Background: Familial multiple coagulation factor deficiencies (FMCFDs) are a group of inherited hemostatic disorders with the simultaneous reduction of plasma activity of at least two coagulation factors. As consequence, the type and severity of symptoms and the management of bleeding/thrombotic episodes vary among patients. The aim of this study was to identify the underlying genetic defect in patients with FMCFDs. Methods: Activity levels were collected from the largest cohort of laboratory-diagnosed FMCFD patients described so far. Genetic analysis was performed using next-generation sequencing. Results: In total, 52 FMCFDs resulted from coincidental co-inheritance of single-factor deficiencies. All coagulation factors (except factor XII (FXII)) were involved in different combinations. Factor VII (FVII) deficiency showed the highest prevalence. The second group summarized 21 patients with FMCFDs due to a single-gene defect resulting in combined FV/FVIII deficiency or vitamin K–dependent coagulation factor deficiency. In the third group, nine patients with a combined deficiency of FVII and FX caused by the partial deletion of chromosome 13 were identified. The majority of patients exhibited bleeding symptoms while thrombotic events were uncommon. Conclusions: FMCFDs are heritable abnormalities of hemostasis with a very low population frequency rendering them orphan diseases. A combination of comprehensive screening of residual activities and molecular genetic analysis could avoid under- and misdiagnosis.

Background: Information about the impact of hemophilia on daily living and information preferences for patients and their caregivers in Central Europe has been limited. Methods: This cross-national survey was conducted between April 1 and October 15, 2020 and utilized a self-administered questionnaire to collect data (Typeform™) from people living with hemophilia in Bulgaria, Croatia, Czech Republic, Hungary, Slovakia and Slovenia. The questionnaire included 22 questions regarding difficulties in daily life and preferences for receiving hemophilia-related information. Respondents were stratified into two main groups, people with hemophilia (PwH) or their caregivers (CPwH). Results were analyzed using descriptive statistics. Results: Of the 364 respondents, 232 were PwH (63.7%) and 132 were CPwH (36.3%). In total, 70.3% of hemophilia patients/caregivers responded that they are kept sufficiently informed about life with hemophilia, with 68.0%, 59.1% and 56.3% of respondents obtaining information from their physicians, patient associations and via digital media (internet and social media), respectively. However, 97.8% of respondents expressed an interest in additional information, particularly new hemophilia treatment options (62.1%), which in contrast to other topics was indicated most frequently by both patients and caregivers in all six countries. Most frequent difficulties in everyday life with hemophilia were identified as mobility problems (41.8%), unexpected bleeding (38.5%), pain (35.4%), and uncertainty with what they can or cannot do (25.0%). During the 2020 COVID-19 pandemic, 52.5% of respondents reported that they did not experience any major change in daily living with hemophilia. Conclusion: Based on our Central European survey, hemophilia mostly affects peoples’ lives by causing mobility difficulties, unexpected bleeding, pain and uncertainty in daily activities. Although the majority of respondents reported being educated about hemophilia, most PwH and CPwH respondents sought additional information, highlighting the need for continuous personalized patient education to cope with present challenges.

The aim of this short review is to provide an update on glucose homeostasis, insulin secretion and pharmacological management of osteoporosis in transfusion-dependent thalassemia (TDT). A retrospective study, documenting the changes in glucose-insulin homeostasis from early childhood to young adulthood, has advanced our understanding of the evolution of glucose regulation in patients with TDT. Magnetic Resonance Imaging (T2* MRI) is considered to be a reliable tool to measure pancreatic iron overload. Continuous glucose monitoring systems (CGMS) can be used in early diagnosis of glucose dysregulation and in disease management in patients with already diagnosed diabetes. Oral glucose-lowering agents (GLAs) are effective and safe for the treatment of diabetes mellitus (DM) in patients with TDT, achieving adequate glycemic control for a substantial period of time. Current modalities for the management of osteoporosis in adults with TDT include inhibitors of bone remodeling such as bisphosphonates and denosumab as well as stimulators of bone formation (e.g., teriparatide), Considering the unique characteristics of osteoporosis associated with TDT, early diagnosis, treatment initiation and treatment duration are critical issues in the management this special population. Advances in the care of TDT patients have led to improved survival and quality of life. Nevertheless, many chronic endocrine complications still remain. Their routine screening and a high index of suspicion are imperative in order to provide timely diagnosis and treatment. (www.actabiomedica.it)

Background: Physical activity is now considered generally beneficial for persons with haemophilia (PWH). However, the specific type and extent of activity and its impact on quality of life (QoL) and bleed protection during exercise is under‐researched. This knowledge gap should significantly impact PWH's ability to manage their condition optimally. Objective: To explore levels of physical activity and understand bleed protection during exercise among PWH as part of the Liberate Life project. Methods: A web‐based survey was conducted across eight European countries between August and September 2023. The online survey was developed by haemophilia treatment experts and patient association representatives according to the Checklist for Reporting Results of Internet E‐Surveys (CHERRIES) method. The 24‐question survey, distributed to PWH or their parents/caregivers, covered topics such as demographics, the impact of haemophilia on daily life, bleed protection understanding and involvement in physical activities. An activity index was used to categorize PWH as ‘more’ or ‘less’ active. Results: Of 374 respondents analysed, PWH engagement in physical activities, mainly low‐impact activities like walking, swimming or cycling, was high (90.9%). Most respondents (74.9%) were ‘less active’ according to the activity index. There was a significant knowledge gap in respondents' understanding of bleed protection provided by factor and non‐factor therapies. Joint health (68.7%), disease severity (69.3%) and capability for physical activity (62.3%) were indicated as key variables influencing PWH QoL. Conclusion: These findings underscore the need for educational programs to improve PWH's understanding of protective factor levels and the role of non‐factor therapies in managing haemophilia.

What is known and objectives Intravenous (IV) replacement therapy with plasma derived or recombinant factor VIII (FVIII) and factor IX concentrates is the mainstay for treatment of patients with haemophilia A and B. Therefore, the current therapy is particularly dependent on the presence of a secure IV access especially in case of emergency. Case description A life‐threatening bleeding event in an 8‐month‐old boy is managed by intraosseous (IO) infusion of recombinant FVIII concentrate. No adverse events have been observed 6 months after the application, and complete heeling has been reported. What is new and conclusion Venous application of factor concentrate remains inevitable in any haemophilic emergency. In case IV access is lacking, an IO institution of factor might be considered. To our knowledge, this represents the first reported case of IO application of recombinant FVIII concentrate in a patient with haemophilia.