Li Ang, Bendapudi Pavan K, Uhl Lynne, Hamdan Ayad, Kaufman Richard M, Makar Robert S
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Harvard Medical School, Boston, Massachusetts.
Transfusion. 2017 Sep;57(9):2151-2158. doi: 10.1111/trf.14181. Epub 2017 Jun 20.
The a disintegrin and metalloprotease with thrombospondin type 1 motifs, member 13 (ADAMTS13) activity assay has become important in distinguishing autoimmune thrombotic thrombocytopenic purpura from other forms of thrombotic microangiopathy (TMA). Although the significance of severe deficiency in ADAMTS13 (activity levels 10% or less) has been well defined, little data are available on the clinical importance of mild to moderate deficiency (activity levels 11%-70%) among patients with TMA.
We conducted a retrospective study using the Harvard TMA Research Collaborative Registry. Among 254 patients who met the inclusion criteria for TMA, 186 patients with ADAMTS13 activity levels greater than 10% were divided into moderate-deficiency (11%-40%), mild-deficiency (41%-70%), and no-deficiency (greater than 70%).
Compared with mild or no deficiency, moderate ADAMTS13 deficiency correlated with older age; higher bilirubin and international normalized ratio; and increased frequency of sepsis, shock, or multiorgan failure. Platelet counts, lactate dehydrogenase levels, and the presence of renal or neurologic dysfunction did not vary across the three patient cohorts. While moderate ADAMTS13 deficiency was associated with increased 90-day mortality in univariate analysis, this association was no longer significant in multivariate analysis. Variables that independetly predicted 90-day mortality in this cohort of patients included Charlson comorbidity index, alanine aminotransferase level, platelet count, creatinine, and the presence of sepsis, shock, or multiorgan failure.
Moderately deficient ADAMTS13 activity identifies a cohort of patients with TMA who are at increased risk for 90-day mortality. The ADAMTS13 activity level in this group is not an independent predictor of poor outcomes but instead appears to be a marker of disease acuity.
具有血小板反应蛋白1型基序的解聚素和金属蛋白酶13（ADAMTS13）活性检测在区分自身免疫性血栓性血小板减少性紫癜与其他形式的血栓性微血管病（TMA）中变得至关重要。尽管ADAMTS13严重缺乏（活性水平为10%或更低）的意义已得到明确界定，但关于TMA患者中轻度至中度缺乏（活性水平为11%-70%）的临床重要性的数据却很少。
我们使用哈佛TMA研究协作登记处进行了一项回顾性研究。在254例符合TMA纳入标准的患者中，186例ADAMTS13活性水平大于10%的患者被分为中度缺乏（11%-40%）、轻度缺乏（41%-70%）和无缺乏（大于70%）。
与轻度或无缺乏相比，ADAMTS13中度缺乏与年龄较大、胆红素和国际标准化比值较高以及败血症、休克或多器官功能衰竭的发生率增加相关。血小板计数、乳酸脱氢酶水平以及肾或神经功能障碍的存在在三个患者队列中没有差异。虽然在单变量分析中ADAMTS13中度缺乏与90天死亡率增加相关，但在多变量分析中这种关联不再显著。在该组患者中独立预测90天死亡率的变量包括查尔森合并症指数、丙氨酸转氨酶水平、血小板计数、肌酐以及败血症、休克或多器官功能衰竭的存在。
ADAMTS13活性中度缺乏可识别出一组TMA患者，他们90天死亡率风险增加。该组中的ADAMTS13活性水平不是不良预后的独立预测因素，而是似乎是疾病严重程度的一个标志物。
