Abstract:Platelet-type von Willebrand disease (PT-VWD) is a rare thrombocytopathy caused by gain-of-function variants in GP1BA, leading to increased binding of von Willebrand factor (VWF). Because its phenotype closely resembles VWD type 2B (VWD 2B), misdiagnosis is common, and distinction requires Ristocetin-induced platelet agglutination (RIPA) mixing studies and molecular genetic analysis. Although individual case reports, case series, and earlier summaries exist, an updated and comprehensive synthesis of all published cases has been lacking. We report a 4-year-old boy presenting with easy bruising, prolonged epistaxis, reduced VWF parameters (VWF collagen-binding activity 0.07 U/mL, VWF-antigen 0.33 U/mL), absence of high-molecular-weight multimers, and enhanced RIPA. Genetic testing identified the pathogenic GP1BA variant p.Met255Val, causing PT-VWD. RIPA mixing studies confirmed the diagnosis. In the course of the disease, the patient developed recurrent mucosal bleeding and a hypersensitivity reaction to tranexamic acid. Therefore, desmopressin was used, and he showed partial clinical benefit from desmopressin without developing thrombocytopenia. To contextualize this case, we performed a literature review (PubMed, May 2025) and identified 67 documented patients with PT-VWD. Over 40% were initially misclassified as VWD 2B. p.Gly249Val and p.Met255Val were the most frequent variants. Baseline thrombocytopenia occurred in approximately one-third of cases, and pregnancy-associated thrombocytopenia was common. According to the literature, platelet transfusions were most effective (in case of major hemorrhage or surgical setting); VWF concentrates or desmopressin showed variable efficacy and occasional transient thrombocytopenia. These data demonstrate the diagnostic challenges of PT-VWD and emphasize the importance of clinical case collection to improve therapeutical management.
Abstract:Factor XI (FXI) inhibition represents an innovative approach to anticoagulation, offering the potential for effective thromboprophylaxis with a reduced risk of bleeding. While intensive clinical research is underway in adult populations, its relevance to the treatment of children remains largely unknown. The evidence base to inform potential paediatric use is still limited, and the extent to which findings from adult studies can be translated to paediatric care has yet to be clarified. This review systematically maps the existing evidence from preclinical and adult studies on FXIa and examines its implications for future paediatric application and treatment strategies.
Abstract:Hemophilia A or B is an inherited bleeding disorder due to a deficiency of factor VIII or IX. Depending on the severity, bleeding may already occur after birth and in very young patients, e.g., intracranial hemorrhage or bleeding in muscle, soft tissue, and joints during surgery or after little accidents. Abstract:Despite great improvements in factor therapy concerning half-life and less frequent injections, remaining issues are the intravenous administration and inhibitor development. Additionally, a primary regular factor prophylaxis maybe more effective to prevent joint bleeds and damages in adolescence and adults. Abstract:Non-factor therapies have been a so-called "game changer" in hemophilia care, most of all due to the subcutaneous application and improved quality of life. Existing data demonstrate a more stable coagulation activation and effective bleeding prevention, also in patients with inhibitors. These novel therapies work either as factor mimetics, providing similarity to the missing factor, or they have a rebalancing effect by targeting natural coagulation inhibitors, such as tissue factor pathway inhibitor, or protein C. Depending on data and the approval situation, these therapies may allow an easier and earlier start of prophylaxis and potentially prevent early bleeding. However, concerns about these new treatments include, e.g., risk of coagulation imbalances and insufficient monitoring. Abstract:This review will comprise an overview of non-factor treatment, such as FVIII mimetics and re-balancing therapies, including working profile, pediatric data, and approval situation in Europe, Switzerland, and the United States.
