Expert review of hematology
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Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, consumption thrombocytopenia, and organ injury. TTP pathophysiology is based on a severe ADAMTS13 deficiency, the specific von Willebrand factor (VWF)-cleaving protease. Areas covered: VWF/ADAMTS13 interaction is specific, and ADAMTS13 conformation has been elucidated recently. ⋯ Plasma therapy remains the first-line treatment of the acute phase of TTP. Additional curative and preemptive rituximab are used in acquired TTP. Clinical trials dedicated to innovative drugs are promising.
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Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated remarkable anti-tumor activity in B-cell malignancies and is under investigation in other hematologic malignancies and solid tumors. While highly efficacious, post-infusion T cell activity often results in massive cytokine release precipitating cytokine release syndrome (CRS), the signature toxicity of CAR T cells. This toxicity is characterized by systemic immune activation resulting in fever, hypotension, respiratory insufficiency and capillary leak. ⋯ Areas covered: This manuscript provides an in-depth overview of the pathogenesis, clinical characteristics, current toxicity management strategies, and future perspectives pertaining to CRS and neurotoxicity. Expert Opinion: As CAR T cell based therapies gain popularity in the management of various malignancies, the complimentary toxicities of CRS and neurotoxicity pose a clinical challenge in practice. Risk adaptive modeling incorporating disease profile, patient demographics, lymphodepletion, cell dosing, CAR T construct, and potentially cytokine gene polymorphisms may be instructive to assess individualized risk and optimal CRS/neurotoxicity management.
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The efficacy of oral iron in treating iron deficiency anemia (IDA) can be limited by poor gastrointestinal (GI) absorption and adverse GI symptoms; intravenous (IV) iron is a well-established alternative. The present study compared the efficacy of two IV iron formulations in patients with IDA: iron isomaltoside (IIM) and ferric carboxymaltose (FCM). ⋯ IIM resulted in a larger increase from baseline hemoglobin than FCM in patients with IDA, but with no difference in the proportion of patients responding. Studies comparing IIM and FCM directly would be needed to confirm these findings.
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Introduction: Despite advances in the treatment of severely injured patients that have resulted in overall improved outcomes, uncontrolled hemorrhage still represents the most common cause of preventable death following major injury. While addressing both endo- and exogenous factors that lead to an acute trauma-induced coagulopathy, massive transfusion plays a key role in managing bleeding trauma patients. However, the best practice for hemostatic control including massive transfusion in these patients is still under debate. ⋯ The recent literature was reviewed and extended by current guidelines and their underlying evidence was incorporated. Expert commentary: Treatment strategies for bleeding trauma patients are still an area of emerging scientific and clinical interest as advances are likely to translate into improved outcomes including survival. To date, damage control resuscitation principles with ratio-based transfusion of packed red blood cells, plasma and platelets still dominate as "gold standard" of care but goal-directed strategies guided either by conventional coagulation tests or viscoelastic assays may demonstrate a better characterization of the underlying coagulopathy thereby allowing individualized and targeted therapies.
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While associated life-threatening and fatal bleeding events are less frequent with the direct factor Xa inhibitors compared to vitamin K antagonists, significant concern surrounding management of major bleeds and urgent periprocedural interruption of these agents exists among clinicians. Andexanet alfa is a recombinant human factor Xa decoy protein developed in response to this clinical gap in the care of patients receiving anticoagulation with factor Xa inhibitors. Areas covered: This paper reviews results from preclinical and healthy-volunteer studies demonstrating the ability of andexanet to rapidly and reliably normalize coagulation indices in patients treated with both direct and indirect factor Xa inhibitors. ⋯ It also provides an overview of the major safety concerns reported in these trials which include allergic and infusion reactions, development of anti-andexanet antibodies and, importantly, thrombosis. Expert commentary: While initial reports on restoration of hemostasis and safety are promising, further study of andexanet is required to gauge its efficacy and toxicity, including a potential prothrombotic effect. Further, its use in patients requiring urgent surgery should be studied.