An association of soluble CD40 ligand (CD154) with adverse reactions to platelet transfusions

Authors

  • Neil Blumberg,

    1. From the Transfusion Medicine Unit and Clinical Laboratories, Department of Pathology and Laboratory Medicine, Hematology-Oncology Unit; and the Department of Medicine and the Lung Biology and Disease Program, the Department of Environmental Medicine, and the Department of Microbiology and Immunology, the University of Rochester Medical Center and Strong Memorial Hospital, Rochester, New York.
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  • Kelly F. Gettings,

    1. From the Transfusion Medicine Unit and Clinical Laboratories, Department of Pathology and Laboratory Medicine, Hematology-Oncology Unit; and the Department of Medicine and the Lung Biology and Disease Program, the Department of Environmental Medicine, and the Department of Microbiology and Immunology, the University of Rochester Medical Center and Strong Memorial Hospital, Rochester, New York.
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  • Chantal Turner,

    1. From the Transfusion Medicine Unit and Clinical Laboratories, Department of Pathology and Laboratory Medicine, Hematology-Oncology Unit; and the Department of Medicine and the Lung Biology and Disease Program, the Department of Environmental Medicine, and the Department of Microbiology and Immunology, the University of Rochester Medical Center and Strong Memorial Hospital, Rochester, New York.
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  • Joanna M. Heal,

    1. From the Transfusion Medicine Unit and Clinical Laboratories, Department of Pathology and Laboratory Medicine, Hematology-Oncology Unit; and the Department of Medicine and the Lung Biology and Disease Program, the Department of Environmental Medicine, and the Department of Microbiology and Immunology, the University of Rochester Medical Center and Strong Memorial Hospital, Rochester, New York.
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  • Richard P. Phipps

    1. From the Transfusion Medicine Unit and Clinical Laboratories, Department of Pathology and Laboratory Medicine, Hematology-Oncology Unit; and the Department of Medicine and the Lung Biology and Disease Program, the Department of Environmental Medicine, and the Department of Microbiology and Immunology, the University of Rochester Medical Center and Strong Memorial Hospital, Rochester, New York.
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  • Supported in part by a Discovery Grant from the James P. Wilmot Cancer Center of the University of Rochester, USPHS Grants DE 011390 and HL 078603.

Neil Blumberg, MD, University of Rochester Medical Center, Box 608, Rochester, NY 14642; e-mail: neil_blumberg@urmc.rochester.edu.

Abstract

BACKGROUND: Removal of stored supernatant abrogates most transfusion reactions to leukoreduced platelets (PLTs), suggesting that PLT-derived soluble mediators are involved. PLTs are the primary source of soluble CD40 ligand (sCD40L). Engagement of the receptor for CD40L induces synthesis of proinflammatory mediators including interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1).

STUDY DESIGN AND METHODS: Supernatants from poststorage leukoreduced PLT concentrates were assayed for white cell– (IL-6, IL-8, MCP-1) and PLT-derived (sCD40L, RANTES) inflammatory mediators. These levels were correlated with clinical outcomes.

RESULTS: Of 534 transfusions, there were 12 reported (2.2%) and 2 unreported reactions (0.4%)—10 febrile and 4 allergic. Transfusions with reactions had significantly higher levels of IL-6 (2.3-fold higher; p = 0.005), IL-8 (2.2-fold higher; p = 0.001), MCP-1 (2.6-fold higher; p = 0.002), and sCD40L (1.24-fold higher; p = 0.015), but not RANTES. (1.14-fold higher; p = 0.22). The vast majority (>93%) of patients transfused with mediator levels in the highest quintile had no reactions. When levels of all five mediators were summed, the reaction rates in the first through fifth quintiles increased from 1 to 7 percent (p = 0.027). All but one reaction occurred in patients with hematologic malignancies (13 reactions/380 transfusions; 3.4%; p = 0.04 vs. other diagnoses).

CONCLUSIONS: These are the first data demonstrating that a PLT-derived mediator, sCD40L, is associated with adverse transfusion events. Existing clinical factors, for example, inflammation or leukopenia, may influence whether infused mediators cause reactions.

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