Takagi Yoko, Kobayashi Yasuko, Hirakata Ayako, Takei Mariko, Ogasawara Satoshi, Yajima Chikage, Ikeuchi Yuka, Matsumoto Akira, Ogawa Yoshiyuki, Handa Hiroshi, Matsumoto Masanori, Arakawa Hirokazu, Takizawa Takumi
Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan.
Department of Hematology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Front Pediatr. 2022 Aug 1;10:931669. doi: 10.3389/fped.2022.931669. eCollection 2022.
Thrombotic microangiopathy (TMA) is a syndrome associated with hemolytic anemia, thrombocytopenia, and various organ disorders. Thrombotic thrombocytopenic purpura (TTP) is a disease that develops when a disintegrin-like and metalloproteinase with thrombospondin type l motif 13 (ADAMTS13) activity decreases to < 10% of that in normal plasma, causing platelet thrombosis in microvessels throughout the body. Currently, ADAMTS13-deficient TMA is diagnosed as TTP. Systemic lupus erythematosus (SLE)-related TMA includes both acquired TTP, in which ADAMTS13 activity is significantly reduced, and secondary TMA, in which ADAMTS13 activity is not reduced. Both diseases have different prognoses.
An 11-year-old girl was admitted to our hospital on suspicion of TMA with thrombocytopenia and hemolytic anemia. Because the patient had hypocomplementemia, SLE-related TMA or complement-related TMA was considered. Therefore, we initiated plasma exchange (PE) for the patient. Subsequently, she fulfilled the pediatric SLE diagnostic criteria, and ADAMTS13 activity was shown to be decreased and the anti-ADAMTS13 antibody titer increased. She was thus diagnosed with acquired TTP caused by SLE. Treatment response was good as a platelet count and ADAMTS13 activity improved with three times of PE, followed by methylprednisolone pulse therapy and administration of mycophenolate mofetil. Renal pathology showed thrombus formation in glomerular arterioles and lupus nephritis categorized as Class III (A) of the International Society of Nephrology and the Renal Pathology Society classification. Because the patient was thought to be in the high-risk group of SLE, three courses of intravenous cyclophosphamide pulse therapy were administered as an additional induction therapy. No recurrence of TTP was observed.
In SLE-related TMA, measurement of ADAMTS13 activity and the anti-ADAMTS13 antibody titer are necessary for diagnosis, and for predicting prognosis and recurrence of the disease; however, in the acute phase of immune-mediated TMA, it is important to initiate proper treatments even before knowing the results to improve prognosis.
血栓性微血管病（TMA）是一种与溶血性贫血、血小板减少和各种器官功能障碍相关的综合征。血栓性血小板减少性紫癜（TTP）是一种当具有血小板反应蛋白1型基序的去整合素样金属蛋白酶13（ADAMTS13）活性降至正常血浆水平的<10%时发生的疾病，导致全身微血管内血小板血栓形成。目前，ADAMTS13缺乏型TMA被诊断为TTP。系统性红斑狼疮（SLE）相关的TMA包括获得性TTP（其中ADAMTS13活性显著降低）和继发性TMA（其中ADAMTS13活性未降低）。这两种疾病的预后不同。
一名11岁女孩因怀疑患有伴有血小板减少和溶血性贫血的TMA而入住我院。由于该患者存在低补体血症，故考虑为SLE相关的TMA或补体相关的TMA。因此，我们为该患者启动了血浆置换（PE）。随后，她符合儿童SLE诊断标准，且显示ADAMTS13活性降低，抗ADAMTS13抗体滴度升高。她因此被诊断为由SLE引起的获得性TTP。经过三次PE治疗，随后进行甲泼尼龙冲击治疗并给予霉酚酸酯，血小板计数和ADAMTS13活性得到改善，治疗反应良好。肾脏病理显示肾小球小动脉有血栓形成，狼疮性肾炎分类为国际肾脏病学会和肾脏病理学会分类的III（A）级。由于该患者被认为属于SLE高危组，故给予三个疗程的静脉环磷酰胺冲击治疗作为额外的诱导治疗。未观察到TTP复发。
在SLE相关的TMA中，测量ADAMTS13活性和抗ADAMTS13抗体滴度对于诊断、预测疾病的预后和复发是必要的；然而，在免疫介导的TMA急性期，即使在得知结果之前启动适当的治疗以改善预后也很重要。
