Amelioration of a von Willebrand disease type 2B phenotype in vivo upon treatment with allele-selective siRNAs.

Treatment options for the bleeding disorder von Willebrand disease type 2B (VWD2B) are insufficient and fail to address the negative effects of circulating mutant von Willebrand factor (VWF). The dominant-negative nature of VWD2B makes functionally defective VWF an interesting therapeutic target. Previous in vitro studies have demonstrated the feasibility of allele-selective silencing of mutant VWF using small interfering RNAs (siRNAs) targeting common single nucleotide polymorphisms (SNPs) in the human VWF gene, an approach that can be applied irrespective of the disease-causing VWF mutation.

Prediction of the chance of successful immune tolerance induction in persons with severe hemophilia A and inhibitors: a clinical prediction model.

Background: Inhibitor eradication to restore factor (F)VIII efficacy is the treatment goal for persons with severe hemophilia A (HA) and inhibitors. Immune tolerance induction (ITI) is demanding and successful in about 70% of people. Until now, it has remained difficult to quantify the probability of ITI success or failure, complicating the decision to initiate or not initiate ITI.

Coagulation assay results at birth in preterm infants: A cohort study highlighting the relevance of local reference values for interpretation.

Background And Objectives: Routine coagulation screens at birth are still standard in some European neonatal intensive care units (NICUs), although interpretation of these results is complex in preterm infants. It is unclear to what extent local coagulation assay results agree with published reference ranges when using different analysers and reagents. We aimed to assess coagulation assay results on day 1 of life in very preterm infants admitted to the NICU.

The severe von Willebrand disease variant p.M771V leads to impaired anterograde trafficking of von Willebrand factor in patient-derived and base-edited endothelial colony-forming cells.

Background: von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by quantitative or qualitative defects in von Willebrand factor (VWF). The p.M771V VWF variant leads to a severe bleeding phenotype in homozygous patients.

Risk assessment and management strategies in older patients with acute pulmonary embolism.

Background: Managing older patients with acute pulmonary embolism (PE) is challenging due to their underrepresentation in clinical trials, comorbidities, and increased complication risk.

Objectives: To evaluate risk assessment and management outcomes in older patients with PE focusing on home and reperfusion treatment.

Methods: A retrospective analysis was conducted on patients aged 70 years or older diagnosed with acute PE at an academic medical center (2015-2022).