Adult‐onset,chronic, cyclic thrombocytopenia in a Rhesus macaque (Macaca mulatta) after dengue virus vaccination and viral challenge |
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| Authors: | Galit H. Frydman Kelly A. Metcalf Pate Robert P. Marini Armelle M. de Laforcade Irene Bosch Vasudevan Bakthavatchalu Sureshkumar Muthupalani Alton G. Swennes Claire E. Lyons Ronald G. Tompkins James G. Fox |
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| Affiliation: | 1. Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA;2. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA;3. Center for Surgery, Innovation & Bioengineering, Massachusetts General Hospital, Boston, MA, USA;4. Harvard Medical School, Boston, MA, USA;5. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA;6. Emergency and Critical Care, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA;7. Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA;8. Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA |
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| Abstract: | An 8‐year‐old, male Rhesus macaque (Macaca mulatta), previously used for dengue virus (DENV) vaccine research with viral challenge, was presented with adult‐onset, chronic, cyclic thrombocytopenia. Platelet number, morphology, and function were evaluated by automated hematology, peripheral blood smears, electron microscopy, flow cytometry, and impedance aggregometry. Bone marrow was evaluated by cytology. Both serum anti‐dengue nonstructural protein 1 (NS1) antibodies and anti‐platelet antibodies were detected by ELISA. Platelet characterization showed a lack of aggregation to all agonists (ADP, ASP, and collagen), increased activation with increased expression of surface marker (HLA‐ABC), and an absence of surface receptor GPIX during clinical episodes of petechiae and ecchymoses, even in the presence of normal platelet counts. Bone marrow aspirates identified potential mild megakaryocytic hypoplasia. All platelet functions and morphologic attributes were within normal limits during clinically normal phases. Presence of anti‐dengue NS1 serum antibodies confirmed a positive DENV titer 8 years postvaccination. Based on the history and clinical findings, a primary differential diagnosis for this chronic, cyclic platelet pathology was autoimmune platelet destruction with potential bone marrow involvement. |
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| Keywords: | Autoimmune
ITP
nonhuman primate platelets |
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