Hematology
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Over the past century, blood banking and transfusion practices have moved from whole blood therapy to components. In trauma patients, the shift to component therapy was achieved without clinically validating which patients needed which blood products. Over the past 4 decades, this lack of clinical validation has led to uncertainty on how to optimally use blood products and has likely resulted in both overuse and underuse in injured patients. ⋯ In addition, studies have shown that resuscitating with plasma (instead of crystalloid) repairs the "endotheliopathy of trauma," or the systemic endothelial injury and dysfunction that lead to coagulation disturbances and inflammation. Data from the Trauma Outcomes Group, the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, and the ongoing Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial represent a decade-long effort to programmatically determine optimal resuscitation practices, balancing risk versus benefits. With injury as the leading cause of death in patients age 1 to 44 years and hemorrhage the leading cause of potentially preventable death in this group, high-quality data must be obtained to provide superior care to the civilian and combat injured.
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Pain is the most common cause for hospitalization and acute morbidity in sickle cell disease (SCD). The consequences of SCD-related pain are substantial, affecting both the individual and the health care system. The emergence of the patient-centered medical home (PCMH) provides new opportunities to align efforts to improve SCD management with innovative and potentially cost-effective models of patient-centered care. ⋯ The question for patients, clinicians, scientists, and policy-makers is how the PCMH can be designed to address pain, the hallmark feature of SCD. This article provides a framework of pain management within the PCMH model. We present an overview of pain and pain management in SCD, gaps in pain management, and current care models used by patients and discuss core PCMH concepts and multidisciplinary team-based PCMH care strategies for SCD pain management.
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What is the correct use of established clotting factors, prothrombin complex concentrates (PCCs), and activated factor VII in bleeding complications of trauma, surgery, and old and new oral anticoagulants? How will new clotting factors, specifically the long-acting factors, change the hemostatic management of coagulation deficiency disorders? From bench to bedside, comparative coagulation studies and clinical trials of modified clotting factors are providing insights to help guide hemostatic management of congenital and acquired bleeding disorders. Comparative thrombin-generation studies and preclinical and clinical trials suggest that PCCs and fresh-frozen plasma are effective in reversing the anticoagulant effects of warfarin, yet there are few data to guide reversal of the new oral anticoagulants dabigatran and rivaroxaban. Although coagulation studies support the use of PCCs to reverse new oral anticoagulants, correlation with clinical response is variable and clinical trials in bleeding patients are needed. ⋯ Data from clinical trials of molecularly modified coagulation factors with extended half-lives suggest the possibility of fewer infusions, reduced bleeds, and better quality of life in persons with hemophilia. Preclinical studies of other novel prohemostatic approaches for hemophilia and other congenital coagulation disorders include RNA interference silencing of antithrombin, monoclonal anti-tissue factor pathway inhibitor (anti-antibody, anti-tissue factor pathway inhibitor) aptamer, bispecific anti-IXa/X antibody, and fucoidans. Understanding the comparative coagulation studies of established prohemostatic agents, the pharmacokinetics of new long-acting clotting factors, and their correlation with bleeding outcomes will provide opportunities to optimize the hemostatic management of both congenital and acquired hemostatic disorders.
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Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. ⋯ Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.
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Perioperative management of antithrombotic therapy is a situation that occurs frequently and requires consideration of the patient, the procedure, and an expanding array of anticoagulant and antiplatelet agents. Preoperative assessment must address each patient's risk for thromboembolic events balanced against the risk for perioperative bleeding. ⋯ The new oral anticoagulants dabigatran and rivaroxaban have shorter effective half-lives, but they introduce other concerns for perioperative management, including prolonged drug effect in patients with renal insufficiency, limited experience with clinical laboratory testing to confirm lack of residual anticoagulant effect, and lack of a reversal agent. Antiplatelet agents must also be considered in the perioperative setting, with particular consideration given to the potential risk for thrombotic complications in patients with coronary artery stents who have antiplatelet therapy withheld.