Haemophilia in Spain

Summary.  . To determine the prevalence of haemophilia A and B and their complications in Spain, and to characterize the health care network providing support to haemophiliac patients. The study examines clinical and genetic characteristics, treatment options, and complications observed during the course of the disease. Cross-sectional multi-centre study. The study population were patients with HA and HB in active follow-up at any Spanish hospital by December 2006. We studied 2400 haemophiliacs, 2081 (86.7%) HA and 319 (13.3%) HB patients. Illness was severe in 32.3% of patients, moderate in 16.4%, and mild in 51.3%. Genetic screening was carried out in 32.6% of the patients. Treatment administered in 2006 consisted of coagulation factor concentrates in 60% of patients. Until December 2006, 45.8% of severely ill patients were taking prophylaxis. The mean number of bleeding episodes in 2006 was four for patients not receiving primary prophylaxis and 1.3 for those taking primary prophylaxis. Thirty percent of patients had established haemophiliac arthropathy in at least one joint; 16.8% of patients were HIV-infected and 34.8% HCV-infected. Inhibitors were detected in 10% of severe HA patients and in 6.5% of severe HB patients. Immune tolerance induction therapy was started in 34 patients. This is the first comprehensive study on the epidemiology of haemophilia in Spain. It will enable us to draw comparisons with neighbouring countries, to assess the quality of care provided to haemophiliacs in Spain, and to provide evidence-based guidance for the even provision and improvement of such care.     

Haemophilia, aging and sexuality

Summary.  The older generation of patients with haemophilia still has musculoskeletal problems which limit activities and participation. One important aspect of male aging is the changes in sexuality. Sexual desire can be disturbed by fatigue, low testosterone or pain. Sexual excitement (erection) may be influenced by diabetes mellitus, arteriosclerosis, hypertension and side effects of antihypertensive and antiviral medication. Sexual response problems can be caused by antidepressant medication. In aging haemophiliacs arthropathy, iliopsoas muscle bleeding, chronic hepatitis C and HIV medications influence sexuality. The haemophilia care professionals should communicate proactively, give information on various practical aspects of sexuality (suggest suitable positions, recommend painkillers, reflect on prescribing erection-enhancing medication, refer to a sexology expert).     

Haemophilia Care in Europe: the ESCHQoL study

The aim of this study was to determine the clinical conditions of patients with haemophilia within Europe as recommended by the European Commission. In this multicentre, cross‐sectional, ambispective study, conducted within 21 European countries patients' clinical data were collected, amongst others haemophilia type, severity, treatment pattern, use of factor products, bleeding, orthopaedic joint scores and infections. A total of 1400 patients, 84.3% with haemophilia A and 15.7% with haemophilia B were enrolled by 42 centres between 2004 and 2006. Thereof, 417 were children (30.0%) and 983 were adults (70.0%). About 70% of patients had severe factor deficiency (<1%). More than half of the adults were carriers of chronic infections (12.6% HIV, 55.8% HCV), compared to only 3.8% children (no HIV, 2.9% HCV). Patients were grouped according to per capita amount of clotting factor used in patients' region of residence in 2005: region 1: >5 IU; region 2: 2–5 IU; region 3: <2 IU. Paediatric and adult patients in region 3 had median numbers of three and eight joint bleeds, respectively, with worse joint scores compared to region 1 with zero and one bleed. Prophylactic therapy was used in only 31.3% children and 8.9% adults with severe haemophilia in region 3 compared to 93.7% and 54.1%, respectively, in region 1. Statistical analysis revealed that residence in areas with low factor consumption/availability is the most prominent risk factor for joint disease. Access of European patients with haemophilia to optimal care with safe factor VIII concentrates is limited and depends on the region of residence.     

Quality of life is associated to the orthopaedic status in haemophilic patients with inhibitors

Inhibitors represent one major complication of haemophilia treatment, as they increase the risk of bleeding, physical disability and mortality. The Cost Of Care Inhibitors Study (COCIS) showed that modern strategies applied to manage patients with inhibitors adsorb high amounts of resources but provide satisfactory levels of Health-Related Quality-of-Life (HR-QoL). This paper focuses on determinants of HR-QoL in inhibitory patients. Fifty adult patients, enrolled by 11 Italian Haemophilia Centres, were clinically assessed and filled in two HR-QoL generic questionnaires: the EuroQol instrument (EQ-5D) and the Short Form-36 (SF-36). According to our results, bleeding frequency and inhibitor titres were not found associated with HR-QoL. Global HR-QoL, and in particular the physical component of wellbeing in these patients was found negatively associated with their orthopaedic condition: the EQ-5D Visual Analogue Scale (P<0.001) scores, the SF-36 domain 'physical functioning' and 'physical component summary' (P<0.01) scores were found significantly correlated with the orthopaedic joint score, even after adjusting for patients' age. These results were confirmed by those from the EQ-5D profile. To conclude, the COCIS study is the first study showing that HR-QoL in inhibitory patients is impaired by their orthopedic status, while other aspects do not seem to influence patients' global wellbeing. Our results suggest that while the management of this complication is satisfactory, the attention has now to be focused on the prevention of the orthopaedic problems in these patients, which nowadays constitute one of the most important aspects to be considered in the haemophilia care.     

Functional impact of custom-made foot orthoses in patients with haemophilic ankle arthropathy

Although foot orthoses are often prescribed to patients with haemophilia (PWH) and ankle arthropathy, the efficacy and biomechanical effects of such devices are not fully understood. We experimentally investigated the effects of orthopedic insoles (OI) and shoes (OS) in PWH presenting ankle arthropathy, with specific attention being paid to pain, spatiotemporal parameters, kinematics and kinetics of lower limb joints, as well mechanical and energetic variables. Using three-dimensional gait analysis (3DGA), synchronous kinematics, kinetics, spatiotemporal, mechanics, and metabolic gait parameters were measured in 16 PWH with ankle arthropathy. The revised Foot Function Index (FFI-R) and 3DGA were determined in patients wearing neutral running shoes at two time points (T0 and T1), with OI (n = 11) or OS (n=5) being subsequently prescribed. Patients, while wearing their orthoses, were re-evaluated using 3DGA, FFI-R, and satisfaction questionnaires (T2). OI and OS provided significant pain relief and comfort improvement in more than half of the patients, with minimal side effects. OI had limited impact on gait pattern, whereas OS significantly improved the propulsive function of the ankle. Biomechanical changes induced by OI and OS were independent of their ability to improve comfort, while being insufficient to influence knee and hip kinematics and kinetics, or mechanical and energetic variables. These findings suggest that OI and OS may have beneficial effects on ankle joints in PWH. Self-reported clinical tools such as FFI-R and satisfaction questionnaires are sufficiently sensitive for assessing the efficacy of foot orthoses in PWH.     

Haemophilia B- in a girl

Summary. Haemophilia B is extremely rare in females and so far 20 cases have been reported. A 9-year-old girl with severe haemophilia symptoms is described, who shows a very low level of factor IX activity (1.5%) and antigen (> 10%), normal XX female karyotype and negative family history of bleeding tendency or consanguinity. This case is probably the fourth report of sporadic female haemophilia B without chromosomal aberration and the first one with quantitative analysis by immunoradiometric assay and enzyme-linked immunosorbent assay of factor IX antigen. This very low factor IX level and severe bleeding tendency of the patient would be consistent with the homozygous state, but since a double mutation is extremely rare the patient's laboratory findings can be more easily explained by extreme lyonization of the normal X-chromosome of a heterozygous carrier.     

Case studies: orthopaedic surgery in adult patients with haemophilia A with inhibitors

Summary.  Whilst orthopaedic surgery in haemophilia patients without inhibitors is now relatively common in specialized centres, until recently there have been only a few sporadic instances of surgery having been undertaken on patients with inhibitors. The availability of recombinant activated factor VII (rFVIIa) for haemostatic cover during surgery allows procedures to be performed that previously may not have been considered possible. Complications associated with thrombosis are rare in haemophilia patients with inhibitors, but bleeding complications remain a concern. Globally, experience of performing orthopaedic surgery in these patients is increasing and many successful outcomes have been reported. However, more knowledge relating to the incidence and type of bleeding complications liable to be encountered, together with further information about appropriate rescue treatment, would be valuable. Data relating to long-term follow-up after surgery would be useful, as would a comparison of outcomes between haemophilia patients with and without inhibitors. Optimal dosing regimens for rFVIIa as surgical cover are still to be determined and further information is required relating to the cost effectiveness of rFVIIa in surgery. Further study should address these issues.     

Septic arthritis in males with haemophilia

Summary.  We used data collected as part of the Universal Data Collection (UDC) surveillance project in haemophilia treatment centers (HTC) to study the incidence, risk factors and impact of septic arthritis among males with haemophilia. Patients participating in UDC on two or more occasions were included. Cases were defined as patients with documented joint infection. Characteristics of the cases were compared with those of haemophilia patients without infection. Among the 8026 eligible patients with 36 015 person-years of follow-up, 30 (0.37%) had a documented joint infection (incidence rate 83 per 100 000 person-years). In a logistic regression model, only increasing age (OR = 6.1 for age ≥30), race/ethnicity other than white (OR = 3.9), presence of inhibitor (OR = 3.9), invasive procedure in the past year (OR = 2.7) and presence of one or more target joints (OR = 3.2) remained statistically significant. Central venous access devices use and hepatitis C virus and HIV infection were not associated with septic arthritis risk after adjusting for potential confounders. Study limitations include possible underestimation of septic arthritis rate in this population and its retrospective design. We conclude that septic arthritis is an uncommon complication of haemophilia occurring primarily in joints most affected by bleeding and reparative surgical interventions.     

Orthopaedic surgery of haemophilia in the 21st century: an overview

Close co-operation between haematologists, orthopaedic surgeons, rehabilitation physicians and physiotherapists is essential for obtaining satisfactory results after orthopaedic procedures that are performed on haemophilic patients. Although continuous prophylaxis could avoid the development of the orthopaedic complications of haemophilia that we still see in the 21st century, such a goal has not been achieved so far, not even in developed countries. Therefore, orthopaedic surgeons are still required to carry out many different surgical procedures, such as arthrocentesis, synoviorthesis, synovectomies, tendon lengthening, articular debridements, alignment osteotomies, joint arthroplasties, nerve releases, opening of compartment syndromes, removal of pseudotumours and osteosynthesis of fractures. Furthermore, the emergence of human immunodeficiency virus has meant that immunosuppressed patients in developed countries sometimes require an arthrotomy for the treatment of spontaneous septic arthritis, or the surgical drainage of a spontaneously infected haematoma (abscess). In addition, they have a high risk of postoperative infection after any surgical procedure, particularly a joint arthroplasty.     

Evaluation of outcome of care in patients with haemophilia

Haemophilia is a potentially disabling condition associated with high financial costs, and so the need for robust measures to evaluate outcome of care is essential. This paper is a review of some of the outcome measures commonly used to evaluate treatment in haemophilia and includes quality of life measures, evaluation of the musculoskeletal system and orthopaedic surgical procedures. Quality-of-life questionnaires are discussed with particular reference to the SF36 and AIMS2. Results of published studies to date have demonstrated variable results. Overall, haemophilia appears to reduce quality of life compared to normal population figures. Several factors are perceived to reduce quality of life, and these include being human immunodeficiency virus (HIV) positive, having impairments, and a history of orthopaedic surgery. The evaluation of the musculoskeletal system is important in order to detect any deterioration over time. Various standardized measurement tools are described. Orthopaedic surgical procedures have also been evaluated in patients with haemophilia. To date, the Hospital for Special Surgery Knee rating scale has been the most commonly used to evaluate the outcome of total knee replacement. The limitations of this system for patients with haemophilia are outlined. Overall, these measures provide useful tools for evaluating outcome, but none have been specifically developed for patients with haemophilia. Further studies would be useful to evaluate these tools and others in more depth.     

Haemophilia in the first years of life

Summary.  Surgery in infants and young children with haemophilia, when preceded by accurate diagnosis and accompanied by safe and effective factor prophylaxis, is not associated with a significant risk of haemorrhage. Haemophilic newborns undergoing circumcision or major surgery prior to diagnosis and in the absence of appropriate haemostatic prophylaxis remain as a concern. Inhibitor development has replaced haemorrhage as the major surgical complication in the developed world, largely because of the intensity of treatment used to secure haemostasis. For that reason only, essential surgery should be performed. Intracranial haemorrhage (ICH) during the neonatal period affects 3.5–4.0% of all haemophilia boys in countries with a good standard of health care, which is considerably (40–80 times) higher than expected in the normal population. Because of the high frequency of sporadic cases, ICH in the neonatal period can only be partially prevented by improved carrier diagnosis and counselling. Infections and thrombosis are the major serious complications of central venous lines. Large differences are seen in the frequency of these complications, the most plausible explanations are probably related to the protocol used for device care, the quality of education and the compliance of the users, an issue addressed in an on-going study.     

The UK Haemophilia Doctors Organisation triennial audit of UK Comprehensive Care Haemophilia Centres

Under the auspices of the United Kingdom Haemophilia Doctors Organisation (UKHCDO) the UK Comprehensive Care Haemophilia Centres (CCCs) have undergone a three yearly formal audit assessment since 1993. This report describes the evolution of the audit process and details the findings of the most recent audit round, the sixth since inception. The audit reports from the 2009 audit round were reviewed by the audit organizing group and a structured analysis of the data was compiled. CCCs in the UK offer a high standard of comprehensive care services. The main areas of concern were the state of the premises (seven centres), lack of dental services (seven centres), physiotherapy (seven centres) and social work support (11 centres). Major concerns were identified at eight centres requiring a formal letter from the chairman of UKHCDO to the chief executive of the host trust. Since inception of the triennial audit process centre report recommendations have resulted in major improvements in the services available at UK CCCs. The audit process is considered to be a highly effective means of improving the quality of care for patients with bleeding disorders and can be used as a model for the introduction of a similar process in other countries.