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Current Opinion in Hematology

Heather L Howie, Krystalyn E Hudson
PURPOSE OF REVIEW: Pathogenic autoantibodies directed against red blood cells (RBCs) may lead to autoimmune hemolytic anemia (AIHA), a severe and sometimes fatal disease. Much of what is known about the etiology and pathogenesis of AIHA has been learned from observations made in human patients and murine models, but many questions remain; importantly, it is still unclear why some people generate RBC-specific autoantibodies. The combination of technological advancements applied to existing models and the development of new AIHA murine models will continue to provide considerable insight into the initiation of AIHA and provide a platform for the design of more effective therapies...
August 30, 2018: Current Opinion in Hematology
Alan Tyndall
PURPOSE OF REVIEW: To summarize the current clinical experience in the use of autologous hematopoietic stem cell transplantation (HSCT) in autoimmune disease and to explore the concept of durable remission induction and tissue de-remodeling via restoration of normal niche function and "immune reset.' RECENT FINDINGS: Controlled clinical trials in systemic sclerosis, multiple sclerosis, and Crohn's disease as well as extensive uncontrolled trial and registry data have established the unique role of HSCT in selected cases...
August 27, 2018: Current Opinion in Hematology
Bo Cai, Mei Guo, Huisheng Ai
PURPOSE OF REVIEW: Microtransplantation (MST) has been successfully used to manage patients with hematological malignancies, especially older patients with acute myeloid leukemia (AML). Recent clinical applications and mechanistic studies of MST are reviewed. RECENT FINDINGS: MST improves complete remission rates which have no significant difference among age groups in older patients with AML. Sufficient courses of postremission therapy lead to prolonged overall survival and reduced relapse rate...
August 24, 2018: Current Opinion in Hematology
Marsha M Wheeler, Jill M Johnsen
PURPOSE OF REVIEW: To summarize recent advances in red blood cell (RBC) blood group genotyping, with an emphasis on advances in the use of NGS next generation sequencing (NGS) to detect clinically relevant blood group gene variation. RECENT FINDINGS: Genetic information is useful in predicting RBC blood group antigen expression in several clinical contexts, particularly, for patients at high-risk for allosensitization, such as multiple transfused patients. Blood group antigen expression is directed by DNA variants affecting multiply genes...
August 22, 2018: Current Opinion in Hematology
Sagi Abelson, Jean C Y Wang
PURPOSE OF REVIEW: Over the past decade, advances in hematopoietic stem cell transplantation (HSCT) have enabled older individuals to undergo the procedure as well as to serve as donors. Recently, aging has been linked with the development of age-related clonal hematopoiesis (ARCH), defined as the gradual clonal expansion of hematopoietic stem and progenitor cells (HSPC) carrying recurrent disruptive genetic variants in individuals without a diagnosis of hematologic malignancy. Here we will review the implications of ARCH in the context of HSCT...
August 16, 2018: Current Opinion in Hematology
Elizabeth A Godbey, Joseph Schwartz
PURPOSE OF REVIEW: We review recent articles pertaining to the use of tranexamic acid (TXA) in populations at risk for massive transfusion. Although there are no recent studies that specifically examine the use of TXA in massive transfusion protocols (MTPs), there are a few studies with subgroups of massive transfusion patients. RECENT FINDINGS: In recent years, many publications have discussed outcomes and safety associated with the addition of TXA to treatment plans for bleeding pediatric, trauma, and postpartum hemorrhage patients...
August 16, 2018: Current Opinion in Hematology
Alexa J Siddon, Barton C Kenney, Jeanne E Hendrickson, Christopher A Tormey
PURPOSE OF REVIEW: The aim of this study was to summarize the basic epidemiology, pathophysiology and management of delayed serologic and delayed haemolytic transfusion reactions (DHTRs), as well as recent developments in our understanding of these adverse events. RECENT FINDINGS: Several studies have identified risk factors for DHTRs, including high alloantibody evanescence rates among both general patient groups and those with sickle cell disease (SCD). Antibody detection is also hampered by the phenomenon of transfusion record fragmentation...
August 16, 2018: Current Opinion in Hematology
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September 2018: Current Opinion in Hematology
Yi Wu
PURPOSE OF REVIEW: The contact system is a plasma protease cascade, which activates the proinflammatory kallikrein-kinin system and the procoagulant intrinsic coagulation pathway. Recent advances demonstrating the novel functions of this system as a key player of innate immune system will be introduced in the present review. RECENT FINDINGS: The role of the contact system is to initiate and participate in pathophysiological responses to injury, mainly the processes of coagulation and inflammation...
September 2018: Current Opinion in Hematology
Julio Scharfstein
PURPOSE OF REVIEW: During Chagas disease, Trypanosoma cruzi alternates between intracellular and extracellular developmental forms. After presenting an overview about the roles of the contact system in immunity, I will review experimental studies showing that activation of the kallikrein-kinin system (KKS) translates into mutual benefits to the host/parasite relationship. RECENT FINDINGS: T. cruzi trypomastigotes initiate inflammation by activating tissue-resident innate sentinel cells via the TLR2/CXCR2 pathway...
September 2018: Current Opinion in Hematology
Charlene V Chabata, James W Frederiksen, Bruce A Sullenger, Ruwan Gunaratne
PURPOSE OF REVIEW: Since the selection of the first thrombin-binding aptamer in 1992, the use of nucleic acid aptamers to target specific coagulation factors has emerged as a valuable approach for generating novel anticoagulant and procoagulant therapeutics. Herein, we highlight the most recent discoveries involving application of aptamers for those purposes. RECENT FINDINGS: Learning from the successes and pitfalls of the FIXa-targeting aptamer pegnivacogin in preclinical and clinical studies, the latest efforts to develop antidote-controllable anticoagulation strategies for cardiopulmonary bypass that avoid unfractionated heparin involve potentiation of the exosite-binding factor X (FX)a aptamer 11F7t by combination with either a small molecule FXa catalytic site inhibitor or a thrombin aptamer...
September 2018: Current Opinion in Hematology
June Li, Jade A Sullivan, Heyu Ni
PURPOSE OF REVIEW: Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder with as of yet, no established clinical prognostic or diagnostic biomarkers. Patients frequently experience a markedly decreased quality of life and may be at risk for severe/fatal haemorrhage. Here, we address discoveries in the pathogenesis of ITP, and novel therapeutic strategies in mouse models and human patients. Consolidation of these findings should be important in providing insight to establish future prognostic protocols as well as cutting-edge therapeutics to target refractory ITP...
September 2018: Current Opinion in Hematology
Evi X Stavrou
PURPOSE OF REVIEW: This review describes the contribution of coagulation factor XII (FXII) in sterile inflammation and wound healing, focusing on recently identified roles for zymogen FXII in neutrophil functions. RECENT FINDINGS: Recent studies have identified an important role for FXII in neutrophil trafficking. In particular, following neutrophil activation, autocrine FXII signals through the urokinase plasminogen activator receptor (uPAR) on the neutrophil surface to upregulate neutrophil functions...
September 2018: Current Opinion in Hematology
David W Essex, Yi Wu
PURPOSE OF REVIEW: The present review provides an overview of recent findings on new members of the protein disulfide isomerase (PDI) family required for thrombosis. RECENT FINDINGS: Twenty years ago PDI was shown to mediate platelet aggregation, and 10 years ago PDI was shown to support thrombosis in vivo. Subsequently, other members of this endoplasmic reticulum family of enzymes, ERp57 and ERp5, were demonstrated to support thrombosis. A fourth member, ERp72, was recently shown to be required for platelet accumulation and fibrin deposition in vivo...
September 2018: Current Opinion in Hematology
Alexandra Sherman, Moanaro Biswas, Roland W Herzog
PURPOSE OF REVIEW: Hemophilia is an X-linked blood coagulation genetic disorder, which can cause significant disability. Replacement therapy for coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) may result in the development of high-affinity alloantibodies ('inhibitors') to the replacement therapy, thus making it ineffective. Therefore, there is interest in directing immunological responses towards tolerance to infused factors. RECENT FINDINGS: In this review, we will discuss latest advancements in the development of potentially less immunogenic replacement clotting factors, optimization of current tolerance induction protocols (ITI), preclinical and clinical data of pharmacological immune modulation, hepatic gene therapy, and the rapidly advancing field of cell therapies...
September 2018: Current Opinion in Hematology
Alisa S Wolberg
PURPOSE OF REVIEW: In spite of significant morbidity and mortality associated with venous thromboembolism, the underlying pathogenesis remains poorly understood. RECENT FINDINGS: Clues to operant pathogenic mechanisms are found in the unique morphology and composition of these thrombi, which have substantial red blood cell and fibrin content. Recent studies have revealed biochemical and biophysical mechanisms that dictate fibrin structure in venous thrombi and promote retention of red blood cells within the contracted clots...
September 2018: Current Opinion in Hematology
Harvey G Roweth, Somayje Parvin, Kellie R Machlus
PURPOSE OF REVIEW: Platelets are small, anucleate cells that circulate within the blood and play essential roles in preserving vascular integrity. However, abnormalities in either platelet production or destruction can result in thrombocytopenia, clinically defined by a platelet count lower than 150 000/μL of whole blood. Thrombocytopenia is frequently associated with impaired hemostatic responses to vascular injury and can be life-threatening because of bleeding complications. Megakaryocytes are the precursor cells responsible for platelet production, a process commonly referred to as thrombopoiesis...
September 2018: Current Opinion in Hematology
Michael Boyiadzis, Theresa L Whiteside
PURPOSE OF REVIEW: Exosomes are cell-derived, biologically active membrane-bound vesicles, and are emerging as key modulators of hematopoiesis. Recent studies have provided a clearer understanding of the mechanisms whereby blast-derived exosomes act to suppress hematopoiesis in acute myeloid leukemia (AML). RECENT FINDINGS: Exosomes released from leukemia blasts have been shown to suppress hematopoietic progenitor cell (HPC) functions indirectly through stromal reprogramming of niche-retention factors and also as a consequence of AML exosome-directed microRNA delivery to HPC...
July 2018: Current Opinion in Hematology
Vijay Menon, Saghi Ghaffari
PURPOSE OF REVIEW: Work in the past decade has revealed key functions of the evolutionary conserved transcription factors Forkhead box O (FOXO) in the maintenance of homeostatic hematopoiesis. Here the diverse array of FOXO functions in normal and diseased hematopoietic stem and progenitor cells is reviewed and the main findings in the past decade are highlighted. Future work should reveal FOXO-regulated networks whose alterations contribute to hematological disorders. RECENT FINDINGS: Recent studies have identified unanticipated FOXO functions in hematopoiesis including in hematopoietic stem and progenitor cells (HSPC), erythroid cells, and immune cells...
July 2018: Current Opinion in Hematology
Léa Verdière, Frédéric Mourcin, Karin Tarte
PURPOSE OF REVIEW: In addition to the recent progresses in the description of the genetic landscape of B-cell non-Hodgkin's lymphomas, tumor microenvironment has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, drug resistance, and late progression/transformation. The purpose of this review is to outline the most recent findings regarding malignant B-cell niche composition and organization supporting direct and indirect tumor-promoting functions of lymphoma microenvironment...
July 2018: Current Opinion in Hematology
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