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pubmed: Curr Op Hem[Jour]



NCBI: db=pubmed; Term="Current Opinion in Hematology"[Jour]



 



Novel targets for anticoagulants lacking bleeding risk.
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Novel targets for anticoagulants lacking bleeding risk.

Curr Opin Hematol. 2017 Jul 20;:

Authors: Bickmann JK, Baglin T, Meijers JCM, Renné T

Abstract
PURPOSE OF REVIEW: Arterial and venous thromboembolic diseases are associated with significant morbidity and mortality and present a major medical burden. Currently used anticoagulants for the prevention or treatment of thromboembolic events including heparins, vitamin K-antagonists and inhibitors of thrombin or factor Xa target enzymes of the coagulation cascade that are critical for fibrin formation. However, fibrin is also necessary for hemostatic mechanisms to terminate blood loss at injury sites. As a result currently used anticoagulants substantially raise the risk of bleeding and are associated with an increase in potentially life-threatening hemorrhage, partially offsetting the benefits of reduced thrombosis.
RECENT FINDINGS: Within the last decade, experimental and preclinical data have revealed the existence of coagulation mechanisms that principally differ in thrombosis and haemostasis. Some coagulation proteins including, XI and XII have a differential role in haemostasis and thrombosis. Targeting these proteins may provide an opportunity to prevent thromboembolic disease without causing bleeding.
SUMMARY: This review summarizes recent studies on selective targeting of coagulation proteins that may allow prevention and treatment of thrombosis without causing bleeding. These novel approaches present a possibility for selective interference with fibrin formation in pathologic thrombosis that may lead to a new generation of safe anticoagulant drugs.

PMID: 28731874 [PubMed - as supplied by publisher]




Is there a standard-of-care for transfusion therapy in thalassemia?
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Is there a standard-of-care for transfusion therapy in thalassemia?

Curr Opin Hematol. 2017 Jul 14;:

Authors: Franchini M, Forni GL, Liumbruno GM

Abstract
PURPOSE OF REVIEW: Thalassemia is the most common form of inherited anemia, characterized by variable clinical phenotypes. The purpose of this review is to summarize the transfusion support in thalassemia patients and the management of transfusion-related iron overload.
RECENT FINDINGS: The most recent evidence on transfusion strategy and iron chelation therapy in thalassemia arising from clinical trials as well as from recommendation guidelines are critically discussed.
SUMMARY: Enhancements in the global care of thalassemia, resulting from the combination of an appropriate transfusion approach and iron chelation therapy, have produced a significant improvement in the quality of life and, finally, in the prognosis of patients affected by this inherited hematologic disorder.

PMID: 28719386 [PubMed - as supplied by publisher]




Prevention of hemolytic disease of the fetus and newborn: what have we learned from animal models?
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Prevention of hemolytic disease of the fetus and newborn: what have we learned from animal models?

Curr Opin Hematol. 2017 Jul 20;:

Authors: Cruz-Leal Y, Marjoram D, Lazarus AH

Abstract
PURPOSE OF REVIEW: This review aims to highlight recent advances in our understanding of how anti-red blood cell (RBC) antibodies prevent erythrocyte immunization with an emphasis on new murine models.
RECENT FINDINGS: New murine models with clinically relevant human erythrocyte antigens have been used to understand the alloimmunization process and its inhibition. The search to elucidate the mechanism of action of IgG-mediated inhibition of erythrocyte alloimmunization has provided new evidence in support of a potential role for epitope masking, immune deviation and/or antigen modulation in this process. In addition, recent evidence suggests that blends of monoclonal antibodies targeting nonoverlapping epitopes on the RBC surface can improve the efficacy of monoclonal antibodies approaching that of polyclonal IgG.
SUMMARY: Animal models with defined alloantigens have helped to identify important mechanistic components that lead to alloimmunization and its inhibition by IgG. A better understanding of the underlying mechanisms leading to hemolytic disease of the fetus and newborn is required to develop the most effective prevention strategies for future patients.

PMID: 28719385 [PubMed - as supplied by publisher]




Rendering factor Xa zymogen-like as a therapeutic strategy to treat bleeding.
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Rendering factor Xa zymogen-like as a therapeutic strategy to treat bleeding.

Curr Opin Hematol. 2017 Jul 07;:

Authors: Thalji NK, Camire RM

Abstract
PURPOSE OF REVIEW: New therapies are needed to control bleeding in a range of clinical conditions. This review will discuss the biochemical properties of zymogen-like factor Xa, its preclinical assessment in different model systems, and future development prospects.
RECENT FINDINGS: Underlying many procoagulant therapeutic approaches is the rapid generation of thrombin to promote robust clot formation. Clinically tested prohemostatic agents (e.g., factor VIIa) can provide effective hemostasis to mitigate bleeding in hemophilia and other clinical situations. Over the past decade, we explored the possibility of using zymogen-like factor Xa variants to rapidly improve clot formation for the treatment of bleeding conditions. Compared to the wild-type enzyme, these variants adopt an altered, low activity, conformation which enables them to resist plasma protease inhibitors. However, zymogen-like factor Xa variants are conformationally dynamic and ligands such as its cofactor, factor Va, stabilize the molecule rescuing procoagulant activity. At the site of vascular injury, the variants in the presence of factor Va serve as effective prohemostatic agents. Preclinical data support their use to stop bleeding in a variety of clinical settings. Phase 1 studies suggest that zymogen-like factor Xa is safe and well tolerated, and a phase 1b is ongoing to assess safety in patients with intracerebral hemorrhage.
SUMMARY: Zymogen-like factor Xa is a unique prohemostatic agent for the treatment of a range of bleeding conditions.

PMID: 28692575 [PubMed - as supplied by publisher]




Introduction to current issue.
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Introduction to current issue.

Curr Opin Hematol. 2017 Jul 03;:

Authors: Schmaier AH

PMID: 28678029 [PubMed - as supplied by publisher]