"Development in well-being and social function among Danish hemophilia patients with HIV: a three-wave panel study spanning 24 years".

BACKGROUND: Between 1975 and 1985 a total of 91 Danish patients with moderate and severe hemophilia (PWH) was infected with HIV constituting a major scandal in the Danish health care system. This study describes the burden of HIV infection among Danish PWH by evaluating changes from 1988 to 2012 in well-being, social function, experiencing stigma and openness about disease among Danish HIV+ PWH. METHODS: Three anonymous surveys were conducted in 1988, 2001 and 2012 targeting all Danish patients with moderate to severe hemophilia. Survey responses were received from 53, 21 and 18 HIV+ PWH respectively. A matched comparison sample of HIV- PWH was identified for each survey-year, using propensity score matching. Differences for each survey-year and trends over time were analyzed using ordinal logistic regression. RESULTS: In 1988, HIV+ PWH had more psychosomatic symptoms than HIV- PWH, but in 2001 life satisfaction was higher among HIV+ PWH than among HIV- PWH. Tests of differences in trend over time showed larger improvements in life satisfaction among HIV+ PWH than HIV- PWH, while HIV- PWH showed an increase in educational level compared to HIV+ PWH. Analysis restricted to HIV+ PWH showed an increase in perceived stigmatization. CONCLUSIONS: Differences between Danish HIV+ and HIV- PWH regarding well-being and psychosomatic symptoms seem to have evened out between 1988 and 2012. However, results suggest that HIV+ PWH still experience stigmatization and lower levels of education.

Real-World Effectiveness of rFIXFc Prophylaxis in Patients with Haemophilia B Switched from Standard Half-Life Therapy in Three European Countries.

INTRODUCTION: The current study describes real-world clinical outcomes and factor usage among patients with haemophilia B switching from standard half-life factor IX (SHL FIX) treatment to recombinant factor IX Fc fusion protein (rFIXFc) prophylaxis in European treatment centres. METHODS: This non-interventional, retrospective, multicentre chart review evaluated medical records from adult and paediatric patients with haemophilia B in Denmark, Germany and the UK. Patients had documented SHL FIX treatment, on-demand or prophylaxis, for ≥ 6 months before starting rFIXFc prophylaxis, and subsequent data for ≥ 6 months afterwards (up to 24 months). Primary endpoints included annualised bleeding rates (ABRs), prophylactic factor consumption and injection frequency. RESULTS: Data from 30 patients (24/30 [80.0%] with severe disease) showed overall mean (standard deviation, SD) ABRs of 4.7 (6.3) on SHL FIX treatment and 1.7 (2.3) after switching to rFIXFc prophylaxis. The reduction in mean (SD) ABRs was greater when switching from SHL FIX on-demand treatment (n = 6), with a decrease from 10.5 (9.9) to 2.6 (4.5), than when switching from SHL FIX prophylaxis (n = 24), with a decrease from 3.3 (4.3) to 1.5 (1.4). Among prior SHL FIX prophylaxis patients, switching to rFIXFc prophylaxis increased the proportion of those with zero bleeds from 21.7% to 45.8% during the 6 months before and after switching, respectively. In the total population, five of six target joints (83.3%) present when patients started rFIXFc prophylaxis subsequently resolved. In patients switching from SHL FIX prophylaxis to rFIXFc prophylaxis, mean (SD) weekly injection frequency was reduced by 1.0 (0.7) and mean (SD) factor consumption was reduced by 27.7 (49.6) IU/kg/week. CONCLUSION: This study demonstrates the effectiveness of rFIXFc prophylaxis in real-world clinical practice. Improvements in both clinical effectiveness and factor usage associated with rFIXFc prophylaxis may potentially reduce patient burden and improve quality of life.

Safety and efficacy of BAY 94-9027, an extended-half-life factor VIII, during surgery in patients with severe hemophilia A: Results of the PROTECT VIII clinical trial.

INTRODUCTION: Ensuring hemostasis during invasive procedures is a challenge in patients with severe hemophilia A. This analysis evaluated efficacy and safety of BAY 94-9027, an extended-half-life recombinant factor VIII (FVIII), in the surgical setting. MATERIALS AND METHODS: Patients participating in an open-label BAY 94-9027 clinical trial who underwent major surgery were included in the analysis. Investigator/surgeon assessment of hemostasis during surgery was the primary outcome. In addition, information about FVIII use, FVIII levels during perioperative period, bleeding complications and FVIII inhibitor development were collected. RESULTS: Data were analyzed for 26 major surgeries (orthopedic, n = 21) in 20 patients aged 13-61 years. BAY 94-9027 provided effective hemostasis during all procedures. FVIII levels 6-8 h post preoperative infusion and prior to the first follow-up infusion were in the range expected to maintain protection in the major surgery setting. The median time from preoperative infusion to the first follow-up infusion (the first infusion administered after the preoperative infusion) was 12.33 (3.6-49.9) h. No intraoperative bleeding complications occurred, and no new inhibitors developed following any surgery. CONCLUSIONS: The results of the study demonstrate that BAY 94-9027 was efficacious and well tolerated in the treatment of patients undergoing major surgeries. Advantages of BAY 94-9027 include the potential for less frequent infusion and reduced factor consumption, which should simplify the management of patients during major surgery.

Fixed doses of N8-GP prophylaxis maintain moderate-to-mild factor VIII levels in the majority of patients with severe hemophilia A.

BACKGROUND: N8-GP is an extended half-life recombinant factor VIII developed for prophylaxis and treatment of bleeds in patients with hemophilia A. OBJECTIVE: To assess pharmacokinetic (PK) characteristics of N8-GP in previously treated patients with severe hemophilia A, model the time spent at hemophilia thresholds of ≥1 and ≤5 IU/dL (moderate) or >5 IU/dL (mild) FVIII levels during N8-GP prophylaxis, and investigate the relationship between N8-GP half-life and von Willebrand factor (vWF). METHODS: PK assessments were obtained from patients with severe hemophilia A (FVIII < 1 IU/dL) participating in 4 clinical trials: pathfinder 1 (20-60 years); pathfinder 2 (12-17 and ≥18 years); pathfinder 5 (0-11 years), and pathfinder 7 (25-71 years). All PK profiles were assessed after washout and considered single-dose PK profiles. Pre- and postdose FVIII activity at steady state was measured at all visits. RESULTS: From 69 patients, 108 PK profiles of N8-GP 50 IU/kg were assessed. Adults/adolescents received 50 IU/kg every 4 days, achieving mean trough levels of 3.0 IU/dL (95% confidence interval, 2.6-3.5, adults) and 2.7 IU/dL (1.8-4.0, adolescents). Children received 60 IU/kg twice weekly, leading to mean trough levels of 1.2 IU/dL (0.8-1.6, 0- to 5-year-olds) and 2.0 IU/dL (1.5-2.7, 6- to 11-year-olds). PK modeling predicted children dosed every 3 days and adults/adolescents dosed every 3 to 4 days would maintain FVIII levels >5 and >1 IU/dL for >80% and 100% of the time, respectively. N8-GP half-life correlated linearly with von Willebrand factor levels in adults/adolescents, less in children. CONCLUSIONS: Prophylaxis with fixed intervals (Q4D/twice weekly) and fixed weight-based dosing (50/60 IU/kg) ensured >1 IU/dL FVIII trough levels in both adults and children.

[Fatal Klippel-Trénaunay syndrome in a child with pulmonary embolism]. / Fatal lungeemboli hos et barn med Klippel-Trénaunays syndrome.

Klippel-Trénaunay syndrome is characterized by the venous varicosities, ipsilateral cutaneous capillary malformations, and bony/soft-tissue overgrowth. Potential complications such as hypercoagulability, thrombosis and pulmonary embolism have been casuistically reported. Here, we describe a child with Klippel-Trénaunay syndrome complicated by a pulmonary embolism leading to sudden death.