Hematology
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Obstetric hemorrhage remains a leading cause of maternal morbidity and mortality worldwide. Many postpartum hemorrhages (PPHs) do not have identifiable risk factors; maternity units should therefore have obstetric hemorrhageprotocols in place for all parturients as every pregnancy has the potential to be complicated by hemorrhage. This review will examine the epidemiology of PPH as well as current recommendations for key elements in obstetric hemorrhage protocols. Recent advances in hematologic management of PPH will be also be reviewed, including: (1) recognition of hypofibrinogenemia as a risk factor for severe PPH, (2) use of antifibrinolytic therapy, and (3) strategies for fibrinogen replacement therapy.
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Randomized clinical trials (RCTs) have determined, in surgical and critically ill patients, relatively safe hemoglobin (Hb) thresholds of 7-8 g/dL to guide restrictive transfusion of red blood cells (RBCs). However, in patients with various hematologic disorders, strong evidence in support of such an approach is sparse and the optimal transfusion practice is yet to be defined. This review focuses on RBC transfusion practice in three hematologic diseases and a treatment strategy, including autoimmune hemolytic anemia, thalassemia, myelodysplastic syndrome, and hematopoietic stem cell transplantation. ⋯ Thus the nuances in the indications of RBC transfusion and the goals to achieve in these specific situations may have been underappreciated. The limited data available highlight the importance of titrating RBC transfusion based on the clinical context and patient characteristics. Future RCTs are necessary to firmly establish the Hb thresholds associated with improved outcomes relevant to these specific patient populations, which will facilitate the personalized decision-making in RBC transfusion.
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Despite many recent advances in the treatment of multiple myeloma, the course of the disease is characterized by a repeating pattern of periods of remission and relapse as patients cycle through the available treatment options. Evidence is mounting that long-term maintenance therapy may help suppress residual disease after definitive therapy, prolonging remission and delaying relapse. For patients undergoing autologous stem cell transplantation (ASCT), lenalidomide maintenance therapy has been shown to improve progression-free survival (PFS); however, it is still unclear whether this translates into extended overall survival (OS). ⋯ Other trials have also investigated thalidomide and bortezomib maintenance for ASCT patients, and both agents have been evaluated as continuous therapy for those who are ASCT ineligible. However, some important questions regarding the optimal regimen and duration of therapy must be answered by prospective clinical trials before maintenance therapy, and continuous therapy should be considered routine practice. This article reviews the available data on the use of maintenance or continuous therapy strategies and highlights ongoing trials that will help to further define the role of these strategies in the management of patients with newly diagnosed multiple myeloma.
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Small-molecule kinase inhibitors, especially the two Food and Drug Administration-approved agents idelalisib and ibrutinib, have changed the treatment landscape for patients with relapsed or refractory chronic lymphocytic leukemia (CLL). However, with these positive changes comes the new challenge of managing patients who relapse after these agents. The number of patients who have relapsed after taking idelalisib and ibrutinib is low, but as the drugs gain wider use and patients are treated for longer, this number is likely to grow. ⋯ As well, identification of mechanisms of resistance is crucial to develop rational strategies for management. Current work has identified mechanisms of resistance to ibrutinib, and resistance to idelalisib is also under active investigation. In this review, we will discuss these mechanisms of resistance, as well as current and potential strategies for the management of kinase inhibitor-resistant CLL.
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Although the direct oral anticoagulants (DOACs) do not require routine monitoring and reduce bleeding compared with warfarin, there are special circumstances in which laboratory measurement or reversal of their anticoagulant effect may be indicated. The dilute thrombin time and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal thrombin time excludes clinically relevant levels and a normal activated partial thromboplastin time probably excludes excess levels of dabigatran. ⋯ Patients with minor and moderate DOAC-associated bleeding can be treated with supportive care and general hemostatic measures. Nonspecific reversal agents (eg, prothrombin complex concentrate, activated prothrombin complex concentrate) are of unproven benefit, carry a risk of thrombosis, and should be reserved for severe bleeding. Specific reversal agents, such as idarucizumab (a monoclonal antibody fragment that binds dabigatran) and andexanet alfa (a recombinant factor Xa variant that binds factor Xa inhibitors but lacks coagulant activity), are in clinical development.