Remuzzi Giuseppe, Galbusera Miriam, Noris Marina, Canciani Maria Teresa, Daina Erica, Bresin Elena, Contaretti Silvia, Caprioli Jessica, Gamba Sara, Ruggenenti Piero, Perico Norberto, Mannucci Pier Mannuccio
Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Villa Camozzi-Ranica, Bergamo, Italy.
Blood. 2002 Aug 1;100(3):778-85. doi: 10.1182/blood-2001-12-0166.
Whether measurement of ADAMTS13 activity may enable physicians to distinguish thrombotic thrombocytopenic purpura (TTP) from hemolytic uremic syndrome (HUS) is still a controversial issue. Our aim was to clarify whether patients with normal or deficient ADAMTS13 activity could be distinguished in terms of disease manifestations and multimeric patterns of plasma von Willebrand factor (VWF). ADAMTS13 activity, VWF antigen, and multimeric pattern were evaluated in patients with recurrent and familial TTP (n = 20) and HUS (n = 29). Results of the collagen-binding assay of ADAMTS13 activity were confirmed in selected samples by testing the capacity of plasma to cleave recombinant VWF A1-A2-A3. Most patients with TTP had complete or partial deficiency of ADAMTS13 activity during the acute phase, and in some the defect persisted at remission. However, complete ADAMTS13 deficiency was also found in 5 of 9 patients with HUS during the acute phase and in 5 patients during remission. HUS patients with ADAMTS13 deficiency could not be distinguished clinically from those with normal ADAMTS13. In a subgroup of patients with TTP or HUS, the ADAMTS13 defect was inherited, as documented by half-normal levels of ADAMTS13 in their asymptomatic parents, consistent with the heterozygous carrier state. In patients with TTP and HUS there was indirect evidence of increased VWF fragmentation, and this occurred also in patients with ADAMTS13 deficiency. In conclusion, deficient ADAMTS13 activity does not distinguish TTP from HUS, at least in the recurrent and familial forms, and it is not the only determinant of VWF abnormalities in these conditions.
通过检测ADAMTS13活性是否能让医生区分血栓性血小板减少性紫癜（TTP）和溶血性尿毒症综合征（HUS），这仍然是一个存在争议的问题。我们的目的是明确ADAMTS13活性正常或缺乏的患者在疾病表现及血浆血管性血友病因子（VWF）多聚体模式方面是否存在差异。对复发性和家族性TTP患者（n = 20）及HUS患者（n = 29）的ADAMTS13活性、VWF抗原及多聚体模式进行了评估。通过检测血浆裂解重组VWF A1 - A2 - A3的能力，在选定样本中证实了ADAMTS13活性胶原结合试验的结果。大多数TTP患者在急性期ADAMTS13活性完全或部分缺乏，部分患者在缓解期仍存在缺陷。然而，9例HUS患者中有5例在急性期及5例在缓解期也发现了ADAMTS13完全缺乏。ADAMTS13缺乏的HUS患者在临床上无法与ADAMTS13正常的患者区分开来。在一部分TTP或HUS患者中，ADAMTS13缺陷是遗传性的，其无症状父母的ADAMTS13水平为正常的一半，这与杂合子携带者状态相符。在TTP和HUS患者中，有间接证据表明VWF裂解增加，ADAMTS13缺乏的患者也出现这种情况。总之，ADAMTS13活性缺乏并不能区分TTP和HUS，至少在复发性和家族性形式中如此，而且在这些情况下它并非VWF异常的唯一决定因素。
