Obesity in the global haemophilia population: prevalence, implications and expert opinions for weight management.

Overweight and obesity may carry a significant disease burden for patients with haemophilia (PWH), who experience reduced mobility due to joint inflammation, muscle dysfunction and haemophilic arthropathy. This review aimed to define the prevalence and clinical impact of overweight/obesity in the global population of PWH. A detailed literature search pertaining to overweight/obesity in haemophilia in the last 15 years (2003-2018) was conducted, followed by a meta-analysis of epidemiological data. The estimated pooled prevalence of overweight/obesity in European and North American PWH was 31%. Excess weight in PWH is associated with a decreased range in motion of joints, accelerated loss of joint mobility and increase in chronic pain. Additionally, the cumulative disease burden of obesity and haemophilia may impact the requirement for joint surgery, occurrence of perioperative complications and the prevalence of anxiety and depression that associates with chronic illness. Best practice guidelines for obesity prevention and weight management, based on multidisciplinary expert perspectives, are considered for adult and paediatric PWH. Recommendations in the haemophilia context emphasize the importance of patient education and tailoring engagement in physical activity to avoid the risk of traumatic bleeding.

Assessment of passive musculoarticular ankle stiffness in children, adolescents and young adults with haemophilic ankle arthropathy.

OBJECTIVES: To measure passive musculoarticular ankle stiffness (PMAAS) and its intra- and interday reliability in adult control subjects without ankle disorders. We also sought to quantify PMAAS in children, adolescents and young adults with haemophilia (CAAwH) taking into account the accurate tibiotalar and subtalar joints structural status obtained by magnetic resonance imaging (MRI). METHODS: We included 23 CAAwH and 23 typically developing boys (TDB) matched by age, weight and height, along with 25 healthy volunteers for reliability assessment. All CAAwH underwent bilateral ankle MRI, with anatomical status assessed using the International Prophylaxis Study Group MRI scale. All CAAwH underwent PMAAS testing for both sides randomly vs the dominant side (DS) in TDBs. For assessing viscous stiffness (VS) and elastic stiffness (ES), eight different oscillation frequencies were randomly repeated three times for each subject. RESULTS: Good-to-excellent intra- and interday reliability was observed for ES and VS variables. No relevant differences were observed between the ankle viscoelastic properties in CAAwH without joint damage and matched TDBs, whereas the study revealed significantly increased ES in the affected ankles of CAAwH with severe unilateral joint involvement compared to the non-affected joint. CONCLUSION: This study confirmed increased ES in the severely affected ankles of CAAwH compared to non-affected sides. No differences in the ankle viscoelastic properties of CAAwH with or without joint damage were observed, however, compared to matched TDB.

Physical and mental quality of life in adult patients with haemophilia in Belgium: the impact of financial issues.

In Belgium, where haemophilia affects approximately 1:7000 people (2011), data on patients' quality of life (QoL) is scarce. This project aims to assess physical and mental QoL (P-QoL and M-QoL) simultaneously, and to analyse the influence of different variables on these two aspects of QoL. After Ethics Committee approval, we contacted 84 adult haemophilia A (HA) and haemophilia B (HB) patients, without current inhibitors, on replacement therapy (on-demand or secondary prophylaxis), regularly followed up at our comprehensive treatment centre. Seventy-one (n = 59 HA, n = 12 HB) replied to our questionnaire, which included the SF36v2 QoL assessment forms. We analysed two groups of variables: one including variables previously associated with decreased QoL, and another including variables with unclear impact on QoL (e.g., patients' understanding of haemophilia-related issues, economical concerns). In our population (mean ± SD age: 45.2 ± 14.7 years old), P-QoL appeared more reduced than M-QoL. P-QoL was strongly influenced by the number of arthropathies while M-QoL was primarily affected by patients' concern of personal costs due to haemophilia. Among this latter group, having knowledge of insurance coverage had a positive impact on M-QoL. Scores did not depend on haemophilia type. QoL was impaired in our haemophilia patients. A simultaneous assessment of P-QoL and M-QoL confirmed the benefit of primary prophylaxis in P-QoL, while originally pointing out the major burden of patients' concerns and poor understanding of haemophilia-related economical issues on their M-QoL. This might become a particularly challenging issue in times of financial crisis.

Recommendations for assessment, monitoring and follow-up of patients with haemophilia.

Over the last few decades, clinical follow-up of patients with haemophilia has become more complex as a result of the introduction of new treatment strategies, the presence of comorbidities related to haemophilia or ageing, as well as the emergence of new tools to evaluate the medical and social consequences of haemophilia. This publication describes the parameters and information that should be documented and the tests, examinations and interventions required for optimal follow-up of a patient with haemophilia. In the absence of formal studies, the present recommendations have been established as result of a series of consensus meetings in the frame of the European Haemophilia Therapy Standardization Board (EHTSB). The following 11 domains were identified: Baseline information, Current status, Treatment, Inhibitor status, Bleeding, Joint status and pain, Comorbidities, Dental care, Physical activities, Social participation and Quality of life. For each domain, details are proposed for the relevant parameters to be captured and monitored as well as the relevant tools that facilitate data collection. Adopting these recommendations should help the individual care of patients and, even though this is not the primary objective of this article, it should also help at national and international level to shape a new approach to haemophilia by working towards a more standardized outcome assessment. Greater standardization should have implications for data collection, improvements in treatment evaluation and optimizing resources.

The relative burden of haemophilia A and the impact of target joint development on health-related quality of life: results from the ADVATE Post-Authorization Safety Surveillance (PASS) study.

Studies with haemophilia A (HA) patients have shown burden in health-related quality of life (HRQOL) when compared with general population norms. In the current study, HA patients' SF-36v2 health survey scores were compared with general population norms and to patients with other chronic conditions. The impact of target joints (TJs) on HRQOL was also examined. The sample was a subset of HA patients enrolled in the Post-Authorization Safety Surveillance (PASS) programme: a prospective open-label study in which ADVATE [Antihaemophilic Factor (Recombinant), Plasma/Albumin-Free Method] was prescribed. A total of 205 patients who were ≥ 18 years old and had SF-36v2 baseline scores were selected for this study. To measure the burden of HA on HRQOL, manova analyses compared these SF-36v2 scores to age- and gender-matched general population US and EU norms and to patients from other chronic condition groups. manova and correlational analyses examined the relations among TJ, age and SF-36v2 scores. Comparisons with general population norms confirm that HA negatively impacts physical, but not mental, HRQOL. Comparison with other chronic conditions shows the physical burden of HA is greater than for chronic back pain but similar to diabetes and rheumatoid arthritis, while the mental burden of HA is less than for all three patient groups. The presence of TJs was negatively associated with physical HRQOL, although this association was much larger for older patients (45+ years) than for younger ones. Physical, but not mental, HRQOL is diminished in HA patients. Target joints are associated with lower physical HRQOL, although this effect is moderated by age.

Current primary care practice in the diagnosis and management of patients with suspected venous thromboembolism and prescription of initiation dose of enoxaparin.

AIM: Ambulatory care of patients with deep vein thrombosis (DVT) has been well validated but limited data exist on the diagnostic and therapeutic management of venous thromboembolism (VTE) in primary care. METHODS: A cross-sectional survey on the clinical conditions for the initiation of once daily (OD) enoxaparin and on the diagnostic and therapeutic strategy of VTE in ambulatory patients using a single-visit questionnaire to be filled out by the general practitioner (GP). RESULTS: Of the 4522 included patients, 2164 (48%) were started on therapeutic OD enoxaparin for confirmed or suspected proximal DVT, 464 (10%) for distal DVT, 493 (11%) for pulmonary embolism (PE), and 742 (16%) for superficial venous thrombosis (SVT). Further indications included bridging of oral anticoagulation in 173 patients (4%), atrial fibrillation in 77 patients (2%) and prevention of VTE in 78 patients (2%). Enoxaparin was initiated on the basis of clinical probability before objective confirmation in 17%, 33%, 53% and 69% of patients with a diagnosis of PE, proximal DVT, distal DVT and SVT, respectively. No objective testing was planned for 3%, 9%, 18% and 41% of patients in these respective categories. Patients were referred to specialist care in 88%, 49%, 42% and 21% of patients with PE, proximal DVT, distal DVT and SVT, respectively. CONCLUSION: Therapeutic OD enoxaparin is prescribed in primary care for the whole clinical spectrum of VTE. However, the diagnostic work-up is unsatisfactory to suboptimal in a substantial proportion of these patients.

Should prophylaxis be used in adolescent and adult patients with severe haemophilia? An European survey of practice and outcome data.

A survey of 21 haemophilia doctors, throughout Europe, who care for a total of approximately 5000 patients with bleeding disorders addressing practice and opinions regarding prophylaxis in patients aged 16-24 years and adults aged over 50 years, is presented. The outcome of adolescent patients who reduced or stopped prophylaxis was recorded. Eighteen of 19 respondents would consider modification of established prophylaxis in the adolescent age group, principal considerations being avoidance of risks of further concentrate exposure, predicted poor compliance and treatment costs. The preferred age for modification was 16-20 years, but there was very little consensus on the particular prophylactic regime recommended. Approximately, half of a cohort of 218 patients with severe haemophilia successfully reduced or stopped prophylaxis when they reached adolescence. Only 26 of 92 (28%) of the patient cohort who stopped prophylaxis, required reintroduction of a prophylactic regime and 12 of 59 (20%) of those who reduced the intensity of prophylaxis had to reintroduce a more intensive regime. A majority of respondents would consider starting prophylaxis in those over 50 years. There was no consensus as to indications for this practice or the nature of the prophylaxis protocol. We conclude that there is an absence of consensus on the management of patients with severe haemophilia, as they pass through adolescence and young adulthood, and reach the age of 50. Aggregate outcome data suggest a significant proportion of patients in the 18-22 years age range may be able to reduce or stop prophylaxis. A substantial number of older patients are on prophylaxis.

Feasibility, safety and cost-effectiveness of transjugular liver biopsy following major surgery in patients with haemophilia.

Prior to the introduction of virally inactivated clotting factor concentrates, the majority of patients with haemophilia became infected with the hepatitis C virus. Although transjugular liver biopsy can be safely performed in these patients, the procedure is associated with a significant financial burden mainly related to replacement therapy with clotting factor. The purpose of this study was to evaluate the feasibility and safety of transjugular liver biopsy in patients with haemophilia substituted with clotting factor concentrates for major surgical procedures. Over the last 5 years, transjugular liver biopsy was performed in nine patients with haemophilia within 1-10 days after orthopaedic (7), thoracic (1) or abdominal surgery (1). All patients had abnormal liver function tests and persistent hepatitis C viraemia. At the time of the biopsy, patients received recombinant factor VIII delivered by dose-adjusted continuous infusion through a central catheter inserted preoperatively in the left internal jugular (n = 8) or in an ante-cubital vein (n = 1). Before the biopsy, basal FVIII levels were raised to 80-100% by a bolus infusion and maintained above 80% for 24 h. The biopsy was informative in all cases. Only one patient developed an episode of supraventricular dysrhythmia. No bleeding or infectious complications were observed. When compared with elective liver biopsy performed outside the postsurgical period, the cost-savings per biopsy were 19 875 +/- 2660 euro. This study shows that intensive replacement therapy required by surgical procedures provides a safe and cost-effective opportunity for transjugular liver biopsy in patients with haemophilia and active hepatitis C.

[Coagulation factors and hemostatic agents]. / Facteurs de coagulation et agents hémostatiques.

A large variety of therapeutic agents are available to prevent or treat hemorrhagic events. An etiologic focusing is essential to permit a rational use of these drugs. Some medications are cheap, others are very expensive, and the clinician has to evaluate the cost-effectiveness of his prescription in each situation.

Pneumoproteinaemia: a new perspective in the assessment of lung disorders.

Here we make the hypothesis that the determination of the concentration of lung specific secretory proteins in serum or pneumoproteinaemia could be used in the evaluation of lung disorders with a similar utility as proteinuria in kidney diseases involving the glomeruli. Human and experimental data indicate that comparable structural and functional features govern the passage of proteins across the lung epithelium/blood barrier and the glomerular filter. The concentrations in serum of some lung-specific secretory proteins, such as the bronchiolar Clara cell 16 kDa protein (CC16) and alveolar surfactant-associated proteins A and B (SP-A and SP-B, respectively), might be used to assess the integrity of the bronchoalveolar/blood barrier known to be disrupted in many lung disorders. In addition, if this barrier is intact or slightly compromised, these proteins might serve as peripheral markers to detect changes in secretory epithelial cells in the lung.