United States. Therapeutic advancements for haemophilia from cryoprecipitate to gene therapy have dramatically altered the natural course of disease. Today, people with haemophilia (PWH) are expected to have a normal life expectancy. Despite this, quality of life for PWH remains compromised beyond the physical sequelae of their illness. People with haemophilia face unique challenges from a young age, and these affect nearly every aspect of life including relationships with family and peers, emotional well-being, and behaviour.Abstract Aim: Despite significant advances in morbidity and mortality outcomes, quality of life for people with haemophilia (PWH) remains compromised. Underrecognized and undertreated mental health disorders decrease quality of life; however, reports are inconsistent regarding the true prevalence of mental health disorders in PWH. Methods: We conducted a systematic literature search of Ovid MEDLINE, EMBASE, Psychinfo and the Cochrane Library, and hand searched the journal Haemophilia to identify records and subsequently conducted a meta-analysis to determine the prevalence of depression, anxiety and attention deficit hyperactivity disorder (ADHD) in patients with congenital haemophilia.Results: Our search strategy identified 2315 records, and 28 studies met eligibility criteria. Meta-analysis demonstrated that PWH are at increased risk of depression (odds ratio (OR) 2.45; 95% confidence interval (CI) 1.64-3.68), anxiety (OR 1.74, 95% CI 1.01-3.00), anxiety/depression (OR 2.60, 95% CI 2.35-2.87) and ADHD (OR 3.48, 95% CI 1.74-6.96). We found considerable heterogeneity among the studies likely due to differences in assessment tools, populations studied and year of publication.This suggests that standardized tools to diagnose mental health disorders in PWH are needed. Additionally, high-quality studies investigating mental health disorders in PWH are necessary to adequately document the prevalence of these disorders. Conclusion:Overall, our meta-analysis suggests that the prevalence of depression, anxiety and ADHD across decades is significantly increased in PWH compared to the general population.

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Introduction:A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET), confirmed that exposure to recombinant FVIII (rFVIII) products doubled the risk of inhibitor development compared to plasma-derived FVIII (pdFVIII) in previously untreated (or minimally treated) patients (PUPs) with severe haemophilia A. SIPPET post hoc analyses showed that early exposure to rFVIII was more immunogenic and that rFVIII could harm low-risk PUPs with non-null mutations. Clinical implications of SIPPET findings for the haemophilia community were unclear. Aim: Study the impact of the SIPPET study and its post hoc analyses on clinical practice for PUPs with severe haemophilia A in the United States. Methods: Members of the North American Hemophilia and Thrombosis Research Society (HTRS) completed two online questionnaires related to SIPPET publications and PUP management (study period: 12/2016-8/2018). Results: Over 50% participated the study. Sixty per cent expressed methodological concerns about the SIPPET study, yet 55% shared the study with new families. During the study period, rFVIII selection fell from 43/61 (70%) to 15/54 (28%) while use of pdFVIII and shared decision-making increased from 5/61 (8%) to 9/54 (17%) and from 4/61 (7%) to 10/54 (19%), respectively. Based on post hoc analyses, 44/54 (82%) would change their clinical practice with 31/44 (70%) using pdFVIII for PUPs. Barriers to translation of SIPPET analyses included study design concerns, non-inclusion of novel therapies, inability to perform genetic testing at diagnosis and risk of plasma-derived infections. Conclusion: Despite the methodological concerns about the SIPPET study, this Grade I evidence appears to have influenced the clinical practice of haemophilia providers in the United States. | 765 SANDE Et Al.

Background: Thrombopoietin receptor agonists are emerging as a therapeutic option for patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). We report our experience of treating children with AA/MDS with romiplostim, thrombopoietin receptor agonist. Observations: Three children (AA, 2; MDS, 1) received romiplostim treatment at a median dose of 10 μg/kg/week (starting dose: 5 μg/kg/wk; 2.5 μg/kg/wk increment). Trilineage hematopoietic recovery occurred at a median of 13 weeks (range: 13 to 16 wk) without adverse events. Hematopoiesis continued to improve after therapy discontinuation (median follow-up: 2.8 y; range: 0.5 to 3.0). Conclusion: Our experience supports the short-term safety and efficacy of romiplostim in children with AA/MDS.

Purpose: Fibroadipose vascular anomaly (FAVA) is a complex vascular anomaly associated with postzygotic somatic PIK3CA mutations. FAVAs can cause significant pain, swelling, and musculoskeletal dysfunction. Treatment options are limited. Sirolimus is a well-tolerated and effective treatment for patients with FAVA. We report our experience of using sirolimus to treat 11 children with FAVAs. Methods: We conducted a retrospective review of all patients with FAVA treated with sirolimus in our institution. Results: Fourteen patients (10 females) were referred for sirolimus therapy for FAVA. Eleven patients were initiated on sirolimus at a mean age of 14 years (range: 9–17.9 years) and were then treated for a mean of 19 months (range: 1–46 months). Five had previously undergone sclerotherapy without benefit. Sirolimus was initiated at a dose of either 2.5 mg/m2 once daily or 0.8 mg/m2 twice daily. Doses were titrated to maintain sirolimus trough levels of 5–15 ng/L. Goals of treatment were improvement in pain and musculoskeletal dysfunction. All 11 patients reported reduced pain; 7 reporting this within 3 weeks of starting sirolimus. This allowed for discontinuation of analgesia. Function improved significantly in 9 of 11, leading to resumption of sports or work participation. Sirolimus side effects were similar to prior reports, most commonly mouth sores, mildly elevated lipids and acne. There was no grade III/IV toxicity. Conclusion: Sirolimus is a well-tolerated and effective treatment for patients with FAVA. Initial symptom improvement is rapid, with significantly reduced pain and improved function. We believe that sirolimus should be considered for all patients with FAVA as a first-line therapy before surgical/interventional approaches.