2026-08-12 | Recurrent Hematuria Unveiling Renal Lymphangioma: A Diagnostic Challenge in a Patient with von Willebrand Disease
Abstract Renal lymphangioma is a rare benign lymphatic malformation that may present with hematuria and flank pain. We report the case of a 16-year-old female with type 2A von Willebrand disease who developed recurrent macroscopic hematuria and left lumbar pain. Imaging revealed a multiloculated intrarenal cystic lesion consistent with renal lymphangioma. After recurrence of symptoms and failure of conservative management, percutaneous intrarenal sclerotherapy with doxycycline was performed under factor replacement, resulting in complete symptom resolution and no recurrence on follow-up. This case highlights the diagnostic challenge in coagulopathic patients and supports sclerotherapy as an effective minimally invasive treatment.
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2026-08-11 | Embryo-Fetal Development and Maternal-Fetal Exposure of the Von Willebrand Factor Binding Aptamer Rondaptivon Pegol (BT200) in Rabbits.
Rondaptivon pegol (BT200) is a PEGylated RNA aptamer that prolongs von Willebrand factor (VWF) and factor VIII half-lives in patients with hemophilia A and von Willebrand disease (VWD) type 2B. Embryo-fetal safety is particularly relevant given the disproportionate disease burden in women with VWD. Data on placental transfer and developmental safety of PEGylated aptamers remain limited. An embryo-fetal development study was conducted in pregnant rabbits. Animals received rondaptivon pegol subcutaneously (0, 1.5, 5, or 15 mg/kg/day) from gestational days (GDs) 7-19. Maternal toxicokinetic samples and pooled fetal plasma concentrations were collected during gestation to quantify transplacental exposure. Rondaptivon pegol was well tolerated, with no maternal toxicity, no effects on implantation, and no treatment-related fetal malformations. Dose-related reductions in mean fetal body weight (<11%) were considered adverse only at the highest dose level. Maternal systemic exposure was supratherapeutic, with mean Cmax ranging from 133 to 807 µg/mL on GD19, far exceeding the human target concentration (∼1.2 µg/mL). Fetal plasma concentrations were <0.25% of maternal levels across all dose groups, confirming minimal placental transfer. The no-observed-adverse-effect level was 5 mg/kg/day. At maternal systemic exposures ranging from 110- to 670-fold above anticipated clinical levels, rondaptivon pegol did not adversely affect implantation, embryonic viability, or fetal development. These findings provide the first quantitative maternal-fetal pharmacokinetic and developmental safety data for a PEGylated aptamer, supporting further clinical evaluation of rondaptivon pegol in women of reproductive age.
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2026-07-13 | The role of von Willebrand factor in gastrointestinal angiodysplasia and obscure gi bleeding: a narrative review.
Gastrointestinal bleeding (GIB) is a major cause of morbidity in von Willebrand disease (vWD), most commonly resulting from angiodysplasia. Current obscure gastrointestinal bleeding (OGIB) algorithms are primarily anatomy-based and often overlook underlying hemostatic disorders, delaying diagnosis and promoting recurrent bleeding. This review summarizes current evidence on the molecular basis, diagnosis, and management of vWD-associated GIB and proposes a mechanism-oriented diagnostic framework. A comprehensive narrative review of experimental, translational, and clinical studies was conducted, focusing on inherited vWD, acquired von Willebrand syndrome (AvWS), gastrointestinal angiodysplasia, endothelial biology, and diagnostic and therapeutic strategies. Deficiency or dysfunction of high-molecular-weight von Willebrand factor (vWF) multimers promotes angiodysplasia by disrupting Weibel-Palade body homeostasis, enhancing Ang-2/Tie2 and VEGF signaling, impairing integrin αvβ3 function, and fostering pro-inflammatory endothelial activation. Genetic and epigenetic modifiers, including FLI1, STXBP5, ABO blood group, and miR-24, further influence vascular susceptibility. Based on these mechanisms, we propose a four-stage diagnostic framework integrating bleeding assessment, platelet function screening, and targeted vWF testing with conventional endoscopic evaluation to facilitate earlier recognition of vWD/AvWS in patients with recurrent or obscure GIB. This strategy supports mechanism-based treatment combining hemostatic replacement therapies with selected anti-angiogenic approaches. vWD-associated GIB should be regarded as a systemic vascular-hemostatic disorder rather than an isolated structural gastrointestinal disease. Integrating hemostatic evaluation into OGIB pathways may improve diagnostic accuracy, reduce unnecessary procedures, and enable personalized management of patients with recurrent bleeding.
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2026-07-06 | Navigating hemostasis: anesthetic challenges in a pituitary tumor with type 2 von Willebrand disease—case report
Introduction The anesthetic management of patients with von Willebrand disease (VWD) present a significant perioperative challenge due to the high risk of hemorrhage. This risk is further elevated in neurosurgical procedures, such as transsphenoidal surgery (TSS) for pituitary neuroendocrine tumors (PitNETs), due to the close proximity to critical neurovascular structures. Case presentation This report describes a 42-year-old male with type 2 VWD and hypothyroidism, diagnosed with a Knosp grade 3A PitNET, who underwent an endoscopic endonasal transsphenoidal resection. A multidisciplinary approach was implemented, including hemodynamic monitoring and targeted replacement of VWF/FVIII concentrate calculated according to plasma levels, maintaining paremeters of VWF ristocetin cofactor/activity (VWF:RCo) (%) and FVIII (%): >80% during the intraoperative period and >50% during the postoperative period. The postoperative course was favorable, with no neurovascular, hemostatic, hemodynamic, or endocrine complications. Discussion The coexistence of VWD and a macro-PitNET creates a profound clinical dilemma that exposes the limitations of conventional perioperative care. While TSS demands strict hemostatic control due to its proximity to major neurovascular structures like the cavernous sinuses and internal carotid arteries, the type 2 VWD directly threatens clot stability and initial platelet plug formation. Given the scarce literature surrounding its neuroanesthetic management, this case report discusses the successful implementation of an individualized strategy. By integrating targeted plasma-derived VWF/FVIII replacement with real-time thromboelastography (TEG) and advanced hemodynamic monitoring, we demonstrate how a coordinated multidisciplinary approach can successfully mitigate overlapping hemorrhagic and neurosurgical risks. Conclusions This case highlights the importance of individualized planning and comprehensive management based on the American Society of Hematology (ASH), International Society on Thrombosis and Haemostasis (ISTH), National Hemophilia Foundation (NHF), and World Federation of Hemophilia (WFH) (ASH–ISTH–NHF–WFH, 2021) guidelines to optimize outcomes in patients with VWD undergoing high-complexity surgery.
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2026-06-19 | Impaired hemostasis in mechanical circulatory support systems: Monitoring with T-TAS® 01, in vitro correction with VWF concentrates, and impact of membrane oxygenators.
Mechanical circulatory support (MCS) systems assist patients with severe cardiac or respiratory failure, but bleeding linked to acquired von Willebrand disease remains a major complication. The T-TAS® 01 system has emerged as a rapid tool for assessing MCS patients' hemostasis. To evaluate hemostatic changes during and after MCS support. Secondary objectives included assessing the impact of the in vitro addition of von Willebrand factor concentrates and exploring differences according to the presence of a membrane oxygenator (MO). This prospective, bicentric study included adults requiring MCS, with hemostatic parameters assessed at three predefined timepoints using conventional laboratory assays and T-TAS® 01. Data were analyzed using linear mixed-effects models. In vitro addition of a VWF/FVIII concentrate (Haemate-P®) was evaluated as an exploratory analysis. A total of 39 patients were included; 56% experienced bleeding complications, of which 23% were clinically relevant. Significant alterations in hemoglobin, platelet counts, and platelet/VWF function were observed during MCS. T-TAS® 01 demonstrated impaired hemostasis during support, with partial recovery after device removal. In vitro addition of Haemate-P® improved T-TAS® 01 parameters. No consistent differences in overall hemostatic dynamics were observed between MO and non-MO devices. MCS is associated with significant and persistent alterations in primary hemostasis. T-TAS® 01 may represent a useful tool for dynamic assessment of these changes. In vitro VWF supplementation improved functional hemostasis parameters, although its clinical implications remain to be established. Differences related to MO presence were not consistent, supporting a shared mechanism of hemostatic dysregulation across MCS devices.
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