Sequential In-Situ Growth of Layered Conjugated Polymers for Optoelectronics Under Electrochemical Control.

Layered optoelectronic devices are manufactured using multistep procedures that require high precision in the spatial positioning of individual materials. Current technology uses costly and tedious procedures and instrumentation. In this work instead, we propose an approach which exploits the fundamental properties of the substrate to direct the growth of the next layer, here controlled by an electrochemical potential. We have electrochemically synthesized and characterized a series of polymeric materials that are most commonly used in the field. The films produced show gradient monomer ratios embedded in the polymeric film as a function of the distance from the working electrode. Under the optimized conditions, reproducible construction of simple electronic elements, e. g., rectifying diodes, is achieved. We argue that the sequential in situ method leads to gradient composition of polymer chains and the film resulting in the rectification of electric current. We discuss how this system can open new avenues in advanced optoelectronic applications, such as organic light-emitting diodes (OLEDs) or field-effect transistors (OFETs).

Reversible Lectin Binding to Glycan-Functionalized Graphene.

The monolayer character of two-dimensional materials predestines them for application as active layers of sensors. However, their inherent high sensitivity is always accompanied by a low selectivity. Chemical functionalization of two-dimensional materials has emerged as a promising way to overcome the selectivity issues. Here, we demonstrate efficient graphene functionalization with carbohydrate ligands-chitooligomers, which bind proteins of the lectin family with high selectivity. Successful grafting of a chitooligomer library was thoroughly characterized, and glycan binding to wheat germ agglutinin was studied by a series of methods. The results demonstrate that the protein quaternary structure remains intact after binding to the functionalized graphene, and that the lectin can be liberated from the surface by the addition of a binding competitor. The chemoenzymatic assay with a horseradish peroxidase conjugate also confirmed the intact catalytic properties of the enzyme. The present approach thus paves the way towards graphene-based sensors for carbohydrate-lectin binding.

Towards Catalytically Active Porous Graphene Membranes with Pulsed Laser Deposited Ceria Nanoparticles.

Porous graphene with catalytically active ceria nanometre-size particles were prepared using pulsed laser deposition (PLD) on graphene produced through chemical vapour deposition (CVD). The reported process provided porous graphene containing ceria nanoparticles as confirmed by HR TEM and XPS. Isotopically labelled 13 C graphene was employed to study desorption of the species containing carbon. Methanol adsorption was utilised to probe the nature of the catalytic activity of prepared ceria decorated graphene. The important role of graphene support for the stabilization of reduced ceria nanoparticles was finally confirmed. Increased dehydrogenation activity of graphene with ceria nanoparticles leading to CO and H2 formation was demonstrated.

The use of sample positioning to control defect creation by oxygen plasma in isotopically labelled bilayer graphene membranes.

Monolayer and isotopically labelled bilayer graphene membranes were prepared on grids for transmission electron microscopy (TEM). In order to create defects in the graphene layers in a controlled way, we studied the sensitivity of the individual graphene layers to the oxygen plasma treatment. We tested samples with different configurations by varying the order of the transfer of layers and changing the orientation of the samples with respect to the plasma chamber. Using Raman spectroscopy, HRTEM and X-ray photoelectron spectroscopy, we demonstrated defect formation and determined the quantity and chemical composition of the defects. By keeping the sample structure and the setup of the experiment unchanged, the significant role of the sample orientation with respect to the chamber was demonstrated. The effect was accounted for by the variation of the accessibility of the sample surface for the reactive species. Therefore, this effect can be used to control the degree of damage in each layer, resulting in differing numbers of defects present on each side of the sample.

Graphene-enhanced Raman scattering on single layer and bilayers of pristine and hydrogenated graphene.

Graphene-enhanced Raman scattering (GERS) on isotopically labelled bilayer and a single layer of pristine and partially hydrogenated graphene has been studied. The hydrogenated graphene sample showed a change in relative intensities of Raman bands of Rhodamine 6 G (R6G) with different vibrational energies deposited on a single layer and bilayer graphene. The change corresponds qualitatively to different doping of graphene in both areas. Pristine graphene sample exhibited no difference in doping nor relative intensities of R6G Raman peaks in the single layer and bilayer areas. Therefore, it was concluded that strain and strain inhomogeneities do not affect the GERS. Because of analyzing relative intensities of selected peaks of the R6G probe molecules, it is possible to obtain these results without determining the enhancement factor and without assuming homogeneous coverage of the molecules. Furthermore, we tested the approach on copper phtalocyanine molecules.

Towards the evaluation of defects in MoS2 using cryogenic photoluminescence spectroscopy.

Characterization of the type and density of defects in two-dimensional (2D) transition metal dichalcogenides (TMDs) is important as the nature of these defects strongly influences the electronic and optical properties of the material, especially its photoluminescence (PL). Defect characterization is not as straightforward as it is for graphene films, where the D and D' Raman scattering modes easily indicate the density and type of defects in the graphene layer. Thus, in addition to the Raman scattering analysis, other spectroscopic techniques are necessary to perform detailed characterization of atomically thin TMD layers. We demonstrate that PL spectroscopy performed at liquid helium temperatures reveals the key fingerprints of defects in TMDs and hence provides valuable information about their origin and concentration. In our study, we address defects in chemical vapor deposition (CVD)-grown MoS2 monolayers. A significant difference is observed between the as-grown monolayers compared with the CVD-grown monolayers transferred onto a Si/SiO2 substrate, which contain extra defects due to the transfer process. We demonstrate that the temperature-dependent Raman and PL micro-spectroscopy techniques enable disentangling the contributions and locations of various defect types in TMD systems.

Validation of the Haemophilia & Exercise Project-Test-Questionnaire (HEP-Test-Q)-An instrument for the assessment of subjective physical functioning in children with haemophilia.

INTRODUCTION: Contemporary haemophilia management recommends sport and physical activity in children with haemophilia. Assessment of subjective physical functioning requires standardized and validated instruments. AIMS: To adapt and psychometrically test the adult Haemophilia & Exercise Project-Test-Questionnaire (HEP-Test-Q) for children (aged 6-17 years). METHODS: In discussion rounds with children, single items of the adult HEP-Test-Q were reformulated to make them understandable without changing the item concept. The validation of the child-adapted version in children with haemophilia (n = 228) included pre-testing with feasibility testing, cognitive interviewing (n = 34), pilot-testing of the revised version in the EIS Study (n = 67) and field-testing in the SO-FIT Study (n = 127). RESULTS: Pre-testing revealed a completion time of 8.2 ± 4.1 minutes and children liked the instrument. Cognitive interviews demonstrated that most items were easy to understand; 9 items were reformulated. Pilot-testing demonstrated good psychometric characteristics in terms of reliability (α = .94 Total Score) and validity. Convergent validity testing showed moderate correlations with the Haemo-QoL (r = -.491), but low correlations with the Petrini Score (r = -.293). Known groups' validity revealed significant differences in clinical subgroups; chronic pain (P < .002) and target joints (P < .021). Field-testing confirmed psychometric characteristics; Cronbach's alpha ranged from α = .80 ("endurance") to α = .94 (Total Score). The child-adapted HEP-Test-Q showed moderate correlations with the PedHAL (r = .634, P < .0001) and the Haemo-QoL SF (r = -.575, P < .0001). Known groups' validity testing proved that the HEP-Test-Q could discriminate between clinical subgroups. CONCLUSION: The child-adapted HEP-Test-Q is a short, practical and acceptable instrument for the assessment of subjective physical functioning. Outcomes can be compared to adults because item concepts are identical to the adult version.

In vitro studies show synergistic effects of a procoagulant bispecific antibody and bypassing agents.

Essentials Patients with hemophilia A and inhibitors receiving emicizumab experience breakthrough bleeding. Safety concerns may exist when combining emicizumab with bypassing agents. Combined bypassing agent and bispecific antibody increased thrombin generation up to 17-fold. Thrombotic effects should be considered when combining emicizumab with plasma bypassing agent. SUMMARY: Background Investigational non-factor products such as emicizumab offer a treatment option for patients with hemophilia and inhibitors. However, their mechanism of action raises questions regarding safety when they are combined with treatments for breakthrough bleeding. Objectives To evaluate in vitro thrombin generation (TG) and clot formation for combinations of activated prothrombin complex concentrate (aPCC), recombinant activated factor VII (rFVIIa), and a sequence-identical analog of emicizumab (SIA). Methods Therapeutic concentrations of SIA (20-600 nm) alone or with aPCC (0.05-1 U mL-1 ), isolated aPCC components or rFVIIa (0.88-5.25 µg mL-1 ) were tested for TG and compared with reference ranges for healthy donor plasma. Coagulation of FVIII-inhibited blood was determined with a widely established method, i.e. rotational thromboelastometry (ROTEM), and confirmed with the Total Thrombus-formation Analysis System. Results and conclusions SIA (600 nm) or aPCC (0.5 U mL-1 ) alone resulted in peak thrombin levels of 21.4 nm and 38.6 nm, respectively, both of which are lower than normal (83.7 ± 29.8 nm). SIA plus aPCC (0.5 U mL-1 ) increased the peak thrombin level 17-fold over SIA alone, exceeding the reference plasma value by 4.2-fold. This hypercoagulable effect occurred with 600 nmSIA combined with as little as 0.25 U mL-1 aPCC, confirmed by ROTEM. FIX was the main driver for enhanced TG. SIA plus rFVIIa (1.75 µg mL-1 ) induced a 1.8-fold increase in the peak thrombin level in platelet-rich plasma, but it did not reach the normal range. These in vitro experiments demonstrate excessive TG after administration of a combination of aPCC and SIA at clinically relevant doses. Careful judgement may be required when breakthrough bleeding is treated in patients receiving emicizumab.

Prophylactic bypassing agent use before and during immune tolerance induction in patients with haemophilia A and inhibitors to FVIII.

The development of high-titre inhibitory antibodies (inhibitors) against factor VIII (FVIII) remains a challenge in the management of patients with haemophilia A (HA). Patients with high-titre inhibitors are more likely to experience uncontrolled bleeding, physical disability from chronic arthropathy and premature death compared with those without this complication. Immune tolerance induction (ITI), utilizing repeated infusions of FVIII, is an effective therapeutic approach to eliminating inhibitory antibodies. This strategy can eradicate FVIII inhibitors, so that FVIII-specific tolerance is induced. However, patients undergoing ITI are still vulnerable to the development of serious and/or repeated bleeding events. The efficacy of bypassing agents in preventing bleeding episodes has been widely proven in patients with HA and inhibitors to FVIII. Evidence suggests that reducing bleeding during ITI can also shorten the time to tolerance. There are concerns with the use of bypassing agents, including the cost of treatment, short half-life, management of non-responders and the risk of thrombosis. Despite these concerns, and the still limited evidence from prospective studies and consensus reports, the use of prophylaxis with bypassing agents during ITI has been gaining support. This review presents a rationale and current data supporting the use of prophylactic bypassing agents as effective and safe therapies to reduce the incidence of joint bleeding due to inhibitors and improve quality of life in patients with HA undergoing ITI.

Selective self-assembly and light emission tuning of layered hybrid perovskites on patterned graphene.

The emission of light in two-dimensional (2-D) layered hybrid organic lead halide perovskites, namely (R-NH3)2PbX4, can be effectively tuned using specific building blocks for the perovskite formation. Herein this behaviour is combined with a non-covalent graphene functionalization allowing excellent selectivity and spatial resolution of the perovskite film growth, promoting the formation of hybrid 2-D perovskite : graphene heterostructures with uniform coverage of up to centimeter scale graphene sheets and arbitrary shapes down to 5 µm. Using cryo-Raman microspectroscopy, highly resolved spectra of the perovskite phases were obtained and the Raman mapping served as a convenient spatially resolved technique for monitoring the distribution of the perovskite and graphene constituents on the substrate. In addition, the stability of the perovskite phase with respect to the thermal variation was inspected in situ by X-ray diffraction. Finally, time-resolved photoluminescence characterization demonstrated that the optical properties of the perovskite films grown on graphene are not hampered. Our study thus opens the door to smart fabrication routes for (opto)-electronic devices based on 2-D perovskites in contact with graphene with complex architectures.

Target plasma factor levels for personalized treatment in haemophilia: a Delphi consensus statement.

BACKGROUND: Prophylactic replacement with factor concentrate is the optimal treatment for persons with severe haemophilia to avoid or minimize bleeding. This ultimately prevents or reduces joint disease and improves life expectancy and quality of life towards values matching those in the normal population. However, uncertainty still exists around the optimal regimens to be prescribed for prophylaxis. An increasing number of treating physicians and patients are showing interest in patient-tailored approaches to prophylaxis, which aim to harmonize the prophylaxis regimen with the patients' bleeding phenotype, levels of physical activity and a variety of other variables. METHODS: A modified Delphi technique was adopted to generate consensus. The expert panel met in person to set the objectives, be trained on the Delphi technique and agree on the desired level of consensus. Three iterations were used to identify the targets, the scenarios and their combinations. RESULTS: Twenty-eight scenarios and eight target levels were identified and used to issue recommendations. The panel reached the desired level of consensus on positive or negative recommendations. Areas where consensus was not reached were identified and proposed as areas for future research. Prospective assessment of the validity of most of the proposed targets is recommended. CONCLUSIONS: We have generated, by expert consensus, target plasma levels of factor concentrate to be used to tailor treatment for persons with haemophilia.

Haemarthrosis model in mice: BSS - Bleeding Severity Score assessment system.

INTRODUCTION: The prophylactic administration of clotting factor concentrate is currently the most effective strategy for the prevention of joint bleeding. As new agents with different mechanisms of action and administration schedules are developed, it will be important to study them in relevant preclinical models. AIM: The aim of this study was the standardization of a mouse haemarthrosis model in a haemophilia mouse and the development and validation of a comprehensive bleeding assessment system, the Bleeding Severity Score (BSS). METHODS AND RESULTS: Four outcome measurements were assessed, two of which, the extra-articular bleeding score and intra-articular bleeding score, were determined to be the most reliable and were summarized into a BSS which was validated using a mouse haemarthrosis variability model. CONCLUSION: Using this model, the haemostatic effect of prospective drugs can be assessed in a clinically relevant joint bleeding model and will significantly increase the value of preclinical studies.

Association of peak factor VIII levels and area under the curve with bleeding in patients with haemophilia A on every third day pharmacokinetic-guided prophylaxis.

INTRODUCTION: We previously showed that pharmacokinetic-guided prophylaxis (PKP) allows the dosing interval to be extended while maintaining a specific trough level. However, the associations of peak factor VIII (FVIII) levels and area under the curve (AUC) with breakthrough bleeding have not been investigated. AIM: The aim of this study was to analyse data from the PKP arm to determine whether peak FVIII levels, AUC and time with FVIII levels in a haemostatically effective range are independent predictors of bleeding during prophylaxis. METHODS: Post hoc analysis of the association of FVIII levels and AUC with annualized bleeding rate in 34 patients on PKP. RESULTS: During 1 year of PKP, 131 bleeding episodes occurred in 24/34 patients. Average peak FVIII levels ranged from 24 to 168 IU dL(-1) , with higher values associated with a decreased risk for all bleeding (joint and non-joint; P < 0.01) and joint bleeding (P < 0.01). Following rFVIII infusion, median percent of time spent with FVIII levels >20 IU dL(-1) was 22%; median AUC was 1363. Both values were significantly associated with a lower ABR when targeting a 1% trough at 72 h. CONCLUSION: When PKP was administered every third day, higher peak FVIII levels, higher AUC and more time spent per week with FVIII levels >20 IU dL(-1) provided increased protection from joint and non-joint bleeding. These data highlight the potential impact of variability in individual pharmacokinetic and bleeding risk and support the need for high peak levels and AUC in some patients treated every third day. The findings do not necessarily apply to alternate-day or other prophylactic dosing regimens.

Health-related quality of life assessment in haemophilia patients on prophylaxis therapy: a systematic review of results from prospective clinical trials.

INTRODUCTION: Prophylaxis is effective in reducing the number of bleeding episodes in patients with severe or moderately severe haemophilia A and B, including those with inhibitors. However, data, predominantly from observational studies, suggest more equivocal effects on health-related quality of life (HRQoL). AIM: To examine the impact of prophylaxis on HRQoL from prospective clinical trials. METHODS: We performed a systematic literature review of clinical trials evaluating the efficacy of prophylaxis with factor VIII, FIX or bypassing agents. Trials assessing HRQoL via validated instruments were selected and summarized. RESULTS: Thirteen trials (haemophilia A [n = 8]; haemophilia B [n = 2]; inhibitors [n = 3]) met all inclusion criteria. HRQoL instruments included the EQ-5D, SF-36, Haem-QoL-A, Haem-A-QoL, Haemo-QoL and CHO-KLAT. Improvements in HRQoL following prophylaxis were observed with the EQ-VAS, SF-36 and haemophilia-specific instruments in adult patients and were associated with reduced pain, fewer restrictions in physical activities and better general health. Prophylaxis led to statistically significant or clinically meaningful HRQoL improvement in six trials and non-significant improvement in four trials; two trials found no improvement and one reported no data. Despite study differences, consistent trends suggested that patients previously treated solely on-demand and those who experienced marked reductions in the frequency of bleeding with prophylaxis had a greater improvement in HRQoL. CONCLUSION: Contrary to findings of observational studies, the results from the majority of prospective trials using validated instruments showed positive trends for improved HRQoL with prophylaxis in adults.

Central venous access device (CVAD) complications in Haemophilia with inhibitors undergoing immune tolerance induction: Lessons from the international immune tolerance study.

INTRODUCTION: Central venous access devices (CVADs) are frequently required as stable long-lasting venous access in children with haemophilia, especially those requiring immune tolerance induction (ITI) for inhibitors. CVAD infection is one of the most frequently reported catheter-related complications in this patient population. AIM: Detailed review of CVAD complications from the International ITI (I-ITI) study and analysis of potential risk factors for such complications. METHODS: Retrospective analysis of prospectively obtained data from the I-ITI study primarily focused on CVAD-related complications. RESULTS: A total of 115 children were recruited and 183 CVADs were placed in 99 subjects resulting in 121,206 CVAD-days observed on-study. A total of 124 CVAD infections were reported in 41 of 99 (41%) subjects with an overall infection rate of 0.94 per 1000 CVAD-days (interquartile ranges 0-1.7). A similar number of infections were observed in the two treatment arms (median: 2 and 3 in high dose and low dose respectively). Infections occurred more frequently in the presence of external catheters than with fully implanted catheters (P = 0.026). Infected patients were significantly younger at the time of CVAD insertion (median age: 22 vs. 25 months, P = 0.020). Patients with Gram-positive infections were also significantly younger than those with Gram-negative infections (median age: 17 vs. 25 months, P < 0.0001). CONCLUSION: CVAD infection was the most common complication observed in children with severe haemophilia and inhibitors in the frame of the I-ITI study. Younger age at CVAD insertion and external CVAD were associated with higher risk for infection. ITI outcome was unaffected by CVAD infections.

US Guidelines for immune tolerance induction in patients with haemophilia a and inhibitors.

INTRODUCTION: The development of anti-factor VIII (FVIII) antibodies (inhibitors) is the most serious treatment-related complication in patients with hemophilia A, rendering standard replacement therapy ineffective, heightening the risk for uncontrollable bleeding and morbidity, decreasing quality of life, and increasing healthcare costs. AIM: Formulate evidence-based guidelines for optimizing immune tolerance induction (ITI) in patients with hemophilia A and inhibitors. METHODS: Results from the International ITI study and other available evidence were used to develop guidelines for ITI. RESULTS: Predictors of ITI success were identified and recommendations made for ITI with regard to candidates, timing, product, regimen, monitoring, defining success, concurrent immunomodulation, duration of treatment, and bleed management before and during ITI. CONCLUSION: Evidence-based recommendations to guide treatment decisions may increase the likelihood of successful inhibitor eradication and the induction of FVIII tolerance in patients with hemophilia A who develop inhibitory antibodies.

Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly?

Inhibitor development in haemophilia patients is challenging especially when undergoing surgical procedures. The development of an inhibitor precludes using factor VIII (FVIII) therapy thereby requiring a bypassing agent (BPA) for surgical bleeding prophylaxis if the FVIII inhibitor titre >5 BU. Concomitant use of anti-inhibitor coagulant complex (AICC) and tranexamic acid has been reported in the literature as a beneficial treatment for this population. Anti-inhibitor coagulant complex is known to cause an increase in thrombin generation and tranexamic acid inhibits fibrinolysis. Hence, the combined used of AICC and tranexamic acid has been limited due to safety concerns over possibilities of increased risk of thrombotic events and disseminated intravascular coagulation. However, the rationale for concomitant therapy is to obtain a potential synergistic effect and to increase clot stability. We conducted a literature review of past studies and individual case reports of concomitant use of AICC and tranexamic acid, which was extensively used during dental procedures. Evidence also exists for concomitant use of the combined therapy in orthopaedic procedures, control of gastrointestinal bleeding, epistaxis and cerebral haemorrhages. Some patients who received the combined therapy had failed monotherapy with a single BPA prior to combined therapy. There were no reports of thrombotic complications related to the concomitant therapy and haemostasis was achieved in all cases. Anti-inhibitor coagulant complex and tranexamic acid therapy was found to be safe, well-tolerated and effective therapy in haemophilia patients with inhibitors. Additional randomized controlled studies should be performed to confirm these findings.

Utility of a Paediatric Bleeding Questionnaire as a screening tool for von Willebrand disease in apparently healthy children.

UNLABELLED: von Willebrand disease (VWD), an inherited bleeding disorder caused by deficiency or dysfunction of von Willebrand factor (VWF) is diagnosed when a personal and often a family history of excessive mucocutaneous bleeding is present along with abnormal laboratory studies. An accurate assessment of haemorrhagic symptoms is key in suspecting VWD but presents a challenge especially in children due to overlap between normal and abnormal bleeding. Bleeding questionnaire (BQ) scores have been validated in adults and have recently been validated in children with VWD for assessing bleeding severity. However, there are limited data supporting their use prospectively in healthy children with bleeding complaints. AIM: The objectives of this study were to obtain normative data from children and validate a paediatric BQ (PBQ) to determine the discriminative ability of its total score and its individual components for identifying children likely to have VWD. METHODS: The PBQ was administered to 1281 multiethnic, healthy children between 30 days and 18 years of age presenting to a general paediatric office and to 35 children with VWD based on VWF antigen, activity and multimer pattern. RESULTS: When children with total BQ scores of 3 or more were predicted to have VWD, the sensitivity was 97.2%, the specificity was 97.1%, the positive predictive value was 48.6% and the negative predictive value was 99.9%. CONCLUSIONS: The PBQ may help discriminate a significant bleeding history from trivial bleeding, may be integrated into the primary care algorithm for evaluating children suspected with VWD.

Safety of radiation exposure after radiosynovectomy in paediatric patients with haemophilia.

Many paediatric patients with haemophilia who might benefit from radiosynovectomy (RS) for the control of synovitis do not undergo the procedure as there is controversy in the literature regarding the safety of radiation exposure after two cases of acute lymphocytic leukaemia in children with haemophilia treated with (32) P RS were reported. The purpose of this review was to analyse the safety of RS in paediatric patients with haemophilia and provide a risk-benefit assessment, which practitioners could apply to their patients. Children undergoing knee RS receive a radiation dose of approximately 0.74 mSv (90 megabecquerels-MBq) and elbow and ankle RSs a dose of approximately 0.32 mSv (30-40 MBq). The radiation dose from natural sources is approximately 2 mSv and the recommended limit for patients (apart from natural sources) is 1 mSv per year. The lifetime cancer risk increases about 0.5% per 100 mSv per year. Considering the risks and benefits of RS, the authors recommend that clinicians consider this procedure in children with inhibitors or in patients without inhibitors when bleeding is recurrent and persistent despite aggressive factor replacement.

Neonatal circumcision in severe haemophilia: a survey of paediatric haematologists at United States Hemophilia Treatment Centers.

Neonatal circumcision in patients with severe haemophilia has not been well studied. We performed a survey of paediatric haematologists from Hemophilia Treatment Centers (HTC) across the United States to better understand the attitudes toward and management of neonatal circumcision in haemophilia patients. Response rate to our survey was 40% (n = 64/159). Thirty-eight percent of respondents (n = 24) said that they would allow this procedure in the newborn period but in many cases this was against medical advice. The most reported concern regarding neonatal circumcision in haemophilia patients was the risk of development of an inhibitor (n = 25; 39%) followed by the concern for bleeding (n = 22; 34%) and issues related to vascular access in the neonate (n = 11; 17%). All respondents recommended at least one preprocedure dose of factor replacement. Twenty-two percent (n = 14) of respondents did not use more than one dose of factor replacement but 32% (n = 21) used 1-2 postoperative doses. The remainder of paediatric haematologists surveyed recommended between 3-5 (16%; n = 10) and 6-10 (3%, n = 2) additional days postoperatively. There was wide variation in both techniques of circumcision as well as adjuvant haemostatic agents used. Only 22% of respondents said that they had an established protocol for management of circumcision in the newborn haemophilia patient. These survey results highlight the need for evidence-based guidelines regarding the optimal management of circumcision in neonates with severe haemophilia.