Tarasco Erika, Bütikofer Lukas, Friedman Kenneth D, George James N, Hrachovinova Ingrid, Knöbl Paul N, Matsumoto Masanori, von Krogh Anne Sophie, Aebi-Huber Isabella, Cermakova Zuzana, Górska-Kosicka Magdalena, Jalowiec Katarzyna A, Largiadèr Carlo R, Prohászka Zoltán, Sinkovits György, Windyga Jerzy, Lämmle Bernhard, Kremer Hovinga Johanna A
Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department for BioMedical Research and.
Blood. 2021 Jun 24;137(25):3563-3575. doi: 10.1182/blood.2020009801.
Hereditary thrombotic thrombocytopenic purpura (hTTP) is a rare thrombotic microangiopathy characterized by severe congenital ADAMTS13 deficiency and recurring acute episodes causing morbidity and premature death. Information on the annual incidence and severity of acute episodes in patients with hTTP is largely lacking. This study reports prospective data on 87 patients from the Hereditary TTP Registry (clinicaltrials.gov #NCT01257269) for survival, frequency, and severity of acute episodes from enrollment until December 2019. The 87 patients, followed up for a median of 4.2 years (range, 0.01-15 years), had a median age at overt disease onset and at clinical diagnosis of 4.6 years and 18 years (range, 0.0-70 years for both), respectively. Forty-three patients received regular plasma prophylaxis, whereas 22 did not, and treatment changed over time or was unknown in the remaining 22. Forty-three patients experienced 131 acute episodes, of which 91 (69%) occurred in patients receiving regular prophylaxis. This resulted in an annual incidence of acute episodes of 0.36 (95% confidence interval [CI], 0.29-0.44) with regular plasma treatment and of 0.41 (95% CI, 0.30-0.56) without regular plasma treatment. More than one-third of acute episodes (n = 51) were documented in children <10 years of age at enrollment and were often triggered by infections. Their annual incidence of acute episodes was significantly higher than in patients aged >40 years (1.18 [95% CI, 0.88-1.55] vs 0.14 [95% CI, 0.08-0.23]). The prophylactic plasma infusion regimens used were insufficient to prevent acute episodes in many patients. Such regimens are burdensome, and caregivers, patients, and their guardians are reluctant to start regular plasma infusions, from which children particularly would benefit.
遗传性血栓性血小板减少性紫癜（hTTP）是一种罕见的血栓性微血管病，其特征为严重的先天性ADAMTS13缺乏以及反复出现的急性发作，可导致发病和过早死亡。目前，关于hTTP患者急性发作的年发病率和严重程度的信息非常匮乏。本研究报告了遗传性TTP注册中心（clinicaltrials.gov #NCT01257269）87例患者从入组至2019年12月的生存情况、急性发作频率和严重程度的前瞻性数据。这87例患者的中位随访时间为4.2年（范围0.01 - 15年），显性疾病发病和临床诊断时的中位年龄分别为4.6岁和18岁（范围均为0.0 - 70岁）。43例患者接受了定期血浆预防治疗，22例未接受，其余22例的治疗随时间变化或情况不明。43例患者经历了131次急性发作，其中91次（69%）发生在接受定期预防治疗的患者中。这使得接受定期血浆治疗的患者急性发作的年发病率为0.36（95%置信区间[CI]，0.29 - 0.44），未接受定期血浆治疗的患者为0.41（95% CI，0.30 - 0.56）。超过三分之一的急性发作（n = 51）记录于入组时年龄<10岁的儿童，且常由感染引发。他们急性发作的年发病率显著高于40岁以上的患者（1.18 [95% CI，0.88 - 1.55] vs 0.14 [95% CI，0.08 - 0.23]）。所使用的预防性血浆输注方案在许多患者中不足以预防急性发作。此类方案负担较重，护理人员、患者及其监护人都不愿开始定期血浆输注，而儿童尤其能从中受益。
