Hamostaseologie最新文献

Hypofibrinogenemia is a congenital fibrinogen disorder characterized by a proportional decrease of functional and antigenic fibrinogen levels. Herein, we present a unique case illustrating the complex genotype-phenotype relationship in hypofibrinogenemia and the inability of low fibrinogen levels to counteract hypercoagulability.A 77-year-old male with factor V Leiden heterozygosity experienced surgery-related deep vein thrombosis at ages 65 and 71, along with poor wound healing and postoperative hematomas. Proportionally reduced functional and antigenic fibrinogen levels revealed hypofibrinogenemia. Whole exome sequencing identified a heterozygous fibrinogen gene cluster deletion and a hemizygous variant (p.Pro265Leu, rs6054) in the fibrinogen β (FGB) gene, both of which are associated with hypofibrinogenemia. The youngest son, who has noticeably higher fibrinogen levels, shares the deletion but does not carry the hemizygous FGB variant. This suggests that the FGB variant (p.Pro265Leu) contributes to a greater reduction in fibrinogen levels.This case suggests that the coexistence of thrombotic risk factors and potentially reduced thrombin clearance-resulting from low fibrinogen levels due to a fibrinogen gene cluster deletion and a hemizygous FGB variant-may shift the hemostatic balance toward thrombosis in a patient with moderate hypofibrinogenemia.

The prevention of intraoperative bleeding in patients with haemophilia is the key to a successful surgical procedure. Daily life of patients with haemophilia A and B significantly improved with prophylaxis with extended half-life factor concentrates (EHL-FVIII and EHL-FIX). The aim of this study was to investigate the efficacy and safety of EHL factor concentrates during surgery.In a retrospective chart review all surgical interventions in our hospital in patients with haemophilia A and B treated with EHL-FVIII or EHL-FIX undergoing surgery between 2016 and 2022 were included. Patients with inhibitors against FVIII or FIX were excluded.A total of 88 surgical interventions (41 minor, 47 major) in 52 patients with haemophilia were performed. The interventions consisted of 70 surgeries in 42 patients with haemophilia A and 18 surgeries in 10 patients with haemophilia B. The replacement therapy during the surgeries was performed with four different EHL FVIII and three different EHL FIX concentrates. Bolus injections were performed directly before surgery and continued after surgery with variable intervals ranging from 8 to 48 hours. The median dose before major surgery was 32.31 IU/kg FVIII and 47.06 IU/kg FIX and before minor surgery was 27.78 IU/kg FVIII and 33.78 IU/kg factor IX. There were 11 complications including 4 bleeding complications during/after surgery. No thromboembolic event and no inhibitor against FVIII or FIX were detected during follow-up.The replacement therapy with EHL factor concentrates in surgical interventions in patients with haemophilia A and B is safe and effective.

The rising incidence of pediatric thrombosis, increasing nearly 10% annually over the past decade, underlines a need for effective preventive strategies, particularly in hospitalized children. This narrative review explores existing literature on venous thromboembolism prevention in pediatric patients to clarify current strategies in children undergoing general, orthopaedic, and Fontan surgeries, and with conditions such as acute lymphoblastic leukemia and gastrointestinal disease. While recent studies have provided some insights into potential preventive strategies, real evidence is lacking on the best practices for thromboprophylaxis in these patient groups. In the absence of substantial studies, clinicians must rely on individual assessments weighting thrombotic and bleeding risk to effectively and safely manage these "uncharted waters."

Management of hemostasis in the perioperative setting, in trauma or in acute care, has considerably changed over the last two decades. Viscoelastic testing and single-factor replacement therapies have become cornerstones of the respective clinical approaches. Here, we illuminate the basic theories for these approaches as well as the important evidence available. Both viscoelastic assays and single-factor replacements are important improvements; their use must be based on the strongest scientific evidence available.

Inherited platelet disorders (IPDs) are rare conditions with diverse underlying pathophysiology which should be suspected in patients presenting with mucocutaneous bleeding or hemorrhages upon hemostatic challenges, in the presence or not of thrombocytopenia. Identifying IPDs is critical for providing appropriate care, preventing misdiagnosis, and avoiding unnecessary interventions, such as splenectomy. Syndromic IPDs, which may be associated with severe complications like kidney failure, infection, and malignancies, underscore the importance of accurate diagnosis and tailored management.Diagnosing IPDs remains challenging, requiring a comprehensive approach that integrates clinical assessment, evaluation of the bleeding history using standardized tools, like the ISTH-BAT, and first-line laboratory tests, such as light transmission aggregometry and flow cytometry. Second-line and specialized tests, including transmission electron microscopy, genetic analysis, and biochemical studies, may provide further insight in complex cases. Technological advancements, including multicolor flow cytometry and microfluidic tools, may in perspective improve IPD diagnostics by providing high-throughput and precise laboratory assays. In particular, mass cytometry and multi-omics may contribute to unraveling IPD pathophysiology, identifying novel markers, and refining disease classification. The application of artificial intelligence shows potential for improving diagnostic accuracy through the automated analysis of platelet morphology and function, from flow cytometry and digital microscopy assays, and for improving the understanding of pathogenic mechanisms of IPD through the examination of big data.This review summarizes current IPD platelet function testing strategies, emphasizing the need for a structured, tiered approach and examining emerging technologies and AI applications that could revolutionize diagnostic workflows, leading to personalized care and to an expanded understanding of IPDs.

Cerebral venous thrombosis (CVT) is a less common type of stroke that can occur across all age groups but predominantly affects children and young adults. Diagnosis is often challenging due to the nonspecific and variable clinical presentation. The disease course is heterogeneous, with CVT-related parenchymal lesions developing in approximately 50 to 60% of cases. Despite some advancements, significant gaps persist in understanding the pathophysiology of CVT, including the mechanisms underlying brain injury. Anticoagulation is the cornerstone of CVT treatment, but strategies targeting secondary mechanisms of parenchymal damage are still lacking. Here, the current state of the field is briefly reviewed, with the aim to introduce a wide audience (neuroscientists and clinicians alike) to the disease and inform clinical practice and future research.