[Stroke alarm-Arterial ischemic stroke as one of the most time-critical emergencies in children and adolescents]. / Notfall-Neuropädiatrie ­ Der arteriell ischämische Schlaganfall als einer der zeitkritischsten Notfälle bei Kindern und Jugendlichen.

Arterial ischemic stroke in childhood and adolescence is one of the most time-critical emergencies in pediatrics. Nevertheless, it is often diagnosed with a considerable time delay which may be associated with low awareness, the sometimes nonspecific clinical presentation with a wide variety of differential diagnoses, and less established 'acute care structures'. The revascularisation strategies in adult stroke care are also potential and promising treatment options for children, even if available evidence is still limited. In the post-acute phase, the etiological work-up is complex due to the multitude of risk factors to be considered. But it is essential to identify each child's individual risk profile as it determines secondary prevention, risk of recurrence and outcome. Long-term care in a multiprofessional, interdisciplinary team must take into account the bio-psycho-social aspects to integrate the child into its social and educational, and later professional environment.

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.

Prospects for research in haemophilia with real-world data-An analysis of German registry and secondary data.

INTRODUCTION AND AIM: Open questions in haemophilia, such as effectiveness of innovative therapies, clinical and patient-reported outcomes (PROs), epidemiology and cost, await answers. The aim was to identify data attributes required and investigate the availability, appropriateness and accessibility of real-world data (RWD) from German registries and secondary databases to answer the aforementioned questions. METHODS: Systematic searches were conducted in BIOSIS, EMBASE and MEDLINE to identify non-commercial secondary healthcare databases and registries of patients with haemophilia (PWH). Inclusion of German patients, type of patients, data elements-stratified by use in epidemiology, safety, outcomes and health economics research-and accessibility were investigated by desk research. RESULTS: Screening of 676 hits, identification of four registries [national PWH (DHR), national/international paediatric (GEPARD, PEDNET), international safety monitoring (EUHASS)] and seven national secondary databases. Access was limited to participants in three registries and to employees in one secondary database. One registry asks for PROs. Limitations of secondary databases originate from the ICD-coding system (missing: severity of haemophilia, presence of inhibitory antibodies), data protection laws and need to monitor reliability. CONCLUSION: Rigorous observational analysis of German haemophilia RWD shows that there is potential to supplement current knowledge and begin to address selected policy goals. To improve the value of existing RWD, the following efforts are proposed: ethical, legal and methodological discussions on data linkage across different sources, formulation of transparent governance rules for data access, redefinition of the ICD-coding, standardized collection of outcome data and implementation of incentives for treatment centres to improve data collection.

Vaccinations are not associated with inhibitor development in boys with severe haemophilia A.

BACKGROUND: Inhibitor development in previously untreated patients (PUPs) with severe haemophilia A is a multifactorial event. It is unknown whether paediatric vaccinations given in close proximity to factor VIII (FVIII) are associated with inhibitor development. OBJECTIVE: To assess whether paediatric vaccinations in close proximity to FVIII within the first 75 exposure days (EDs) are associated with inhibitor development in PUPs with severe haemophilia A. METHODS: We included 375 PUPs with severe haemophilia A (<0.01 IU/mL) from the PedNet Registry who had received vaccinations between the first and 75th ED or inhibitor development. Inhibitor risk was compared between patients who did and who did not receive vaccinations within 24, 72 or 120 hours of FVIII infusion. Unadjusted and adjusted hazard ratios were calculated for any or repeated vaccinations in close proximity to FVIII, using Cox regression. RESULTS: Inhibitor development occurred in 77 of 375 patients (20.5%). Overall inhibitor development appeared similar or lower in patients receiving vaccinations in close proximity to FVIII as compared to patients receiving vaccinations without FVIII: for 24 hours, this was 19.2% and 21.4% (P = .186), for 72 hours, 16.4% and 27.3% (P = .023) and for 120 hours, 18.3% and 25.0% (P = .085), respectively. CONCLUSION: We found no association between vaccinations given in close proximity to FVIII exposure within the first 75 EDs and inhibitor development. Our data do not support avoiding administration of FVIII at time of routine vaccinations.

Using routine Haemophilia Joint Health Score for international comparisons of haemophilia outcome: standardization is needed.

INTRODUCTION: Haemophilia Joint Health Score (HJHS) is the most sensitive validated score for physical examination of joint health in haemophilia. HJHS performed at regular intervals can be used for clinical monitoring as well as for comparative outcomes research. AIM: To determine whether routinely collected HJHS could be used to compare outcome of three different prophylactic regimens in children with severe haemophilia A (primary) and which parameters caused variability in HJHS (secondary). METHODS: International retrospective observational multi-centre study comparing routine HJHS in 127 children with severe haemophilia A born from 1995 to 2009, from London, Stockholm and Utrecht centres. Patient and treatment data were collected from the European Paediatric Network for Haemophilia Management registry and patient files. The independent effects of regimens, physiotherapists, age and inhibitor status on HJHS were explored, using multivariable regression analysis. RESULTS: Prophylaxis varied across participating centres, with differences in initial frequency of infusions (1× per week vs. 3× per week), age at reaching infusions ≥3× per week, and dose kg(-1) week(-1) at HJHS assessment. Evaluation at median age of 11 years showed an illogical association of HJHS with treatment regimen: the least intensive regimen had the lowest HJHS. The HJHS increased with age and history of inhibitor, as expected (internal validity). But the comparison of prophylactic regimens was obscured by systematic differences in assessment between physiotherapists, both within and between centres. CONCLUSION: Inter-physiotherapist discrepancies in routine HJHS hamper comparison of scores between treatment regimens. For multi-centre research, additional inter-observer standardization for HJHS scoring is needed.

The EPIC study: a lesson to learn.

INTRODUCTION: Inhibitory antibodies to factor VIII occur in about 30% of previously untreated patients (PUPs) and are the most serious complication of haemophilia A. It is unclear why some patients develop inhibitors and others do not. AIMS: The Early Prophylaxis Immunologic Challenge (EPIC) study was designed to test the hypothesis that inhibitor incidence in PUPs with severe or moderately severe haemophilia A could be reduced when a once-weekly FVIII prophylaxis starts with 25 IU kg(-1) rAHF-PFM before 1 year of age and immunological danger signals are minimized. METHODS: These signals were minimized by avoiding: surgery; the first FVIII infusion during severe bleeding or an infection; central venous access devices and administering vaccinations intramuscularly 3-4 days before or after FVIII. RESULTS: Eight of the 19 treated subjects (42.1%) developed confirmed inhibitors. Eleven of the 19 treated subjects were PUPs without any prior exposure to FVIII. Three of them (27.3%) developed a confirmed inhibitor together with FVIII-binding antibodies. The study was stopped because the likelihood to reach the primary objective was minimal, a decision endorsed by the data safety monitoring board. CONCLUSION: Because of early termination, the EPIC study hypothesis could not be corroborated. Nonetheless, our data analyses indicate that the current definition of an inhibitor only based on plasma inhibitor activity ≥0.6 BU mL(-1) may not always reflect the presence of FVIII-neutralizing antibodies. The findings of this study teach us that low-level inhibitor activity results need in addition a confirmatory test and/or the assessment of the therapeutic response.

How to achieve full prophylaxis in young boys with severe haemophilia A: different regimens and their effect on early bleeding and venous access.

To facilitate early prophylaxis, step-up regimens starting prophylaxis with infusions 1× week(-1) were introduced. Choice of initial regimen may affect outcome. This study aims to classify initial prophylactic regimens and compare them on short-term outcome. From the 'European Paediatric Network for Haemophilia Management' (PedNet) registry, patients with severe haemophilia A without inhibitors, born 2000-2012, receiving prophylaxis were included. Treatment centres were classified according to the initial frequency of prophylactic infusions and the age at reaching infusions ≥3× week(-1) . Bleeding, and central venous access device (CVAD) use were compared at age 4 years. In 21 centres with 363 patients, three regimens were identified: (i) start prophylaxis with ≥3× week(-1) infusions before age three (full: 19% of centres, 18% of patients); (ii) start 1-2× week(-1) , increasing frequency as soon as possible (asap), reaching ≥3× week(-1) before age three (43% of centres, 36% of patients); (iii) start 1-2× week(-1) , increasing frequency according to bleeding (phenotype), reaching ≥3× week(-1) after age three (38% of centres, 46% of patients). Prophylaxis was started at median 1.2 years on the full and asap regimen vs 1.8 years on the phenotype regimen. Complete prevention of joint bleeds was most effective on the full regimen (32% full vs. 27% asap and 8% phenotype), though at the cost of using most CVADs (88% full vs. 34% asap and 22% phenotype). The three prophylaxis regimens identified had different effects on early bleeding and CVAD use. This classification provides the first step towards establishing the optimum prophylactic regimen.

Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN).

The bleeding patterns of severe von Willebrand's disease (VWD) adversely affect quality of life, and may be life threatening. There is a presumed role for prophylaxis with VWF-containing concentrates, but data are scarce. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is not responsive to other treatment(s).Using a retrospective design, the effect of prophylaxis was studied. Availability of records to document, or reliably assess, the type and frequency of bleeding episodes prior to, and after, the initiation of prophylaxis was required. Annualized bleeding rates were calculated for the period prior to prophylaxis, during prophylaxis and by primary bleeding indication defined as the site accounting for more than half of all bleeding symptoms. The Wilcoxon signed-rank test of differences in the medians was used. Sixty-one subjects from 20 centres in 10 countries were enrolled. Data for 59 were used in the analysis. The median age at onset of prophylaxis was 22.4 years. Type 3 VWD accounted for the largest number (N = 34, 57.6%). Differences in bleeding rates within individuals during compared with before prophylaxis were significant for the total group (P < 0.0001), and for those with primary bleeding indications of epistaxis (P = 0.0005), joint bleeding (P = 0.002) and GI bleeding (P = 0.001). The effect of prophylaxis was similar among those age < 18 years and those ≥ 18. One person developed an inhibitor during treatment. We conclude that prophylactic treatment of VWD is efficacious.

Treatment of children with severe haemophilia A and inhibitors: a health economic evaluation for Germany.

BACKGROUND: Decision makers request increasingly for high levels of evidence when allocating resources in medical care. This is hardly feasible for rare diseases. The objective was to analyze clinical and economic aspects of different immune tolerance induction (ITI) strategies for children with severe haemophilia A and inhibitors. METHODS: A decision model, time frame 18 years (base case: 2 year old boy), was constructed from a German statutory health insurance (SHI) perspective. Compared were high-dose (HD) ITI, low-dose (LD) ITI, 'ITI with risk assessment', on-demand (OD) treatment with bypassing agents. Clinical data were derived from structured literature research and expert opinion. Sensitivity analyses were conducted for parameters with wide statistical ranges. RESULTS: Base case analysis: total costs for HD ITI amounted to €3.4 million with 40.9% ITI costs, 51 joint bleeds, 36 hospital days; LD ITI, €2.4 million with 21.4% ITI costs, 74 joint bleeds, 52 hospital days; 'ITI with risk assessment', €2.7 million with 27.6% ITI costs, 53 joint bleeds, 37 hospital days; OD treatment, €1.7 million, 146 joint bleeds, 104 hospital days. Incremental costs per bleed avoided with HD ITI decreased from €1 million to €0.15 million with increase of joint bleeds from 3 to 20 per year, when compared to 'ITI with risk assessment' in sensitivity analysis. CONCLUSION: 'ITI with risk assessment' is cost-saving with comparable outcomes to HD ITI. However, patient-related factors like bleeding frequency have to determine treatment decisions in individual patients. More clinical data is needed to increase the significance of model -calculations.

Identification and long-term observation of early joint damage by magnetic resonance imaging in clinically asymptomatic joints in patients with haemophilia A or B despite prophylaxis.

Severe haemophilia is associated with recurrent joint bleeds, which can lead to haemophilic arthropathy. Subclinical joint bleeds have also been associated with joint damage detected using magnetic resonance imaging (MRI). We investigated the development of early changes in clinically asymptomatic joints using MRI in haemophilia A or B patients receiving prophylactic therapy. In this single-centre retrospective cohort study, patients with clinical evidence of joint damage in one ankle and one clinically asymptomatic ankle, in which we performed an MRI scan of both ankles in one session, were enrolled. MRI findings were graded using a 4-point scoring system (0 = normal findings and III = severe joint damage). Since 2000, 38 MRIs in 26 patients have been performed. Starting at a median age of 4 years, 23 patients received prophylaxis 2-3 times weekly. On-demand treatment was performed in three patients. Eight patients (31%) presented with an MRI score of 0, 12 (46%) had a score of I, four (15%) had a score of II, and two (8%) had a score of III in the clinically unaffected ankle. The six patients with MRI scores of II and III had started regular prophylaxis between the ages of 2 years and 15 years; none had developed an inhibitor or experienced a clinically evident bleed in the asymptomatic ankle. During our study, five of 26 patients had a worsening of MRI findings without experiencing a joint bleed. Early morphological changes in clinically asymptomatic ankles can be detected using MRI, despite adequate prophylaxis.

Hereditary angioedema (HAE) in children and adolescents--a consensus on therapeutic strategies.

Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.

Repeated coagulation testing in children. Does it improve the diagnostic value?

BACKGROUND: Mild bleeding disorders (BD) such as von Willebrand disease (VWD) type I are often difficult to diagnose because of inconclusive laboratory results. Our study examines the diagnostic value of repeated testing. PATIENTS, METHODS: Prospective study on 200 children. Extensive laboratory testing was done twice and a standardized history was taken. RESULTS: 165 patients completed the study (median age 5.6 years). Main reason for referral was aPTT prolongation (n = 109). The initial diagnosis was upheld in 74/165 (44.8%) children. Of 18 patients rated normal, 8 had to be reclassified as possible VWD later. Ten patients were diagnosed VWD I. In 36 patients possible VWD was found, 13 of these had normal results at the second visit while in 6 VWD became more likely. The main diagnosis was lupus-anticoagulant (n=79), normalizing in 24. A total of 88 children underwent surgery during the study period. CONCLUSION: Our study shows frequent changes in the diagnosis and highlights the limitations of single laboratory tests in detecting mild BD. Clinical and laboratory abnormalities have to be followed and tests must be repeated in unclear cases. Normal values at one point do not exclude a BD.

Inhibitor-immunology-study. Evaluation of inhibitor development in haemophilia B.

UNLABELLED: The development of inhibitors in haemophilia B is one of the most important complications of replacement therapy, affecting mortality and morbidity. Inhibitor development is based on complex immunological factors, and to date, only little is known about its underlying mechanisms. Here, we present first results of the haemophilia B group of our Inhibitor-Immunology study. PATIENTS, METHODS: So far we have analysed 15 patients with haemophilia B. Four of them developed a high titre inhibitor; the remaining 11 had no inhibitor. We evaluated 9 SNPs in 8 genes (CD40, CTLA-4 , IL-1ß, IL-10, TLR2 , TLR4, TLR9, TNF-α). We compared the distribution of these alleles between inhibitor and non-inhibitor haemophilia B patients and between haemophilia B patients and a normal male control population. HLA typing was performed in all patients. Results, discussion: There appears to be a trend towards a skewed distribution of TLR 9, IL-10 and CTLA4 alleles in haemophilia B patients. Due to the limited number these differences are, however, not statistically significant. The t-test of all patients with inhibitor versus without inhibitor was significant for HLA-A*03 and DPB1*0401 and borderline for DRB1*0201.

New early prophylaxis regimen that avoids immunological danger signals can reduce FVIII inhibitor development.

SUMMARY: The most problematic complication of haemophilia A treatment is the development of inhibitors to FVIII. The highest risk of developing inhibitors is during the first 20 exposure days (EDs). If the patient can be brought through this high risk period without inhibitor development, the subsequent risk is low. Therefore, as a pilot project, we developed a prophylaxis regimen for the first 20-50 EDs specifically designed to induce tolerance to the administered FVIII and to minimize inhibitor development by avoiding immunological danger signals. Twenty-six consecutive previously untreated patients (PUPs) with severe haemophilia A were treated with the new prophylaxis regimen and the incidence of inhibitor development in this group was compared with that in a historical control group of 30 consecutive PUPs treated with a standard joint protection prophylaxis regimen (40-50 IU kg(-1), three times a week). There were no significant differences between the study and control groups in patient-related inhibitor risk factors such as ethnicity (all Caucasian), severity of haemophilia (all <1% FVIII), severity of FVIII gene mutation (P < 0.0006) nor in some treatment-related factors such as product type, age at first exposure, vaccination regimen or the need for surgery. 14 of 30 subjects given standard prophylaxis but only one of the 26 subjects given the new regimen developed an inhibitor (P = 0.0003, odds ratio 0.048, 95% CI: 0.001-0.372). Our results indicate that minimizing danger signals during the first 20 EDs with FVIII may reduce the risk of inhibitor formation. These results should be confirmed in a larger prospective clinical study.

AHEAD. Advate in HaEmophilia A outcome Database.

The clinical picture of haemophilia A patients is often characterised by recurrent bleedings, in particular joint bleeds. Thus far, long-term data on the outcome of haemophilia A patients are scarce as regards the development of target joints, joint replacement, lost days from school or work due to bleedings, and the quality of life, as most previous studies were limited to the aspects of safety and efficacy. The Baxter-initiated AHEAD (Advate in HaEmophilia A outcome Database) study is a multi-centre, prospective, non-interventional observational study of haemophilia A patients. All patients with a residual FVIII activity of £5% who are being treated with ADVATE are eligible. There are no limitations in terms of patient age or treatment regimen. AHEAD is scientifically supported by a renowned interdisciplinary steering board and is intended to yield data on 500 patients in up to 30 haemophilia centres, collected during a period of four years. The large patient population has been chosen in order to ensure a valid database. The objective of the study is to record haemophilia-related arthropathies, which will be defined based on imaging techniques (e. g. MRI, X-ray, ultrasound) and the judgment of the attending physician. In addition, extensive data will be collected on joint replacement surgeries, pseudotumour development, bleeding-related pain, quality of life (age-related questionnaires: Haem-A-QoL, Haemo-QoL, SF10, SF12v2), risk factors (diabetes mellitus, arterial hypertension, nicotine abuse), blood group, gene mutation, physical activity, and on the efficacy and safety of Advate. The patient data will be entered into an electronic CRF system at the centres. Plausibility checks during data entry, regular monitoring visits, and the option of auditing all serve to ensure a high data quality for AHEAD. The first patient was enrolled in the study in early June 2010; recruitment is planned to continue until the end of 2011. The Ethics Committee of the University of Bonn has given its favorable opinion.

Postoperative bleeding in paediatric ENT surgery. First results of the German ESPED trial.

Bleeding after ear-nose-and throat surgery in children is a serious complication. With the help of the German Surveillance Unit for Rare Paediatric Disorders (Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland; ESPED) a two year survey was performed to record the incidence, severity, reasons and treatment of haemorrhages. During the study period, 1069 bleeds were reported from 720 paediatric hospitals and departments of otorhinolaryngology after adenoidectomy and tonsillectomy. 713 reports could be analyzed. Two deaths occurred after adenoidectomy. Although laboratory screening was performed in more than 70% of all cases, bleeding complications were neither foreseeable nor preventable. Inherited coagulopathies were rare and in most cases not detected, neither by laboratory screening nor by taking a history. Since preoperative measures cannot help much to improve the situation, all efforts have to be taken to improve the postoperative period, especially since more than 20% of the hemorrhages occurred during weekends. Guidelines on postoperative care and behaviour should therefore be implemented and parents and patients must be informed on bleeding risks and on what to do in case of emergency. If bleeding occurs, extensive coagulation testing is mandatory.

Coagulation testing in the evaluation of suspected child abuse.

Every year in Germany nearly 3000 cases of child abuse were reported. When children are presented at emergency units with suspicious injuries and bruises a detailed documentation an evaluation is necessary after emergency treatment. As differential diagnosis inherited or acquired bleeding disorders should be excluded. In addition to a detailed evaluation of personal and family history and a physical evaluation different coagulation test to exclude defects of primary and secondary hemostasis should be performed. Clinician must know the limitations of these tests and keep in mind that an abnormal coagulation test does not exclude child abuse. Coagulation defects may be the consequence of child abuse and neglect or the two conditions may coexist.

Haemostatic testing prior to elective surgery in children? Not always!

In Germany, preoperative coagulation tests are commonly used, based on the belief that these tests should identify patients with an increased bleeding risk. However, published evidence does not longer support this approach for both traditional screening tests and novel techniques of global assessment of haemostasis. Unselected screening yields many false positive results and detects irrelevant disorders. It leads to postponement of surgery, anxiety in parents and patients, and is not cost effective. Even worse, it does not reliably detect relevant bleeding disorders such as the most common coagulopathy, von Willebrand disease. The bleeding history of patients and their relatives is a more effective tool to detect patients at risk. According to international guidelines and a joint statement of different German medical societies, a standardized questionnaire should be mandatory in preoperative screening. A diagnostic pathway should be employed to identify patients in whom specific tests are helpful. Because neither laboratory tests nor questionnaires can infallibly predict or exclude perioperative bleeding, guidelines for the management of these unexpected situations have to be established.

[Relevance of a single dose of 270 microg/kg recombinant factor VIIa for the treatment of patients with haemophilia and inhibitors - Recommendations from the GTH experts]. / Stellenwert der Einzelgabe von 270 microg/kg rekombinantem Faktor VIIa in der Behandlung von Hämophilie-Patienten mit Hemmkörpern - Empfehlungen der Experten.

Recombinant factor VIIa (rFVIIa; NovoSeven) is, besides other indications, authorised for the treatment of bleeding episodes in patients with hereditary haemophilia A or B and inhibitors. Based on the results of three clinical studies, marketing authorisation was granted for the single dose of 270 microg/kg body weight rFVIIa for the treatment of mild to moderate bleeding episodes in patients with haemophilia A or B with inhibitors in March 2007. Thereupon, an expert group analysed the relevance of this additional treatment option for clinical routine. Compared with the repeated application of 90 microg/kg body weight rFVIIa, quality of life may be improved if the single dose of 270 microg/kg body weight rFVIIa reduces the number of injections. The single dose has a benefit for those patients who require several rFVIIa applications or who do not respond adequately to low doses. Moreover, patients with poor venous access or patients who fear injections or reject them (especially children) may benefit from the single dose. The prescription of 270 microg/kg body weight rFVIIa as a single dose instead of multiple dosing of 90 microg/kg body weight is basically an individual and indication-related decision.