Supplementary Material for: Thrombotic Thrombocytopenic Purpura Triggered by Chronic Lymphocytic Leukemia: A Case Report

Background: Chronic lymphocytic leukemia (CLL) is an incurable lymphoproliferative disorder characterized by the accumulation of mature malignant B-cells in the blood, bone marrow, and secondary lymphoid tissues. While it has a heterogenous clinical course, individuals with CLL are at increased risk for autoimmune complications, infections, and secondary non-hematologic secondary malignancies. Peripheral autoimmune cytopenias are a well-known phenomenon in CLL. However, other autoimmune complications, including immune thrombotic thrombocytopenic purpura (TTP), are rare and less investigated. We hereby report the first case of a patient with TTP triggered by CLL.

Case report: A 74-year-old male presented with fatigue, cough, left upper quadrant abdominal pain, and diffuse petechiae over the proceeding several weeks. The initial laboratory work was suggestive of anemia and thrombocytopenia with hemoglobin of 9.4 g/dl and platelets at 6 x 109/L. He was initially started on corticosteroids and intravenous immunoglobulin. Additional laboratory studies revealed a microangiopathic hemolytic with lactate dehydrogenase 1,124 U/L; total bilirubin 3.9; haptoglobin undectectable. The direct Coombs’ test was negative, and review of peripheral smear showed 5-6 schistocytes per high power field. Leukocyte count 15.6 x 109/L with absolute lymphocyte count of 4.0 K/ul. ADAMTS13 activity was < 9%. A diagnosis of TTP was made, and he was initiated on directed therapy. A bone marrow biopsy was ultimately performed, given the concern of immune-mediated or disease-related cytopenias and for confirmation of CLL. Subsequent bone marrow biopsy and flow cytometry confirmed the diagnosis of CLL.

Conclusion: Our case illustrates the first case of TTP precipitated by CLL. This case highlights the immune dysregulation underlying CLL and the autoimmune phenomena that may develop as a result.

背景：慢性淋巴细胞白血病（Chronic lymphocytic leukemia, CLL）是一类无法治愈的淋巴增殖性疾病，以成熟恶性B细胞在血液、骨髓及次级淋巴组织中异常蓄积为特征。尽管其临床病程具有显著异质性，CLL患者发生自身免疫并发症、感染及继发性非血液系统恶性肿瘤的风险均显著升高。外周血自身免疫性血细胞减少是CLL中已被广泛认知的现象，但包括免疫性血栓性血小板减少性紫癜（immune thrombotic thrombocytopenic purpura, TTP）在内的其他自身免疫并发症则较为罕见，相关研究亦相对匮乏。本文报告了首例由CLL诱发的TTP病例。

病例报告：一名74岁男性患者，在此前数周内出现乏力、咳嗽、左上腹疼痛及全身弥漫性瘀点。初始实验室检查提示贫血与血小板减少，血红蛋白水平为9.4 g/dl，血小板计数为6×10⁹/L。患者初始接受糖皮质激素与静脉注射免疫球蛋白治疗。进一步实验室检查显示存在微血管病性溶血性贫血：乳酸脱氢酶为1124 U/L，总胆红素为3.9，结合珠蛋白未检出。直接库姆斯试验（direct Coombs’ test）呈阴性，外周血涂片镜检可见每高倍视野下5~6个裂红细胞（schistocytes）。白细胞计数为15.6×10⁹/L，绝对淋巴细胞计数为4.0 K/ul。ADAMTS13活性＜9%。确诊为TTP后，患者接受了针对性治疗。鉴于怀疑存在免疫介导或疾病相关的血细胞减少，且需明确CLL诊断，最终对患者实施了骨髓活检。后续骨髓活检与流式细胞术（flow cytometry）结果证实了CLL的诊断。

结论：本病例为首例由CLL诱发的TTP病例，凸显了CLL背后的免疫失调机制，以及由此可能引发的自身免疫相关异常表现。