Flatland Bente, Fry Michael M, Baek Seung J, Bahn Jae H, LeBlanc Casey J, Dunlap John R, Carroll Roger C, Kosiba Deborah J, Millsaps Doris J, Schleis Stephanie E
Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.
Vet Clin Pathol. 2011 Jun;40(2):207-14. doi: 10.1111/j.1939-165X.2011.00320.x. Epub 2011 May 9.
An 8-year-old female spayed Pug dog was presented for evaluation of cutaneous lesions occurring secondary to immunosuppressive treatment of presumed immune-mediated thrombocytopenia. Abnormal hematologic findings included persistent thrombocytopenia, macrothrombocytes, and variably shaped, often fusiform, blue cytoplasmic inclusions in neutrophils. May-Hegglin anomaly (MHA) was suspected based on the morphologic appearance of platelets and neutrophils. Examination of cells by transmission electron microscopy revealed normal platelet ultrastructure; neutrophil inclusions had features similar to those reported for inclusions in human MHA. Neutrophil function was within normal limits based on flow cytometric analysis. Thrombelastography indicated a prolonged clotting time (r), and PlateletMapping showed a lack of response to 2 μM ADP compared with a moderate response in the control dog. Immunocytochemical staining of blood smears using 2 commercially available antibodies against MYH9 protein (nonmuscle myosin heavy chain II) yielded negative results. However, genomic DNA sequencing analysis of the dog's MYH9 gene identified a single point mutation, resulting in substitution of lysine for glutamine at the 1841 amino acid position; this mutation is identical to one identified in people with MHA. To our knowledge, this is the first report of an MYH9 mutation in the dog. MHA-associated macrothrombocytopenia may be mistaken for immune-mediated thrombocytopenia.
一只8岁已绝育的雌性哈巴狗因疑似免疫性血小板减少症接受免疫抑制治疗后出现皮肤病变而前来评估。血液学异常表现包括持续性血小板减少、大血小板以及中性粒细胞中形状各异（常为梭形）的蓝色胞质内含物。基于血小板和中性粒细胞的形态学表现，怀疑为May-Hegglin异常（MHA）。通过透射电子显微镜检查细胞发现血小板超微结构正常；中性粒细胞内含物具有与人类MHA中报道的内含物相似的特征。基于流式细胞术分析，中性粒细胞功能在正常范围内。血栓弹力图显示凝血时间（r）延长，血小板功能分析显示与对照犬的中度反应相比，对2 μM ADP缺乏反应。使用两种市售抗MYH9蛋白（非肌肉肌球蛋白重链II）抗体对血涂片进行免疫细胞化学染色，结果为阴性。然而，对该犬MYH9基因的基因组DNA测序分析发现一个单点突变，导致第1841个氨基酸位置的赖氨酸被谷氨酰胺取代；该突变与在患有MHA的人中发现的突变相同。据我们所知，这是犬类中MYH9突变的首次报道。与MHA相关的大血小板减少症可能会被误诊为免疫性血小板减少症。
