Long-term neuropsychological sequelae, emotional wellbeing and quality of life in patients with acquired thrombotic thrombocytopenic purpura

Neurological symptoms related to microthrombosis are the hallmark of acute manifestations of acquired thrombotic thrombocytopenic purpura. Despite the achievement of hematological remission, patients may report persisting neurological impairment that affects their quality of life. To assess the long-term neuropsychological consequences of acute thrombotic thrombocytopenic purpura, we recruited 35 acquired thrombotic thrombocytopenic purpura patients (77% females, median age at onset 41 years, interquartile range 35-48) regularly followed at our out-patient clinic of thrombotic microangiopathies in Milan (Italy) from December 2015 to October 2016. Patients underwent a psychological evaluation of memory and attentional functions, emotional wellbeing and health-related quality of life at least 3 months after their last acute thrombotic thrombocytopenic purpura event (median 36 months, interquartile range 17-54). During the psychological consultation, 17 patients (49%) referred persisting subjective neurological impairment in the frame of a remission phase, with at least one symptom as disorientation, loss of concentration, dizziness, lack of balance, headache and diplopia. Neuropsychological assessment revealed lower scores than the Italian general population pertaining to direct, indirect and deferred memory. A higher degree of impairment of memory domains was found in patients with neurological involvement at the time of presentation of the first acute thrombotic thrombocytopenic purpura episode. Anxiety and depression were detected in 7 (20%) and 15 (43%) patients, respectively. Health-related quality of life was lower than the Italian general population, with mental domains more impacted than physical domains (mean difference 58.43, 95% confidence interval [-71.49, -45.37]). Our study demonstrates compromised memory and attention functions, persisting anxiety/depression symptoms and a generally reduced quality of life in patients surviving from acute acquired thrombotic thrombocytopenic purpura. New clinical strategies should be considered to improve these symptoms

Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency.

IntroductionHereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.AimThe aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.MethodsSubjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL−1) received 25 IU kg−1 pdFX as on‐demand treatment or short‐term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end‐of‐study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.ResultsSixteen enrolled subjects (six aged 12–17 years; 10 aged 18–58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half‐life were 2.00 (2.12; 1.79–2.37) IU dL−1 per IU kg−1 and 29.4 (28.6; 25.8–33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.ConclusionThese results demonstrate that a dose of 25 IU kg−1 pdFX is safe and efficacious for on‐demand treatment and short‐term prophylaxis in subjects with moderate or severe hereditary FX deficiency

Socioeconomic Mediators of Racial and Ethnic Disparities in Congenital Heart Disease Outcomes: A Population-Based Study in California.

Background Racial/ethnic and socioeconomic disparities exist in outcomes for children with congenital heart disease. We sought to determine the influence of race/ethnicity and mediating socioeconomic factors on 1-year outcomes for live-born infants with hypoplastic left heart syndrome and dextro-Transposition of the great arteries. Methods and Results The authors performed a population-based cohort study using the California Office of Statewide Health Planning and Development database. Live-born infants without chromosomal anomalies were included. The outcome was a composite measure of mortality or unexpected hospital readmissions within the first year of life defined as &gt;3 (hypoplastic left heart syndrome) or &gt;1 readmissions (dextro-Transposition of the great arteries). Hispanic ethnicity was compared with non-Hispanic white ethnicity. Mediation analyses determined the percent contribution to outcome for each mediator on the pathway between race/ethnicity and outcome. A total of 1796 patients comprised the cohort (n=964 [hypoplastic left heart syndrome], n=832 [dextro-Transposition of the great arteries]) and 1315 were included in the analysis (n=477 non-Hispanic white, n=838 Hispanic). Hispanic ethnicity was associated with a poor outcome (crude odds ratio, 1.72; 95% confidence interval [CI], 1.37-2.17). Higher maternal education (crude odds ratio 0.5; 95% CI , 0.38-0.65) and private insurance (crude odds ratio, 0.65; 95% CI , 0.45-0.71) were protective. In the mediation analysis, maternal education and insurance status explained 33.2% (95% CI , 7-66.4) and 27.6% (95% CI , 6.5-63.1) of the relationship between race/ethnicity and poor outcome, while infant characteristics played a minimal role. Conclusions Socioeconomic factors explain a significant portion of the association between Hispanic ethnicity and poor outcome in neonates with critical congenital heart disease. These findings identify vulnerable populations that would benefit from resources to lessen health disparities

No association between chromosome 12p13 single nucleotide polymorphisms and early-onset ischemic stroke

[No abstract available

Burden of mild haemophilia A: Systematic literature review

Introduction Although the clinical manifestations of severe haemophilia A (HA) are well studied, the challenges, if any, of living with mild HA are not clearly delineated to date. Aim To assess available evidence of clinical risks and societal/economic impacts of disease in adult patients with mild HA using a systematic literature review. Methods Prespecified study selection criteria were applied in a comprehensive literature search. Included studies varied in design and reported outcomes of interest for adults (&gt;= 13 years of age) with mild HA. Results Seventeen studies with a total of 3213 patients met eligibility criteria (published or presented in English, 1966-2017). Most studies were observational, and the outcomes reported were too sparse and dissimilar to support a formal meta-analysis. Mean annual bleeding rates ranged from 0.44 to 4.5 episodes per patient per year. Quality of life (QoL; SF-36 General Health) was impacted compared to healthy controls. Health care costs and productivity were seldom assessed and no robust comparisons to healthy controls were available. Conclusion Quantifying outcomes for adult patients with mild HA remains challenging, with estimates of key QoL and cost data often based on small data sets and without comparison to population norms. Therefore, the clinical impact of mild haemophilia may be under-represented and unmet needs may remain unaddressed. As paradigm-changing therapies for HA emerge, stronger knowledge of mild HA can guide the development of care options that minimize burden and enhance the QoL for this segment of the haemophilia community, and for the haemophilia community in totality

Factor XIII deficiency diagnosis: Challenges and tools

Factor XIII deficiency (FXIIID) is a rare hereditary bleeding disorder arising from heterogeneous mutations, which can lead to life-threatening hemorrhage. The diagnosis of FXIIID is challenging due to normal standard coagulation assays requiring specific FXIII assays for diagnosis, which is especially difficult in developing countries. This report presents an overview of FXIIID diagnosis and laboratory methods and suggests an algorithm to improve diagnostic efficiency and prevent missed or delayed FXIIID diagnosis. Assays measuring FXIII activity: The currently available assays utilized to diagnose FXIIID, including an overview of their complexity, reliability, sensitivity, and specificity, as well as mutational analysis are reviewed. The use of a FXIII inhibitor assay is described. Diagnostic tools in FXIIID: Many laboratories are not equipped with quantitative FXIII activity assays, and if available, limitations in lower activity ranges are important to consider. Clot solubility tests are not standardized, have a low sensitivity, and are therefore not recommended as routine screening test; however, they are the first screening test in almost all coagulation laboratories in developing countries. To minimize the number of patients with undiagnosed FXIIID, test quality should be improved in less well-equipped laboratories. Common country-specific mutations may facilitate diagnosis through targeted genetic analysis in reference laboratories in suspected cases. However, genetic analysis may not be feasible in every country and may miss spontaneous mutations. Centralized FXIII activity measurements should also be considered. An algorithm for diagnosis of FXIIID including different approaches dependent upon laboratory capability is proposed