Zyklusstörungen sind ein häufiges gynäkologisches Problem bei Jugendlichen. Die verstärkte Menstruation („heavy menstrual bleeding“, HMB) in Form von Hypermenorrhoe und Menometrorrhagie ist eine klinische Herausforderung. Sie kann die Lebensqualität von jungen Frauen erheblich beeinträchtigen. Während die meisten Fälle auf die physiologische Unreife der hypothalamisch-hypophysär-ovariellen Achse zurückzuführen sind, dürfen andere pathologische Ursachen – insbesondere angeborene Blutungsleiden – nicht übersehen werden. Diese Übersichtsarbeit hat zum Ziel, diagnostische Fallstricke sowie Behandlungsstrategien für HMB bei Jugendlichen zusammenzufassen, mit besonderem Schwerpunkt auf der Erkennung und Behandlung von angeborenen Blutungsleiden und der individuellen Anpassung der Therapie an die besonderen Bedürfnisse der jugendlichen Patientinnen. Wir haben aktuelle Literatur, Leitlinienempfehlungen sowie illustrative klinische Fälle zusammengefasst, um einen strukturierten Überblick über diagnostische und therapeutische Ansätze bei HMB bei Jugendlichen zu geben. Die Mehrheit der HMB-Fälle bei Jugendlichen ist auf anovulatorische Zyklen zurückzuführen. Bis zu 20

Congenital platelet disorders are rare and targeted treatment is usually not possible. Inherited platelet function disorders (iPFDs) can affect surface receptors and multiple platelet responses such as defects of platelet granules, signal transduction, and procoagulant activity. If iPFDs are also associated with a reduced platelet count (thrombocytopenia), it is not uncommon to be misdiagnosed as immune thrombocytopenia. Because the bleeding tendency of the different platelet disorders is variable, a correct diagnosis of the platelet defect based on phenotyping, function analysis, and genotyping is essential, especially in the perioperative setting. In the case of a platelet receptor deficiency, such as Bernard-Soulier syndrome or Glanzmann thrombasthenia, not only the bleeding tendency but also the risk of isoimmunization after platelet transfusions or pregnancy has to be considered. Platelet granule disorders are commonly associated with either intrinsically quantitative or qualitative granule defects due to impaired granulopoiesis, or granule release defects, which can also affect additional signaling pathways. Functional platelet defects require expertise in the clinical bleeding tendency in terms of the disorder when using antiplatelet agents or other medications that affect platelet function. Platelet defects associated with hematological-oncological diseases require comprehensive information about the patient including the clinical implication of the genetic testing. This review focuses on genetics, clinical presentation, and laboratory platelet function analysis of iPFDs with or without reduced platelet number. As platelet defects affecting the cytoskeleton usually show thrombocytopenia, but less impaired or normal platelet functional responses, they are not specifically addressed.

Toll-like receptors (TLRs) are pivotal in modulating immune responses and have been implicated in bone remodeling. This in vivo study investigates the impact of TLR2 and TLR4 signaling on trabecular bone structure using micro-computed tomography in a murine model. Sacrum and lumbar vertebrae (L5, L6) from wildtype (WT), TLR2-knockout (TLR2-KO), and TLR4-knockout (TLR4-KO) mice were analyzed, with trabecular parameters such as connectivity density (Conn-Dens), trabecular thickness (DT-TbTh), and variability metrics (DT-Tb,(1/N),SD and DT-TbThSD) assessed. The results revealed significant differences among genotypes: TLR4-KO mice exhibited increased variability in trabecular distribution, indicating less stable bone structures, while TLR-KO mice showed lower variability in trabecular thickness, suggesting enhanced uniformity and robustness. BV/TV and 3D reconstructions highlighted lower bone volume fractions in the sacrum compared to lumbar vertebrae across genotypes, consistent with human observations of reduced sacral bone volume in spondyloarthritis (SpA). Interestingly, bone changes were independent of immunization-induced SpA, emphasizing a direct role in TLR signaling. These findings provide novel insights into the role of TLRs in bone microarchitecture and suggest implications for bone-related pathologies, particularly those involving inflammatory pathways. Future research may explore the translational relevance of TLR-mediated mechanisms in osteopenia and osteoporosis.

In this article, our goal is to offer an introduction and overview of the diagnostic approach to inherited platelet function defects (iPFDs) for clinicians and laboratory personnel who are beginning to engage in the field. We describe the most commonly used laboratory methods and propose a diagnostic four-step approach, wherein each stage requires a higher level of expertise and more specialized methods. It should be noted that our proposed approach differs from the ISTH Guidance on this topic in some points. The first step in the diagnostic approach of iPFD should be a thorough medical history and clinical examination. We strongly advocate for the use of a validated bleeding score like the ISTH-BAT (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool). External factors like diet and medication have to be considered. The second step should rule out plasmatic bleeding disorders and von Willebrand disease. Once this has been accomplished, the third step consists of a thorough platelet investigation of platelet phenotype and function. Established methods consist of blood smear analysis by light microscopy, light transmission aggregometry, and flow cytometry. Additional techniques such as lumiaggregometry, immune fluorescence microscopy, and platelet-dependent thrombin generation help confirm and specify the diagnosis of iPFD. In the fourth and last step, genetic testing can confirm a diagnosis, reveal novel mutations, and allow to compare unclear genetics with lab results. If diagnosis cannot be established through this process, experimental methods such as electron microscopy can give insight into the underlying disease.

Bone disorders such as osteoporosis, osteopenia, and osteoarthritis affect millions worldwide, creating an urgent need for earlier and more accurate assessment of bone health. High-resolution imaging has transformed this field: micro-computed tomography remains the research gold standard for ex vivo and preclinical studies, while high-resolution peripheral quantitative computed tomography enables in vivo clinical assessment of trabecular and cortical bone microarchitecture. Combined with finite element analysis and machine learning, these modalities enable biomechanical modelling, predictive risk stratification, and progress toward personalised treatment. Remaining challenges include cost, limited availability, motion artefacts, and lack of standardisation. This review summarises current advances in imaging and computational methods, highlights their respective strengths and limitations, and outlines future directions required to translate these technologies into routine clinical practice.

Inherited platelet disorders (IPD) are a heterogeneous group of diseases causing bleeding, which are often challenging to diagnose. To improve the diagnostic process for these disorders, the ThromKidplus study group of the Permanent Pediatric Commission of the Society for Thrombosis and Haemostasis Research (GTH) has updated the AWMF Guideline for the "Diagnosis of Inherited Platelet Disorders" (AWMF Registry Number 086-003).Key updates in the guideline include a detailed diagnostic algorithm, emphasizing the use of standardized questionnaires, thorough patient history, and specific laboratory tests such as light transmission aggregometry (LTA), flow cytometry, and genetic testing. Updated guidelines for pre-analytics standardize sample preparation and handling to ensure reliable test results. Updated protocols for aggregometry and flow cytometry aim to enhance diagnostic accuracy. The integration of next-generation sequencing (NGS) provides comprehensive genetic analysis, and a new chapter on future developments highlights emerging technologies and research fields.This guideline supports the diagnosis of IPD close to the patient's residence, limits the diagnostic process to essential steps, and assists in counseling affected individuals and their families, ensuring that the diagnosis provides especially quality of life benefits to the patient.

INTRODUCTION:To enhance the treatment quality in haemophilia centres (HC), the German, Austrian and Swiss Society for Thrombosis and Haemostasis Research (GTH) started in 2017 the development of guidelines to define the structural and process quality of HC, essentially related to the EUHANET guidelines. AIM:A certification process for HC located in Germany, Austria and Switzerland started in 2019. METHODS:Within the first 5 years, 17 Haemophilia Comprehensive Care Centres (HCCC; ≥ 40 patients with severe HaemA/HaemB or vWD Type 3) and 6 Haemophilia Treatment Centres (HTC; ≥ 10 patients) were certified following a 1-day on-site audit performed by two trained haemophilia doctors. Experienced quality management staff supported the audit preparation in the HC. The entire certification process was coordinated by the accredited certification body ClarCert. RESULTS:In the vast majority of the HCs, the precise specifications of the GTH guidelines in combination with the intensive audit preparation resulted in a mean number of only 2.80 nonconformities per audit (range 0-14). In addition, a mean number of 5.96 (range 2-13) recommendations were documented by the auditors. The feedback of the centres showed a high level of satisfaction with an excellent rating for both the professional auditors and ClarCert as the organizing certification body. CONCLUSION:After the successful implementation of the certification process, a certificate is now an essential prerequisite for HC in Germany to conclude separate contracts regarding comprehensive care with health insurance bodies.

Die vorliegende aktualisierte Leitlinie soll einen praxisnahen Leitfaden für die Diagnostik und Therapie von Personen mit Hämophilie (Persons with Haemophilia, PwH) in Österreich darstellen. In der Hämophilie-Therapie gibt es wenige vergleichende Interventionsstudien, daher haben die Empfehlungen einen meist niedrigen Evidenzgrad und beruhen auf einem Expertenkonsensus. Als wesentliche Grundlage dieser Leitlinie dienen die internationalen Guidelines der „World Federation of Hemophilia (WFH)“ aus dem Jahr 2020. Diese wurden den nationalen Gegebenheiten und Erfahrungen angepasst. Behandelt werden Diagnostik und Verlaufskontrollen, medikamentöse sowie begleitende Therapieoptionen und Prophylaxe, weiters spezielle Aspekte bei Kindern und Erwachsenen mit schwerer Hämophilie, Messung von Outcomes, die Vorgehensweise bei Traumen, speziellen Blutungen und Eingriffen einschließlich Zahnextraktionen, das Thema Hemmkörper sowie mögliche Probleme bei Konduktorinnen und psychosoziale Aspekte bei Hämophilie.

Wir berichten über den Fall eines 10-jährigen Patienten mit einer plötzlich aufgetretenen Hemiparese und Fazialisparese der rechten Körperhälfte. Als Ursache dieses kindlichen Schlaganfalls fand sich eine Angiographie-positive, nichtprogrediente Großgefäßvaskulitis als Subtyp einer cPACNS. Eine unmittelbare Diagnostik und Therapie der geschilderten Notfallsituation führte zu einer annähernden Restitutio ad integrum. Die cPACNS ist eine relevante Differenzialdiagnose eines kindlichen Schlaganfalls.

Parietal thinning was detected in a 72-year-old with recurrent headaches. Quantification of bone loss was performed applying two- and three-dimensional methods using computerized tomographies. Two-dimensional methods provided accurate measurements using single-line analyses of bone thicknesses (2.13 to 1.65 and 1.86 mm on the left and 4.44 to 3.08 and 4.20 mm on the right side), single-point analyses of bone intensities (693 to 375 and 403 on the left and 513 to 393 and 411 Houndsfield Units on the right side) and particle-size analyses of low density areas (16 to 22 and 12 on the left and 18 to 23 and 14 on the right side). Deteriorations between days 0 and 220 followed by bone stability on day 275 were paralleled using the changed volumes of bone defects to 1200 and finally 1133 mm3 on the left side and to 331 and finally 331 mm3 on the right side. Interfolding as measurement of the bones’ shape provided changes to −1.23 and −1.72 mm on the left and to −1.42 and −1.30 mm on the right side. These techniques suggest a stabilizing effect of corticosteroids between days 220 and 275. Reconstruction of computerized tomographies appears justified to allow for quantification of bone loss during long-term follow-up.

Background/Objectives: Hemophilia A is associated with frequent bleeding episodes, joint damage, and reduced bone mineral density (BMD). The role of coagulation factors and inflammatory cytokines on bone metabolism, particularly on osteoblast function, is of increasing interest. However, significant inter-species differences in bone remodeling raise concerns about the translatability of findings from murine models to human systems. This study aims to investigate the effects of human coagulation factors and cytokines on bone formation, focusing on inter-species differences in the cell viability and mineralization of murine and human osteoblasts. Methods: Murine MC3T3-E1 and human SaOs-2 osteoblasts were cultured in osteoblast differentiation medium supplemented with various coagulation factors (FVIII, vWF, vWF-FVIII, FIX, FX, thrombin, and FVIII-thrombin) or cytokines (IL-6, TNF-α). Cell viability was assessed at both two-week and three-week time points using the CCK-8 assay, and mineralization was evaluated via Alizarin red S staining. Results: Coagulation factors significantly enhanced cell viability in human osteoblasts but had no effects on the murine counterpart. FX inhibited mineralization in human cells, while murine cells showed no significant changes. TNF-α stimulated mineralization in murine osteoblasts but inhibited it in human cells, highlighting species-specific responses to inflammatory cytokines. Similar trends in response patterns were observed at two and three weeks, with greater consistency at the later time point. Conclusions: These findings reveal critical inter-species differences in osteoblast responses to coagulation factors and cytokines, raising questions about the validity of using murine models to study human bone metabolism. Future research must account for these differences to ensure that preclinical models accurately reflect human pathophysiology, particularly in the context of hemophilia A.

This review summarizes the rationale and current data on the use of thrombopoietin receptor agonists (TPO-RAs) for treating severe thrombocytopenia in infants, children, and adolescents. It focuses on substances that have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for pediatric patients. Romiplostim and eltrombopag are already established as second-line treatment for persistent or chronic immune thrombocytopenia (ITP). As in adults, TPO-RAs are currently also evaluated in severe aplastic anemia (SAA), chemotherapy-induced thrombocytopenia (CIT), myelodysplastic syndromes (MDS), and poor engraftment after hematopoietic stem cell transplantation in pediatric and adolescent patients. Moreover, studies on the implication of TPO-RA in treating rare inherited thrombocytopenias, such as Wiskott-Aldrich syndrome (WAS), congenital amegakaryocytic thrombocytopenia (CAMT), or MYH9-associated thrombocytopenia, deserve future attention. Current developments include testing of avatrombopag and lusutrombopag that are approved for the treatment of thrombocytopenia associated with chronic liver disease (CLD) in adult patients. In pediatric and adolescent medicine, we expect in the near future a broader use of TPO-RAs as first-line treatment in primary ITP, thereby considering immunomodulatory effects that increase the rate of sustained remission off-treatment, and a selective use in rare inherited thrombocytopenias based on current clinical trials.

Abstract Since the 1970s, specialized hemophilia centers have been established to optimize the complex and costly treatment of patients with severe bleeding disorders. In 2019, the first GTH guidelines on the structural and process quality of hemophilia centers were published. On this basis, a procedure for the certification of hemophilia centers has been established under the technical leadership of the GTH. These GTH guidelines are essentially based on the European Guidelines for the Certification of Haemophilia Centers published in 2013, created by the European Haemophilia Network (EUHANET). In 2023, this European guideline was revised by the EAHAD Accreditation and Audit of Haemophilia Centers Working Group. On this background, the GTH guidelines have now been revised to take relevant updates to the European guidelines into account.

Introduction Hemophilia A (HA) patients are prone to low bone mineral density (BMD), independent of commonly known risk factors [1]. Recent research suggests that coagulation factor VIII (FVIII) could potentially act through direct interactions with key bone-regulating pathways (e.g. RANK/RANKL/OPG axis, Wnt/ß-catenin pathway, cytokines) or indirectly through downstream processes (e.g. thrombin production) [2]. Despite these promising leads, the connection between FVIII and bone health remains elusive. Therefore, cell culture experiments involving primary bone cells are pivotal to understand the impact of coagulation and inflammation on bone health.

This guideline is intended to provide practical guidance for the diagnosis and treatment of haemophilia in Austria. Few randomized controlled interventional trials are available addressing the treatment of haemophilia, therefore recommendations are usually based on low level of evidence and represent expert consensus.This guideline is based on the WFH guideline, published in 2020, and adapted according to the national circumstances and experience.It includes recommendations and suggestions for diagnosis and follow-up visits and pharmacological therapies for treatment and prophylaxis. Further topics comprise special aspects in children and adults with severe haemophilia, outcome measurement, and management of trauma, special bleedings and interventions, including dental procedures, inhibitors, management of haemophilia carriers, and psychosocial aspects.

Since the 1970s, specialized hemophilia centers have been established to optimize the complex and costly treatment of patients with severe bleeding disorders. In 2019, the first GTH guidelines on the structural and process quality of hemophilia centers were published. On this basis, a procedure for the certification of hemophilia centers has been established under the technical leadership of the GTH. These GTH guidelines are essentially based on the European Guidelines for the Certification of Haemophilia Centers published in 2013, created by the European Haemophilia Network (EUHANET). In 2023, this European guideline was revised by the EAHAD Accreditation and Audit of Haemophilia Centers Working Group. On this background, the GTH guidelines have now been revised to take relevant updates to the European guidelines into account.