结缔组织病继发的血栓性血小板减少性紫癜临床特点及治疗分析

王甜甜; 曹俊杰; 刘旭辉; 范峥; 裴仁治; 陆滢

doi:10.16766/j.cnki.issn.1674-4152.002409

结缔组织病继发的血栓性血小板减少性紫癜临床特点及治疗分析

doi: 10.16766/j.cnki.issn.1674-4152.002409

宁波大学附属人民医院血液科，浙江宁波 315040

基金项目:

浙江省医药卫生科技计划项目 2017KY144

详细信息

通讯作者:
王甜甜，E-mail：wtt_0820@126.com

中图分类号: R593.2 R554.6
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- 被引次数: 0
出版历程
- 收稿日期: 2021-08-21
- 网络出版日期: 2022-08-20

Clinical characteristics and treatment of thrombotic thrombocytopenic purpura secondary to connective tissue disease

Department of Hematology, the Affiliated People ' s Hospital of Ningbo University, Ningbo, Zhejiang 315040, China

摘要

摘要: 目的探讨结缔组织病继发的血栓性血小板减少性紫癜(TTP)临床特点与治疗方法。方法回顾分析2014年1月—2017年6月宁波大学附属人民医院收治的8例结缔组织病继发的TTP患者的临床特点、实验室特征、治疗方案、疗效和生存情况。结果 8例TTP患者均为首次诊断结缔组织病，起病急，临床表现不典型，vWF金属蛋白裂解酶(ADAMTS13)活性均为0，ADAMTSI3抑制物阳性。所有患者临床诊断TTP后立即给予血浆置换、甲泼尼龙1~2 mg/kg治疗。1例患者治疗后血小板计数上升，后放弃治疗。其余7例患者治疗后血小板计数恢复至正常中位时间为12(4~18)d，ADAMTS13活性在治疗后1个月均恢复至100%，ADAMTS13抗体转阴。7例患者后期加用环孢素、硫唑嘌呤或环磷酰胺等免疫抑制剂治疗，3例患者每3个月加用100 mg利妥昔单抗维持治疗，7例患者持续缓解，其中2例患者在治疗后6个月常规监测ADAMTS13活性下降至30%，抗体再次阳性，加用小剂量利妥昔单抗治疗后1个月ADAMTS13活性恢复至正常。结论结缔组织病继发的TTP患者临床表现不典型，对临床高度怀疑或确诊TTP，应尽快完善ADAMTS13活性及抑制物测定，并尽早给予小剂量利妥昔单抗联合血浆置换治疗，后期给予小剂量利妥昔单抗维持治疗，减少复发。
- 结缔组织病 /
- 血栓性血小板减少性紫癜 /
- 利妥昔单抗
Abstract: Objective To analyze the clinical characteristics and treatment of thrombotic thrombocytopenic purpura (TTP) secondary to connective tissue disease (CTD) and explored the treatments of TTP. Methods We retrospectively reviewed clinical manifestations, laboratory examinations and treatment, efficacy, and survival of 8 TTP patients secondary to CTD admitted to the Affiliated People ' s Hospital of Ningbo University from January 2014 to June 2017. Results All 8 patients with TTP were diagnosed with CTD for the first time. All patients presented with acute onset and atypical clinical presentation. ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13, ADAMTS13) activities were 0 and its inhibitors were positive. All the patients received the treatment of plasma exchange plus steroid (1-2 mg/kg). One patient ' s platelet count increased after treatment, and then gave up treatment. In rest 7 patients, the median time of platelet recovered to normal after treatment was 12 (4-18) days, ADAMTS13 activity returned to 100% and ADAMTS13 antibody turned negative in 1 month after the treatment. Seven cases received treatment with cyclosporine, azathioprine or cyclophosphamide later. Three patients received maintenance therapy with rituximab 100 mg every 3 months. Seven patients remained in hematologic remissions. Among them, the activity of ADAMTS13 decreased to 30% and its inhibitors were positive in 2 patients at 6 months after the treatment by routine monitoring. ADAMTS13 activity returned to normal adding a small dose of rituximab therapy after 1 month. Conclusion TTP secondary to CTD has an atypical clinical manifestations, high clinical suspicion or diagnosis of TTP, as soon as possible to improve ADAMTS13 activity and inhibitor determination, and small dose of rituximab combined with plasma exchange is given as early as possible. Low-dose rituximab maintenance therapy is given to reduce relapse.
- Connective tissue disease /
- Thrombotic thromboeytopenic purpura /
- Rituximab

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表 1 8例TTP患者的临床资料及预后

Table 1. The clnical data and prognosis of TTP patients

病例	性别	年龄(岁)	诊断	血红蛋白(g/L)	血小板计数(×10⁹/L)	间接胆红素(μmol/L)	乳酸脱氢酶(U/L)	血浆置换次数(次)	治疗方法	预后
1	男性	47	未分化结缔组织病	82	32	45.2	538	6	甲泼尼松龙+静注人丙种球蛋白	良好
2	男性	73	未分化结缔组织病	59	25	63.6	1 256	4	大剂量甲泼尼松龙	死亡
3	男性	62	未分化结缔组织病	63	13	89.3	764	15	大剂量甲泼尼松龙+利妥昔单抗	良好
4	女性	26	系统性红斑狼疮	74	8	52.0	1 372	8	甲泼尼松龙+静注人丙种球蛋白	良好
5	女性	53	系统性红斑狼疮	42	18	56.0	635	10	甲泼尼松龙+小剂量利妥昔单抗	良好
6	女性	46	系统性红斑狼疮	72	21	31.6	482	6	甲泼尼松龙+小剂量利妥昔单抗	良好
7	女性	42	干燥综合征	89	16	49.0	963	4	甲泼尼松龙+小剂量利妥昔单抗	良好
8	女性	56	未分化结缔组织病	68	9	64.8	854	12	甲泼尼松龙+小剂量利妥昔单抗	良好

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