Acquired haemophilia A: A 15-year population-based review of incidence rate, patient demographics and treatment outcomes.

INTRODUCTION: Acquired haemophilia A (AHA) is a rare bleeding disorder characterized by autoantibodies against coagulation factor VIII (FVIII). Estimates of AHA incidence are largely based on registry data, which may be prone to referral bias. Population-based studies can enhance our understanding of the epidemiology, presentation and outcomes of AHA. METHODS: We conducted a retrospective, population-based cohort study of all AHA diagnosed and treated in Manitoba, Canada over a 15-year period. Using records from the sole provincial reference laboratory, we identified all patients with FVIII inhibitors who did not have congenital haemophilia.  Using a piloted case report form, patient data was ascertained from hospital and bleeding disorder clinic records. RESULTS: From 2006 to 2021, we identified 34 patients with AHA, corresponding to a population-based incidence rate of AHA of 1.78 cases per million per year. The median age at presentation was 76 years and most cases were idiopathic (79%). Almost all patients (97%) presented with bleeding, of which 58% were considered major bleeds and required haemostatic agents in 67%. Longstanding unexplained bleeding symptoms were commonly reported, suggesting delayed diagnosis. Immunosuppressive therapy (IST) was administered in 88% of patients. Remission was achieved in 79% of patients; median time to remission was 2.1 months. There were two deaths due to bleeding. No deaths due to IST were reported. CONCLUSION: The population-based incidence of AHA in Manitoba is 1.78 cases/million/year. Bleeding is common and can be life-threatening. AHA outcomes are encouraging with the use of haemostatic agents and IST. Serious treatment-associated morbidity and mortality is uncommon.

Patent Foramen Ovale Treatment Strategies Correspond to an Index Predicting Pathogenicity.

BACKGROUND: Percutaneous closure of patent foramen ovale (PFO) in patients with cryptogenic stroke (CS) may reduce the risk of recurrent stroke. By performing closure only in those with high risk of recurrent PFO related strokes, patient selection may be improved. The Risk of Paradoxical Embolism (RoPE) score is a point-based index developed to estimate the probability that the index CS was attributable to patent foramen ovale. We aimed to evaluate whether management strategies using conventional clinical judgement for patients with CS and PFO corresponded with RoPE scores. METHODS: We performed a single-centre retrospective chart review of adult patients with CS or transient ischemic attack who were evaluated for PFO closure from January 1, 2011 to December 31, 2017. Patients were categorized based on the treatment strategy of percutaneous closure or medical management. RoPE scores were computed and clinical outcomes evaluated. RESULTS: A total of 154 patients were included: 63 patients underwent percutaneous closure and 91 patients were treated medically. Mean RoPE scores for closure and medical groups were 6.9±1.5 and 4.7±1.9, respectively (p<0.001). For patients who underwent percutaneous closure, successful device delivery was achieved in all patients and there were no immediate complications. CONCLUSION: In this single-centre study, patients selected for percutaneous PFO closure based on conventional clinical judgement were more likely to have elevated PFO attributable risk, based on the RoPE score.

Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials.

OBJECTIVE: Iron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron therapy on fatigue and physical capacity in IDNA adults. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). SETTING: Primary care. PARTICIPANTS: Adults (≥18 years) who were iron deficient but non-anaemic. INTERVENTIONS: Oral, intramuscular or intravenous iron supplementation; all therapy doses, frequencies and durations were included. COMPARATORS: Placebo or active therapy. RESULTS: We identified RCTs in Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health, SportDiscus and CAB Abstracts from inception to 31 October 2016. We searched the WHO's International Clinical Trials Registry Platform for relevant ongoing trials and performed forward searches of included trials and relevant reviews in Web of Science. We assessed internal validity of included trials using the Cochrane Risk of Bias tool and the external validity using the Grading of Recommendations Assessment, Development and Evaluation methodology. From 11 580 citations, we included 18 unique trials and 2 companion papers enrolling 1170 patients. Using a Mantel-Haenszel random-effects model, iron supplementation was associated with reduced self-reported fatigue (standardised mean difference (SMD) -0.38; 95% CI -0.52 to -0.23; I2 0%; 4 trials; 714 participants) but was not associated with differences in objective measures of physical capacity, including maximal oxygen consumption (SMD 0.11; 95% CI -0.15 to 0.37; I2 0%; 9 trials; 235 participants) and timed methods of exercise testing. Iron supplementation significantly increased serum haemoglobin concentration (MD 4.01 g/L; 95% CI 1.22 to 6.81; I2 48%; 12 trials; 298 participants) and serum ferritin (MD 9.23 µmol/L; 95% CI 6.48 to 11.97; I2 58%; 14 trials; 616 participants). CONCLUSION: In IDNA adults, iron supplementation is associated with reduced subjective measures of fatigue but not with objective improvements in physical capacity. Given the global prevalence of both iron deficiency and fatigue, patients and practitioners could consider consumption of iron-rich foods or iron supplementation to improve symptoms of fatigue in the absence of documented anaemia. PROSPERO REGISTRATION NUMBER: CRD42014007085.