Analysis of characteristics and prognostic factors of patients with thrombotic thrombocytopenic purpura
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摘要: 目的 获得性血栓性血小板减少性紫癜(TTP)是一种罕见且危及生命的微血管血栓形成疾病。分析我中心HCU 10年间获得性TTP患者的诊断和临床诊疗经过，以总结经验以及提高TTP危重症临床诊治水平。方法 回顾性分析在本院就诊的79例获得性TTP患者的临床资料，记录基本临床信息，进行统计学分析，观察和评价疗效以及预后相关影响因素。结果 在79例患者中，男女比例为1∶2.29，发病中位年龄48(14~77)岁。自身免疫性相关抗体检查异常比例60.6%，以抗SSA表达阳性或弱阳性最多。急性起病，临床表现以三联征多见，包括血小板减少(96.2%)、微血管病性溶血性贫血(93.1%)、神经系统症状(89.6%)，48.1%的患者血小板在10×109/L以下。起病时ADAMTS13活性检测的59例患者中81.4%活性呈重度减低(< 10%)。第一次住院患者中14例发生死亡，死亡率达17.7%；54例接受血浆置换(PEX)治疗联合大剂量糖皮质激素，47例在治疗过程中好转，有效率达87.03%。好转患者PEX中位次数为10(3~18)次。PEX次数(P < 0.001)、加用利妥昔单抗治疗(P=0.012)、不伴严重神经系统症状(P=0.042)、低胆红素与较好的治疗效果相关。共45例患者观察到血小板计数恢复至150×109/L以上，恢复中位天数第11(4~29)天。治疗前乳酸脱氢酶(P=0.038)、胆红素水平(P=0.039)、PEX次数(P < 0.001)以及加用利妥昔单抗(P=0.05)是影响血小板恢复正常的因素。结论 TTP大部分患者起病时ADAMTS13活性呈重度减低，PEX是获得性TTP最重要的治疗，尽早启动PEX可降低死亡率，使血小板快速恢复正常。前线加用利妥昔单抗，可以改善患者预后。
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关键词:
- 血栓性血小板减少性紫癜 /
- ADAMTS13 /
- 血浆置换 /
- 利妥昔单抗 /
- 预后
Abstract: Objective Acquired thrombotic thrombocytopenic purpura(TTP) is a rare and life-threatening microvascular thrombosis disorder. This study aims to summarize the diagnosis and clinical management of acquired TTP patients over a 10-year period in our HCU, in order to improve the clinical diagnosis and treatment of this disease.Methods A retrospective analysis was conducted on the clinical data of 79 patients with acquired TTP who were treated in our hospital. Basic clinical information was recorded, and statistical analysis was performed to observe and evaluate the efficacy and prognostic factors.Results Among the 79 patients, the male-to-female ratio was 1∶2.29, with a median age of onset at 48 years. The abnormal rate of autoimmune-related antibody tests was 60.6%, with anti-SSA positivity or weak positivity being the most common. The disease onset was acute, and the clinical manifestations were mostly the triad, including thrombocytopenia(96.2%), microangiopathic hemolytic anemia(93.1%), and neurological symptoms(89.6%). Platelet counts were below 10×109/L in 48.1% of patients. Among the 59 patients who underwent ADAMTS13 activity testing at onset, 81.4% had severely decreased activity(< 10%). Among the first-time hospitalized patients, 14 died, with a mortality rate of 17.7%. Fifty-four patients received plasma exchange(PEX) therapy combined with high-dose glucocorticoids, and 47 improved during treatment, with an effectiveness rate of 87.03%. The median number of PEX for improved patients was 10 (range 3-18). PEX frequency(P < 0.001), the addition of rituximab treatment(P=0.012), the absence of severe neurological symptoms(P=0.042), and lower bilirubin levels at onset were associated with better treatment outcomes. A total of 45 patients were observed to have platelet counts recover to above 150×109/L, with a median of 11 days (range 4-29 days). According to Cox univariate regression analysis, pretreatment LDH levels(P=0.038), bilirubin levels(P=0.039), the number of PEX(P < 0.001), and the addition of rituximab(P=0.05) were independent prognostic factors affecting platelet recovery.Conclusion Most patients with TTP have severely decreased ADAMTS13 activity at onset. PEX is the most important treatment for acquired TTP. Early initiation of PEX can reduce mortality and normalize platelet counts. Rituximab may improve the prognosis of patients before second line.-
Key words:
- thrombotic thrombocytopenic purpura /
- ADAMTS13 /
- plasma exchange /
- rituximab /
- prognosis
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表 1 79例获得性TTP诊时临床相关特征
指标 数值范围 例数(%) 年龄/岁 14~77 性别 男 24(30.4) 女 55(69.6) PLT/(×109/L) 1~9 36(45.6) ＞9且≤19 29(36.7) ＞19 14(17.7) 总胆红素/(μmol/L) 8.7~565.0 >60 29(36.7) 肌酐/(mmol/L) 21.9~724.6 >116 24(30.4) 严重神经系统表现 33(41.8) 发热 40(50.6) 自免相关指标 抗核抗体滴度>1000 13(16.5) SSA(+) 35(44.3) 破碎红细胞比例/% 1.2~13.8 LDH/(U/L) 161.0~2 671.0 
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表 2 ADAMTS13酶活性以及抑制物检测
指标 例数(%) ADAMTS13酶活性/%(59例) < 5 40(67.8) ≥5且＜10 8(13.6) ≥10且＜30 7(11.9) ≥30 4(6.8) 抑制物滴度(26例) < 1 7(26.9) 1~3 14(53.8) >3 5(19.2)
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表 3 不同预后组TTP临床特征比较分析
组别 年龄/岁 总胆红素/ (μmol/L) 肌酐/ (mmol/L) PLT/ (×109/L) LDH/ (U/L) ADAMTS13活性/% PEX/次 预后良好组 46.27 52.90 86.47 17.94 962.70 7.72 12.94 预后不良组 49.85 80.76 95.19 13.88 1 072.36 12.26 3.20 P 0.442 0.049 0.481 0.423 0.393 0.433 < 0.001
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表 4 不同预后组TTP临床特征比较分析
例(%) 组别 性别(女) 伴严重神经症状 有自免因素 使用利妥昔单抗 预后良好组 37/55 15/33 28/50 23/26 预后不良组 18/55 18/33 22/50 3/26 P 0.609 0.042 0.14 0.012
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表 5 影响初诊获得性TTP患者PLT恢复正常的危险因素分析
因素 B SE Exp(B) P 性别 -0.071 0.528 0.931 0.893 LDH 0.002 0.001 1.002 0.038 胆红素水平 -0.007 0.003 0.993 0.039 PLT 0.025 0.015 1.025 0.107 严重神经 -0.294 0.495 0.745 0.553 ADAMTS13活性 0.008 0.009 1.008 0.376 PEX总次数 -0.206 0.060 0.814 < 0.001 利妥昔单抗使用情况 0.793 0.435 2.210 0.050
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