血栓性血小板减少性紫癜

Thrombotic thrombocytopenic purpura (TTP) is a potential diagnosis in any patient with haemolytic anaemia and thrombocytopenia - 95% of cases are fatal if left untreated.

症状通常不具有特异性，但是一半患者会出现神经系统异常。尽管常常可见发热、肾衰、溶血性贫血、血小板减少和神经系统功能改变五联征，但大部分患者并无完整的五联征。

外周血涂片检查十分关键，可显示微血管病性溶血性贫血伴红细胞破碎（裂红细胞）和血小板减少的证据。

对于疑似病例建议进行紧急血液学会诊。

血浆置换治疗联合皮质类固醇是急性获得性（特发性）TTP的主流治疗方法。卡普勒斯珠单抗 (caplacizumab) 可能作为成人患者的处方辅助治疗。

肾功能障碍和神经系统功能障碍是主要的并发症。

TTP is a clinical syndrome characterised by microangiopathic haemolytic anaemia and thrombocytopenic purpura.[1]Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017 Feb;15(2):312-22. https://www.doi.org/10.1111/jth.13571 http://www.ncbi.nlm.nih.gov/pubmed/27868334?tool=bestpractice.com Although the original descriptions included a pentad of microangiopathic haemolytic anaemia, thrombocytopenic purpura, neurological dysfunction, renal dysfunction, and fever, most patients do not have the entire pentad. There are no pathognomic features of TTP. Without treatment, TTP is typically fatal. Pathophysiology involves the absence of von Willebrand factor cleaving enzyme (ADAMTS-13), resulting in unusually large von Willebrand multimers that lead to platelet aggregation and subsequent thrombocytopenia and microthrombi. Some evidence suggests that at least 33% of patients with idiopathic TTP may have severe ADAMTS-13 deficiency.[2]Vesely SK, George JN, Lammle B, et al. ADAMTS-13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood. 2003;102:60-68. http://bloodjournal.hematologylibrary.org/content/102/1/60.full http://www.ncbi.nlm.nih.gov/pubmed/12637323?tool=bestpractice.com For the diagnosis of TTP, ADAMTS-13 activity levels of <5% to 10% are diagnostic.[1]Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017 Feb;15(2):312-22. https://www.doi.org/10.1111/jth.13571 http://www.ncbi.nlm.nih.gov/pubmed/27868334?tool=bestpractice.com [3]Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost. 2020 Oct;18(10):2496-502. https://www.doi.org/10.1111/jth.15010 http://www.ncbi.nlm.nih.gov/pubmed/32914526?tool=bestpractice.com [4]Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug;158(3):323-35. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09167.x/full http://www.ncbi.nlm.nih.gov/pubmed/22624596?tool=bestpractice.com

英国血液学标准委员会 (The British Committee for Standards in Haematology) 提议对 TTP 进行如下分组：[4]Scully M, Hunt BJ, Benjamin S, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol. 2012 Aug;158(3):323-35. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09167.x/full http://www.ncbi.nlm.nih.gov/pubmed/22624596?tool=bestpractice.com

急性特发性 TTP（TTP 最常见的类型，也是本文的重点内容）

先天性 TTP

HIV 相关性 TTP

妊娠相关性 TTP

药物相关性 TTP

胰腺炎相关性 TTP

TTP has also been described with COVID-19 infection.[5]Tehrani HA, Darnahal M, Vaezi M, et al. COVID-19 associated thrombotic thrombocytopenic purpura (TTP); a case series and mini-review. Int Immunopharmacol. 2021 Apr;93:107397. http://www.ncbi.nlm.nih.gov/pubmed/33524803?tool=bestpractice.com [6]Altowyan E, Alnujeidi O, Alhujilan A, et al. COVID-19 presenting as thrombotic thrombocytopenic purpura (TTP). BMJ Case Rep. 2020 Dec 17;13(12):e238026. https://casereports.bmj.com/content/13/12/e238026.long http://www.ncbi.nlm.nih.gov/pubmed/33334760?tool=bestpractice.com

Haemolytic uraemic syndrome is a similar syndrome but usually has a more pronounced renal component and is caused by Shiga toxin produced by certain E coli infections. Atypical haemolytic uraemic syndrome (aHUS) is a complement-mediated microangiopathy which clinically may masquerade as TTP, but is due to abnormalities in complement regulation.[1]Scully M, Cataland S, Coppo P, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017 Feb;15(2):312-22. https://www.doi.org/10.1111/jth.13571 http://www.ncbi.nlm.nih.gov/pubmed/27868334?tool=bestpractice.com [7]Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361:1676-1687. http://www.ncbi.nlm.nih.gov/pubmed/19846853?tool=bestpractice.com See the BMJ Best Practice topic: 'Haemolytic uraemic syndrome' for more information on aHUS.