In more than half of the individuals with a clinically relevant bleeding tendency who are referred to hemostasis experts, no biological etiology can be found after extensive laboratory testing. These persons are diagnosed with an unexplained bleeding tendency or "bleeding disorder of unknown cause" (BDUC). The mucocutaneous bleeding phenotype of individuals with BDUC is generally comparable to that of individuals with inherited bleeding disorders such as von Willebrand disease or platelet function disorders.
View Article and Find Full Text PDFThe development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) poses a major challenge in hemophilia A (HA) treatment. The formation of FVIII inhibitors is a CD4+ T-cell dependent mechanism which includes antigen presenting cells (APCs), B- and T-helper lymphocytes. APCs present FVIII derived peptides on major histocompatibility complex class II (MHC-II) to CD4+ Tcells.
View Article and Find Full Text PDFBackground: The main complication in hemophilia A treatment is the development of inhibitory antibodies against factor (F)VIII. Immune tolerance induction, the gold standard for eradicating anti-FVIII antibodies, is efficient in only 60% to 80% of cases. This underscores the need for more efficient induction of tolerance in patients with hemophilia A with FVIII inhibitors.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFBackground 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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFBackground: Postthrombotic syndrome (PTS) is a chronic condition following deep vein thrombosis (DVT) and is associated with pain, swelling, and restricted use of the affected limb. In pediatric age groups, its incidence and risk factors are not well-known.
Methods: This observational cohort study of all consecutive children (≤18 years) with DVT treated at the Emma Children's Hospital Amsterdam between January 2001 and January 2021 was conducted to identify incidence and risk factors for PTS in neonates aged ≤2 months and children aged >2 months.
Importance: Red blood cell (RBC) transfusions are frequently administered to preterm infants born before 32 weeks of gestation in the neonatal intensive care unit (NICU). Two randomized clinical trials (Effects of Transfusion Thresholds on Neurocognitive Outcomes of Extremely Low-Birth-Weight Infants [ETTNO] and Transfusion of Prematures [TOP]) found that liberal RBC transfusion thresholds are nonsuperior to restrictive thresholds, but the extent to which these results have been integrated into clinical practice since publication in 2020 is unknown.
Objective: To describe neonatal RBC transfusion practice in Europe.
Background: To enable personalized treatment and shared decision-making in chronic care, relevant health information is collected. However, health information is often fragmented across hospital information systems, digital health apps, and questionnaire portals. This also pertains to hemophilia care, in which scattered information hampers integrated care.
View Article and Find Full Text PDFObjective: To describe the incidence of major bleeds according to different platelet counts in very preterm infants, and to explore whether this association is influenced by other risk factors for bleeding.
Design: Observational cohort study.
Setting: A Dutch tertiary care neonatal intensive care unit.
People with nonsevere hemophilia (PWNSH) are phenotypically more diverse than those with severe hemophilia. Perceptions relating to a "nonsevere" phenotype have contributed to fewer research initiatives, fewer guidelines on optimal management, and a lack of standards for surveillance and clinical assessment for affected individuals. In many cases, episodes of abnormal bleeding could, if investigated, have led to earlier diagnosis.
View Article and Find Full Text PDFBackground: Pharmacokinetic (PK)-guided dosing is used to individualize factor (F)VIII and FIX replacement therapy.
Objectives: This study investigates the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B.
Methods: In this multicenter, prospective cohort study, people of all ages with hemophilia received prophylactic treatment with factor concentrates based on individual PK parameters.
Objectives: Anti-factor VIII (FVIII) antibodies have been reported to exhibit both neutralizing and non-neutralizing characteristics. This is the first study investigating the full spectrum of FVIII-specific antibodies, including non-neutralizing antibodies, very-low titer inhibitors, and inhibitors, in a large nationwide population of persons with hemophilia A of all severities.
Methods: All persons with hemophilia A (mild (FVIII > 5-40 IU/dL)/moderate [FVIII 1-5 IU/dL)/severe (FVIII < 1 IU/dL)] with an available plasma sample who participated in the study between 2018 and 2019 were included.
Introduction: Non-severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility and safety has never been investigated.
Aim: We assessed the feasibility and safety of combination treatment in nonsevere haemophilia A patients.
Factors influencing the activation of neutrophils in SCD and the potential neutrophil-mediated ameliorating effects of therapies in SCD.
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