Frydman Galit H, Metcalf Pate Kelly A, Marini Robert P, de Laforcade Armelle M, Bosch Irene, Bakthavatchalu Vasudevan, Muthupalani Sureshkumar, Swennes Alton G, Lyons Claire E, Tompkins Ronald G, Fox James G
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Vet Clin Pathol. 2017 Jun;46(2):238-247. doi: 10.1111/vcp.12497. Epub 2017 May 18.
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.
一只8岁雄性恒河猴（猕猴属），此前用于登革病毒（DENV）疫苗研究并接受过病毒攻击，出现了成年期慢性周期性血小板减少症。通过自动血液学检查、外周血涂片、电子显微镜检查、流式细胞术和阻抗聚集法评估血小板数量、形态和功能。通过细胞学检查评估骨髓情况。采用酶联免疫吸附测定法检测血清抗登革热非结构蛋白1（NS1）抗体和抗血小板抗体。血小板特征显示，在瘀点和瘀斑临床发作期间，即使血小板计数正常，对所有激动剂（二磷酸腺苷、花生四烯酸和胶原）均缺乏聚集反应，随着表面标志物（HLA-ABC）表达增加激活增强，且缺乏表面受体GPIX。骨髓穿刺发现潜在的轻度巨核细胞发育不全。在临床正常阶段，所有血小板功能和形态学特征均在正常范围内。抗登革热NS1血清抗体的存在证实疫苗接种8年后DENV滴度呈阳性。根据病史和临床检查结果，这种慢性周期性血小板病变的主要鉴别诊断为自身免疫性血小板破坏并可能累及骨髓。
