Management of pregnancy and childbirth in Glanzmann thrombasthenia: A case series and review.

To illustrate the challenges in the management of women with Glanzmann thrombasthenia (GT) planning a pregnancy, we conducted a literature review and present a case series of eight women giving detailed descriptions of reproductive health problems, platelet alloimmunisation, treatment to prevent post-partum haemorrhage and neonatal outcomes. ART, assisted reproductive therapy; PPH, post-partum haemorrhage; rFVIIa, recombinant activated factor VII.

Clotting Factor Concentration During Menstrual Phases in Women With and Without Heavy Menstrual Bleeding: A Systematic Review and Meta-Analysis.

Background: Cyclic sex-hormone fluctuation impacts clotting factor concentrations, being lowest during the follicular phase of the menstrual cycle. This pattern is unexplored in women with heavy menstrual bleeding (HMB), but potentially affects the timely diagnosis of underlying bleeding disorders.

Aim: Comparing clotting factor fluctuation in the follicular versus luteal phase, between women with and without HMB.

Current Practice Regarding Bleeding Disorders of Unknown Cause in the Netherlands: A National Survey.

Introduction: About 40%-70% of persons with a clinically relevant bleeding tendency who are referred to haemostasis experts are classified as having a 'bleeding disorder of unknown cause' (BDUC) as no biological entity can be found after extensive laboratory testing. Currently, guidelines are under development regarding diagnostic assessment and management to minimize variation in clinical practice.

Aim: Investigate current practices regarding BDUC in the Netherlands.

The 'Stop TPO-RA in ITP Patients' study: Clinical and immune modulatory effects of romiplostim tapering.

Sustained remissions off-treatment (SROTs) after tapering of thrombopoietin receptor agonists (TPO-RAs) have been reported in 15%-50% of patients with immune thrombocytopenia (ITP). The STIP (Stop TPO-Receptor Agonist in ITP Patients) study is a prospective trial aimed to investigate the clinical effects of romiplostim tapering. Adult patients (22/40) with ITP ≥3 months received romiplostim for 1 year, were tapered and followed for 1 year.

Elevated levels of (active) von Willebrand factor during anticoagulation are associated with early recurrence of venous thromboembolism.

Background: Venous thromboembolism (VTE) can recur shortly after stopping anticoagulation, highlighting the need for reliable biomarkers to identify high-risk patients during treatment.

Objectives: To determine whether platelet and endothelial markers predict VTE recurrence.

Methods: We used data and samples from the randomized controlled VISTA trial (2011-2015), which included patients with unprovoked VTE who were treated with vitamin K antagonists for 6 months.

Proteomic analysis indicates lower abundance of platelet α-granule proteins in Glanzmann thrombasthenia.

Background: Glanzmann thrombasthenia (GT) is an inherited platelet function disorder caused by mutations in the fibrinogen receptor αβ. The deficiency can be quantitative (type I/II) or qualitative (type III). It causes lack of platelet aggregation and leads to a moderate to severe bleeding tendency.

Assessing differential application of thromboprophylaxis regimes related to risk of pulmonary embolism and mortality in COVID-19 patients through instrumental variable analysis.

Thrombotic complications are common in Coronavirus disease 2019 (COVID-19) patients, with pulmonary embolism (PE) being the most frequent. Randomised trials have provided inconclusive results on the optimal dosage of thromboprophylaxis in critically ill COVID-19 patients. We utilized data from the multicentre CAPACITY-COVID patient registry to assess the effect of differential application of Low Molecular Weight Heparin (LMWH) dose protocols on PE and in-hospital mortality risk in critically ill COVID-19 patients.

The Use of Primary Care Physiotherapy for Persons With Bleeding Disorders in the Netherlands-A Retrospective Study of Health Records.

Introduction: Patients with musculoskeletal complaints as a result of their bleeding disorder can benefit from primary care physiotherapy. The current study aims to describe physiotherapy services provided in primary care to patients with bleeding disorders and to what extent treatment was already in concordance with treatment recommendations as published in a clinical practice guideline in April 2024.

Methods: Researchers collected data from medical notes of primary care physiotherapists in the Netherlands treating a patient with a bleeding disorder.

Bleeding symptoms in persons with rare bleeding disorders and a heterozygous genotype: data from the Rare Bleeding Disorders in the Netherlands study.

Background: Limited data exist on persons with rare bleeding disorders possessing a heterozygous genotype, as most studies focus on biallelic genotypes and more severe coagulation factor deficiencies. A growing body of evidence suggests that persons with a heterozygous genotype experience clinically relevant bleeding symptoms.

Objectives: This study aimed to explore the incidence of bleeding symptoms and postoperative bleeding in persons with a heterozygous genotype.

A rapid whole-blood adenosine triphosphate secretion test can be used to exclude platelet-dense granule deficiency.

Background: Delta storage pool disease (δ-SPD) is a rare platelet function disorder (PFD) characterized by a deficiency of dense granules or defective granule secretion, leading to bleeding diathesis. Diagnostics of δ-SPD are difficult and lack standardization, leading to underestimation of its prevalence. Current diagnostic methods are based on granule content assays or lumi-aggregometry, which have limited availability.

No correlation between thrombin generation and emicizumab levels: implications for monitoring emicizumab therapy.

Background: Emicizumab, a bispecific antibody that mimics factor (F)VIII, has significantly improved hemophilia A management. Although emicizumab levels can be measured, tools for estimating the hemostatic efficacy of emicizumab are lacking. Thrombin generation (TG) assays can distinguish bleeding phenotypes in persons with hemophilia A on FVIII prophylaxis and may also be used during emicizumab therapy.

Disease characteristics and outcomes of acute myeloid leukemia in germline deficiency (Familial Platelet Disorder with associated Myeloid Malignancy).

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, -FPD), caused by monoallelic deleterious germline variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date.

Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab.

Background: Efanesoctocog is a B-domain-deleted, Fc-fusion factor (F)VIII linked to the D'D3 domain of von Willebrand factor and 2 XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab.

Objectives: To test whether the bovine chromogenic FVIII assay, specifically calibrated for efanesoctocog, could provide an accurate assessment of efanesoctocog activity.

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.

Functional characterization of a nanobody-based glycoprotein VI-specific platelet agonist.

Background: Glycoprotein (GP)VI is a platelet-specific collagen receptor required for platelet activation during hemostasis. Platelet reactivity toward collagen is routinely assessed during diagnostic workup of platelet disorders. GPVI can be activated by inducing receptor clustering with suspensions of fibrillar collagen or synthetic cross-linked collagen-related peptide (CRP-XL).

A bispecific antibody approach for the potential prophylactic treatment of inherited bleeding disorders.

Inherited bleeding disorders such as Glanzmann thrombasthenia (GT) lack prophylactic treatment options. As a result, serious bleeding episodes are treated acutely with blood product transfusions or frequent, repeated intravenous administration of recombinant activated coagulation factor VII (rFVIIa). Here we describe HMB-001, a bispecific antibody designed to bind and accumulate endogenous FVIIa and deliver it to sites of vascular injury by targeting it to the TREM (triggering receptor expressed on myeloid cells)-like transcript-1 (TLT-1) receptor that is selectively expressed on activated platelets.

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.

Psychometrics of patient-reported outcomes measurement information system in von Willebrand disease, inherited platelet function disorders, and rare bleeding disorders.

Background: Patient-reported outcomes measurement information system (PROMIS) measures can be used to measure patient-reported outcomes. PROMIS measures, including computer adaptive tests (CATs) and short forms, have demonstrated the ability to adequately assess outcomes in patients with hemophilia. It is, however, unclear if PROMIS measures are suitable for patients with von Willebrand disease (VWD), inherited platelet function disorders (IPFDs), and rare bleeding disorders (RBDs).

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.

Metabolic blood profile and response to treatment with the pyruvate kinase activator mitapivat in patients with sickle cell disease.

Mitapivat is an investigational, oral, small-molecule allosteric activator of pyruvate kinase (PK). PK is a regulatory glycolytic enzyme that is key in providing the red blood cell (RBC) with sufficient amounts of adenosine triphosphate (ATP). In sickle cell disease (SCD), decreased 2,3-DPG levels increase the oxygen affinity of hemoglobin, thereby preventing deoxygenation and polymerization of sickle hemoglobin.

Limited value of testing for factor XIII and α2-antiplasmin deficiency in patients with a bleeding disorder of unknown cause.

Introduction: In patients with an increased bleeding tendency, extensive diagnostic blood testing is often performed. When results of tier 1 assays of primary haemostasis are normal, protocols recommend additional testing to rule out rare disorders including coagulation factor XIII (FXIII) and α2-antiplasmin (α2AP) deficiency.

Aim: To evaluate the added diagnostic value of FXIII and α2AP levels in patients with a bleeding disorder of unknown cause (BDUC).

Navigating the challenges: a case report on managing a complicated postpartum course in type 3 von Willebrand disease with alloantibodies.

Background: Von Willebrand disease (VWD) type 3 is characterized by a complete deficiency of von Willebrand factor (VWF), resulting in a severe bleeding phenotype. Treatment often requires administration of VWF concentrates/factor (F)VIII. However, the development of alloantibodies is a rare complication, resulting in ineffective recovery and allergic reactions.