Huang Yezi, Zhou Lixia, Song Yuan, Zou Wanting, Tang Aiping, Tao Si, Tang Duozhuang
Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Front Med (Lausanne). 2025 Jan 8;11:1525062. doi: 10.3389/fmed.2024.1525062. eCollection 2024.
Congenital thrombotic thrombocytopenic purpura (cTTP) is a thrombotic microangiopathy (TMA) characterized by severe hereditary ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13) deficiency caused by mutations. This rare autosomal recessive genetic disorder is often misdiagnosed as immune thrombocytopenia (ITP) or hemolytic uremic syndrome (HUS). Here, we report a 21-year-old male cTTP patient with a compound heterozygous mutation. The patient was admitted for acute thrombocytopenia, with a 5-year history of chronic thrombocytopenia and 1 month of renal dysfunction. Initially diagnosed with ITP, he was treated with immunosuppressive therapy, including glucocorticoids and intravenous immunoglobulin, which provided temporary relief but failed to prevent recurrent thrombocytopenia. Ultimately, cTTP was confirmed by the low ADAMTS13 0% activity and two heterozygous variants (c.1335del and c.1045C > T) in the gene, and the patient received prophylactic fresh-frozen plasma (FFP) infusions every 2-3 weeks regularly. Interestingly, the patient also exhibited elevated sC5b-9 levels during the acute phase, necessitating differentiation from HUS. This report highlights a cTTP caused by a compound heterozygous mutation, although its pathogenesis requires further investigation. Given the atypical clinical manifestations of cTTP, it is necessary to conduct ADAMTS13 activity and even genetic testing in patients with recurrent thrombocytopenia and end-organ damage.
先天性血栓性血小板减少性紫癜（cTTP）是一种血栓性微血管病（TMA），其特征是由突变导致严重的遗传性ADAMTS13（含Ⅰ型血小板反应蛋白基序的解聚素和金属蛋白酶13）缺乏。这种罕见的常染色体隐性遗传疾病常被误诊为免疫性血小板减少症（ITP）或溶血性尿毒症综合征（HUS）。在此，我们报告一名21岁的男性cTTP患者，其存在复合杂合突变。该患者因急性血小板减少入院，有5年慢性血小板减少病史及1个月肾功能不全病史。最初被诊断为ITP，接受了包括糖皮质激素和静脉注射免疫球蛋白在内的免疫抑制治疗，虽有暂时缓解，但未能预防血小板减少复发。最终，通过低ADAMTS13活性0%以及该基因中的两个杂合变异（c.1335del和c.1045C>T）确诊为cTTP，患者定期每2 - 3周接受一次预防性新鲜冰冻血浆（FFP）输注。有趣的是，该患者在急性期还表现出sC5b - 9水平升高，这需要与HUS进行鉴别。本报告强调了由复合杂合突变引起的cTTP，尽管其发病机制仍需进一步研究。鉴于cTTP的非典型临床表现，对于反复出现血小板减少和终末器官损害的患者，有必要进行ADAMTS13活性甚至基因检测。
