An inventory of healthy weight practices in federally funded haemophilia treatment centres in the United States.

In the haemophilia population, obesity has an adverse effect on health care cost, chronic complications and joint disease. Although staff of federally funded Hemophilia Treatment Centers in the United States (HTCs) anecdotally recognize these outcomes, practices to promote healthy weights have not been reported. This evaluation identifies routine practices among HTCs in body mass index (BMI) assessment, perceptions about need to address obesity and roles in offering evidence-based strategies to promote healthy weights. A telephone survey was developed to assess HTCs practices including patient BMI assessment and counselling, perceptions about the importance of healthy patient weights, and HTCs roles in weight management. Ninety of the 130 federally funded HTCs contacted elected to participate and completed the telephone survey. Of these, 67% routinely calculated BMI and 48% provided results to patients. Approximately one-third classified obesity correctly for children (30%) and adults (32%), using the Centers for Disease Control and Preventions BMI cut-offs. Most HTCs (87%) reported obesity as an issue of 'big' or 'moderate' concern and 98% indicated HTC responsibility to address this issue. Most centres (64%) address patient weight during comprehensive visits. One-third (33%) of centres include a nutritionist; of those without, 61% offer nutrition referrals when needed. Most (89%) HTCs do not have a protocol in place to address healthy weights; 53% indicated that guidelines are needed. HTCs offer services to help improve weight outcomes. Training programmes for calculating and interpreting BMI as well as identifying appropriate guidelines to apply to the HTC patient population are needed.

Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia.

Osteoporosis in adult males is an under-recognized problem. Patients with haemophilia have several predisposing factors for developing decreased bone mineral density (BMD) including prolonged periods of immobility, reduced weight bearing and co-morbidities associated with bone loss. To establish prevalence and risk factors associated with decreased BMD in patients with haemophilia. Adults with moderate or severe haemophilia A or B underwent dual-energy X-ray absorptiometry (DXA). BMD was correlated to laboratory values, joint mobility measurements and physical activity questionnaires. Thirty patients completed evaluations. The median age was 41.5 years (range 18-61). Median lowest T-score by DXA was -1.7 (range: -5.8 to +0.6), with the femoral neck being the site of the lowest T-scores. Based on World Health Organization criteria, 70% of patients had decreased BMD. Twenty-seven per cent of the participants (n = 8) had osteoporosis and 43% (n = 13) had osteopenia. Variables associated with increased bone loss included lower serum 25-hydroxyvitamin D levels (P = 0.03), lower body mass index (P = 0.047), lower activity scores (P = 0.02), decreased joint range of motion (P = 0.046), HIV (P = 0.03), HCV (P = 0.02), history of inhibitor (P = 0.01) and age (P = 0.03). Adults with haemophilia are at increased risk for developing osteoporosis. A history of HCV and HIV infections, decreased joint range-of-motion, decreased activity levels, history of an inhibitor and low body weight predict bone loss and suggest a population to target for screening. A high prevalence of vitamin D insufficiency was observed. Future studies should investigate interventions, including vitamin D supplementation, to prevent bone loss and fractures for this at-risk population.

Treatment of chronic haemophilic synovitis in humans with D-penicillamine.

Chronic proliferative synovitis secondary to haemathroses is a major complication in patients with severe haemophilia. Current management strategies include prophylactic infusions of the missing coagulation factor, corticosteroids, synoviorthesis and/or synovectomy with variable degrees of benefit. In addition, patients with coagulation factor inhibitors are not amenable to the invasive therapeutic modalities. The gross and microscopic findings of the synovitis in haemophilic arthritis are remarkably similar to those seen in patients with rheumatoid arthritis, although the pathophysiology of these two conditions are quite different. Haemophilic arthropathy, in the later stages, resembles degenerative rather than inflammatory joint disease. Oral D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in 16 patients. Ten patients had an unequivocal response, while three had a reduction in palpable synovium and three had no response. Thus 81% of the patients had a beneficial response. Minor reversible drug side-effects occurred in two patients (proteinuria in one and a rash in the second). The results of this study suggest that D-penicillamine is an effective and safe drug for the treatment of haemophilic chronic synovitis.

Immune tolerance for haemophilia patients with inhibitors: analysis of the western United States experience. The Tri-Regional Nursing Group.

The experience with immune tolerance (IT) induction therapy for haemophilia patients with inhibitors, instituted during 1990-97 at 17 haemophilia treatment centres in the western United States, was reviewed. IT was instituted in 104 of 139 (75%) of all identified haemophilia A and haemophilia B patients with inhibitors. Doses and schedules for IT varied but most patients were treated with a daily administration of 25-200 units kg-1 day-1. Successful immune tolerance (defined as Bethesda Unit titres < 1.0) was achieved in 57 of 81 (78%) patients who completed therapy. IT success was significantly greater for those patients with historic titres < 100 BU (P < 0.0003) and those with titres of < 10 BU at initiation of IT (P < 0.0001). IT success was uniformly achieved in 16 patients with low to moderate responding inhibitors. IT in infants < 2 years of age was problematic due to the presence of high titre inhibitors and complications of venous access. Frequent complications of IT included increased bleeding during intravenous access device insertion (20%) and infections associated with venous access devices (64%). IT is widely accepted as a treatment modality for haemophilia patients with inhibitors. Patient participation in IT regimens and management during therapy is facilitated greatly by the efforts of treatment centre nurse coordinators who are knowledgeable about haemophilia and its complications. Additional clinical trials will be necessary to define better initial dose, schedule, dose adjustment and success/failure criteria for IT.

Spinal epidural hematoma in a hemophilic infant.

PURPOSE: Although intracranial hemorrhage remains a leading cause of death in hemophilia, spinal epidural hematoma is seen rarely. Decompressive laminectomy has a high associated morbidity, and recent reports have suggested that patients can be treated conservatively without surgical intervention. PATIENTS AND METHODS: We present a case of spontaneous spinal epidural hematoma diagnosed by MRI scan in a 6-month-old hemophilic infant. Immediate treatment with factor VIII replacement was instituted. RESULTS: There was rapid and complete clinical and radiographic resolution. CONCLUSION: This case shows that selected hemophilic patients with spinal epidural hematoma can be spared surgical decompression by prompt medical attention.

Danazol-induced factor VIII and IX bypassing activity in hemophiliacs.

Danazol, a synthetic androgen reported to increase factor VIII and IX activity levels, was given to 6 hemophiliacs. With danazol therapy (600 mg/da) the APTTs shortened by 30-45% of pre-treatment times. However, the activity levels of the deficient factors did not increase significantly nor consistently with the APTT change. The prothrombin times and activity levels of factors XI and XII also did not change during the study period. Addition of plasma from danazol-treated patients to plasma with a known factor VIII inhibitor and to plasma from an untreated severe hemophilia A patient caused a similar shortening of the respective APTTs. Absorption of the danazol plasma with precipitating antibody against factor VIII and IX did not remove the APTT correcting principal. The data suggest that danazol may cause the de novo appearance of an intrinsic coagulation pathway activator having factor VIII and IX bypassing activity.

Treatment of hemophilic arthritis with D-penicillamine: a preliminary report.

Current medical management programs for established joint diseases in hemophiliacs are unsatisfactory and do not modify the eventual outcome. D-penicillamine, a drug effective in the proliferative synovitis of rheumatoid arthritis, was evaluated in a rabbit model of hemarthroses-induced arthritis and in four hemophiliacs with chronic synovitis. The animals had intra-articular injections of citrate (left knees) and autologous citrated whole blood (right knees). Eight weeks later, the rabbits were divided into two groups: no treatment and D-penicillamine (50 mg/kg/day, IM) until sacrificed at 6 months. The saline-injected joints showed no inflammation and no iron deposition. The blood-injected knees showed iron deposition in both groups, the D-penicillamine animals had marked suppression of chronic inflammation. Of the four patients treated, three had clinical responses (reduction in synovial thickness, reduction in number of bleeds in the affected joint). One patient, who did not respond, developed mild-moderate proteinuria. Those patients who responded received between 5.3 and 7.1 mg/kg/day of the drug. Mild abnormalities in platelet aggregation were seen in the responders. This preliminary study suggests that D-penicillamine is beneficial in the chronic synovitis/arthritis induced by hemarthroses. Further trials are recommended.

Effect of danazol on coagulation parameters and bleeding in hemophilia.

Danazol was given orally at a dose of 600 mg/day to six hemophiliacs for eight to 14 weeks. All patients showed a significant decrease in activated partial thromboplastin time (APTT) beginning with the first measurement (two weeks) and persisting until use of the drug was discontinued. However, a corresponding increase in the deficient factor activity could not be consistently demonstrated. Despite the shortened APTT, bleeding episodes continued in the severe hemophiliacs and the patient with Christmas disease. In four patients, bleeding appeared to increase in severity or change in pattern, and in two cases the bleeding manifestations did not respond to usual factor infusions but responded to discontinuation of the drug therapy and further factor replacement. Euglobulin lysis times were measured in five patients (one hemophiliac and four with nonhemophilic conditions) who were receiving danazol. The lysis times were markedly shortened. Increased fibrinolytic activity may be responsible for the increased bleeding manifestations in danazol-treated hemophiliacs.