. daily treatment) and trough levels,especially the evidence for association of time below1% FVIII activity and bleeding frequency [22,23].Pharmacokinetic studies have shown that dailytreatment with a FVIII concentrate gives the mostconstant factor level and over time would alsodecrease the factor total requirement. This approachis not feasable in most haemophilia individualsowing to the practicalities around venous access.The third issue is of tapering or discontinuingprophylaxis. It is well recognized that up to 35%of young subjects tend to stop prophlaxis as soon asthey are beyond teenage years [24]. This is partly forpractical reasons but also because of the fact thataround one-third of severe haemophilia patients havea relatively mild bleeding tendency and are able todecrease and even stop treatment after early prophy-laxis. Unfortunately, it is difficult to clearly identifythis subgroup. Randomized controlled trials (RCT)looking at this might not be feasible and it is hopedthat EAHAD could offer a platform for collaborative



prospective observational studies, with the advan-tage of large number of patients and longer follow-up period.

Anti-FVIII inhibitors arising in childhood – what�snew?

Elizabeth A. ChalmersInhibitor development is the most important com-

plication of prophylaxis and treatment with factorreplacement therapy in the developed countries. Thiscomplication is a �nightmare� for both patients andtreating physicians owing to the high morbidity andmortality. This complication occurs in around one-third of haemophilia A patients over their lifetime.Until recently, little was known of risk factors foralloantibody development. This is particularlyimportant, as it allows individualized treatmentstrategies depending on the patient�s risk for inhibitordevelopment. Dr Chalmers discussed the recentstudies on predictors for inhibitor development[25,26]. It is recognized that African- Americanshave double the risk for inhibitors when comparedwith Caucasian Americans, and family history ofinhibitors also appears important. Large gene dele-tions, nonsense mutations and intron 22 inversioncarry more than 30% risk. HIGGS is a genome-widestudy correlating mutations with alloantibodies.Polymorphisms in immune response genes like inter-leukin (IL)-1b, IL-4 and IL-10 have been shown tocorrelate with an increased risk of inhibitor devel-opment. Environmental variables include age at firstexposure, which does not seem to be an independentrisk factor as it is influenced by the type of geneticmutation of the patient. The CANAL study [27] hasidentified intensity of treatment as a risk factor butprophylaxis seems to have a protective effect. Con-comitant immune system challenges are also impor-tant but the exact mechanisms are unclear. Whethera particular concentrate carries a higher risk thanothers is still a matter of debate with different resultsfrom different trials.

Another study, SIPPETT (Survey of Inhibitors inPlasma-Product Exposed Toddlers), is looking intothe circumstances of inhibitor development, includ-ing recurrences and in vitro predictors in childrenexposed to plasma products.

Inhibitors in haemophilia B – an intriguingcomplication

Jørgen IngerslevAlloantibodies to FIX are rare, occurring in

around 1–3% of severe haemophilia B patients in

total. Their appearance is not only associated withthe decreased efficacy of FIX concentrates but also anincreased risk of anaphylaxis and nephrotic syn-drome when rechallenged with FIX transfusions.Jørgen Ingerslev explained that in these circum-stances, bypassing agents might not be efficacious inall instances. Furthermore, FEIBA can cause anam-nesis as it contains FIX. As in haemophilia A, thereseems to be an increased incidence of inhibitors inthose patients with large deletions in the FIX gene,and protein load substitution is higher than withFVIII or FVII (5.0, 0.1 and 0.5 lg IU)1, respectively).However, owing to their infrequent occurrence, FIXinhibitors are much less well characterized than thosein haemophilia A. Prospective studies are needed todetail the clinical circumstances leading to inhibitordevelopment, reasons behind the low success rates ofITI, antibody specificities and FIX immunoglobulin E(IgE) and complement biology.

New products with enhanced efficacy for treatinghaemophilia

Claude NegrierProf. Claude Negrier presented an overview of

new products in the pipeline for the treatment ofhaemophilia. The advent of purified plasma-derivedand recombinant factors has revolutionized themanagement of haemophilia. The concerns aroundinfection transmission have receded with the adventof recombinant FVIII technology and the morerecent elimination of all albumin and animal pro-teins. Despite this, there are unmet needs that makecompliance an issue in this treatable disorder.Current research is focussed on recombinant factorconcentrates with longer half-life, higher potencyand/or lower immunogeneicity, translating to anindividualized treatment plan with potential forincreased compliance. Some of the products invarious phases of clinical development include longhalf-life recombinant factor molecules, e.g. pegylat-ed FVIII, pegylated liposomal FVIII [28], glycope-gylated long-acting rFVIIa (t½ �15 h), polysialicacid conjugation with lysine residues by reduction,genetic fusion of FVIIa to albumin through aflexible glycine-serine linker and antibodies to low-density lipoprotein receptor-related protein [29].The haemostatic potential can be increased byproducts with increased potency, including the Bdomain-depleted FVIII and modification of thethrombin deactivation site making FVIII moleculesresistant to thrombin inactivation [30,31]; NN1731characterized by a three-aminoacid substitutionin rFVIIa; antibodies that have the property to



exogenously activate FIX and cause thrombingeneration [32]. Other avenues for increasing thehaemostatic potential include nonanticoagulant sul-fated polysaccharide, fucoidan or pentosan poly-sulfate that antagonise tissue factor pathwayinhibitor [33]; recombinant porcine FVIII and anti-idiotypic antibodies [34]. Prof. Negrier ended with avery important comment that although suchimprovements would serve to enhance QoL forhaemophilia patients, they would probably beavailable only in developed countries making theinequalities of care even bigger across the world. Itis imperative that ways of producing large volumesof factors are developed. A potential example couldbe the use of transgenic animals that can secrete thefactors in question in their milk. Recently, thistechnology has been used successfully in the pro-duction of recombinant human antithrombin. Sim-ilar processes could possibly result in lowering theprice of factor concentrates increasing their avail-ability and affordability.

Health status in older persons with haemophilia andhow they manage their condition

Sylvia von MackensenDr von Mackensen presented data from a recent

QoL, multicentre, case-controlled study in elderly(‡65 years) Italian patients with severe haemophilia.This was an interesting and important study as withthe advent of FVIII concentrates, the life expectancyof haemophilia patients in the developed countrieshas increased. The age-matched controls werehealthy with no history of bleeding. It was estimatedthat 6.4% (46 patients) of the Italian Haemophiliapopulation fulfilled the entry criteria. Geriatric andhaemophilia assessments together with standardizedQoL instruments were used. It was noted that lesshaemophilia subjects than controls were married(64% vs. 91%). Chronic pain was a prominentfeature with 37% of the patients admitting to intensepain. As expected, patients also had a worse ortho-paedic score and had more co-morbidities (e.g. viralinfections) than controls. Hypertension was alsomore prevalent in the patient group whereas hyper-cholesterolaemia and cardiovascular disease weremore frequent in the control group. Elderly haemo-philia people had decreased autonomy in daily lifeneeding help with dressing, bathing and transporta-tion. Their balance and gait were also more com-promised. However, there were no significantdifferences detected in the mental state of the twocohorts. In general, QoL was reduced among thepatients. They also felt less secure as regards their

past, present and future activities (e.g. caring fornephews). These observations are important inplanning for the future health care needs of thispopulation.

Conclusion

Major improvements in haemophilia care have beenmade over the last three decades. However, inheritedbleeding disorders are still relatively uncommonwhen compared with other chronic medical condi-tions that affect the global population. In view ofthis, it is of paramount importance that haemophiliatreaters find ways to collaborate in order to conductappropriate and clinically relevant research to gainmore insight on individual conditions and provideevidence-based strategies. It is hoped that theEAHAD will be an impetus and act as a platformfor collaborative research and the promotion ofuniform high-quality care across Europe and in doingso will contribute to enhanced global care for thosewith bleeding disorders.

Acknowledgements

The authors would like to thank the EAHADorganization committee for reviewing and editingthe manuscript.

Disclosures

The authors stated that they had no interests whichmight be perceived as posing a conflict or bias.

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