Alterations of platelet function and clot formation kinetics after in vitro exposure to anti-A and -B

Authors

  • Majed A. Refaai,

    Corresponding author
    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
      Majed A. Refaai, MD, University of Rochester Medical Center, 601 Elmwood Avenue, Box 608, Rochester, NY 14642; e-mail: majed_refaai@urmc.rochester.edu.
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  • Jessie Carter,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Kelly F. Henrichs,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Donna C. Davidson,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Stephen J. Pollock,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Ann E. Casey,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Sherry L. Spinelli,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Richard P. Phipps,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Charles W. Francis,

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • Neil Blumberg

    1. From the Department of Pathology and Laboratory Medicine, the Department of Microbiology and Immunology, the Department of Environmental Medicine, the James P. Wilmot Cancer Center, and the Department of Medicine, University of Rochester, Rochester, New York.
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  • This work was supported by NIH Grants ES01247, HL095467, and HL100051.

Majed A. Refaai, MD, University of Rochester Medical Center, 601 Elmwood Avenue, Box 608, Rochester, NY 14642; e-mail: majed_refaai@urmc.rochester.edu.

Abstract

BACKGROUND: ABO-mismatched platelets (PLTs) are commonly transfused despite reported complications. We hypothesized that because PLTs possess A and B antigens on their surface, ABO-mismatched transfused or recipient PLTs could become activated and/or dysfunctional after exposure to anti-A or -B in the transfused or recipient plasma. We present here in vitro modeling data on the functional effects of exposure of PLTs to ABO antibodies.

STUDY DESIGN AND METHODS: PLT functions of normal PLTs of all ABO types were assessed before and after incubation with normal saline, ABO-identical plasma samples, or O plasma samples with varying titers of anti-A and anti-B (anti-A/B). Assays used for this assessment include PLT aggregation, clot kinetics, thrombin generation, PLT cytoskeletal function, and mediator release.

RESULTS: Exposure of antigen-bearing PLTs to O plasma with moderate to high titers of anti-A/B significantly inhibits aggregation, prolongs PFA-100 epinephrine closure time, disrupts clot formation kinetics, accelerates thrombin generation, reduces total thrombin production, alters PLT cytoskeletal function, and influences proinflammatory and prothrombotic mediator release.

CONCLUSIONS: Our findings demonstrate a wide range of effects that anti-A/B have on PLT function, clot formation, thrombin generation, PLT cytoskeletal function, and mediator release. These data provide potential explanations for clinical observations of increased red blood cell utilization in trauma and surgical patients receiving ABO-nonidentical blood products. Impaired hemostasis caused by anti-A/B interacting with A and B antigens on PLTs, soluble proteins, and perhaps even endothelial cells is a potential contributing factor to hemorrhage in patients receiving larger volumes of ABO-nonidentical transfusions.

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