604. Dysfunctional Platelet Aggregation in Patients with Acute Lassa Fever
Session: Poster Abstract Session: Immunology - Host Response
Thursday, October 5, 2017
Room: Poster Hall CD
Posters
  • Poster for IDWeek 2017.pdf (4.9 MB)
  • Background:

    Lassa Fever is an acute viral hemorrhagic fever (VHF) endemic to West Africa that affects about 300,000 people per year causing severe multisystem disease with an estimated mortality rate of 30% to 70%.  Severe cases with hemorrhage are associated with the presence of a circulating plasma inhibitor of platelet aggregation that was first identified over 25 years ago by McCormick et al. and determined to be present in acute but not convalescent serum. Despite being recognized in several other VHFs it had not been further characterized. We aim to assess platelet function via aggregometry in patients with acute Lassa fever.

    Methods:

    This study was conducted at the Kenema Government Hospital (KGH) and Viral Hemorrhagic Fever Laboratory in Kenema, Sierra Leone.  De-identified samples from patients presenting to the KGH Lassa Ward who met clinical criteria for acute Lassa fever and were positive for Lassa antigen (Ag) or Lassa-specific IgM were used. Additional clinical data including blood chemistries were obtained (Abaxis Piccolo Xpress). Plasma samples were dialyzed using a synthetic membrane to remove EDTA, and then tested in mixing assays with platelets from an uninfected control subject. Light aggregation with adenosine diphosphate (ADP) 5µM and collagen 5mg/mL (CHRONOLOG 450 aggregometer and AGGRO/LINK 8 software) was used.

    Results:

    22 patients were included in the analysis. 11 patients were Ag+/IgM- and 11 patients were Ag-/IgM+.  Normal platelets from an uninfected control showed decreased aggregation responses to ADP and collagen after 4 minutes when mixed with plasma in 4/22 patients with acute Lassa fever compared to plasma from uninfected controls or TyrodeÕs solution. Platelet aggregation dysfunction was also associated with death and with clinical laboratory markers consistent with more severe disease, including detectable Ag and elevated AST.

    Conclusion:

    Our preliminary results demonstrate that dysfunctional platelet aggregation is associated with severe disease and mortality and may play an important role in the pathogenesis of acute Lassa infection. Rapid diagnosis of specific coagulation abnormalities could be used to risk-stratify Lassa fever patients at time of initial presentation.

    Lucy E. Horton, MD, MPH1,2, Brian M. Sullivan, PhD2, Robert F. Garry, PhD3, Donald S. Grant, MD4, Roberto Aiolfi, PhD2, Zaverio M. Ruggeri, MD2 and Michael B.A. Oldstone, MD, PhD2, (1)Infectious Diseases, UC San Diego, San Diego, CA, (2)The Scripps Research Institute, La Jolla, CA, (3)Tulane University, New Orleans, LA, (4)Kenema Government Hospital, Kenema, Sierra Leone

    Disclosures:

    L. E. Horton, None

    B. M. Sullivan, None

    R. F. Garry, None

    D. S. Grant, None

    R. Aiolfi, None

    Z. M. Ruggeri, None

    M. B. A. Oldstone, None

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