Publications (8)23.12 Total impact
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Article: Continuous infusion in haemophilia: current practice in Europe.
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ABSTRACT: Continuous infusion (CI) of factor VIII (FVIII) is an effective method for replacement therapy in haemophilia. Recently, concerns have been raised regarding association of CI with the development of inhibitors. The aim of this study was to gain information on the current practices in Europe regarding CI and the true inhibitor incidence after this mode of therapy. In a cross sectional study performed in 22 Comprehensive Care Centres (CCCs), we evaluated CI techniques, treatment protocols, efficacy, safety and complications of CI including inhibitors. Thirteen (59%) CCCs reported a total of 1079 CI treatments, given peri-operatively or for major bleeds, in 742 patients. Most centres used 'adjusted dose' CI aimed at median target FVIII level of 0.8 IU mL(-1). CI was haemostatically very effective with a low incidence of complications: median incidence of postoperative bleeding was 1.8%, six centres observed phlebitis in 2-11% of CI treatments. Only nine (1.2%) patients developed inhibitors (0.45% of 659 severe and 7.2% of 83 mild haemophilia patients). Additional analysis of inhibitor patients revealed several confounding factors (low number of prior FVIII exposure days, high steady-state factor levels during CI, high-risk genotype). In this unprecedentedly large cohort, CI treatment appears to be an effective and safe treatment that does not increase the risk of inhibitor development in patients with severe haemophilia. Thus, previous small case series reports suggesting that CI may increase inhibitors cannot be confirmed. Inhibitor risk in mild haemophilia could not be evaluated as the influence of other, potentially confounding, risk factors could not be excluded.Haemophilia 04/2012; 18(5):753-9. · 2.60 Impact Factor -
Article: Pain management in patients with haemophilia: a European survey.
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ABSTRACT: There are no evidence-based guidelines on pain management in people with haemophilia (PWH), who may suffer acute, disabling pain from haemarthroses and chronic arthropathic pain. To review evidence and to investigate current clinical practice in pain assessment and management in PWH the European Haemophilia Therapy Standardisation Board undertook a literature review and a survey in 22 Haemophilia Treatment Centres (HTC), using a questionnaire and seven clinical scenarios. Consensus was sought on pain assessment and management in PWH. Few clinical studies on pain management in PWH were identified. The HTCs care for 1678 children (47% severe haemophilia, 84% on prophylaxis, 17% with arthropathy and 8% with chronic pain) and 5103 adults (44% severe haemophilia, 40% on prophylaxis, 67% with arthropathy and 35% with chronic pain). Analgesics are prescribed by HTCs in 80% of cases (median; range 0-100%) and in 10% (median; range 0-80%) are bought over the counter. Pain and analgesic use are assessed when reported by patients and at check-ups. Only eight centres use a specific pain scale and/or have specific pain guidelines. Two HTCs arrange regular consultations with pain specialists. For acute pain, the preferred first-line drug is paracetamol for children, and paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for adults. Children with chronic pain are treated with paracetamol or NSAIDs, whereas adults usually receive Cox-2 inhibitors. Second-line therapy is heterogeneous. There is little published evidence to guide pain assessment and management in PWH, and clinical practice varies considerably across Europe. General and specific recommendations are needed.Haemophilia 04/2012; 18(5):743-52. · 2.60 Impact Factor -
Article: Neonatal bleeding in haemophilia: a European cohort study.
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ABSTRACT: Birth is the first haemostatic challenge for a child with haemophilia. Our aim was to examine the association between perinatal risk factors and major neonatal bleeding in infants with haemophilia. This observational cohort study in 12 European haemophilia treatment centres (HTC) incorporated 508 children with haemophilia A or B, born between 1990 and 2008. Risk factors for bleeding were analysed by univariate analysis. Head bleeds occurred in 18 (3·5%) children within the first 28 d of life, including three intraparenchymal bleeds, one subdural haematoma and 14 cephalohaematomas. Intra-cranial bleeds were associated with long-term neurological sequelae in two (0·4%) cases; no deaths occurred. Assisted delivery (forceps/vacuum) was the only risk factor for neonatal head bleeding [Odds Ratio (OR) 8·84: 95% confidence interval (CI) 3·05-25·61]. Mild haemophilia and maternal awareness of her haemophilia carrier status seemed to be protective (OR 0·24; 95%CI 0·05-1·05 and OR 0·34; 95%CI 0·10-1·21, respectively), but due to the low number of events this was not statistically significant. We found no association between neonatal head bleeding and country, maternal age, parity, gestational age or presence of HTC. Maternal awareness of carrier status protected against assisted delivery (unadjusted OR 0·37; 95%CI 0·15-0·90; adjusted OR 0·47 (95%CI 0·18-1·21).British Journal of Haematology 12/2011; 156(3):374-82. · 4.94 Impact Factor -
Article: Management of acute haemarthrosis in haemophilia A without inhibitors: literature review, European survey and recommendations.
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ABSTRACT: Acute haemarthrosis is a frequent type of bleeding in individuals with haemophilia. Delayed and/or inadequate treatment can trigger a series of pathological changes within the joint, leading to a painful and disabling arthropathy. The early management of intra-articular bleeding has the potential to prevent chronic joint disease and may include a combination of factor replacement, rest, ice, rehabilitation and, in certain cases, joint aspiration. Little data are, however, available regarding the optimal management of acute haemarthrosis, especially with respect to replacement therapy and the use of adjunctive therapies (aspiration, avoidance of weight bearing and immobilization, as well as the use of anti-inflammatory medication and embolization). To provide more insight into the management of acute haemarthrosis in patients with haemophilia, a literature review was conducted. Concomitantly, current management was surveyed in 26 European haemophilia comprehensive care centres representing 15 different countries. The review highlights the need for future robust studies to better define the appropriate replacement therapy and the role of adjunctive therapies such as aspiration. The survey reveals much heterogeneity in the management of acute haemarthrosis across the EU. Within the constraints discussed, treatment recommendations are presented that reflect the literature, current practice and the clinical experience of the European Haemophilia Therapy Standardisation Board (EHTSB).Haemophilia 02/2011; 17(3):383-92. · 2.60 Impact Factor -
Article: Postauthorization safety surveillance of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method] demonstrates efficacy, safety and low-risk for immunogenicity in routine clinical practice.
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ABSTRACT: Postauthorization safety surveillance of factor VIII (FVIII) concentrates is essential for assessing rare adverse event incidence. We determined safety and efficacy of ADVATE [antihaemophilic factor (recombinant), plasma/albumin-free method, (rAHF-PFM)] during routine clinical practice. Subjects with differing haemophilia A severities and medical histories were monitored during 12 months of prophylactic and/or on-demand therapy. Among 408 evaluable subjects, 386 (95%) received excellent/good efficacy ratings for all on-demand assessments; the corresponding number for subjects with previous FVIII inhibitors was 36/41 (88%). Among 276 evaluable subjects receiving prophylaxis continuously in the study, 255 (92%) had excellent/good ratings for all prophylactic assessments; the corresponding number for subjects with previous FVIII inhibitors was 41/46 (89%). Efficacy of surgical prophylaxis was excellent/good in 16/16 evaluable procedures. Among previously treated patients (PTPs) with >50 exposure days (EDs) and FVIII≤2%, three (0.75%) developed low-titre inhibitors. Two of these subjects had a positive inhibitor history; thus, the incidence of de novo inhibitor formation in PTPs with FVIII≤2% and no inhibitor history was 1/348 (0.29%; 95% CI, 0.01-1.59%). A PTP with moderate haemophilia developed a low-titre inhibitor. High-titre inhibitors were reported in a PTP with mild disease (following surgery), a previously untreated patient (PUP) with moderate disease (following surgery) and a PUP with severe disease. The favourable benefit/risk profile of rAHF-PFM previously documented in prospective clinical trials has been extended to include a broader range of haemophilia patients, many of whom would have been ineligible for registration studies.Haemophilia 11/2010; 16(6):866-77. · 2.60 Impact Factor -
Article: Replacement therapy for invasive procedures in patients with haemophilia: literature review, European survey and recommendations.
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ABSTRACT: Although most surgical and invasive procedures can be performed safely in patients with haemophilia, the optimal level and duration of replacement therapy required to prevent bleeding complications have not been established conclusively. For providing more insight into optimal therapy during invasive procedures, a literature review of surgical procedures in patients with haemophilia was conducted. Concomitantly, current practice was surveyed in 26 European Haemophilia Comprehensive Care Centres, representing 15 different countries. The review identified 110 original papers published between 1965 and 2007. Of these, only two studies were randomized controlled trials. Target levels and the duration of replacement therapy in the published studies were as follows. For major orthopaedic surgery: preoperative targets were 80-90%; postoperative targets showed a high degree of variation, with trough levels ranging from 20% to 80%, duration 10-14 days; for liver biopsy, 70-100%, 1-7 days; tonsillectomy: 90-100%, 5-11 days; indwelling venous access device insertion: 100%, 3-10 days; circumcision: 50-60%, 2-4 days; dental surgery: 30-50%, single treatment. With the exception of dental surgery, current practice in Europe, as assessed by the survey, was largely in agreement with published data. In conclusion, this study provides both a comprehensive review and a large survey of replacement therapy in patients with haemophilia undergoing invasive procedures; these data have informed the consensus practical treatment recommendations made in this paper. This study highlights the need for better-designed studies in order to better define minimal haemostatic levels of replacement therapy and optimal treatment duration.Haemophilia 06/2009; 15(3):639-58. · 2.60 Impact Factor -
Article: Should prophylaxis be used in adolescent and adult patients with severe haemophilia? An European survey of practice and outcome data.
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ABSTRACT: 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.Haemophilia 10/2007; 13(5):473-9. · 2.60 Impact Factor -
Article: Recommendations for postmarketing surveillance studies in haemophilia and other bleeding disorders.
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ABSTRACT: Prospective surveillance studies to monitor drug safety in the postapproval period are rarely employed systematically, although they are of greatest value for caregivers, drug users and regulatory authorities. Safety issues have affected not only conventional pharmaceuticals, but also especially coagulation factors in haemophilia treatment. The reputation of postmarketing surveillance (PMS) studies has been questionable, mainly due to their misuse to solicit prescriptions. Other weaknesses include inappropriate design, lack of standardized observation, limited follow-up periods, absence of rigour in identifying potential adverse drug effects, and infrequent publication. Although well-designed clinical trials represent the gold standard for generating sound clinical evidence, a number of aspects would make PMS studies valuable, if properly conducted. One of their main advantages is broader inclusion, and absence of an 'experimental' design. Lack of proper guidelines, and standardization may constitute a reason for the generally low quality of PMS studies. This paper proposes guidelines for haemophilia-specific PMS studies, in order to improve the acceptance of a basically valuable tool. In the absence of consistent regulatory guidance it will be especially important that the design and supervision of PMS studies involves physicians from the beginning. This will not only make such studies more scientifically relevant, but also help to implement them into daily clinical practice. Specifically in haemophilia, PMS studies may provide valuable data on clinical outcomes, or Quality of Life, which is of great importance when considering adequate standards of care in haemophilia patients.Haemophilia 08/2005; 11(4):353-9. · 2.60 Impact Factor
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- Haemophilia (5)
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Institutions
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2007–2011
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The Bracton Centre, Oxleas NHS Trust
Dartford, ENG, United Kingdom
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