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Topic Review
SARS-CoV-2 Vaccination-Associated Coagulopathy
Coronavirus Disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is frequently complicated by thrombosis. In some cases of severe COVID-19, fibrinolysis may be markedly enhanced within a few days, resulting in fatal bleeding. In the treatment of COVID-19, attention should be paid to both coagulation activation and fibrinolytic activation. Various thromboses are known to occur after vaccination with SARS-CoV-2 vaccines. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occur after adenovirus-vectored vaccination, and is characterized by the detection of anti-platelet factor 4 antibodies by enzyme-linked immunosorbent assay and thrombosis in unusual locations such as cerebral venous sinuses and visceral veins. Treatment comprises high-dose immunoglobulin, argatroban, and fondaparinux. Some VITT cases show marked decreases in fibrinogen and platelets and marked increases in D-dimer, suggesting the presence of enhanced-fibrinolytic-type disseminated intravascular coagulation with a high risk of bleeding. In the treatment of VITT, evaluation of both coagulation activation and fibrinolytic activation is important, adjusting treatments accordingly to improve outcomes.
  • 1.7K
  • 21 Mar 2022
Topic Review
Platelet Factor 4
Antibodies against platelet factor 4 (PF4), a protein released from alpha-granules of activated platelets, may cause a number of pathophysiological conditions. The most commonly known is heparin-induced thrombocytopenia (HIT), which develops in a small proportion of people treated with the anticoagulant drug heparin.
  • 1.6K
  • 29 Jan 2022
Topic Review
Near-Haploidy and Low-Hypodiploidy in B-Cell Acute Lymphoblastic Leukemia
B-cell acute lymphoblastic leukemia (B-ALL) is characterized by an uncontrolled proliferation of blood cells in the bone marrow. Hypodiploidy with less than 40 chromosomes is a rare genetic abnormality in B-cell acute lymphoblastic leukemia (B-ALL). This condition can be classified based on modal chromosome number as low-hypodiploidy (30–39 chromosomes) and near-haploidy (24–29 chromosomes), with unique cytogenetic and mutational landscapes. 
  • 1.6K
  • 10 Jan 2022
Topic Review
Oxidative Stress and Therapy in Sickle Cell Disease
Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb), which affects approximately a million people worldwide. It is characterized by a single nucleotide substitution in the β-globin gene, leading to the production of abnormal sickle hemoglobin (HbS) with multi-system consequences. HbS polymerization is the primary event in SCD. Repeated polymerization and depolymerization of Hb causes oxidative stress that plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e., by decreasing the oxidant formation or repairing the induced damage. 
  • 1.6K
  • 31 May 2022
Topic Review
Monoclonal Antibodies for Acute Myeloid Leukemia/Myelodysplastic Syndromes
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent an unmet clinical need whose prognosis is still dismal. Alterations of immune response play a prominent role in AML/MDS pathogenesis, revealing novel options for immunotherapy. Among immune system regulators, CD47, immune checkpoints, and toll-like receptor 2 (TLR2) are major targets. Magrolimab antagonizes CD47, which is overexpressed by AML and MDS cells, thus inducing macrophage phagocytosis with clinical activity in AML/MDS. Sabatolimab, an inhibitor of T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), which disrupts its binding to galectin-9, has shown promising results in AML/MDS, enhancing the effector functions of lymphocytes and triggering tumor cell death. Several other surface molecules, namely CD33, CD123, CD45, and CD70, can be targeted with monoclonal antibodies (mAbs) that exert different mechanisms of action and include naked and conjugated antibodies, bispecific T-cell engagers, trispecific killer engagers, and fusion proteins linked to toxins. 
  • 1.6K
  • 20 Jul 2022
Topic Review
Neurotoxicity in Acute Lymphoblastic Leukemia Treatment
Immunotherapy is a milestone in the treatment of poor-prognosis pediatric acute lymphoblastic leukemia (ALL) and is expected to improve treatment outcomes and reduce doses of conventional chemotherapy without compromising the effectiveness of the therapy. However, both chemotherapy and immunotherapy cause side effects, including neurological ones. 
  • 1.6K
  • 17 May 2022
Topic Review
Mechanisms of CLL Cell Stimulation via BcR
The engagement of the B cell receptor (BcR) on the surface of leukemic cells represents a key event in chronic lymphocytic leukemia (CLL) since it can lead to the maintenance and expansion of the neoplastic clone. This notion was initially suggested by observations of the CLL BcR repertoire and of correlations existing between certain BcR features and the clinical outcomes of single patients. Based on these observations, tyrosine kinase inhibitors (TKIs), which block BcR signaling, have been introduced in therapy with the aim of inhibiting CLL cell clonal expansion and of controlling the disease. Indeed, the impressive results obtained with these compounds provided further proof of the role of BcR in CLL.
  • 1.5K
  • 01 Dec 2022
Topic Review
Fetal Hemoglobin in Sickle Hemoglobinopathies
Fetal hemoglobin (HbF; α2γ2), encoded by two nearly identical γ-globin genes (HBG2, HBG1) that are part of the β-globin gene (HBB) cluster (11p15.4), comprises 70 to 90% of the hemolysate in newborns, falling to <1% after 12 months. HbF usually consists of 4 to 10% of total hemoglobin in adults of African descent with sickle cell anemia. Rarely, their HbF levels reach more than 30%. High HbF levels are sometimes a result of β-globin gene deletions or point mutations in the promoters of the HbF genes. 
  • 1.5K
  • 01 Aug 2022
Topic Review
Inherited Thrombocytopenias (IT)
Inherited thrombocytopenias (IT) are a group of hereditary disorders characterized by a reduced platelet count sometimes associated with abnormal platelet function, which can lead to bleeding but also to syndromic manifestations and predispositions to other disorders. 
  • 1.5K
  • 25 Apr 2021
Topic Review
Hematopoiesis
Hematopoiesis is a stepwise process through which hematopoietic stem cells (HSCs) differentiate to progenitor cells that demonstrate a restricted potential and eventually further differentiate to form all mature blood and immune cells. 
  • 1.5K
  • 07 Sep 2021
Topic Review
The Identity of Thrombosis
Since “two-path unifying theory” of hemostasis was published, it has been confirmed that hemostasis is blood clotting mechanism forming “hemostatic plug” in bleeding from external and internal bodily injury, and is also thrombosis promoting mechanism in intravascular injury by producing “thrombus”.
  • 1.5K
  • 10 Nov 2022
Topic Review
Immunotherapeutic Approaches for Angioimmunoblastic T-cell Lymphoma
Escaping the immune system is the main characteristic of a tumor cell. In order to limit the anarchic proliferation of cancer cells, chemotherapies are often used in tumors that have no specific treatment yet, such as AITL. These therapies are proposed to limit the proliferation of dividing cells, i.e., healthy cells as well as tumor cells. This explains the poor benefits of such treatment and the major risk of relapse or even the absence of signs of remission. Importantly, targeting a specific cancer cell type without inducing an effect on healthy cells requires an in-depth knowledge of its phenotype and its surface markers, which can serve as an asset for the development of specific therapies, in particular immunotherapies. If some healthy cells are affected, it is called on-target off-target effects because certain cancer epitopes are partially expressed on non-malignant cells. These therapies include, for example, monoclonal antibodies and chimeric antigen receptors. 
  • 1.5K
  • 25 May 2022
Topic Review
Apoptosis in Acute Myeloid Leukemia
More than 97% of patients with acute myeloid leukemia (AML) demonstrate genetic mutations leading to excessive proliferation combined with the evasion of regulated cell death (RCD). The most prominent and well-defined form of RCD is apoptosis, which serves as a defense mechanism against the emergence of cancer cells. Apoptosis is regulated in part by the BCL-2 family of pro- and anti-apoptotic proteins, whose balance can significantly determine cell survival. Apoptosis evasion plays a key role in tumorigenesis and drug resistance, and thus in the development and progression of AML. Research on the structural and biochemical aspects of apoptosis proteins and their regulators offers promise for new classes of targeted therapies and strategies for therapeutic intervention.
  • 1.5K
  • 21 Oct 2022
Topic Review
Adult Post-Transplant Lymphoproliferative Disorder
Post-transplant lymphoproliferative disorder (PTLD) is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence depending on different patient-, therapy-, and transplant-related factors. The pathogenesis of PTLD is complex, with most cases of early PLTD having a strong association with Epstein–Barr virus (EBV) infection and the iatrogenic, immunosuppression-related decrease in T-cell immune surveillance. Without appropriate T-cell response, EBV-infected B cells persist and proliferate, resulting in malignant transformation. Classification is based on the histologic subtype and ranges from nondestructive hyperplasias to monoclonal aggressive lymphomas, with the most common subtype being diffuse large B-cell lymphoma-like PTLD. Management focuses on prevention of PTLD development, as well as therapy for active disease. Treatment is largely based on the histologic subtype.
  • 1.5K
  • 09 Dec 2022
Topic Review
Paracetamol Intake and Hematologic Malignancies
Hematologic malignancies are a heterogeneous group of diseases of diverse incidence, prognosis, and etiology that cause 1.3 million cases and more than 700,000 deaths every year worldwide. These malignancies show a stable trend in the last decades, but an increased incidence is observed for myeloma in women.
  • 1.4K
  • 21 Jun 2021
Topic Review
Rotational Thromboelastometry (ROTEM®)
Rotational thromboelastometry (ROTEM) is a viscoelastic method, which provides a graphical and numerical representation of induced hemostasis in whole blood samples. Its ability to quickly assess the state of hemostasis is used in the management of bleeding from a variety of causes. 
  • 1.4K
  • 01 Nov 2023
Topic Review
New treatment strategies for β-thalassemia
Beta-thalassemia (β-thalassemia) is an autosomal recessive inherited disease characterized by decreased production of the β-globin chains of hemoglobin (Hb) A. The normal structure of HbA is two α- and two β-globin chains. Individuals with β-thalassemia are either homozygous or double heterozygotes for mutations in the β-globin gene.
  • 1.4K
  • 13 Jul 2021
Topic Review
Gene Therapy for Patients with Hemophilia A
The standard of care for hemophilia A has been intravenous administration of exogenous factor VIII (FVIII), either as prophylaxis or episodically. Gene therapy is a treatment strategy used to repair or provide a functional copy of a gene that is either absent or expressed as a non-functional protein. Treating a genetic disease with gene therapy requires that the transgene (or its protein product) be delivered to the physiologically relevant target tissue or tissues, be stably expressed, and not interfere with the functional integrity of the cells in these tissues. The ultimate goal of gene therapy for patients with hemophilia A is the production of a treatment that is given as a one-time infusion and that allows adequate long-term expression of the deficient FVIII, with the maintenance of steady-state plasma FVIII concentrations. This would minimize (or ideally eliminate) bleeding episodes and thereby decrease the patient and societal burden of the disease.
  • 1.4K
  • 29 Nov 2022
Topic Review
Large Granular Lymphocytic Leukemia
Large Granular Lymphocytic Leukemia (LGLL) represents about 2–5% of chronic lymphoproliferative disorders and predominantly affects the elderly (median age at diagnosis 66 years). Although the reported incidence is around 0.2 cases/1,000,000, the true prevalence may be much higher due to a large proportion of indolent, undiagnosed cases and, often, an inability to distinguish it from reactive cytotoxic T-cells (CTL) lymphoproliferation. The majority of LGLL cases are of the T subtype (i.e., derived from CTL), whereas only <10% are of natural killer (NK) cells origin.
  • 1.4K
  • 26 Sep 2021
Topic Review
Phosphatidylserine
Cancer is among the leading causes of death worldwide. In recent years, many cancer-associated biomarkers have been identified that are used for cancer diagnosis, prognosis, screening, and early detection, as well as for predicting and monitoring carcinogenesis and therapeutic effectiveness. Phosphatidylserine (PS) is a negatively charged phospholipid which is predominantly located in the inner leaflet of the cell membrane. In many cancer cells, PS externalizes to the outer cell membrane, a process regulated by calcium-dependent flippases and scramblases. Saposin C coupled with dioleoylphosphatidylserine (SapC-DOPS) nanovesicle (BXQ-350) and bavituximab, (Tarvacin, human–mouse chimeric monoclonal antibodies) are cell surface PS-targeting drugs being tested in clinical trial for treating a variety of cancers. Additionally, a number of other PS-selective agents have been used to trigger cytotoxicity in tumor-associated endothelial cells or cancer cells in pre-clinical studies.
  • 1.4K
  • 25 May 2022
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