Bleeding disorder of unknown cause: an illustrated review on current practice, knowledge gaps, and future perspectives.

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.

Enhanced thrombin and plasmin generation profiles in alpha-2-antiplasmin-deficient patients: Data from the Rare Bleeding disorders in the Netherlands study.

Background: α2-Antiplasmin (A2AP) deficiency is a rare and often unidentified disorder characterized by increased fibrinolysis and subsequent bleeding. Global hemostasis assays may increase insight into the altered coagulation and fibrinolysis in these patients.

Objectives: To explore thrombin and plasmin generation profiles in A2AP-deficient patients, corresponding A2AP activity levels and associated bleeding phenotypes.

Primary postpartum hemorrhage in women with von Willebrand disease and carriers of hemophilia: a retrospective analysis.

Background: Between 2002 and 2011, the incidence of severe primary postpartum hemorrhage (PPH) in Dutch women with von Willebrand disease (VWD) and hemophilia carriers (HCs) was 8% vs 4.5% in the general population.

Objectives: To determine the contemporary incidence of severe primary PPH in women with VWD and HCs.

Targeted exome analysis in patients with rare bleeding disorders: data from the Rare Bleeding Disorders in the Netherlands study.

Background: Rare coagulation factor deficiencies and disorders of fibrinolysis (defined as rare bleeding disorders [RBDs]) present with a heterogeneous bleeding phenotype, and bleeding severity is difficult to predict.

Objectives: Describe underlying rare genetic variants in the Dutch RBD population and investigate the relationship between genotype, laboratory phenotype, and clinical phenotype.

Methods: The Rare Bleeding Disorders in the Netherlands is a cross-sectional, nationwide study conducted between October 1, 2017, and November 30, 2019.

Predictive performance of pharmacokinetic-guided prophylactic dosing of factor concentrates in hemophilia A and B.

Background: 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.

Tachyphylaxis and reproducibility of desmopressin response in perioperative persons with nonsevere hemophilia A: implications for clinical practice.

Background: Desmopressin is frequently used perioperatively in persons with nonsevere hemophilia A. However, increase in factor (F)VIII:C after desmopressin use is interindividually highly variable. Tachyphylaxis has only been reported in test setting for persons with hemophilia A, with a remaining response of approximately 70% after a second dose compared with that after a first dose.

Peri-operative desmopressin combined with pharmacokinetic-guided factor VIII concentrate in non-severe haemophilia A patients.

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.

The Use of Galactomannan Antigen Assays for the Diagnosis of Invasive Pulmonary Aspergillosis in the Hematological Patient: A Systematic Review and Meta-Analysis.

The optimal cut-off value of the optical density index of the galactomannan antigen assays (GM) for diagnosing invasive pulmonary aspergillosis in hematological patients is a disputed topic. This article conducts a systematic review with a meta-analysis to establish which optical density index (ODI) cut-off value should be implemented into clinical practice. Pubmed, Embase and Cochrane databases were searched (N = 27).

Little discrepancy between one-stage and chromogenic factor VIII (FVIII)/IX assays in a large international cohort of persons with nonsevere hemophilia A and B.

Background: Accurate measurements of coagulation factor activity form an essential part of hemophilia management and are performed by the one-stage or chromogenic assay. Current literature suggests that approximately one-third of persons with nonsevere hemophilia A exhibit assay discrepancy, albeit with a high variability between studies. Such data are scarce in nonsevere hemophilia B.

High prevalence of postpartum hemorrhage in women with rare bleeding disorders in the Netherlands: retrospective data from the RBiN study.

Background: Women with rare bleeding disorders (RBDs), including coagulation factor deficiencies and fibrinolytic disorders, may have a higher risk of postpartum hemorrhage (PPH). Information on this patient category is lacking in the existing PPH guidelines because data on PPH in patients with RBDs are scarce.

Objective: To describe the prevalence of PPH in women with an RBD and evaluate the use of peripartum hemostatic prophylaxis.

The value of leukapheresis for treatment of priapism as presenting feature of chronic myeloid leukemia-Case report and review of literature.

Priapism is a rare presenting feature of chronic myeloid leukemia (CML) in male patients. Treatment aims to relieve symptoms and to prevent erectile dysfunction. Several treatment modalities exist, however no standard treatment is recommended.

Fibrinolytic assays in bleeding of unknown cause: Improvement in diagnostic yield.

Introduction: Analysis of fibrinolytic disorders is challenging and may potentially lead to underdiagnosis of patients with an increased bleeding tendency.

Aim: To compare clinical characteristics, laboratory measurements, and treatment modalities in a monocenter cohort of patients in whom fibrinolytic studies were performed.

Methods: Retrospective study of patients in whom fibrinolytic studies were performed between January 2016 and February 2020 in the Hemophilia Treatment Center, Nijmegen-Eindhoven-Maastricht, the Netherlands.

Design of a Prospective Study on Pharmacokinetic-Guided Dosing of Prophylactic Factor Replacement in Hemophilia A and B (OPTI-CLOT TARGET Study).

In resource-rich countries, almost all severe hemophilia patients receive prophylactic replacement therapy with factor concentrates to prevent spontaneous bleeding in joints and muscles to decrease the development of arthropathy and risk of long-term disability. Pharmacokinetic (PK)-guided dosing can be applied to individualize factor replacement therapy, as interindividual differences in PK parameters influence factor VIII (FVIII) and FIX activity levels. PK-guided dosing may therefore lead to more optimal safeguarding of FVIII/FIX levels during prophylaxis and on demand treatment.

[Dog saliva causes rare and life-threatening infection].

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening syndrome. Due to its heterogeneous presentation, nonspecific findings, and rarity, this diagnosis is often initially overlooked. This contributes to the high mortality.

Treatment of patients with rare bleeding disorders in the Netherlands: Real-life data from the RBiN study.

Background: Patients with rare inherited bleeding disorders (RBDs) exhibit hemorrhagic symptoms, varying in type and severity, often requiring only on-demand treatment. Prolonged bleeding after invasive procedures is common. Adequate peri-procedural therapy may reduce this bleeding risk.

Von Willebrand disease type 2M: Correlation between genotype and phenotype.

Background: An appropriate clinical diagnosis of von Willebrand disease (VWD) can be challenging because of a variable bleeding pattern and laboratory phenotype. Genotyping is a powerful diagnostic tool and may have an essential role in the diagnostic field of VWD.

Objectives: To unravel the clinical and laboratory heterogeneity of genetically confirmed VWD type 2M patients and to investigate their relationship.

Fixed Versus Variable Dosing of Prothrombin Complex Concentrate for Bleeding Complications of Vitamin K Antagonists-The PROPER3 Randomized Clinical Trial.

Study Objective: To determine if a fixed dose of 1000 IU of 4-factor prothrombin complex concentrate (4F-PCC) is as effective as traditional variable dosing based on body weight and international normalized ratio (INR) for reversal of vitamin K antagonist (VKA) anticoagulation.

Methods: In this open-label, multicenter, randomized clinical trial, patients with nonintracranial bleeds requiring VKA reversal with 4F-PCC were allocated to either a 1,000-IU fixed dose of 4F-PCC or the variable dose. The primary outcome was the proportion of patients with effective hemostasis according to the International Society of Thrombosis and Haemostasis definition.

Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial): an open-label, multicentre, randomised, controlled trial.

Background: Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels.

Health and treatment outcomes of patients with hemophilia in the Netherlands, 1972-2019.

Introduction: We conducted six cross-sectional nationwide questionnaire studies among all patients with hemophilia in the Netherlands from 1972 until 2019 to assess how health outcomes have changed, with a special focus on patients >50 years of age.

Methods: Data were collected on patient characteristics, treatment, (joint) bleeding, joint impairment, hospitalizations, human immunodeficiency virus and hepatitis C infections, and general health status (RAND-36).

Results: In 2019, 1009 patients participated, of whom 48% had mild, 15% moderate, and 37% severe hemophilia.

Impact of extreme weight loss on factor VIII concentrate pharmacokinetics in haemophilia.

We explored the effects of extreme weight loss after gastric bypass surgery on factor VIII concentrate pharmacokinetic (PK) parameters in a patient with haemophilia A. We present a 32-year-old man with severe haemophilia A, with a body mass index (BMI) of 42.6 kg/m who underwent laparoscopic sleeve gastrectomy.

Maternal and neonatal bleeding complications in relation to peripartum management in hemophilia carriers: A systematic review.

Currently, there is no consensus on the optimal management to prevent postpartum hemorrhage (PPH) in hemophilia carriers. We aimed to evaluate peripartum management strategies in relation to maternal and neonatal bleeding outcomes by performing an extensive database search up to August 2020. Seventeen case-reports/series and 11 cohort studies were identified of overall 'poor' quality describing 502 deliveries.