Thrombosis and sickle cell disease

Sickle cell disease (SCD) is characterized by the presence of sickle hemoglobin, which has the unique property of polymerizing when deoxygenated. The pathophysiology of acute and chronic clinical manifestations of SCD have shown the central role of dense, dehydrated red cells in acute and chronic clinical manifestations of this pathology. Recent studies have indicated that SCD is characterized by a hypercoagulable state that contributes to the vaso-occlusive events in microcirculation, leading to acute and chronic sickle cell-related organ damage. This review discusses, in the context of SCD, (1) abnormalities in the coagulation system, (2) perturbation of platelet activation and aggregation, (3) vascular endothelial dysfunction, (4) the contribution of cell inflammatory responses, and (5) the connection with nitric oxide metabolism. We also review the available studies on the therapeutic approaches in clinical management of hypercoagulability in SCD

Care of patients with hemoglobin disorders during the COVID-19 pandemic: An overview of recommendations.

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global health emergency.1 Compared to the general population, patients with hemoglobin disorders such as sickle cell disease (SCD) or thalassemia are expected to be more severely affected by COVID-19 due to their preexisting chronic morbidities.2 The Centers for Disease Control and Prevention does not report any specific indications for patients with hemoglobinopathies. However, it can be hypothesized that the rapid spread of the virus may render these patients fragile when fighting the infection. SCD, a hematological condition with functional asplenia, puts patients at a greater risk to develop acute pulmonary complications, including viral infections.2 A study by Hussain et al reported four SCD cases that tested positive for COVID-19.3 These cases initially presented to the emergency department for a typical vaso-occlusive crisis (VOC), and the clinical course of their SARS-CoV-2 infection was rather mild. Patients had a history of respiratory complications, such as acute chest syndrome (ACS), asthma, or pulmonary embolism, which may be potential risk factors for progressive COVID-19 pulmonary disease in patients with SCD.3 A series of isolated cases of ACS in SCD patients positive for COVID-19 has been recently reported.4,5 Therefore, very little clinical experience of infected patients with SCD currently exists. For this reason, we believe that certain recommendations must be followed by healthcare professionals treating any SCD patient infected with SARS-CoV-2

Oral ferroportin inhibitor vamifeport for improving iron homeostasis and erythropoiesis in β-thalassemia: current evidence and future clinical development

Introduction: In β-thalassemia, imbalanced globin synthesis causes reduced red blood cell survival and ineffective erythropoiesis. Suppressed hepcidin levels increase ferroportin-mediated iron transport in enterocytes, causing increased iron absorption and potentially iron overload. Low hepcidin also stimulates ferroportin-mediated iron release from macrophages, increasing transferrin saturation (TSAT), potentially forming non-transferrin-bound iron, which can be toxic. Modulating the hepcidin–ferroportin axis is an attractive strategy to improve ineffective erythropoiesis and limit the potential tissue damage resulting from iron overload. There are no oral β-thalassemia treatments that consistently ameliorate anemia and prevent iron overload. / Areas covered: The preclinical and clinical development of vamifeport (VIT-2763), a novel ferroportin inhibitor, was reviewed. PubMed, EMBASE and ClinicalTrials.gov were searched using the search term ‘VIT-2763ʹ. / Expert opinion: Vamifeport is the first oral ferroportin inhibitor in clinical development. In healthy volunteers, vamifeport had comparable safety to placebo, was well tolerated and rapidly decreased iron levels and reduced TSAT, consistent with observations in preclinical models. Data from ongoing/planned Phase II studies are critical to define its potential in β-thalassemia and other conditions associated with iron overabsorption and/or ineffective erythropoiesis. If vamifeport potentially increases hemoglobin and reduces iron-related parameters, it could be a suitable treatment for non-transfusion-dependent and transfusion-dependent β-thalassemia

Morbidity and mortality of sickle cell disease patients is unaffected by splenectomy: evidence from three decades of follow-up in a high-income setting

Sickle cell disease (SCD) is a globally widespread hereditary red cell disorder characterized by the production of pathological hemoglobin S (HbS).1 Patients with SCD include homozygous subjects for HbS (SS) and compound heterozygotes with HbS/HbC (SC) or HbS/β+/0-thalassemia (Sβ0/β+). In Italy, SCD is endemic with HbS/β+/0-thalassemia being prevalent in areas of southern Italy. In the last two decades, the number of SCD patients across Italy has increased due to migration from sub-Saharan Africa and th

Investigating rare haematological disorders - A celebration of 10 years of the Sherlock Holmes symposia

The Sherlock Holmes symposia have been educating haematologists on the need for prompt recognition, diagnosis and treatment of rare haematological diseases for 10 years. These symposia, which are supported by an unrestricted educational grant from Sanofi Genzyme, encourage haematologists to consider rare disorders in differential diagnoses. Improvement in rare disease awareness is important because diagnostics and the availability of effective therapies have improved considerably, meaning that rare haematological diseases can be accurately diagnosed and successfully managed, particularly if they are identified early. The Sherlock Holmes symposia programme includes real-life interactive clinical cases of rare haematological disorders that require awareness from the physician, to be diagnosed at an early stage. The audience are encouraged to examine each case as if they were detectives, look for clues from the clinical history and presentation, consider the potential causes, assess which tests would be required to make a definitive diagnosis and suggest optimal treatment options. To celebrate the 10-year anniversary of the Sherlock Holmes symposia, this article describes a number of clinical cases that include anaemia, thrombocytopaenia and splenomegaly among the presenting symptoms, to illustrate the importance of rigorous differential diagnosis in the identification of rare haematological disorders

The EHA research roadmap: anemias

In 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by one to two section editors who were leading international experts in the field. In the five years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including eleven sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The eleven EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cellbased Immune Therapies; and Gene Therap