Seminars in hematology
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The treatment of aplastic anemia is currently with immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) and cyclosporine, to which two thirds of patients respond. However, a significant proportion of these responders relapse and many have persistent cytopenias. The management of these patients is challenging. ⋯ A recent trial has shown that eltrombopag, a thrombopoeitin mimetic, is efficacious in the treatment of patients with severe aplastic anemia (SAA) refractory to IST. There is evidence that this drug works by directly stimulating marrow stem and progenitor cells thereby promoting hematopoietic recovery in patients with bone marrow failure. Several trials are ongoing in our institution using this very promising drug in combination therapy in the upfront treatment of SAA, in IST-refractory SAA and in moderate disease.
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Seminars in hematology · Apr 2014
ReviewDirect oral anticoagulants in the prevention of venous thromboembolism: evidence from major clinical trials.
Hospitalized medical and surgical patients encompass a group of patients in whom venous thromboembolism (VTE) poses a major concern on morbidity and mortality. Recently, direct oral anticoagulants for the prevention of VTE have been developed to overcome the drawbacks of the food/drug interactions and the need for frequent laboratory monitoring and dose adjustments associated with the use of vitamin K antagonists and the inconvenience of the subcutaneous administration of low-molecular-weight heparins and fondaparinux. The novel oral anticoagulants that have been tested in major clinical trials for VTE prevention in medical and surgical patients are the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, rivaroxaban, and edoxaban, which will be the focus of this review. While the new drugs proved to be highly effective and safe in the prevention of VTE following major orthopedic surgery, they failed to show a favorable benefit-to-risk profile in hospitalized medical patients receiving extended anticoagulation beyond the hospital stay.
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Seminars in hematology · Apr 2014
ReviewPerioperative management issues of direct oral anticoagulants.
The treatment repertoire of oral anticoagulation has changed dramatically over the past few years from one class of vitamin K1 antagonists to an increasing number of direct oral anticoagulants (DOACs). Clinicians are confronted with the problem of managing patients on novel agents in the critical setting before, during, and after surgery, where the risk of bleeding and thrombosis are increased simultaneously. ⋯ The following review considers perioperative management issues in various categories, including minor elective surgery, major elective surgery, and acute surgery. This review is a credo to personalized medicine where the patient's underlying thromboembolic risk status, the potential bleeding risk, or actual hemorrhagic manifestation determine the selection of multi-modal targeted management strategies.
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Seminars in hematology · Oct 2013
ReviewGenomic characterization of the inherited bone marrow failure syndromes.
The inherited bone marrow failure syndromes (IBMFS) are a set of clinically related yet heterogeneous disorders in which at least one hematopoietic cell lineage is significantly reduced. Many of the IBMFS have notably increased cancer risks, as well as other physical findings. Highly penetrant germline mutations in key pathways, such as DNA repair, telomere biology, or ribosomal biogenesis, are causative of Fanconi anemia (FA), dyskeratosis congenita (DC), and Diamond-Blackfan anemia (DBA), respectively. ⋯ Panels of large numbers of genes are being used to molecularly characterize patients with IBMFS, such as FA and DBA. NGS is also accelerating the discovery of the genetic etiology of previously unclassified IBMFS. In this review, we will highlight recent studies that have employed NGS to ascertain the genetic etiology of IBMFS, namely, FA, DC, DBA, and TAR, and discuss the translational utility of these findings.
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Trauma is a leading cause of death and disability. Hemorrhage is the major mechanism responsible for death during the first 24 hours following trauma. One quarter of severely injured patients present in the emergency room with acute coagulopathy of trauma and shock (ACOT). ⋯ The resuscitation-associated coagulopathy (RAC) is secondary to a combination of acidosis, hypothermia and dilution from intravenous blood and fluid therapy. RAC may further aggravate acidosis and hypoxia resulting in a vicious cycle. This review focuses on the biology of the trauma-associated coagulopathy, and reviews current therapeutic strategies.