Transfusion
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Retrospective studies suggest that the transfusion of older, stored red blood cells (RBCs) may be associated with increases in mortality, serious infections, multiorgan failure, thrombosis, and hospital length of stay. Our research is based on the overarching hypothesis that the adverse effects associated with transfusion of older, stored RBCs result from the acute delivery of hemoglobin iron to the monocyte-macrophage system. To test this "iron hypothesis," we are recruiting healthy human volunteers to donate double, leukoreduced, RBC units. ⋯ The primary study outcome will compare laboratory iron measures and proinflammatory cytokines after transfusion of fresh or older, stored RBCs. Similar studies using allogeneic RBC transfusions will be performed in chronically transfused patients with either sickle cell disease or β-thalassemia. Although prospective, randomized studies will ultimately determine the existence of adverse effects from transfusing older, stored RBCs, our goal is to determine the mechanism(s) for this potential effect.
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The specific negative clinical manifestations associated with the transfusion of stored red blood cells (RBCs) and the corresponding mechanisms responsible for such phenomena remain poorly defined. Our recent studies document that leukoreduced older RBC units potentiate transfusion-related toxicity in trauma patients. ⋯ The central mechanisms proposed to mediate this microcirculatory alteration include: 1) the loss of RBC-dependent control of nitric oxide-mediated homeostasis concerning vasodilation and 2) immune cell and complement activation. In this review, we outline the background for our hypothesis and detail our current investigations toward the understanding of this pathophysiology.
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The majority of fresh-frozen plasma (FFP) is transfused in the United States in the management of acquired bleeding disorders. The prothrombin time (PT), and its derivative the international normalized ratio (INR), is the most common test used to detect the presence and gauge the severity of these disorders. Observation studies have shown that the PT correlates poorly with clinical bleeding and that transfusion of plasma often achieves no measurable change in the INR nor is of any known clinical benefit. ⋯ A program of engagement and interdiction using evidence-based guidelines can successfully decrease the use of FFP without any observable increase in unexpected bleeding.
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In September 2009, the National Heart, Lung, and Blood Institute convened the State-of-the-Science Symposium in Transfusion Medicine to identify Phase II and/or III clinical trials that would provide important information to advance transfusion medicine. ⋯ The proposal themes not only represent inquiries about the indications for transfusion, but also epitomize the lack of consensus when clinical practice lacks a strong evidence base. Ultimately, the purpose of this publication is to provide a "blueprint" of ideas for further development rather than endorse any one specific clinical trial design.
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Red blood cell (RBC) transfusions are associated with inflammation and thrombosis, both arterial and venous, the mechanisms of which are not understood. Although a necessary life-saving procedure in modern medicine, transfusions have rarely been subjected to modern assessments of efficacy and safety, including randomized trials. ⋯ These mediators likely play a direct role in the inflammatory and prothrombotic properties of RBC transfusions. Methods such as leukoreduction, washing of RBCs, and rejuvenation may improve the quality of RBC transfusions.