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Notes: Summary.  A survey was conducted in 2002 to determine the pattern of factor prophylaxis use in boys ≤18 years of age with haemophilia followed in North American treatment centres. Responses were obtained from 4553 cases (74% haemophilia A, 26% haemophilia B). The frequency of prophylaxis, defined as factor infusion greater than or equal to once per week for ≥45 weeks per year, was significantly higher for haemophilia A vs. haemophilia B cases (51% vs. 32%, P〈 0.0001), and for boys with severe haemophilia A living in Canada vs. the USA (77% vs. 47%, P〈 0.0001). Use of full-dose prophylaxis, defined as the infusion of 25–40 IU kg−1 of factor VIII on alternate days (minimum three times per week) or 25–40 IU kg−1 of factor IX twice weekly, was similar for boys ≤5 years of age in both Canada and the USA (30% and 33% haemophilia A and 35% and 13% haemophilia B). Reasons for initiating prophylaxis included a history of joint bleeding (88%) and age ≤2 years (23%). For prophylaxis triggered by joint bleeding, 38% of haemophilia treatment centres indicated that they would initiate prophylaxis after the first joint bleed and 66% after a history of target joint bleeding, defined most frequently as 2–4 bleeds over a 3–6 consecutive month period. A central venous line was used to ensure easy venous access for full-dose prophylaxis therapy in 80% of boys ≤5 years of age. These data offer a basis for projecting long-term factor concentrate needs for persons with haemophilia living in North America.

Notes: Summary.  Participants in an international conference on prophylactic therapy for severe haemophilia developed a consensus summary of the findings and conclusions of the conference. In the consensus, participants agreed upon revised definitions for primary and secondary prophylaxis and also made recommendations concerning the need for an international system of pharmacovigilance. Considerations on starting prophylaxis, monitoring outcomes, and individualizing treatment regimens were discussed. Several research questions were identified as needing further investigation, including when to start and when to stop prophylaxis, optimal dosing and dose interval, and methods for assessment of long-term treatment effects. Such studies should include carefully defined cohorts, validated orthopaedic and quality-of-life assessment instruments, and cost-benefit analyses.

Notes: Summary.  Arthropathy is associated with the greatest cost and morbidity to persons with haemophilia. Clinical protocols have been developed empirically to prevent or retard the development of joint disease using routine infusions of replacement factor concentrate. However, randomized clinical trials to determine optimal therapy to prevent joint disease in persons with severe haemophilia are lacking. Two clinical trials are ongoing to answer important clinical questions about the prevention of arthropathy. The first, a US randomized clinical trial, is comparing an aggressive multiple-infusion episode-based protocol to standard alternate-day prophylaxis to determine whether prevention of joint disease requires prevention of the bleeding event, per se, or can be achieved by promoting complete resolution of each bleeding event in the joint. This study included the development and validation of sensitive new physical and imaging scales to detect the earliest signs of joint disease in young children. The second, a single-arm, open-label Canadian study, is asking whether prevention of joint disease in young children can be individualized by escalating the dose and frequency of routine replacement infusions of factor concentrate based upon the clinical course of haemophilia in the affected child. Both of these studies will contribute valuable information regarding optimal therapy and will help establish evidence-based medicine for the management of severe haemophilia.

Notes: Summary.  The goal of the project was to develop and evaluate theory-based interventions designed to change sexual behaviour and promote safer sex practices of HIV seropositive young men and adolescents with haemophilia to prevent transmission to sexual partners and offspring. Safer sex was defined as abstinence, consistent condom use, or ‘outercourse’ (intimate, non-intercourse sexual behaviour). This project utilized the Transtheoretical Model developed by Prochaska and DiClemente, which describes behaviour change as an incremental, stage-based process. The 1-year intervention protocol consisted of two individual sessions and two peer-centred activities. One hundred and four adolescents, residing in 22 states, participated. Pre- and post-intervention evaluations were conducted to measure stage progression for participants. The number who were in the action or maintenance stage of change for safer sex was significantly greater at post-test than at pre-test (79 vs. 62%, P 〈 0.0001). Participants also reported an increased use of outercourse. In addition, significant increases in self-efficacy and knowledge regarding safer sex were demonstrated. Following these stage-based interventions, participants were significantly more likely to be engaging in safer sex behaviours than they were previously. These intervention activities can be adapted for use with other adolescent populations and for other behaviour change goals in adolescents with haemophilia.

Notes: Prophylaxis, or the practice of routine replacement infusions of clotting factor concentrate in persons with severe haemophilia, is a demanding medical regimen. Prophylactic infusions require direct venepuncture or sterile entry into a central venous access device on a regular basis. A telephone survey was conducted to elicit information regarding the barriers to compliance with prophylaxis. The Mountain States Regional Haemophilia and Thrombosis Center has recommended prophylaxis to 52 male patients with haemophilia A or B. The haemophilia nurse attempted to contact all of these patients or their parents, and contact was made with 38 (73.1%) of them. Respondents were asked about the following issues: their decision to initiate prophylaxis; their self-rated compliance; the challenges, barriers, and facilitators of prophylaxis; and their perceived value of the therapy. Four patients (10.5%) elected not to begin prophylaxis. Of the 34 persons who began prophylaxis, 20 respondents (58.8%) rated their compliance as excellent. Nearly one-third of the families with excellent compliance (giving 75–100% of prescribed infusions) stated that the time-consuming nature of prophylaxis was the most significant challenge of the regimen. In addition, 58.3% of the families that gave less than the prescribed number of infusions reported that the time commitment was the primary reason for missing infusions. Knowledge of the benefits of prophylaxis was the primary facilitator of compliance for 44.1% of families. Ninety-seven percent of respondents rated prophylaxis as very valuable. These data show that despite the known benefits of prophylaxis, it is a demanding medical regimen, and compliance is imperfect. In addition, this study underscores the importance of providing continuing support and education for patients and families who are implementing prophylaxis.

Notes: We hypothesized that magnetic resonance imaging (MRI) scans taken prior to radiosynoviorthesis may be predictive of response to the procedure in persons with haemophilia. Specifically, response would be inversely related to the severity of synovial hyperplasia. Radiosynoviorthesis was administered to 21 joints with recurrent haemorrhage (target joints). A detailed self-report of haemorrhage history, joint evaluation with scoring according to the World Federation of Haemophilia orthopaedic joint and pain scales, plain radiographs, and MRI studies of the joints were performed pre- and post-radiosynoviorthesis. To augment comparison of the MRI findings to those assessed using the Arnold-Hilgartner and Pettersson scales, a provisional MRI scale for evaluation of haemophilic arthropathy was designed. We found the MRI findings prior to the procedure were not predictive of clinical response; independent of the severity of synovial hyperplasia, most joints bled less and showed improvement by the WFH orthopaedic score. There was generally no change in the severity of synovial hyperplasia after the procedure. We conclude that MRI evaluation is not routinely indicated prior to radiosynoviorthesis.

Notes: Summary.  Routine infusions of factor VIII to prevent bleeding, known as prophylaxis, and other intensive therapies are being more broadly applied to patients with haemophilia. These therapies differ widely in replacement product usage, cost, frequency of venous access and parental effort. In order to address residual issues relating to recommendations, implementation, and evaluations of prophylaxis therapy in persons with haemophila, a multinational working group was formed and called the International Prophylaxis Study Group (IPSG). The group was comprised of haemophilia treaters actively involved in studies of prophylaxis from North America and Europe. Two expert committees, the Physical Therapy (PT) Working Group and the Magnetic Resonance Imaging (MRI) Working Group were organized to critically assess existing tools for assessment of joint outcome. These two committees independently concluded that the WFH Physical Examination Scale (WFH PE Scale) and the WFH X-ray Scale (WFH XR Scale) were inadequately sensitive to detect early changes in joints. New scales were developed based on suggested modifications of the existing scales and called the Haemophilia Joint Health Score (HJHS) and the International MRI Scales. The new scales were piloted. Concordance was measured by the intra-class correlation coefficient of variation. Reliability of the HJHS was excellent with an inter-observer co-efficient of 0.83 and a test-retest value of 0.89. The MRI study was conducted using both Denver and European scoring approaches; inter-reader reliability using the two approaches was 0.88 and 0.87; test-retest reliability was 0.92 and 0.93. These new PT and MRI scales promise to improve outcome assessment in children on early preventive treatment regimens.

Notes: Summary.  The hallmark of severe haemophilia, defined as a circulating level of factor (F) VIII (haemophilia A cases) or FIX (haemophilia B cases) of 〈 1%, is recurrent bleeding into muscles and joints (haemarthroses) from an early age of life. The inevitable result of such bleeding is progressive joint damage, leading to disabling arthritis that is typically evident within the first 2 decades of life in people with haemophilia who have limited or no access to regular factor replacement therapy, or those in whom factor replacement therapy is ineffective because of the presence of high-titre inhibitors. For children with severe haemophilia and no evidence of inhibitors, the unwanted musculoskeletal complications of severe haemophilia can be effectively prevented by the early initiation of a programme of long-term factor prophylaxis. In order to achieve the best outcome (a perfect musculoskeletal status for age) the programme of prophylaxis should be started before the onset of joint damage (primary prophylaxis). The gold standard primary prophylaxis regimen (the Malmö protocol) was pioneered and tested in Sweden and involves the infusion of 20–40 IU of FVIII per kg body weight on alternate days (minimum three times per week) for haemophilia A cases, and 20–40 IU kg−1 of FIX twice weekly for haemophilia B cases. This protocol is, however, demanding on peripheral veins and very expensive. Modifications of the parent protocol such as starting primary prophylaxis with once-weekly infusions via peripheral veins with rapid escalation to full-dose prophylaxis or dose escalation based on frequency of bleeding are increasingly implemented in haemophilia treatment centres in countries that can afford the high cost of such programmes. These modified programmes can be achieved in the majority of young children with severe haemophilia without the need for central venous access devices (e.g. Port-a-Caths) and with avoidance of device-associated complications such as infection and thrombosis. In at least one centre, experience with arteriovenous fistulae as a strategy to ensure reliable venous access is being accumulated. The issues of compliance (adherence) to recommended prophylaxis protocols and when, if ever, to stop a programme of primary prophylaxis once started are real and require ongoing prospective studies. Such studies should incorporate outcome measures such as health-related quality-of-life and economic analyses.

Notes: Summary.  Venous access is essential for delivery of haemophilia factor concentrate. Wherever possible, peripheral veins remain the route of choice, and the use of central venous access devices (CVADs) should be limited to cases of clear need in patients with caregivers able to exercise diligence in CVAD care and should continue no longer than necessary. CVADs are of recognized value for repeated administration of coagulation factors in haemophilia, particularly for prophylaxis and immune tolerance therapy and in young children. Evidence to guide best practices has been fragmentary, and standardized methods for CVAD usage have yet to be established. We have developed management recommendations based upon available published evidence as well as extensive clinical experience. These recommendations address patient and CVAD selection; CVAD placement, care and removal; caregiver/patient guidance; and complications, including infection and thrombosis. In the absence of inhibitors, ports are recommended, primarily because of fewer associated infections than with external catheters. For patients with inhibitors, ports also appear to be associated with fewer infections. Infection is the most frequent complication, and recommendations to prevent and treat infections are supported by extensive clinical data and experience. Strict adherence to handwashing and aseptic technique are essential elements of catheter care. Evidence-based data regarding the detection and treatment of CVAD-related thrombotic complications are limited. Caregiver education is an integral part of CVAD use and the procedural practices of users should be regularly re-assessed. These recommendations provide a basis for sound current CVAD practice and are expected to undergo further refinements as new evidence is compiled and clinical experience is gained.

Notes: Background/objectives: haemophilia is a lifelong bleeding disorder associated with significant morbidity. Because of this for almost 25 years there has been a national network of specialized haemophilia treatment centres (HTCs). Despite this, there is little published information about HTC utilization. We chose to study utilization and satisfaction with care received from the Colorado HTC as compared with that received at other nonspecialized sites.Research design: a survey was designed in collaboration between Colorado Department of Public Health and Environment (CDPHE) and the Denver Mountain States Regional Hemophilia Center personnel for telephone administration by CDPHE personnel to all persons with haemophilia (pwh) residing in Colorado in 1994.Subjects: one hundred forty-five persons with haemophilia (77% of those eligible) participated in the survey.Results: the majority of respondents received care from the HTC. Persons less than 21 years of age and those with severe disease were significantly more likely to do so. Satisfaction with care received at the HTC was greater than that received at other sites (P 〈 0.01). Issues of concern were insurer restricted access to the HTC and the lack of haemophilia knowledge of non-HTC providers.Conclusions: if HTCs and other specialty centres are to survive in an increasingly managed care environment, in addition to increased patient satisfaction, data documenting improved patient outcome with specialty centre directed care will be necessary to facilitate referral.