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Hemophilia is one of the most common serious congenital coagulation factor deficiency diseases characterized by decreased function or absence of factor VIII or factor IX that is associated with significant morbidity and mortality. Aim: the current study aimed to evaluate the effect of family centered care model on caregivers of children with hemophilia. Design: A quasiexperimental research design (one group pre-posttest) was used. Setting: the study was conducted at inpatient department and outpatient clinic in Badr University Hospitals affiliated to Helwan University Hospitals and Mustafa Hassan pediatric Hospital affiliated to Fayoum University Hospitals. Sample: the study involved 60 children and their accompanying caregivers suffering from hemophilia disease. Tool: consists of four tools to assess: I: A structured interviewing questionnaire sheet to assess caregivers' knowledge regarding hemophilia disease (one group pre/posttest). II: Observational checklist to assess caregivers' reported practice regarding care of their children with hemophilia. III: caregiver's coping patterns, IV: The Family-Centered Care (FCC) scale for caregivers. Results: the current results referred that there was statistically significant difference between family centered care scale and their total knowledge and their total practices regarding hemophilia pre and post intervention. Also, there were statistically significant a positive correlation between their total knowledge, their total practices, their total coping and family centered care scale. Conclusion: the present study concluded that there was a positive effect of implementation of model on improving knowledge, practices and coping pattern of the studied caregivers. Recommendations: encourage family centered care programs periodically for caregivers having children with hemophilia to help them improve care for their children and reduce complications of the disease. [ABSTRACT FROM AUTHOR]

Hemophilia A is a coagulation disorder where the main clinical manifestation is the presence of hemorrhage. The aim of the study was to characterize hemophilia A through the results obtained in a case study of a child from Ecuador. The epidemiological study, at a descriptive level, was a clinical case that consisted of a 3-year-old Ecuadorian male patient, who at 3 months of age presented spontaneous hematomas in the lower limbs and back area. At 5 months of age, he was diagnosed with acute bronchitis with a clinical picture accompanied by nausea, vomiting and greenish liquid stools with mucus. Physical examination showed the presence of hydrocele in the first 2 months of birth. Laboratory data indicated that the patient had decreased coagulation factor VIII (less than 0.3), classifying the disease as mild. The patient's family tree indicated that the maternal uncle had hemophilia A, so there was a 50% probability that the patient presented the pathology. The present study reported the case of a 3-year-old male patient with hemophilia A, concluding that it is of utmost importance for the physician to thoroughly investigate the patient's family history and make an early diagnosis by taking an umbilical cord blood sample to determine the levels of coagulation factors. [ABSTRACT FROM AUTHOR]

Children with haemophilia present a bleeding risk and a challenge for dentists. Guidelines on the dental management of haemophilia patients are largely based on expert consensus. Many existing guidelines also provide generic guidance mainly for adult patients, which have been adapted for children. However, children have unique needs that require additional considerations. With limited evidence available, it is important that dentists have an understanding of the principles of both medical and dental management and have a close collaboration with the haematologist at all times. Therefore, this paper provides some key principles related to various aspects of dental management of children with haemophilia. Furthermore, there has been a recent update to the World Federation of Haemophilia (WFH) Guidelines for the Management of Haemophilia, with references to novel medical therapies for haemophilia. Hence, this paper also aims to inform dentists with the standard and newer medical therapies for haemophilia, including a specific focus on the novel agent Emicizumab and the associated dental considerations. [ABSTRACT FROM AUTHOR]

Hemophilia is a sex-linked recessive disorder characterized by a lack of blood factors necessary for clotting. This review aims to investigate the benefits of sports activities in children with hemophilia in terms of both physical and psychological wellness. Sports activity is necessary for children with hemophilia to preserve joints’ range of motion, reduce joint bleeding, improve muscle mass and strength, enhance proprioception and prevent secondary chronic diseases. In the past, high-impact sports were usually forbidden in children with hemophilia because of their high bleeding risk. Recent studies, however, have shown that prophylaxis therapy can allow a hemophilic child to take part in vigorous activities or high-impact sports. The benefits of sports activity in children with hemophilia are expressed by a better muscular trophism and an improved bone mineral density. Moreover, physical activity has a positive impact on children’s psychosocial well-being. Due to prophylaxis therapy, the quality of life of children with hemophilia is similar to their peers, and this has allowed an improvement in sports participation, including team sports. [ABSTRACT FROM AUTHOR]

Comparison of personalized and standard prophylaxis - based on octocog alfa in pediatric patients with hemophilia A. Studies on a general population (adults and children) demonstrate a statistically significant advantage of personalized over standard prophylaxis in terms of annual bleeding rate (ABR) and annual joint bleeding rate (AJBR) while studies on a pediatric population included insufficiently large populations, however, their results demonstrate a numerical advantage of personalized approach over standard prophylaxis regimen. [ABSTRACT FROM AUTHOR]

The article presents abstracts of research studies related to pediatric exercise science. They include "Voluntary fluid intake and core temperature responses in adolescent tennis players: sports beverage versus water, " by M. F. Bergeron, J. L. Waller, and E. L. Marinik in "Br. J. Sports Med.," "Physical fitness, functional ability and quality of life in children with severe haemophilia: a pilot study," by J. Van Der Net, R. C. Vos, R. H. H. Engelbert, M. H. Van Der Berg, P. J. M. Helders, and T. Takken in "Hemophilia," and "Normal physical working capacity in prepubertal children with type 1 diabetes compared with healthy controls," by E. Heyman, D. Briard, A. Gratas-Delamarche, P. Delamarche, and M. De Kerdanet in "Acta Pediatr."

Aim: Regular physical activity is important to prevent damage and protect joint health in hemophilic individuals. However, hemophilia patients tend to limit their physical activity due to frequent bleeding. There may be some factors, such as fear of movement or kinesiophobia under these attitudes. For this reason, this study aimed to research the relationship between kinesiophobia and physical activity levels in adult hemophilic individuals. Material and Methods: This study was performed with a retrospective study design. A total of 44 patients included in this study; 33 were hemophilia A, 11 were hemophilia B. All hemophilic individuals were male and between the ages of 18-60 (mean=35.30±12.04). Tampa Scale for Kinesiophobia (TSK) was used to determine fear of movement. To determine the physical activity levels of individuals, the “International Physical Activity Questionnaire-Short Form” was used. The results were analyzed using Spearman correlation analysis and Mann-Whitney U test. Results: There was no statistical correlation between kinesiophobia degree and physical activity level (p=0.616, r=−0.081). There was also no significant difference in kinesiophobia scores between hemophilia A and hemophilia B (z=-0.707, p=0.479). High kinesiophobia levels (TSK score of ≥37) were present in 90.9% of patients. According to physical activity levels, 36.4 % of patients had low, 34.1 % had moderate and 29.5 % had high physical activity levels. Hemophilia A patients had higher physical activity levels than hemophilia B (z=-2.400, p=0.016). Conclusion: These results showed no correlation between physical activity level and kinesiophobia, but high kinesiophobia rates in adult hemophilic individuals. Hemophilia patients should be educated and encouraged about safe and fearless physical activity. [ABSTRACT FROM AUTHOR]

Background: Health-related quality of life (HRQoL) has been brought up for decades in haemophilia patients. However, no data to date are available about HRQoL in children with haemophilia using long-term follow up data. This nearly 4-year follow-up study aimed to assess the long-term HRQoL of haemophilia children.Methods: A prospective cohort study among 42 children with haemophilia and their parents was conducted in August 2014 in a children's hospital; follow-up was completed in January 2018. Primary endpoint was the change in patient HRQoL evaluated by Canadian Haemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) from baseline to year 4; secondary endpoint was the impact of bleeding rates, physical activity restriction, financial burden and treatment (prophylaxis vs on-demand treatment) on HRQoL, as well as the impact of treatment on event-free survival.Results: Totally 42 patients (mean age, 5.48[SD, 4.63] years) and 42 parents were included. 38 families completed 4-year follow up. Patients reported a small increase in HRQoL from baseline to year 4. The mean scores of child self-report and parent proxy report of CHO-KLAT at baseline were 60.69 (SD = 20.28) and 61.01 (SD = 12.14), respectively. Scores at follow-up were 64.69 (SD = 13.71) and 65.33 (SD = 15.78), respectively. Haemophilia patients without physical activity restriction, living in urban areas, and receiving prophylactic treatment and home injection, had higher average values for HRQoL scores than the others. Bleeding rates were proportionally negatively correlated with HRQoL. Patients who had received prophylactic treatment had better event-free survival.Conclusions: Haemophilia decreased HRQoL of patients, but this effect weakened after 4 years. HRQoL of children is influenced by severity of haemophilia, bleeding rates, physical activity restriction, financial burden and treatment. Prophylactic treatment is a key factor contributing to event-free survivor prognosis and the optimal form of therapy for childhood haemophilia. [ABSTRACT FROM AUTHOR]

Objective: To assess the reliability and validity of six patient‐reported outcomes (PRO) instruments for evaluating health‐related quality of life in adults with mild‐severe hemophilia B and caregivers of children with hemophilia B, including affected women/girls. Methods: Adults with hemophilia B and caregivers completed separate online surveys containing several PRO instruments, which were administered to adult participants only (EQ‐5D‐5L, Brief Pain Inventory v2 Short Form, Hemophilia Activities List, and International Physical Activities Questionnaire), both adults and caregivers (Patient Health Questionnaire [PHQ‐9]), or caregivers only (Generalized Anxiety Disorder 7‐Item [GAD‐7] scale). Construct validity and item‐total correlation were assessed using Pearson product‐moment correlation, internal consistency was assessed using Cronbach's alpha coefficient, and known‐group validity was assessed by comparisons to self‐reported characteristics based on the Kruskal‐Wallis test. Results: Patient‐reported outcomes instruments generally showed satisfactory reliability for adults (n = 299) and caregivers (n = 150). In adults, PRO instruments generally showed high construct validity. Most PRO instruments showed expected significant differences among known groups for adults and caregivers. PHQ‐9 and GAD‐7 did not show significant differences among caregiver age groups. Conclusions: Patient‐reported outcomes instruments administered in B‐HERO‐S demonstrated reliability and validity in the broader population of adults with hemophilia B and caregivers when including all severities and genders. [ABSTRACT FROM AUTHOR]

Background& Objectives: People with hemophilia constitute a significant proportion of the population and an oral health care professional faces a considerable challenge while treating them. This study aimed to assess the oral health and dentition status as well as fear of dental treatment in patients with hemophilia and compare it with age-matched healthy subjects.Patients& Methods: This single-center, case-control cross-sectional study was performed on 100 subjects with hemophilia and 100 age-matched healthy controls. Oral health and dentition status was recorded for all the subjects and scored using the simplified oral hygiene index (OHI-S), plaque index, and the dmft/DMFT index.Results: There were a total of 41 children and 59 adults in the hemophilia group and 36 children and 64 adults in the healthy group. When compared to healthy subjects it was observed that individuals with hemophilia had higher debris and calculus scores which was indicative of poor orodental status. There was no significant difference observed in the DMFT scores among the study groups.Interpretation& Conclusions: The oral hygiene of the hemophilics was poorer when compared to the healthy controls. The findings highlight the need for establishing interdisciplinary care for such individuals. [ABSTRACT FROM AUTHOR]

Haemophilia is characterized by a congenital deficiency of clotting factor VIII or IX. One of the consequences of haemophilia is joint bleedings. Repetitive haemathroses induce cartilage damage and chronic synovitis leading to joint deterioration, and to definitive haemophilic arthropathy which is source of walking disability. Three‐dimension gait analysis (3DGA) appears particularly relevant in the case of haemophilia because it allows an evaluation of several joints in weight‐bearing situations. The purpose of this study was to review the interest and the contribution of 3DGA in the management of patients with haemophilia. The greatest interest of gait analysis would be to detect early walking changes with a non‐invasive and well‐tolerated examination, especially in paediatric population. In adulthood, this technic may be also useful to help detect walking worsening in patients known to have already arthropathy. However, it takes time to realize and needs expensive equipment, which limits its possibility of routine use. Although generalizations of these results remain difficult, especially to compare patients with haemophilia to normal population. Indeed, in the studies, patient groups are small and usually heterogeneous in terms of age and target joints. It certainly results of the rarity of the disease. So, it could be interesting to perform a study with a larger cohort in order to allow subgroup analysis, helping to define clearly the place of 3DGA in the strategy of haemophilia evaluation. [ABSTRACT FROM AUTHOR]

Abstract Background Hemophilia is an inherited bleeding disorder. With proper treatment and self-care, persons with hemophilia can maintain an active, productive lifestyle. Hemophilia can be mild, moderate, or severe, depending on the degree of plasma clotting factor deficiency. The aim of the study was to assess the utility of ISTH-BAT in diagnosis, determining severity of the bleeding condition in newly diagnosed and known hemophilia patients, compare the bleeding score (BS) in adult and pediatric groups and investigate its association with plasma factor levels. Methods ISTH-BAT was used to assess BS in a total of 115 patients, 78 with hemophilia A, and 37 with hemophilia B and in 100 controls. Results BS was significantly higher in HA and HB patients as compared to controls, with no significant difference between HA and HB. The BS was very similar in newly diagnosed compared to known hemophilia patients, lower in pediatric compared to adult and higher in severe compared to mild HA patients. Conclusion The ISTH BAT can help identify hemophilia patients. Therefore it is a useful tool to distinguish between affected and unaffected individuals with bleeding. Moreover, an important finding of our study is that there is no major difference between the scores in known and newly diagnosed patients. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia is one of the most common inherited bleeding disorders in the Emergency Department (ED). The most dangerous site of bleeding is the central nervous system. Aims: To describe the characteristics of haemophiliacs arrived to our ED following a head trauma and to analyse the incidence of intracranial haemorrhage (ICH). Materials and Methods: Retrospective, analytical, observational study, conducted in a Paediatric ED. We included haemophilic patients aged from birth to 16 years who consulted after a head trauma over a 6‐year period. Data collected included age, type of haemophilia and head trauma, symptoms, prophylaxis status, CT imaging, treatment and number of visits to the ED. Results: About 46 males and 85 episodes were analysed. The median age was 2.38 years. Severe haemophilia A was the most frequent type of disease (50%). All head injuries were mild, and the most frequent mechanism was a collision with an object (38.8%). In 62 episodes (72.9%) the patients were asymptomatic. The rest 23 events had symptomatology, being the most common headache (26%), emesis (21.7%) and drowsiness (17.4%). Head CT was obtained in 31 episodes, founding altered results in 10 (6 of them corresponding to ICH). All the patients with ICH had symptomatology. About 37 episodes required admission. Conclusion: Intracranial haemorrhage is one of the most dangerous events in haemophiliacs and it may occur after a head trauma. Our study suggests that, in case of head trauma, CT must be obtained in symptomatic patients and in those with additional risk factors. Asymptomatic patients must have prolonged observation. [ABSTRACT FROM AUTHOR]

Introduction: Individuals with bleeding disorders have a high risk of bleeding complications with surgical procedures. Careful planning and management of peri‐operative treatment is vital for their safety. Yet, inter‐provider communication and communication between patients/families and providers is not reliable. Aim: Our haemophilia treatment centre (HTC) created a care gap report that used the electronic medical record to inform our team when patients with bleeding disorders were scheduled for procedures. Methods: An electronic medical record‐based patient registry was linked to the hospital’s surgical schedule and a report was run daily by HTC staff for the upcoming 14 days. We determined the number of surgeries scheduled for patients with a bleeding disorder without the knowledge of the HTC, identified by the care gap report during the 6 months prior to and 2 years after implementing the report. Results: Had the report been in effect 6 months prior, the majority of surgery cases would have been detected and planned for an average of 10 days prior to the procedure. Following implementation, the report identified 62 of 225 surgeries on patients with known bleeding disorders where the HTC did not have prior communication from the patient/family or surgical team. Conclusion: This surgery care gap report provides the date and time of procedures on bleeding disorder patients without relying on contact from patients/families or the surgical team. Its use has resulted in an improved peri‐operative process for patients with bleeding disorders undergoing surgical procedures and potentially prevented surgery cancellations. [ABSTRACT FROM AUTHOR]

Introduction: Intracranial haemorrhage in children with inherited bleeding disorders is a potentially life‐threatening complication and presents a significant therapeutic challenge. Aim: To define the characteristics, management and outcomes of intracranial haemorrhage presenting in UK children ≤16 years of age with inherited bleeding disorders from 2003 to 2015. Method: Retrospective analysis of children treated at UK haemophilia centres. Results: Of 66 children presenting with Intracranial haemorrhage (ICH), 82% had haemophilia A or B, 3% VWD and 15% a rare IBD. The IBD was a severe phenotype in 91%. The rates of ICH were 6.4 and 4.2 per 1000 patient years for haemophilia A and B, respectively. Median age at presentation was 4 months (33% neonates; 91% children <2 years of age). In neonates, delivery was spontaneous vaginal (SV) in 11, instrumental in 6, caesarean in 4 and unknown in 1. In children with haemophilia, the risk of ICH after instrumental delivery was 10.6 times greater than after SV delivery. Trauma was more common in children >2 years (67%) than in children 1 month to 2 years (18%; P = .027). Prior to ICH, only 4.5% of children were on prophylaxis. 6% of haemophiliacs had an inhibitor. The median duration of initial replacement therapy was 15 days. Mortality was 13.5%. Neurological sequelae occurred in 39% of survivors, being more common following intracerebral bleeding. In haemophilia survivors, 52% subsequently developed a FVIII inhibitor. Conclusion: Intracranial haemorrhage occurs most frequently in children with severe IBDs, during the first 2 years of life and in children not receiving prophylaxis. Intracranial haemorrhage often occurs without documented trauma. [ABSTRACT FROM AUTHOR]

Aim: For previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long‐term clinical outcomes and costs of treatment with high‐dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). Methods: From the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. Results: All 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient‐years. The median age of starting home treatment was 1.1 years. The mean (SD) annual treatment costs (€ per kg) were 4391€ (3852). For ages 1‐3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07‐0.46) and so was AJBR at 0.06 (0‐0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383 448€ (259 085). The expected ITI payback period was 1.81 (95% CI 0.62‐12.12) years. Conclusions: Early high‐dose prophylaxis leads to excellent long‐term clinical outcomes, and early childhood ITI therapy seems to turn cost‐neutral generally already in 2 years. [ABSTRACT FROM AUTHOR]

Introduction: Venous access is essential in patients with haemophilia for administration of factor concentrates. Peripheral venipuncture may be challenging, particularly in young children or during immune tolerance induction (ITI). Central venous access devices (CVADs) carry a significant risk for complications. An alternative for venous access is peripheral arteriovenous shunts (AVSs), but there is sparse documentation in the literature. The aim of this study was to document our experience with AVS over 12 years in 27 boys with severe haemophilia. Methods: For AVS creation, a subcutaneous vein is connected end‐to‐side with an artery at the wrist (Cimino) or at the forearm (Gracz shunt). Factor concentrates were substituted as for intermediate size surgery. To prevent shunt occlusion, heparin (5 units/kg/h) was given during the first 3 days. Results: Indications for AVS creation were prophylaxis start (n = 20) and ITI (n = 7). Age at shunt insertion was median 1.5 years (minimum 8 months; maximum 11.7 years). Shunt maturation was achieved within a median of 3 weeks after surgery (1.5 weeks; 18 weeks). Age when home treatment was established was median 2.1 years (9 months; 11.7 years). Four patients required AVS revisions due to stenosis, but 26 of 27 patients (96%) achieved good long‐term shunt function. There were few other complications. Conclusion: Arteriovenous shunts provide a good alternative to CVAD and carry a lower risk of complications. AVSs allow earlier start of prophylaxis and home therapy with an improved quality of life for patients and families. [ABSTRACT FROM AUTHOR]

Introduction: Central venous access devices (CVADs) facilitate repeated or urgent treatments for paediatric haemophilia patients, but are associated with complications. This study examined the burden of illness, healthcare utilization and costs for CVADs in a real‐world hospital setting. Materials and Methods: This study included haemophilia patients ages ≤18 years with discharges during 2006‐2014 in the US Premier Healthcare Database. Haemophilia was identified using ICD‐9 diagnosis codes and CVAD exposure using billing information. After matching haemophilia patients with and without CVADs on demographic and clinical characteristics, we compared infection, thrombosis, length of stay (LOS), inflation‐adjusted hospital cost (2014 $USD) and readmission outcomes using generalized estimating equation models adjusted for hospital teaching status. Results: Among 4793 paediatric haemophilia patients treated at one of 548 hospitals, a total of 197 patients were identified with CVAD exposure. The matched sample included 310 haemophilia patients (155 CVAD and 155 non‐CVAD). CVAD cases had greater frequencies of all‐cause infections (29% vs 17%, P = .01) and thrombosis (6% vs 1%, P = .06), longer adjusted mean LOS (9.5 vs 4.7 days, P = .002), higher adjusted mean inpatient total hospitalization costs ($47200 vs $25389, P = .02) as well as more inpatient and outpatient visits at 30‐, 60‐ and 90‐days (P < .05 for all differences) compared with non‐CVAD patients. Conclusion: Paediatric haemophilia patients with CVADs experienced greater infection rates, healthcare utilization and higher hospitalization costs compared with non‐CVAD patients. The results of this study may inform further research efforts to understand the costs and benefits of novel treatment alternatives for young haemophilia patients requiring CVADs. [ABSTRACT FROM AUTHOR]

Purpose (1) To report a case of successful non-operative management of a pediatric pseudoaneurysm in a patient with severe factor V deficiency. (2) To review the literature on pediatric pseudoaneurysms managed with a trial of conservative therapy. Methods A review of the literature was conducted on OVID-Medline for case reports or series of pediatric pseudoaneurysms managed conservatively (observation or external compression). Only superficial, radiologically confirmed pseudoaneurysms managed conservatively were included. Demographic data, etiology, treatment modalities, success rates, and definitive management for cases where conservative management failed were examined. Results Twelve case reports of 13 pseudoaneurysms met inclusion criteria. Including our case, the mean age was 7 years and the most common pseudoaneurysm etiology was iatrogenic (57%). Seventy-nine per cent (11/14) of pseudoaneurysms resolved with conservative management, and 21% (3/14) proceeded to surgery due to increasing size, bleeding, or pain. Of those pseudoaneurysms successfully treated conservatively, 18% (2/11) developed a complication. Five pseudoaneurysms occurred in patients with coagulopathies, all of which resolved conservatively. Conclusion In stable, asymptomatic superficial pediatric pseudoaneurysms, a trial of conservative management and close follow-up is a reasonable option, even in patients with coagulopathies. [ABSTRACT FROM AUTHOR]

Introduction: Hemophilia is a genetic disease caused by deficiency of factor VIII or IX. Awareness about the disease condition among parents and children also is as important to manage the disease effectively. Objectives: To assess the knowledge on hemophilia among mothers' of children with hemophilia and youth with hemophilia. Methodology: A cross sectional survey was conducted at hemophilia center(Manipal, Karnataka). In total, 23 mothers' of children and 27 youth with moderate and severe hemophilia were included. The participants were selected based on purposive sampling. Approval was taken from the ethical committee. Demographic proforma and knowledge questionnaire was used to collect the data. The data was analyzed using SPSS 16.0 version. Results: The mean age of the participants were 13.68 years. Out of 50 participants 42 had moderate and 8 had severe hemophilia. Moderate knowledge was found among 43.5% of mothers' and 66.7% of youth with hemophilia. Conclusion: This study shows that mothers' knowledge on hemophilia is limited and highlights the importance of continual education of parents and youth about their disease. [ABSTRACT FROM AUTHOR]

Summary: Development of inhibitors to coagulation factor VIII or IX is still the most challenging complication in haemophilia care. ‘Bypassing agents’ may be used to treat a bleed but the eradication of the inhibitor by immune tolerance induction (ITI) is the main objective in the treatment of a patient with haemophilia who has developed neutralizing antibodies. Several options exist for ITI and the patient may be at ‘good’ or ‘bad risk’ for successful outcome with different regimens. This paper offers a review of current regimens to be considered in the treatment of a bleed in a patient with an inhibitor but the main focus is the aspects of different choices in the management of the child or the adult with severe or mild forms of haemophilia A or B, who has developed an inhibitor. There are also some final outlooks on new and emerging treatment possibilities. [ABSTRACT FROM AUTHOR]

Recurrent joint bleeds and silent bleeds are the most common clinical feature in patients with hemophilia. Every bleed causes an immediate inflammatory response and is the leading cause of chronic crippling arthropathy. With the help of infrared thermography we wanted to detect early differences between a group of clinical non-symptomatic children with hemophilia (CWH) with no history of clinically detected joint bleeds and a healthy age-matched group of children. This could help to discover early inflammation and help implement early treatment and preventative strategies. It could be demonstrated that infrared thermography is sensitive enough to detect more signs of early inflammatory response in the CWH than in healthy children. It seems to detect more side differences in temperature than clinical examination of silent symptoms detects tender points. Silent symptoms/tender points seem to be combined with early local inflammation. Using such a non-invasive and sensor-based early detection, prevention of overloading and bleeding might be achieved. [ABSTRACT FROM AUTHOR]

Introduction: As the pharmacokinetics (PK) of factor VIII (FVIII) is individualized in children with haemophilia A (HA), PK parameters may be indicators of patients' bleeding phenotype and instruction for their personalized replacement program. Aim: The aim of this study was to investigate the possible relationship between PK/FVIII level and bleeding frequency in Chinese paediatric patients with severe (HA). Methods: A total of 24 patients were enrolled in Beijing Children's Hospital from February to October 2015, all of whom were given 50 IU/kg of FVIII concentrates after a 72‐hours washout period. Samples' activities (FVIII:C) were tested at 5 time points, using WinNonlin software for PK testing, and then the individual half‐life(t1/2) and the time (h) of FVIII concentrations <1 IU/dL within a week during prophylaxis were calculated. Baseline and the annual bleeding rate (ABR), annual joint bleeding rate (AJBR) were recorded and analyzed. Results: The mean t1/2 of FVIII was 10.20 ± 2.72 hours and the mean time of FVIII <1 IU/dL in 1 week was 44.7 hours (−38.56 to 102.33 hours). A significant relationship between t1/2 of FVIII and ABR0/AJBR0 (baseline bleeding) was found (R2 = 0.75 and 0.62, P < .001). Besides, baseline and the annual bleeding rate during prophylactic treatment of haemophilia had a positive correlation with the time (hours) of FVIII <1 IU/dL in 1 week (R2 = 0.67 and 0.52, P < .001). Conclusion: t1/2 was an important indicator to prevent bleeding in severe HA; the frequency of bleeding will be reduced with the increased of t1/2 of FVIII. The data also demonstrates that increasing the time with a FVIII<1 IU/dL is associated with an increased rate of bleeding during prophylaxis. [ABSTRACT FROM AUTHOR]

Objective: To explore the influence of medical insurance policy and charity assistance projects on the uptake and discontinuation of regular prophylaxis treatment in Chinese severe haemophilia A children. Methodology: This retrospective study was conducted on children with severe haemophilia A, who received FVIII prophylaxis treatment at 12 haemophilia centres in China from 1 November 2007 to 31 May 2013. Results: The average duration of prophylaxis treatment received by haemophilia children significantly increased from 16.7 weeks in 2008 to 32.8 weeks in 2012 (P < .001). The main reason for prophylaxis acceptance included dissatisfaction with previous “on‐demand” regimens, availability of improved local medical insurance policies and patient/family awareness of haemophilia. The main reason for subsequent discontinuation of prophylaxis was economic instability. The upper limit of insurance was up to RMB 150 000/y (~USD: 22 000/y) for 80.1% of the insured patients and would be sufficient to cover the continuous low‐dose prophylaxis regimen. However, for many patients the burden of out‐of‐pocket copayment cost represented a risk for poor adherence to regular prophylaxis. In about two third of the patients, the annual out‐of‐pocket copayment cost amounted to >50% of their average annual disposable income. Many patients therefore required assistance from the charity assistance projects, but nonadherence remained prevalent. Conclusion: Medical insurance policy and charity assistance projects helped haemophilia children to accept and continue prophylaxis regimens. It was the proportion of the out‐of‐pocket copayment cost rather than the upper limit of insurance reimbursement that restricted long‐term regular low‐dose prophylaxis in China. [ABSTRACT FROM AUTHOR]

Objectives: To assess the reliability of the IPSG MRI scale for tibiotalar (TTJ) and subtalar joint (STJ) changes in young haemophilic patients, correlating MRI findings with functional scores and 3D‐rearfoot kinematics. Methods: A total of 37 haemophilic patients underwent bilateral MRI of the footankle, clinical evaluation and quantitative assessment of their 3D‐rearfoot kinematics during walking. TTJ and STJ soft tissues were assessed twice along with osteochondral changes by two radiologists using the IPSG MRI scale. Inter‐ and intra‐observer reproducibility of MRI scoring were tested by means of kappa statistics. Correlational analyses were performed between MRI findings and the Haemophilia Joint Health Score 2.1 (HJHS) and 3D‐rearfoot kinematic data. Results: The intra‐reader reliability of MRI scoring was good to excellent (Kappa: 0.62‐1), whereas the inter‐reader reliability was moderate to good (Kappa: 0.54‐0.79). Weak yet significant correlations were found between the frontal plane rearfoot range of motion (ROM) during loading response of gait and STJ score, as well as between frontal plane rearfoot ROM during the terminal stance phase and the rearfoot osteochondral lesions. Conclusion: The IPSG score appears applicable to not only the TTJ but also the STJ. Contrary to TTJ lesions, those of the STJ do not correlate with the HJHS but do with 3D‐rearfoot kinematic data. [ABSTRACT FROM AUTHOR]

The discussion of prophylactic therapy in haemophilia is largely focused on joint outcomes. The impact of prophylactic therapy on intracranial haemorrhage ( ICH) is less known. This study aimed to analyse ICH in children with haemophilia, with a focus on different prophylaxis regimens and sequelae of ICH. We conducted a multicentre retrospective and prospective study that included 33 haemophilia centres from 20 countries. Inclusion criteria were children and adolescents born between 1993 and 2014, with severe haemophilia A or B without inhibitors. Participants were categorized by prophylaxis regimen: full, partial or none, based on dose and dose frequency of regular infusions. The cohort study included 1515 children: 29 cases of ICH over 8038 patient years were reported. The incidence of ICH in the prophylaxis group, 0·00033 cases of ICH/patient year, was significantly lower compared to the no prophylaxis group, 0·017 cases of ICH/patient year ( RR 50·06; P < 0·001) and the partial prophylaxis group, 0·0050 cases of ICH/patient year ( RR 14·92; P = 0·007). In the on-demand-group, 8% (2/24) children with ICH died and 33% had long-term sequelae, including intellectual and behavioural problems, paresis and epilepsy. Children on regular, frequent prophylaxis have a low risk of ICH compared to those using non-frequent or no prophylaxis. [ABSTRACT FROM AUTHOR]

The article discusses the results of a survey of the extent and patterns of prophylaxis use in adults and children with severe haemophilia in countries with access to long-term prophylaxis conducted by the International Prophylaxis Study Group (IPSG). Topics covered include definition of severe haemophilia A or B, number of patients on immune tolerance induction (ITI) and the number on BA-prophylaxis.

Objectives Adequate management of haemophilia patients requires early detection of joint impairment in relatively asymptomatic patients. This study sought to quantify the impact of the ankle's structural impairment on muscle strength in children, adolescent and young adults with haemophilia (CAAwH). Methods Twenty-three CAAwH underwent bilateral magnetic resonance imaging ( MRI) assessing the anatomical status of tibiotalar joint ( TTJ) and subtalar joint ( STJ) using the International Prophylaxis Study Group MRI scale. An isokinetic dynamometer enabled a detailed evaluation of muscle strength at slow and fast speed. In parallel, 10 typically developing healthy boys ( TDB) participated in a 1-week interval test-retest assessment to assess the test's reliability. Results Forty-six MRI ankle scores were obtained, with 11 patients unilaterally affected and one bilaterally. Of the 13 affected feet, nine showed abnormalities at TTJ, three at the posterior STJ and the remaining one at both joints. Muscle strength was not reduced in CAAwH exhibiting TTJ and/or STJ arthropathy, as compared to healthy TDB, nor was there any difference between the CAAwH's affected or unaffected sides. Conclusion Contrarily to adult patients, CAAwH with repeated ankle bleeding may be less impaired than current structural evaluations imply, with possibly a latency between the occurrence of structural and functional damage. [ABSTRACT FROM AUTHOR]

The purpose of this review was to summarize the current knowledge on the utilization of magnetic resonance imaging (MRI) and ultrasound (US) for assessing arthropathy in children and adolescents with haemophilia and to recognize the limitations of each imaging modality and pitfalls in the diagnosis of soft tissue and osteochondral abnormalities. Awareness of MRI and US limitations and pitfalls in the assessment of joints in persons with haemophilia is essential for accurate diagnosis and optimal management of haemophilic arthropathy. [ABSTRACT FROM AUTHOR]

The protocol for first-line immune tolerance induction (ITI) for children with severe haemophilia A which considered both cost-effectiveness and the long-term musculoskeletal outcome aimed at minimizing breakthrough bleeding developed by the UK Haemophilia Centre Doctors' Organisation Inhibitor and Paediatric Working Parties is outlined. Topics covered include patient stratification, recommendations in the initiation of ITI, and monitoring ITI and dose adjustment.

Introduction Although the regular replacement of clotting factor concentrates (prophylaxis) has been well established as the standard of care for severe haemophilia, the high cost of factor concentrates has limited access to prophylaxis in countries with under-developed or developing economies. Aims We studied the health gap that could be addressed by providing unlimited access to clotting factor concentrates with implementation of long-term prophylaxis initiated from an early age in life. Methods We performed a cross-sectional study of a random, representative sample of boys with moderate and severe haemophilia at three haemophilia treatment centres in Sao Paulo, Brazil, and one centre in Toronto, Canada. Results Canadian subjects were more often treated with prophylaxis, and began treatment at an earlier age. Fewer Canadian subjects had bleeds within the preceding 6 months (19 vs. 34, P = 0.003). Canadian subjects had lower (better) Pettersson radiographic scores (1.5 vs. 6.0, P = 0.0016), lower (better) Hemophilia Joint Health Scores (5.5 vs. 10.5, P = 0.0038), higher (better) Activity Scale for Kids scores (96.6 vs. 92.0, P = 0.033), more time spent in vigorous activity, and higher (better) social participation scores. Conclusions Our findings suggest that increasing access to clotting factor concentrates for young boys with severe haemophilia is a global imperative. [ABSTRACT FROM AUTHOR]

Background: No study has reported the status and chronological trend of prophylactic recombinant factor VIII (rFVIII) use in Chinese pediatric patients with hemophilia A (HA).Objective: We aimed to analyze the status and trend of rFVIII-containing prophylaxis in Chinese pediatric patients with HA.Methods: ReCARE (Retrospective study in Chinese pediatric hemophilia A patients with rFVIII contained REgular prophylaxis) was a retrospective study conducted in 12 hemophilia treatment centers across China. The trend of prophylaxis was evaluated by determining the mean duration of prophylaxis, mean injection frequency (per week), mean dose of each injection (IU/kg), mean total dose injected/week (IU) and proportion of rFVIII consumption relative to factor VIII (FVIII) consumption over the study period.Results: We analyzed 183 male pediatric patients with HA (mean age, 7.1 ± 4.23 years), who received intermittent prophylaxis between 1 November 2007 and 31 May 2013. The mean duration of prophylaxis with rFVIII increased from 16.72 weeks in 2008 to 32.77 in 2012. Per injection dose of rFVIII increased significantly from 2008 to 2013 (25.89 to 28.31 IU/kg, p < .001). An increase was also reported in the mean total FVIII consumed (699.97 ± 173.25 IU in 2008 and 891.30 ± 730.341 in 2013) and mean proportion of rFVIII used (33.33 ± 57.73% in 2008 to 85.50 ± 29.077% in 2013).Conclusion: Our data revealed an overall improvement in treatment dosage and duration with an increase in the number of patients receiving prophylaxis. The total proportion of rFVIII also increased gradually indicating the development of economy and safety awareness.Trial Registration: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT02263066). [ABSTRACT FROM AUTHOR]

Background Prophylaxis is the gold standard for the treatment of children with severe hemophilia. In the last years a new approach to prophylaxis based on annual bleeding rate (ABR), pharmacokinetics (PK) and lifestyle of each patient has begun to be adopted in hemophilia treatment. Aim Aim of our observational retrospective study was to evaluate whether in a group of children with severe hemophilia A (HA) a tailored approach may be used to replace standard therapy, reducing costs. Methods PK evaluation was carried out in six hemophiliac children followed at our Hemophilia Center, and already receiving recombinant factor VIII (rFVIII) on prophylaxis, using a computing program ( MyPKfit® ). Bayesian curve was created for each child and tailored prophylaxis was estimated considering a trough level of 1%. Results The weekly frequency of infusions was reduced in one patient, while it was slightly increased in three children. As to the remaining children, only the dosage was changed. Scheduled follow-up revealed a complete adherence to treatment, a reduction of bleeds using PK-regimen and a general improvement in the quality of life. The comparison between the direct and indirect costs of treatment during standard and PK-driven prophylaxis showed a total saving of € 54,797.40 (− 10.67%) in case of tailored prophylaxis. Conclusion A therapeutic approach based on PK and clinical characteristics of each patient may change standard treatment. Based on our results, tailored prophylaxis could be an effective option for children with HA reducing costs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to semi-quantitatively assess the evidence on the value of ultrasound ( US) for assessment of haemophilic arthropathy ( HA) in children and adults based on the following questions: (1) Does early diagnosis of pathological findings, using available US techniques, impact the functional status of the joint? (2) Do current available US techniques have the ability to accurately detect pathological changes in target joints in haemophilic patients? (3) Does treatment (prophylaxis) improve US evidence of haemophilic arthropathy in children and adults? (4) Is there any association between various US scoring systems and other clinical/radiological constructs? Of the 6880 citations identified searching databases such as MEDLINE, Embase, CENTRAL and Web of Science, 20 articles investigating either the diagnostic accuracy of US and/or US scanning protocols and scoring systems for assessment of HA met the inclusion criteria for the study. Of these, 14 articles evaluating the diagnostic accuracy of US were assessed by two independent reviewers for reporting quality using the Standards for Reporting of Diagnostic Accuracy ( STARD) tool and for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 ( QUADAS-2) tool. Using STARD, 1/14 studies (7%) was scored as of high reporting quality and 8/14 (57%), of moderate quality. Assessment with QUADAS-2 reported 2/14 (14%) studies as having high methodological quality and 6/14 (43%) as having moderate quality. There is fair evidence (Grade B) to recommend US as an accurate technique for early diagnosis of HA, to demonstrate that US scores correlate with clinical/ US constructs and to prove an association between US findings and functional status of the joint. However, there is insufficient evidence (Grade I) to conclude that US-detectable findings in HA are sensitive to changes in therapy. [ABSTRACT FROM AUTHOR]

Introduction Central venous access devices facilitate home treatment in boys with haemophilia. These are usually fully implanted lines, referred to as ports. Caregivers are taught to manage the port using sterile techniques and maintaining patency by flushing with saline or heparin solution. National and international guidelines for the home care of ports are lacking. Aim To evaluate if infection or occlusion rates differ between home care regimens used for ports in children with haemophilia. Methods Children with ports were identified from the PedNet registry. Data on the homecare policy were acquired from each centre. To ensure a complete data set for each port, only ports that had been removed were included in the study. Three care groups were defined: 'aseptic non touch technique', 'sterile technique' and 'fully sterile technique'. Outcomes within and between the groups were analysed. Results A total of 240 children with 352 ports were studied. Insertion occurred at a median age of 1.32 years. The median port duration was 2.94 years with a total of 215 688 port days in children without and 183 852 in children with inhibitors. Infection was the most common cause of port removal (34%); there was no significant difference with infection as reason for removal between the different care groups. Occlusion was not more frequent in centres that did not use heparin. Conclusion Use of sterile gloves and gowns did not reduce the risk of port infection. Using less stringent sterile techniques for accessing ports is easier for caregivers and in addition may have health economic benefits. [ABSTRACT FROM AUTHOR]

Children with hemophilia (A or B) are at risk for bleeding episodes, which rank from mild mucosal/soft tissues bleeding to life-threatening hemorrhages. This report describes the dental/medical management provided to an 8.10-year-old patient suffering from uncontrolled bleeding after a surgical procedure to expose both permanent upper central incisors, in which hemophilia was a pure incidental finding. Additionally, diverse precautions to be considered during the dental clinical treatment of hemophilic children are discussed. [ABSTRACT FROM AUTHOR]

Hemophilia is the most common of the severe bleeding disorders and if not properly managed since early infancy can lead to chronic disease and lifelong disabilities. However, it enjoys the most efficacious and safe treatment among the most prevalent monogenic disorders. Hemophilia should be considered in the neonatal period in the case of unusual bleeding or in the case of positive family history. Later, hemophilia should be suspected mainly in males because of abnormal bruising/bleeding or unusual bleeding following invasive procedures--for example, tonsillectomy or circumcision. Prophylactic treatment that is started early with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is, therefore, the gold standard of care for hemophilia A and B in most countries with adequate resources. Central venous access catheters and arterovenous fistulas play an important role in the management of hemophilia children requiring repeated and/or urgent administration of coagulation factor concentrates. During childhood and adolescence, personalized treatment strategies that suit the patient and his lifestyle are essential to ensure optimal outcomes. Physical activity is important and can contribute to better coordination, endurance, flexibility and strength. The present article focuses also on questions frequently posed to pediatric hematologists like vaccinations, day-care/school access and dental care. [ABSTRACT FROM AUTHOR]

Introduction Treatment for boys with haemophilia in China is rapidly improving; however, comprehensive outcomes have not been examined prospectively. Aim The aim of this study was to evaluate the effect of short-term full-dose prophylaxis compared to on-demand treatment, on the Health-Related Quality of Life ( HR-QoL) of boys with severe haemophilia A ( HA) in China. Methods Boys with severe HA ( FVIII<1%) completed 3 months of on-demand treatment and 3 months of full-dose prophylaxis (25 FVIII IU per kg 3x per week). The primary outcomes were child- and parent-reported Canadian Hemophilia Outcomes - Kids Life Assessment Tool ( CHO- KLAT) scores. The number and type of bleeds and Activities Scale for Kids ( ASK) scores were also recorded. Results Analyses included 23 boys between 4 and 15.9 years of age. The number of bleeds decreased by 94% on prophylaxis ( P < 0.0001, Wilcoxon Signed-Rank test). The mean child-reported CHO- KLAT scores for boys ≥7 years (n = 20) was 61.4 (±10.9) during on-demand treatment and 61.9 (±11.4) following short-term prophylaxis ( P = 0.72, paired t-test). The mean parent-reported CHO- KLAT score during the on-demand phase was 54.4 (±10.5) with an increase of 3.8 points (±8.1; P = 0.04, paired t-test) following prophylaxis. Conclusions Child-reported CHO- KLAT scores were lower in boys with severe HA in China than reported in countries with access to full-dose prophylaxis. Boys reported higher HR-QoL scores than their parents. Small improvements in ASK scores were noted following the prophylaxis phase. These changes were only significant in the parent-reported CHO- KLAT scores. Longer term prospective clinical trials are needed in China to determine the impact of prophylaxis on HR-QoL in boys with severe HA. [ABSTRACT FROM AUTHOR]

Introduction Children growing up with haemophilia are at greater risk for psychosocial problems than their healthy peers. Providing psychosocial care to children with haemophilia and their families is indispensable, since psychosocial factors can have a significant impact on health and health-related quality of life (HRQOL). Aims Our aim was to give a description of psychosocial care provided by the multidisciplinary team of the Hemophilia Comprehensive Care Centre (HCCC) at the Emma Children's Hospital in Amsterdam, the Netherlands. With this overview, other caregivers and hospitals can benefit in organizing their psychosocial care for children with haemophilia. Methods The focus of the psychosocial care provided by the multidisciplinary team is on preventing psychosocial problems and medical-related stress, and supporting and equipping the child with haemophilia and its parents with as many skills as possible to lead an independent life with a high HRQOL. Results Core elements of the psychosocial care are therefore monitoring and screening of HRQOL (e.g. in daily clinical practice via ), psychoeducation (haemophilia camp, haemophilia school, disease-specific activities, meetings for girls, parent meetings), practical help (Emma at Work, an employment agency for adolescents and young adults; Educational Facility and school visits), psychosocial interventions (the On Track group intervention and the Haemophilia Coping and Perception Test) and individual care (psychological counselling and referrals). Conclusion By providing this overview of psychosocial support offered and by sharing this knowledge, psychosocial care can become more structured and consistent between HCCCs around the world. Potentially, processes and outcomes of care can be improved. [ABSTRACT FROM AUTHOR]

The article discusses the clinical management of a 5-week-old boy with severe haemophilia A who required a major cardiac surgery. It describes the plasma activities of all coagulation factors and effects of consumption/haemodilution. It highlights the significance of carefully monitoring coagulation status in all infants referred for such life-saving procedures.

The psychosocial impact of hemophilia on work was recently investigated in the Hemophilia Experiences, Results and Opportunities ( HERO) study. The findings revealed that hemophilia had an impact for adults with moderate/severe hemophilia and caregivers of children with hemophilia. HERO did not specifically evaluate impact on education in adults/children with mild/moderate hemophilia or the impact on employment of spouses/partners of caregivers of affected children. The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study evaluated the impact of hemophilia on the lives of adult men/women with mild-severe hemophilia B and caregivers of boys/girls with hemophilia B and their spouses/partners. Many adults with hemophilia B (94%) reported that hemophilia had a negative effect on their ability to complete a formal education, often attributed to the inability to attend or concentrate in school as a result of hemophilia-related bleeding or pain. Most adults with hemophilia B (95%) and caregivers/partners (89%/84%) indicated that hemophilia had a negative impact on employment. Most adults with hemophilia were employed (81%), with construction/manufacturing (35%) as the most frequently reported industry; many worked in jobs requiring manual labor (39%). Of those unemployed, 62% never worked, and those who stopped working reported that they left the workforce due to financial issues (59%), including insurance coverage/co-pays, or hemophilia-related issues (55%). Nearly one-third of caregivers voluntarily left the workforce to care for children with hemophilia. These results suggest a need to focus more effort on career counseling for adults with hemophilia B and caregivers of affected children, especially around mild/moderate hemophilia, as this population may not be as well informed regarding potential impact in school and the workplace. [ABSTRACT FROM AUTHOR]

The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B- HERO-S) initiative was launched in an effort to address specific gaps in the understanding of the psychosocial impact of mild-moderate-severe hemophilia B. The original Hemophilia Experiences, Results and Opportunities ( HERO) qualitative study evaluated the needs of people with hemophilia A or B in multiple countries; however, a majority of participants had the more common moderate-severe hemophilia A. The B-HERO-S study was designed in collaboration with the hemophilia community to evaluate the needs of adults with hemophilia B and caregivers of children with hemophilia B, including affected women and caregivers of girls with hemophilia. The report presented here describes participant demographics and comorbidities, as well as treatment regimens and access to treatment. Bleeding symptoms were reported by 27% of mothers of children with hemophilia B who participated. Women were more likely than men to self-report arthritis and depression/anxiety as comorbidities associated with hemophilia B. More adults and children with hemophilia B were on routine treatment than on on-demand treatment, and a high percentage of adults with moderate hemophilia B received routine treatment (86%). Many adults with hemophilia B (78%) and caregivers (69%) expressed concern about access to factor in the next 5 years, and of adults with hemophilia B, women more commonly experienced issues with access to factor in the past than did men (72% vs 44%). The findings of the B-HERO-S study reveal potential unmet needs of some patients with mild-moderate hemophilia B, and the results may be leveraged to inform patient outreach by hemophilia treatment centers and education initiatives. [ABSTRACT FROM AUTHOR]

In China, care of patients with severe hemophilia primarily involves insufficient dosing of on-demand treatment and secondary low-dose prophylaxis (10 IU/kg 2× /wk). We sought to evaluate 3× /wk, standard-dose prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS; Bayer) compared with on-demand treatment in Chinese children with severe hemophilia A. Children and adolescents aged 2–16 years with severe hemophilia A, no inhibitors, and no prophylaxis for >6 consecutive months before study entry were eligible for this 24-week, interventional, sequential-treatment study. Patients received rFVIII-FS on demand for 12 weeks followed by a 12-week prophylaxis period (25 IU/kg 3× /wk). The primary efficacy endpoint was comparison of the annualized bleeding rate (ABR) of all bleeds in the prophylaxis versus on-demand phase. Additional variables included ABR of joint bleeds, school attendance/activity, daily activity, and hemophilia Joint Health Score (HJHS). Thirty patients (median age, 12 years) were treated and analyzed. Compared with on-demand treatment, prophylaxis reduced median (quartile [Q1; Q3]) ABR of all bleeds (57.5 [44.5; 73.9] vs 0 [0; 4.0]) and joint bleeds (34.5 [26.1; 56.5] vs 0 [0; 4.0]). Median (range) total HJHS improved after both the prophylaxis and on-demand phases (8.0 [0–48.0] and 11.0 [0–55.0], respectively) compared with baseline (16.0 [0–56.0]). School attendance/activity and daily activity improved with prophylaxis versus on demand. No inhibitors or treatment-related adverse events were reported. In this first prospective, standard-dose, secondary prophylaxis study in China, rFVIII-FS prophylaxis reduced bleeding and improved health outcomes versus on-demand treatment in children with severe hemophilia A. [ABSTRACT FROM AUTHOR]

Introduction Primary factor VIII ( FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life ( T1/2) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy. Aims To determine immunogenicity, pharmacokinetics ( PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII ( BAX 855) based on full-length recombinant FVIII ( ADVATE) in paediatric previously treated patients ( PTPs) with severe haemophilia A. Methods PTPs <12 years without history of FVIII inhibitors received twice-weekly infusions of 50 ± 10 IU kg−1 BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg−1 were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg−1. Results T1/2 and mean residence time were extended 1.3- to 1.5-fold compared to ADVATE ( n = 31), depending on the analysis used. The point estimate for the mean annualized bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3 IU kg−1 of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16 (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target joints resolved. No subject developed FVIII inhibitors or persistent binding antibodies that affected safety or efficacy. No adverse reactions occurred. Conclusion Twice-weekly prophylaxis with BAX 855 was safe and efficacious in paediatric PTPs with severe haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction High-titre factor VIII ( FVIII) inhibitors complicate peri-operative haemostasis. Recombinant porcine FVIII (r- pFVIII) may provide an alternative haemostatic agent for high-risk procedures and allow FVIII activity monitoring. Aim Devise an effective haemostatic plan for repair of a progressively symptomatic aortic coarctation in a 5-year-old male with immune tolerance induction ( ITI) refractory high-titre FVIII inhibitors. Methods Preprocedure human FVIII inhibitor titre was 58 Bethesda Units mL−1 ( BU) and cross-reacted to neutralize porcine FVIII at 30 BU. Daily ITI with plasma-derived FVIII concentrate was supplemented with anti-B-cell and anti-plasma cell immunotherapy to reduce FVIII inhibitor titres. Potential haemostatic agents were evaluated in comparative ex vivo thrombin generation assays ( TGA). Results Four weeks after immunosuppression, human and porcine inhibitor titres declined to 16 and 2 BU respectively. TGA with r- pFVIII was less robust than with activated prothrombin complex concentrate ( aPCC); however, r- pFVIII was selected for cardiac surgery to secure the ability to assay FVIII levels throughout this high-bleeding risk procedure. Haemostasis with r- pFVIII was excellent; initial trough FVIII activity levels ranged from 0.81-1.17 IU mL−1. On postoperative day 3, peak and trough levels markedly declined suggesting a rising porcine inhibitor titre. Postprocedure prophylaxis was transitioned to aPCC, informed by TGA. Conclusions R- pFVIII provided effective peri-procedural haemostasis with no adverse events. Rapid neutralization of r- pFVIII after the first 60 hours, despite intensive immune suppression, accentuates the importance of careful monitoring. Use of TGA can support bypassing agent selection for convalescence. The comparative cost of r- pFVIII may limit its use to high morbidity clinical scenarios. [ABSTRACT FROM AUTHOR]

Aim To describe the prevalence and complications in babies ≤2 years with haemophilia. Methods We used a standardized collection tool to obtain consented data on eligible babies aged ≤2 years with haemophilia enrolled in the Centers for Disease Control and Prevention Universal Data Collection System surveillance project at US Hemophilia Treatment Centers ( HTCs). Results Of 547 babies, 82% had haemophilia A, and 70% were diagnosed within one month of birth. Diagnosis was prompted by known maternal carrier status (40%), positive family history (23%), bleeding (35%) and unknown 2%; 81% bled during the first two years. The most common events were bleeding (circumcision, soft tissue, oral bleeding) and head injury. There were 46 episodes of intracranial haemorrhage ( ICH) in 37 babies (7%): 18 spontaneous, 14 delivery related, 11 traumatic, 2 procedure related and 1 unknown cause. Of the 176 central venous access devices ( CVADs) in 148 (27%) babies, there were 137 ports, 22 surgically inserted central catheters and 20 peripherally inserted central catheters. Ports had the lowest complication rates. Inhibitors occurred in 109 (20%) babies who experienced higher rates of ICH (14% vs. 5%; P = 0.002), CVAD placement (61% vs. 19%; P < 0.001) and CVAD complications (44% vs. 26%; P < 0.001). The most common replacement therapy was recombinant clotting factor concentrates. Conclusion Bleeding events in haemophilic babies ≤2 years were common; no detectable difference in the rates of ICH by the mode of delivery was noted. Neonatal factor exposure did not affect the inhibitor rates. Minor head trauma, soft tissue and oropharyngeal bleeding were the leading indications for treatment. [ABSTRACT FROM AUTHOR]

Aim Using diffusional kurtosis imaging ( DKI) to assess the impact of emotional disorders on microstructural changes of the brain in children with haemophilia A. Materials and Methods Diffusional kurtosis imaging was acquired from haemophilia A ( n = 22) and controls ( n = 22) using a 3T scanner. A regression analysis of frontal, cingulate, hippocampus, insula and amygdala regions of interest ( ROIs) was conducted. Clinical data and results of psychological tests were collected. A paired t-test was used to analyse the differences between the two groups' ROIs, and the Spearman test was used to analyse the correlation between ROIs and psychological tests or clinical data. Results Fractional anisotropy ( FA) in the left middle cingulate and right hippocampus; mean diffusion ( MD) in the frontal lobe, right anterior cingulate and right middle cingulate showed varying degrees of increase in the ROI compared to controls ( P < 0.003). MD in the frontal lobe and the course of disease ( P < 0.05), FA in the right hippocampus and the social score of the self-consciousness scale ( P < 0.01) had a positive correlation. Conclusion Our study is the first to evaluate the relationship between emotion disorders and cognitive changes in the microstructure of the brain in children with haemophilia A, suggesting that DKI provides more information about tissue microstructural changes than do the conventional image method and traditional psychological tests. [ABSTRACT FROM AUTHOR]