Isolated thrombocytopenia in pregnancy: A monocentric retrospective study of 63 pregnancies in 59 women.

Thrombocytopenia during pregnancy is often thought to be associated with severe bleeding manifestations. Three are the main disorders associated with this condition: gestational thrombocytopenia (GT), immune thrombocytopenia (ITP), and inherited thrombocytopenias (ITs). Reaching the correct diagnosis of this condition has relevant therapeutic and outcome implications.

Association of human leucocyte antigen loci with vaccine-induced immune thrombotic thrombocytopenia: Potential role of the interaction between platelet factor 4-derived peptides and MHC-II.

No risk factors have been identified for vaccine-induced immune thrombotic thrombocytopenia (VITT) so far. The aim of this study was to identify human leucocyte antigen (HLA) alleles potentially associated with VITT susceptibility. Specific HLA class II alleles were detected with significantly higher frequency in VITT patients compared with Italian controls: DPB1*17:01, DQA1*05:01, and DRB1*11:04.

Exome sequencing in 116 patients with inherited thrombocytopenia that remained of unknown origin after systematic phenotype-driven diagnostic workup.

Inherited thrombocytopenias (IT) are genetic diseases characterized by low platelet count, sometimes associated with congenital defects or a predisposition to develop additional conditions. Next-generation sequencing has substantially improved our knowledge of IT, with more than 40 genes identified so far, but obtaining a molecular diagnosis remains a challenge especially for patients with non-syndromic forms, having no clinical or functional phenotypes that raise suspicion about specific genes. We performed exome sequencing (ES) in a cohort of 116 IT patients (89 families), still undiagnosed after a previously validated phenotype-driven diagnostic algorithm including a targeted analysis of suspected genes.

Expert opinion on the use of platelet secretion assay for the diagnosis of inherited platelet function disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology.

Assessment of platelet secretion is crucial for diagnosing suspected inherited platelet function disorders (IPFD). A previous survey of the SSC on Platelet Physiology of the ISTH and a comprehensive review highlighted that most of the platelet secretion assays (PSAs) lack standardization and validation. The aim of this study was to provide expert consensus guidance on the use of PSAs for IPFD diagnosis.

A Novel Mutation in Reveals the Role of the Cytoplasmic Domain of GPIbβ in the Pathophysiology of Bernard-Soulier Syndrome and GPIb-IX Complex Assembly.

Bernard-Soulier syndrome (BSS) is an autosomal-recessive bleeding disorder caused by biallelic variants in the , , and genes encoding the subunits GPIbα, GPIbβ, and GPIX of the GPIb-IX complex. Pathogenic variants usually affect the extracellular or transmembrane domains of the receptor subunits. We investigated a family with BSS caused by the homozygous c.

The ISTH bleeding assessment tool as predictor of bleeding events in inherited platelet disorders: Communication from the ISTH SSC Subcommittee on Platelet Physiology.

Background: The ISTH Bleeding Assessment Tool (ISTH-BAT) has been validated for clinical screening of suspected von Willebrand disease (VWD) and for bleeding prediction. Recently it has been validated for subjects with inherited platelet disorders (IPD) (BAT-VAL study).

Objectives: To determine whether the ISTH-BAT bleeding score (BS) predicts subsequent bleeding events requiring treatment in IPD patients.

Dysregulation of oncogenic factors by GFI1B p32: investigation of a novel germline mutation.

GFI1B is a transcription factor essential for the regulation of erythropoiesis and megakaryopoiesis, and pathogenic variants have been associated with thrombocytopenia and bleeding. Analysing thrombocytopenic families by whole exome sequencing, we identified a novel GFI1B variant (c.648+5G>A), which causes exon 9 skipping and overexpression of a shorter p32 isoform.

Venous thromboembolism and COVID-19: a single center experience from an academic tertiary referral hospital of Northern Italy.

Preliminary evidence supports the notion that COVID-19 patients may have an increased susceptibility to develop venous thromboembolism (VTE). However, the magnitude of this association still needs to be defined. Furthermore, clinical predictors of thrombogenesis, and the relationship with the inflammatory status are currently unknown.

Clinical management, ethics and informed consent related to multi-gene panel-based high throughput sequencing testing for platelet disorders: Communication from the SSC of the ISTH.

Molecular diagnostics of inherited platelet disorders (IPD) has been revolutionized by the implementation of high-throughput sequencing (HTS) approaches. A conclusive diagnosis using HTS tests can be obtained quickly and cost-effectively in many, but not all patients. The expanding use of HTS tests has raised concerns regarding complex variant interpretation and the ethical implications of detecting unsolicited findings such as variants in IPD genes RUNX1, ETV6, and ANKRD26, which are associated with increased leukemic risk.

Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report.

Healthy subjects frequently report minor bleedings that are frequently 'background noise' of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical.

Validation of the ISTH/SSC bleeding assessment tool for inherited platelet disorders: A communication from the Platelet Physiology SSC.

Background: Careful assessment of bleeding history is the first step in the evaluation of patients with mild/moderate bleeding disorders, and the use of a bleeding assessment tool (BAT) is strongly encouraged. Although a few studies have assessed the utility of the ISTH-BAT in patients with inherited platelet function disorders (IPFD) none of them was sufficiently large to draw conclusions and/or included appropriate control groups.

Objectives: The aim of the present study was to test the utility of the ISTH-BAT in a large cohort of patients with a well-defined diagnosis of inherited platelets disorder in comparison with two parallel cohorts, one of patients with type-1 von Willebrand disease (VWD-1) and one of healthy controls (HC).

Antithrombotic prophylaxis for surgery-associated venous thromboembolism risk in patients with inherited platelet disorders. The SPATA-DVT Study.

Major surgery is associated with an increased risk of venous thromboembolism (VTE), thus the application of mechanical or pharmacologic prophylaxis is recommended. The incidence of VTE in patients with inherited platelet disorders (IPD) undergoing surgical procedures is unknown and no information on the current use and safety of thromboprophylaxis, particularly of low-molecular-weight-heparin in these patients is available. Here we explored the approach to thromboprophylaxis and thrombotic outcomes in IPD patients undergoing surgery at VTE-risk participating in the multicenter SPATA study.

Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial.

Patients with inherited thrombocytopenias often require platelet transfusions to raise their platelet count before surgery or other invasive procedures; moreover, subjects with clinically significant spontaneous bleeding may benefit from an enduring improvement of thrombocytopenia. The hypothesis that thrombopoietin-mimetics can increase platelet count in inherited thrombocytopenias is appealing, but evidence is scarce. We conducted a prospective, phase II clinical trial to investigate the efficacy of the oral thrombopoietin-mimetic eltrombopag in different forms of inherited thrombocytopenia.

Loss-of-function mutations in cause a new form of inherited thrombocytopenia.

Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet count that may result in bleeding tendency. Despite progress being made in defining the genetic causes of ITs, nearly 50% of patients with familial thrombocytopenia are affected with forms of unknown origin. Here, through exome sequencing of 2 siblings with autosomal-recessive thrombocytopenia, we identified biallelic loss-of-function variants in This gene encodes for a receptor-like PTP, PTPRJ (or CD148), which is expressed abundantly in platelets and megakaryocytes.

ACTN1 mutations lead to a benign form of platelet macrocytosis not always associated with thrombocytopenia.

The inherited thrombocytopenias (IT) are a heterogeneous group of diseases resulting from mutations in more than 30 different genes. Among them, ACTN1-related thrombocytopenia (ACTN1-RT; Online Mendelian Inheritance in Man: 615193) is one of the most recently identified forms. It has been described as a mild autosomal dominant macrothrombocytopenia caused by mutations in ACTN1, a gene encoding for one of the two non-muscle isoforms of α-actinin.

MYH9-Related Thrombocytopenia: Four Novel Variants Affecting the Tail Domain of the Non-Muscle Myosin Heavy Chain IIA Associated with a Mild Clinical Evolution of the Disorder.

-related disease (-RD) is an autosomal-dominant thrombocytopenia caused by mutations in the gene for non-muscle myosin heavy chain IIA (NMMHC-IIA). Patients present congenital macrothrombocytopenia and inclusions of NMMHC-IIA in leukocytes, and have a variable risk of developing kidney damage, sensorineural deafness, presenile cataracts and/or liver enzymes abnormalities. The spectrum of mutations found in -RD patients is limited and the incidence and severity of the non-congenital features are predicted by the causative variant.

Hereditary thrombocytopenias: a growing list of disorders.

The introduction of high throughput sequencing (HTS) techniques greatly improved the knowledge of inherited thrombocytopenias (ITs) over the last few years. A total of 33 different forms caused by molecular defects affecting at least 32 genes have been identified; along with the discovery of new disease-causing genes, pathogenetic mechanisms of thrombocytopenia have been better elucidated. Although the clinical picture of ITs is heterogeneous, bleeding has been long considered the major clinical problem for patients with IT.

Bleeding risk of surgery and its prevention in patients with inherited platelet disorders.

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study.