Association between cigarette smoking, genetic polymorphism and myelodysplasia: a multicentric case-control study.

Background: Both cigarette smoking (CGS), through its role as a benzene source, and some metabolic detoxyfiying enzymes (EDTOX) polymorphisms that hamper its inactivation, are considered as risk factors for the development of myelodysplastic neoplasms (MDS) and related disorders. This study aims to confirm such associations.

Patients And Methods: We recruited 61 patients diagnosed with MDS following FAB Group criteria and 180 adults without peripheral blood cytopenia, and we analyzed: i) the crude odds-ratio (OR) for MDS between smokers and non-smokers, ii) the crude OR for MDS between homozygous individuals for the mutation NQO1C-T, or harboring deletions in the genes codyfing for GSTM1 y GSTT1, and those who did not show such genotypes, and iii) the OR for MDS between smokers and non-smokers, adjusted for other potential risk factors.

Platelet C3G: a key player in vesicle exocytosis, spreading and clot retraction.

C3G is a Rap1 GEF that plays a pivotal role in platelet-mediated processes such as angiogenesis, tumor growth, and metastasis by modulating the platelet secretome. Here, we explore the mechanisms through which C3G governs platelet secretion. For this, we utilized animal models featuring either overexpression or deletion of C3G in platelets, as well as PC12 cell clones expressing C3G mutants.

Key Genes of the Immune System and Predisposition to Acquired Hemophilia A: Evidence from a Spanish Cohort of 49 Patients Using Next-Generation Sequencing.

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by the presence of autoantibodies against factor VIII (FVIII). As with other autoimmune diseases, its etiology is complex and its genetic basis is unknown. The aim of this study was to identify the immunogenetic background that predisposes individuals to AHA.

Inherited Thrombocytopenia Caused by Variants in Crucial Genes for Glycosylation.

Protein glycosylation, including sialylation, involves complex and frequent post-translational modifications, which play a critical role in different biological processes. The conjugation of carbohydrate residues to specific molecules and receptors is critical for normal hematopoiesis, as it favors the proliferation and clearance of hematopoietic precursors. Through this mechanism, the circulating platelet count is controlled by the appropriate platelet production by megakaryocytes, and the kinetics of platelet clearance.

The Limitations and Unmet Needs of the Five Cornerstones to Guarantee Lifelong Optimization of Prophylaxis in Hemophilia Patients.

Prophylaxis to prevent bleeding is highly recommended for hemophilia patients. The development of new drugs and tools for modeling personalized prophylaxis provides the means for people with hemophilia to lead active lives with a quality of life comparable to that of nonhemophilic individuals. The choice of regimens must be made on a highly individual basis.

Novel variants in GALE cause syndromic macrothrombocytopenia by disrupting glycosylation and thrombopoiesis.

Glycosylation is recognized as a key process for proper megakaryopoiesis and platelet formation. The enzyme uridine diphosphate (UDP)-galactose-4-epimerase, encoded by GALE, is involved in galactose metabolism and protein glycosylation. Here, we studied 3 patients from 2 unrelated families who showed lifelong severe thrombocytopenia, bleeding diathesis, mental retardation, mitral valve prolapse, and jaundice.

Bleeding Complications Associated with Pregnancy with Primary Immune Thrombocytopenia: A Meta-Analysis.

 Immune thrombocytopenia (ITP) during pregnancy has received little attention from researchers. Reliable information about the outcome of mothers and newborns is required to properly counsel women who are pregnant or planning to become pregnant. Our primary outcomes were the frequency and severity of maternal and neonatal bleeding events in the setting of ITP in pregnancy.

Novel Therapies to Address Unmet Needs in ITP.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder that causes low platelet counts and subsequent bleeding risk. Although current corticosteroid-based ITP therapies are able to improve platelet counts, up to 70% of subjects with an ITP diagnosis do not achieve a sustained clinical response in the absence of treatment, thus requiring a second-line therapy option as well as additional care to prevent bleeding. Less than 40% of patients treated with thrombopoietin analogs, 60% of those treated with splenectomy, and 20% or fewer of those treated with rituximab or fostamatinib reach sustained remission in the absence of treatment.

Functional Alterations Involved in Increased Bleeding in Hereditary Hemorrhagic Telangiectasia Mouse Models.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal-dominant genetic disorder involving defects in two predominant genes known as endoglin (; HHT-1) and activin receptor-like kinase 1 (; HHT-2). It is characterized by mucocutaneous telangiectases that, due to their fragility, frequently break causing recurrent epistaxis and gastrointestinal bleeding. Because of the severity of hemorrhages, the study of the hemostasis involved in these vascular ruptures is critical to find therapies for this disease.

A novel nonsense variant in TPM4 caused dominant macrothrombocytopenia, mild bleeding tendency and disrupted cytoskeleton remodeling.

Background: Rare inherited thrombocytopenias are caused by alterations in genes involved in megakaryopoiesis, thrombopoiesis and/or platelet release. Diagnosis is challenging due to poor specificity of platelet laboratory assays, large numbers of culprit genes, and difficult assessment of the pathogenicity of novel variants.

Objectives: To characterize the clinical and laboratory phenotype, and identifying the underlying molecular alteration, in a pedigree with thrombocytopenia of uncertain etiology.

Clinical Efficacy and Safety of Fanhdi, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study.

Objective: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients.

Methods: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis.

Inherited Platelet Disorders: An Updated Overview.

Platelets play a major role in hemostasis as ppwell as in many other physiological and pathological processes. Accordingly, production of about 10 platelet per day as well as appropriate survival and functions are life essential events. Inherited platelet disorders (IPDs), affecting either platelet count or platelet functions, comprise a heterogenous group of about sixty rare diseases caused by molecular anomalies in many culprit genes.

Role of Thrombopoietin Receptor Agonists in Inherited Thrombocytopenia.

In the last decade, improvements in genetic testing have revolutionized the molecular diagnosis of inherited thrombocytopenias (ITs), increasing the spectrum of knowledge of these rare, complex and heterogeneous disorders. In contrast, the therapeutic management of ITs has not evolved in the same way. Platelet transfusions have been the gold standard treatment for a long time.

Abdominal aortic aneurysm and acute appendicitis: a case report and review of the literature.

Background: Abdominal aortic aneurysm and acute appendicitis occur relatively frequently in elderly patients. However, the co-occurrence of the two pathologies is very rare and serious.

Case Presentation: We present the case of an elderly Caucasian patient who was aware of having an abdominal aortic aneurysm but refused treatment and was subsequently admitted to the hospital's emergency department with acute abdominal symptoms.

Characterization of the Platelet Phenotype Caused by a Germline RUNX1 Variant in a CRISPR/Cas9-Generated Murine Model.

-related disorder (-RD) is caused by germline variants affecting the gene. This rare, heterogeneous disorder has no specific clinical or laboratory phenotype, making genetic diagnosis necessary. Although international recommendations have been established to classify the pathogenicity of variants, identifying the causative alteration remains a challenge in -RD.

Cost-per-responder analysis for eltrombopag and rituximab in the treatment of primary immune thrombocytopenia in Spain.

Objective: Splenectomy, thrombopoietin receptor agonists and rituximab are  the second-line treatments for steroid-resistant adult primary immune  thrombocytopenia. The last two are becoming the most widely used treatments  to avoid splenectomy adverse effects and inconveniences. However, the choice  between rituximab and thrombopoietin receptor agonists is unclear.

Acquired Haemophilia A in Association with Influenza A and Urinary Tract Infection.

Unlabelled: Acquired haemophilia A (AHA) is a rare autoimmune disorder caused by an autoantibody against any circulating coagulation factor, especially factor VIII (FVIII). The lack of awareness of this condition suggests that diagnosis is a challenge and usually delayed, which leads to suboptimal treatment. Consequently, early diagnosis is mandatory to prevent potentially life-threatening bleeding complications.

C3G contributes to platelet activation and aggregation by regulating major signaling pathways.

C3G is a GEF (guanine nucleotide exchange factor) for Rap GTPases, among which the isoform Rap1b is an essential protein in platelet biology. Using transgenic mouse models with platelet-specific overexpression of C3G or mutant C3GΔCat, we have unveiled a new function of C3G in regulating the hemostatic function of platelets through its participation in the thrombin-PKC-Rap1b pathway. C3G also plays important roles in angiogenesis, tumor growth, and metastasis through its regulation of the platelet secretome.

Transcriptomic analysis of patients with immune thrombocytopenia treated with eltrombopag.

In the last years, the use of thrombopoietin receptor agonists (TPO-RA), eltrombopag and romiplostim, has improved the management of immune thrombocytopenia (ITP). Moreover, eltrombopag is also active in patients with aplastic anemia and myelodysplastic syndrome. However, their mechanisms of action and signaling pathways still remain controversial.

Management of Adult Patients with Primary Immune Thrombocytopenia (ITP) in Clinical Practice: A Consensus Approach of the Spanish ITP Expert Group.

Background And Objective: Diagnosis and management of primary immune thrombocytopenia (ITP) have changed dramatically in the last decade. The aim of the study was to obtain information about the opinion of the Spanish ITP Group (GEPTI) members regarding the best clinical practices for diagnosis and management of adult patients with ITP.

Materials And Methods: A two-round Delphi method was carried out by sending to 129 experts a 90-item questionnaire developed by 11 specialists, with a 4-point Likert scale ("never," "sometimes," "frequently," and "always") for the assessment of responses.

Atrial Fibrillation in Active Cancer Patients: Expert Position Paper and Recommendations.

Improvements in survival among cancer patients have revealed the clinical impact of cardiotoxicity on both cardiovascular and hematological and oncological outcomes, especially when it leads to the interruption of highly effective antitumor therapies. Atrial fibrillation is a common complication in patients with active cancer and its treatment poses a major challenge. These patients have an increased thromboembolic and hemorrhagic risk but standard stroke prediction scores have not been validated in this population.