Expert review of hematology
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Introduction: Heparin-induced thrombocytopenia (HIT) is known for its strong association with thrombosis and distinct pathogenesis involving anti-PF4/polyanion antibodies that activate platelets strongly through clustering of platelet FcγIIa receptors. Autoimmune HIT (aHIT) refers to a subgroup of patients whose HIT antibodies have both heparin-dependent and heparin-independent platelet-activating properties. aHIT patients have atypical clinical presentations including delayed-onset HIT, persisting (refractory) HIT, heparin 'flush' HIT, fondaparinux-associated HIT, severe thrombocytopenia (platelet count <20 × 109/L) with overt disseminated intravascular coagulation, and spontaneous HIT syndrome. Areas covered: This article reviews all available literature describing the use of high-dose intravenous immunoglobulin (IVIG) as an adjunct treatment to anticoagulation in HIT patients. ⋯ A new case of aHIT successfully treated with IVIG is presented. Use of IVIG to prevent acute HIT with planned heparin reexposure in antibody-positive patients is also discussed. Expert opinion: High-dose IVIG appears to rapidly inhibit HIT antibody-induced platelet activation and has the potential to become an important treatment adjunct for HIT, particularly in patients with aHIT.
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Key paper evaluation: Craddock C, et al. Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia. J Clin Oncol. 2019; 37: 580-8. ⋯ Efficacy and safety should be confirmed in larger, ideally randomized, studies. Further research on mechanism of action of this combination, comparison with other treatment combinations (e.g. AZA + venetoclax) and use during other disease stages are needed.
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Review Meta Analysis
Prothrombin complex concentrate for vitamin K antagonist reversal in acute bleeding settings: efficacy and safety.
Introduction: Current guidelines recommend the administration of prothrombin complex concentrate in combination with vitamin K for normalization of coagulation in patients presenting with vitamin K antagonist-associated major bleeding, but until recently no adequately powered comparative trials had been conducted to support these recommendations. In this article, the authors review the evidence from studies assessing prothrombin complex concentrate treatment in these patients. ⋯ Expert opinion: It is hoped that the results from studies discussed here will inform future guideline updates; however, local clinical practice may also occasionally act as a barrier to adoption of guideline recommendations. There is an urgent need for further RCTs/prospective trials directly comparing PCC and plasma administration in acute bleeding settings.
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Introduction: Immunotherapy has revolutionized the treatment of cancer. Antibodies, antibody drug conjugates, and bispecific antibodies have improved outcomes in various cancers especially lymphomas. Chimeric antigen receptor T cell (CAR-T) is a step forward in the immunotherapy paradigm for the treatment of Lymphomas. ⋯ This has triggered cost-effective analysis and nationwide discussions about the reimbursement process of such treatment. In spite of these challenges, CAR-T treatment is a huge step forward with a very bright future. Novel CAR-T targeting a variety of antigens in different cancers seems promising in near future.
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Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening disease characterized by a severe functional deficit in the von-Willebrand cleaving protease ADAMTS13, due to autoantibody production. The once-dismal prognosis of the disease has been changed by the discovery of the dramatic efficiency of therapeutic plasma exchange (TPE). Areas covered: This review focuses on the history and recent developments in the use of TPE for iTTP with a special emphasis on the consequences for TPE practice of the recent introduction of new highly effective immunosuppressive strategies and anti-von Willebrand factor (vWF) therapies. Expert opinion: Although TPE still represents the cornerstone, emergency treatment of iTTP, their duration, and associated complications could be dramatically reduced in the future by the systematic addition of early immunosuppression using corticosteroids and rituximab as well as an anti-vWF therapy with caplacizumab.