Treatment regimens and outcomes in severe and moderate haemophilia A in the UK: The THUNDER study

Introduction: The THUNDER study provides an analysis of treatment patterns and outcomes in UK patients with severe or moderate haemophilia A (SHA/MHA) in 2015. Methods: Patients with SHA or MHA registered with the UK National Haemophilia Database (NHD) were segregated by severity, inhibitor status and age. Haemophilia joint health score (HJHS) was derived from NHD records and treatment regimen and annualized bleed/joint‐bleed rate (ABR/AJBR) from Haemtrack (HT) in HT‐compliant patients. Results: We report 1810 patients with SHA and 864 with MHA. Prophylaxis was used in 94.9% (n = 130/137) of HT‐compliant children <12 years with SHA, falling to 74.1% (n = 123/166) aged ≥40 years. Median ABR increased with age (1.0, IQR 0.0‐5.0, <12 years; 3.0 IQR, 1.0‐8.0, ≥40 years). Inhibitors were present in 159 (8.8%) SHA and 34 (3.9%) MHA. Median ABR increased from 2.0 (<12 years) to 21.(≥40 years) in SHA inhibitor patients using prophylaxis. Prophylaxis was used by 68.8% of HT‐compliant MHA patients (n = 106) (median FVIII baseline 0.01 IU/mL) associated with a median (IQR) ABR of 3.0 (1.0‐7.0). Median HJHS (n = 453) increased with age in SHA and MHA. Median (IQR) HJHS was higher in SHA inhibitor (17.0, 0.0‐64.5) than non‐ or past inhibitor patients (7.0, 0.0‐23.0). Conclusions: Increasing ABR with age persists despite current prophylaxis regimens.SHA and MHA had similar ABR/AJBR and HJHS, leading to a suspicion that a subgroup of MHA may be relatively undertreated. More intensive prophylaxis may improve outcomes, but this requires further study

EUHASS: The European Haemophilia Safety Surveillance system

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Development of resistance to activated protein C during pregnancy

We measured activated protein C (APC) anticoagulant activity in 20 healthy women at 14‐20, 28 and 36 weeks gestation, and at 1 d post‐partum. Significant reductions in the mean APC sensitivity ratio (APC‐SR) were observed at all stages of pregnancy studied compared with the mean APC‐SR obtained for baseline measurements carried out at &gt; 8 weeks post‐partum. APC resistance was seen in 8/19 (42%) and in 11/20 (55%) women at 14‐20 and 28 weeks gestation respectively. The development of resistance to APC may contribute to the increased risk of thrombosis during pregnancy

Development of resistance to activated protein C during pregnancy

We measured activated protein C (APC) anticoagulant activity in 20 healthy women at 14‐20, 28 and 36 weeks gestation, and at 1 d post‐partum. Significant reductions in the mean APC sensitivity ratio (APC‐SR) were observed at all stages of pregnancy studied compared with the mean APC‐SR obtained for baseline measurements carried out at &gt; 8 weeks post‐partum. APC resistance was seen in 8/19 (42%) and in 11/20 (55%) women at 14‐20 and 28 weeks gestation respectively. The development of resistance to APC may contribute to the increased risk of thrombosis during pregnancy

Association of patient, treatment and disease characteristics with patient‐reported outcomes: results of the ECHO registry

Introduction Patient-reported outcomes (PROs) in people living with haemophilia A (PLWHA) are often under-reported. Investigating PROs from a single study with a diverse population of PLWHA is valuable, irrespective of FVIII product or regimen. Aim To report available data from the Expanding Communications on Haemophilia A Outcomes (ECHO) registry investigating the associations of patient, treatment and disease characteristics with PROs and clinical outcomes in PLWHA. Methods ECHO (NCT02396862), a prospective, multinational, observational registry, enrolled participants aged ≥16 years with moderate or severe haemophilia A using any product or treatment regimen. Data collection, including a variety of PRO questionnaires, was planned at baseline and annually for ≥2 years. Associations between PRO scores and patient, treatment and disease characteristics were determined by statistical analyses. Results ECHO was terminated early owing to logistical constraints. Baseline data were available from 269 PLWHA from Europe, the United States and Japan. Most participants received prophylactic treatment (76.2%), with those using extended-half-life products (10.0%) reporting higher treatment satisfaction. Older age and body weight >30 kg/m2 (>BMI) were associated with poorer joint health. Older age was associated with poorer physical functioning and work productivity. Health-related quality of life and pain interference also deteriorated with age and >BMI; >BMI also increased pain severity scores. Conclusion ECHO captured a variety of disease characteristics, treatment patterns, PROs and clinical outcomes obtained in real-world practice with ≤1 year's follow-up. Older age, poorer joint health and >BMI adversely affected multiple aspects of participant well-being

Clinical risk factors in the development of inhibitors in non-severe hemophilia A patients: the first results of the INSIGHT case-control study

Clinical epidemiolog

Factor VIII light chain mutations and cysteine substitutions predispose for inhibitor development in mild and moderate haemophilia A: first results from the INSIGHT study

Clinical epidemiolog