The identification of high risk knee bleeds in adolescents with severe haemophilia A

One hundred and thirty-seven knee bleeds treated with an initial dose of 11–16 units of factor VIII/kg have been reviewed in an attempt to find the predictive factors for bleeds requiring retransfusion. Thirty-two bleeds (23.4%) were retransfused within 48 hours because of extension of bleeding or poor progress. Fifty-nine per cent of bleeds which were retransfused presented with pain and 72% were tender at presentation. These figures contrasted with those for bleeds which were not retransfused of 30% and 45%. The difference in each case is significant. Forty-seven per cent of retransfused bleeds presented with less than 50% of normal movement against 12% who were not retransfused. This difference was also highly significant. It is suggested that knee bleeds presenting with pain, tenderness and/or more than 50% restriction of movement should be considered for higher initial doses of factor VIII.     

Participation in sports and physical activity of haemophilia patients

Modern therapy options offer haemophiliacs more and more possibilities for an active participation in sports. The purpose of the present study was to investigate the attitude of these patients towards sports, their participation in school and leisure time sports activities, and differences between juveniles and adults. We investigated 44 children and adolescents (aged from 4 to 16 years) and 27 adults (aged from 18 to 72 years) with haemophilia by means of a questionnaire. 79.6% of the juvenile patients participated always or almost always in school sports, while this percentage was significantly (P < 0.05) lower in the former school time of the adults (37%). Sports play an important or very important role in leisure time activities for 75% of the adolescent and 55.5% of the adult haemophiliacs (P < 0.05). Bleeding complications occurred in 17.6% of all patients; there was no correlation with any particular type of sports. There were only slight differences between both groups, regarding their motivation to participate in sports activities. The main reasons involved social aspects and having fun. The results show that the modern therapy of haemophilia probably leads to a more positive attitude towards sports and to a wider spectrum of practised sports. This, however, may be associated with an increasing potential of health risks, which require a high level of sports medical care.     

Haemophilia Joint Health Score in healthy adults playing sports

To evaluate outcome of prophylactic clotting factor replacement in children with haemophilia, the Haemophilia Joint Health Score (HJHS) was developed aiming at scoring early joint changes in children aged 4–18. The HJHS has been used for adults on long‐term prophylaxis but interpretation of small changes remains difficult. Some changes in these patients may be due to sports‐related injuries. Evaluation of HJHS score in healthy adults playing sports could improve the interpretation of this score in haemophilic patients. The aim of this study was to evaluate the HJHS scores in a cohort of young, healthy men participating in sports. Concomitant with a project collecting MRI images of ankles and knees in normal young adults, HJHS scores were assessed in 30 healthy men aged 18–26, participating in sports one to three times per week. One physiotherapist assessed their clinical function using the HJHS 2.1. History of joint injuries was documented. MRI images were scored by a single radiologist, using the International Prophylaxis Study Group additive MRI score. Median age of the study group was 24.3 years (range 19.0–26.4) and median frequency of sports activities was three times per week (range 1–4). Six joints (five knees, one ankle) had a history of sports‐related injury. The median overall HJHS score was 0 out of 124 (range 0–3), with 60% of subjects showing no abnormalities on HJHS. All joints were normal on MRI. These results suggest that frequent sports participation and related injuries are not related with abnormalities in HJHS scores.     

Physical activity levels and participation in sport in Irish people with haemophilia

Summary.  Physical activity and sport are associated with a range of health and social benefits. The aim of this study was to assess the level of sports participation and physical activity of Irish people with haemophilia (PWH). A questionnaire was administered to Irish PWH attending the National Centre for Hereditary Coagulation Disorders over a 3-month period. This included the International Physical Activity Questionnaire (IPAQ) and the Haemophilia Activities List (HAL). Comparisons with EU average data from European Physical Activity Surveillance System for physical activity scores (IPAQ) were made using independent t -tests and percentage variance. Relationships between age, functional limitation (based on HAL) and IPAQ scores were tested with Pearson's correlation. Sixty-one questionnaires were completed, representing 12% of the Irish haemophilia population. Age ranged from 16 to 63; all levels of severity were included. Forty-six percent of Irish PWH achieved a high level of physical activity, but overall physical activity [total metabolic equivalents of task (MET) min] in the group was only 66% of the EU average. Elderly patients and those with more functional limitations (with lower HAL scores) were significantly less active. Sports participation levels were in line with other PWH at 66%. Although 55% reported bleeds resulting from sport and 31% reported having had a significant injury attributable to sport, overall sport was viewed in a positive light. Irish PWH are physically active and play a wide range of sports. Further efforts are needed to achieve optimal safety and to ensure that maximum benefit is gained.     

Physical activity participation and bleeding characteristics in young patients with severe haemophilia

Summary.  Patients with haemophilia are now widely advised to participate in sport activities. However, no extensive data are available about their actual participation. The aim of this study was to describe the type; intensity and duration of leisure time physical activity (PA) among young patients with severe hemophilia and to assess whether there are differences in bleeding profile and muscle strength in related to activity intensity. Forty-four boys (ages 12–25 years) with severe haemophilia were studied. PA was assessed by the Godin and Shephard (G&S) questionnaire. Bleeding profile was determined based on a one month diary filled by each patient. Muscle strength of the lower limbs muscles was assessed using a hand held dynamometer. Only three subjects did not perform any PA. Twenty-five of the participants performed strenuous PA at least once a week. An inverse, moderate association ( r _p =–0.45, P  < 0.002) was found between the G&S score and age. There were no significant differences in bleeding frequency or pain but a significant difference in the cause of bleed was found: those who exercised strenuously showed a higher proportion of bleeds due to traumatic reasons ( P  <   0.01). No differences in muscle strength values were noted in related to activity intensity also no linear association was noted between muscle strength and bleeding profile. Further investigation, including prospective studies, is needed in order to assess the temporal sequencing between training and the occurrence of bleeds and bleeds cause.     

When to start and when to stop primary prophylaxis in patients with severe haemophilia

Summary.  Primary prophylactic treatment of patients with severe haemophilia has been shown to reduce the number of bleeding episodes and to minimize the development of arthropathy. However, since the use of clotting factor concentrates is associated with considerable cost and not all patients with severe haemophilia have a severe bleeding phenotype, there is still no consensus about when to start prophylaxis, which dosing regimen to use, and if or when the treatment should be stopped when the patient becomes elderly. Some care providers are also concerned about the use of central venous lines in very young children. Even though most available data indicate that prophylaxis should be started during the first years of life, it may be possible to adjust the dose and dose interval depending on the bleeding pattern. The use of an individualized prophylactic regimen may also improve cost-effectiveness and make the use of this treatment modality more feasible. Studies to further address this issue are warranted.     

When to start and when to stop primary prophylaxis in patients with severe haemophilia

Summary. Primary prophylactic treatment of patients with severe haemophilia has been shown to reduce the number of bleeding episodes and to minimize the development of arthropathy. However, since the use of clotting factor concentrates is associated with considerable cost and not all patients with severe haemophilia have a severe bleeding phenotype, there is still no consensus about when to start prophylaxis, which dosing regimen to use, and if or when the treatment should be stopped when the patient becomes elderly. Some care providers are also concerned about the use of central venous lines in very young children. Even though most available data indicate that prophylaxis should be started during the first years of life, it may be possible to adjust the dose and dose interval depending on the bleeding pattern. The use of an individualized prophylactic regimen may also improve cost‐effectiveness and make the use of this treatment modality more feasible. Studies to further address this issue are warranted.     

Participation and risk-taking behaviour in sports in children with haemophilia

Summary.  The aim of this study was to investigate participation in sports activities and risk-taking behaviour in children with haemophilia and the relationship to personal and health related factors. Ninety-nine children (mean age 12.6 years) completed questionnaires regarding participation in sports and physical education, medication, health related quality of life, and perceived motor competence. Furthermore, weight, height, active range of motion, pain, and muscle strength were assessed. Based on a risk exposure factor (REF) we defined subgroups with low, medium, and high risk when participating in sport. Most children participate in sport five times a week (mean 140 min per week), and little absence during school sports was reported. In general, prophylaxis was not tailored to sport activities. Boys with haemophilia preferred other sports than their Dutch contemporaries. The top-5 being soccer, swimming, tennis, gymnastics, and cardio-fitness for the former; soccer, gymnastics, tennis, hockey, and swimming for the latter. Significant differences between the low risk group and both other groups were found for sport intensity, total energy expenditure (EE) and average risk factor (ARF), however the medium and high-risk groups did not differ in ARF. REF and sport participation increased associated with increasing interest in athletic and motor activities. No significant differences were found between REF groups regarding age, Z-BMI, Z-AROM, Z-Muscle force, and the presence of painful joints. As in normal peers motivation to participate in sport depends upon the enthusiasm and interest, in children with haemophilia choice of sports differs, probably related to sport advice.     

Orthopaedic issues in sports for persons with haemophilia

Summary.  Persons with haemophilia should not feel limited in their ability to participate in sports. After consultation with a physician or other health-care provider and with a proper understanding of the risks involved and the strategies for managing these risks, patients with haemophilia can – and should – enjoy physical activities. We have analysed numerous reports of sports injury statistics and used them to rank a variety of sports according to their degree of injury risk. In addition, we have developed a brief orthopaedic examination and a five-item fitness check that evaluates the level of physical fitness of patients with haemophilia. Using these tools, we can appropriately recommend specific sports activities best suited for each patient. In addition, we recommend that patients who regularly participate in sports maintain adequate levels of clotting factor through the use of regular prophylaxis. With proper physical evaluation and preparation, patients with haemophilia can realize the physical and emotional benefits of participation in sports.     

Assessing the effectiveness and cost-effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease

Abstract . Miners AH, Sabin CA, Tolley KH, Lee CA (Royal Free Hospital School of Medicine, London; University Hospital Queen's Medical Centre, Nottingham; and Royal Free Hampstead NHS Trust, London, UK). Assessing the effectiveness and cost-effectiveness of prophylaxis against bleeding in patients with severe haemophilia and severe von Willebrand's disease. J Intern Med 1998; 244 : 515–22. Objectives To assess the effectiveness and cost-effectiveness of prophylaxis with clotting factor against bleeding in patients with severe haemophilia and von Willebrand's disease (vWD). Design Treatment details that related to 179 patients with severe (< 1 u dL^?1) haemophilia A, B and vWD were retrospectively examined for the period 1980–95. A subgroup of these patients, 25 adults and 22 children, who had previously received treatment on demand and who had switched to treating with prophylaxis, were studied in order to examine the effects of the change. The cost-effectiveness of prophylaxis was also analysed using another subgroup of 38 patients and by adjusting their treatment details by age and method of treatment. Setting Data were obtained on patients who were solely registered at the Royal Free Hospital Haemophilia Centre (RFHHC), London, UK. Outcome measure Bleeds. Results The median annual number of bleeds decreased from 23.5 (range 1–107) in 1980, to 14 (range 0–45) in 1995 (P < 0.0001). Switching from treating on demand to prophylaxis reduced bleeding frequency in 41 out of 47 patients within the period of 1 year. At the base scenario, switching to prophylaxis cost an additional £547 per averted bleed; however, this figure was highly sensitive to certain variables. Conclusion Prophylaxis can reduce bleeding frequency but requires more clotting factor than treatment on demand. More detailed proof of cost-effectiveness is likely to require the use of modelling techniques.     

Participation in sports by Dutch persons with haemophilia

Patients with haemophilia are now widely advised to participate in sports. However, no extensive data are available about their actual participation. A self-administered questionnaire was used to investigate sports participation by persons with haemophilia in the Netherlands. All 293 questionnaires that were distributed have been returned; 217 were from people with severe haemophilia A or B (this is 40% of the severely affected Dutch population with haemophilia). Of this group, 155 (71%) participate in one or more sports: 66 swim, 36 cycle, 21 play tennis, 18 do fitness exercises, 16 ice skate, 10 ski and 10 play table tennis; in total 44 different sports are mentioned. Of a group of 16 persons with haemophilia who are unable to run, 10 (63%) participate in sport and of a group of 91 who can only run sometimes, 64 (70%) engage in sports. This shows that there are ample opportunities for persons with haemophilia to participate in sports, even if they are unable to run. Severely affected persons with haemophilia are as active as the general Dutch population; in fact, a higher proportion swims and/or cycles. In conclusion, sports participation in the Netherlands by persons with haemophilia is in accordance with World Federation of Hemophilia directives.     

Sequential combined bypassing therapy is safe and effective in the treatment of unresponsive bleeding in adults and children with haemophilia and inhibitors

Summary. Some 10–20% of bleeding events in haemophilia patients with high‐responding inhibitors cannot be controlled with bypassing agents. However, sequential combined bypassing therapy (SCBT) has been reported to be successful in five children. To extend this observation, a survey was undertaken by the European Haemophilia Treatment Standardisation Board (EHTSB) in children and adults. Data were collected from all centres belonging to the EHTSB network by a retrospective medical record review. SCBT courses were defined as the administration of both recombinant activated factor VIIa (rFVIIa) and activated prothrombin complex concentrate (APCC) within 12 h. A web‐based database was prepared to collect data on SCBT courses in a standardized and anonymous manner from patients’ files. Eleven inhibitor patients underwent SCBT (nine haemophilia A; two haemophilia B). Two children had refractory knee haemarthrosis and one, an unresponsive calf haematoma. Five adults had significant bleeds following major surgery, one had lower limb compartmental syndrome and one a post‐traumatic upper limb haematoma and haemarthrosis. SCBT administration alternated one APCC dose to 1–3 rFVIIa doses: dosing intervals ranged between 3 and 6 h; APCC (20–80 U kg^?1) was given every 8–12 h; rFVIIa (90–270 μg kg^?1) was given every 3–12 h. Bleeding control was achieved in 12–24 h in all patients. SCBT was discontinued after 1–15 days. No clinical adverse events were observed, but a significant increase in D‐dimer levels was seen in three/five patients who were assessed. SCBT was efficacious without adverse events; nevertheless, due to potential risks, it remains a salvage treatment. A prospective clinical trial is needed to provide further evidence.     

A cost evaluation of treatment alternatives for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil

Summary.  The first-line treatment for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil is currently activated prothrombin complex concentrate (aPCC), with recombinant activated factor VII (rFVIIa) used as second-line therapy or as a last resort. The aim of this study was to determine the cost and effectiveness of these treatments from the perspective of the Brazilian National Health Service. A decision analysis model was constructed to assess total direct medical costs (including drug costs, costs of outpatient or inpatient care, ambulance transportation and cost of concomitant medications) of first-line treatment with aPCC or rFVIIa. Clinical outcome and resource utilization data were obtained both retrospectively and prospectively and validated by the consensus of an expert panel of Brazilian haematologists. A total of 103 bleeds in 25 patients were included in the analysis. rFVIIa resolved bleeds more quickly (4.4 h) than aPCC (62.6 h) and was more effective (100% vs. 56.7% respectively). Mean total direct medical costs (from initiation to cessation of bleed) were estimated to be US$13 500 (aPCC) and US$7590 (rFVIIa). Extensive sensitivity analyses confirmed the cost-effectiveness of rFVIIa. Compared with aPCC, rFVIIa was more effective and less expensive when used as first-line treatment for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil. rFVIIa should be considered a first-line treatment for the management of these patients.     

Risks and benefits of sports and fitness activities for people with haemophilia

Summary. Physical activity is a key component of a healthy lifestyle. Exercise and physical activity have been shown to help maintain a healthy body weight, reduce stress, increase self‐esteem and feelings of wellbeing, control blood pressure, and prevent heart disease and diabetes. Children with haemophilia may feel restricted from competing in sports through parental concern or pain and difficulty in moving, or they may rebel against such restrictions, thus leaving themselves open to serious injury. Several groups have attempted to classify sports activities with regard to the level of risk involved; however, these are not consistent. It is important to match the child's abilities with the sport in which they want to take part, and suggest alternatives if this is not possible. Prevention of injury should not depend solely on use of factor concentrates.