El Sissy Maha H, El Hafez A Abd, El Sissy A H
Department of Clinical Pathology, University of Cairo, Cairo, Egypt.
Acta Haematol. 2014;132(1):30-5. doi: 10.1159/000355645. Epub 2013 Dec 31.
Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening disorder, characterized by thrombocytopenia, microangiopathic hemolytic anemia, widespread microvascular thrombi and consequent clinical sequelae due to ischemic organ damage. TTP is most commonly associated with deficiency or inhibition of von Willebrand factor-cleaving protease (ADAMTS13) activity. ADAMTS13 mutations and polymorphisms have been reported in childhood congenital TTP, but their significance in adult-onset TTP is still under investigation. Two mutations stand out: the single base insertion 4143insA in exon 29 and the missense mutation R1060W in exon 24 have both been observed in several unrelated families, mainly in adult-onset TTP, and over a wide geographic area. Our objective in this study is to identify the prevalence of R1060W missense mutation in exon 24 ADAMTS13 in a sample of adult Egyptian TTP patients. Thirty-one adult-onset TTP patients were included in this study, with a male/female ratio of 1:4. Twenty-six cases (84%) presented with acute idiopathic TTP, 2 cases were drug abusers and 3 cases were pregnant. None of the study cases provided a history of suspicious TTP symptoms during childhood (2 cases gave a history of episodes of thrombocytopenia during childhood). All cases showed statistically significant decreased ADAMTS13 activity compared to normal controls (p < 0.001). The study revealed a high statistical difference regarding the ADAMTS13 inhibitor level in primary versus secondary cases (p = 0.003). None of our Egyptian cases or of the healthy normal controls are positive for exon 24 missense mutation. Larger studies and regional and national TTP registries are recommended.
血栓性血小板减少性紫癜（TTP）是一种急性危及生命的疾病，其特征为血小板减少、微血管病性溶血性贫血、广泛的微血管血栓形成以及因缺血性器官损伤导致的临床后遗症。TTP最常与血管性血友病因子裂解蛋白酶（ADAMTS13）活性缺乏或受抑制有关。ADAMTS13突变和多态性已在儿童先天性TTP中报道，但它们在成人发作性TTP中的意义仍在研究中。有两个突变较为突出：外显子29中的单碱基插入4143insA和外显子24中的错义突变R1060W，这两个突变均在几个不相关的家族中被观察到，主要见于成人发作性TTP，且分布在广泛的地理区域。本研究的目的是确定埃及成年TTP患者样本中外显子24的ADAMTS13中R1060W错义突变的患病率。本研究纳入了31例成人发作性TTP患者，男女比例为1:4。26例（84%）表现为急性特发性TTP，2例为药物滥用者，3例为孕妇。所有研究病例在儿童期均无可疑TTP症状史（2例有儿童期血小板减少发作史）。与正常对照组相比，所有病例的ADAMTS13活性均有统计学显著降低（p < 0.001）。研究显示，原发性与继发性病例的ADAMTS13抑制剂水平存在高度统计学差异（p = 0.003）。我们的埃及病例和健康正常对照中外显子24错义突变均为阴性。建议进行更大规模的研究以及建立地区和国家TTP登记处。
