■移植相关血栓性微血管病(TA-TMA)是造血干细胞移植的致命并发症,其特征是严重的血小板减少症,溶血性贫血,和器官功能障碍。为了响应几种可能的触发器,血管性血友病因子(VWF)的动态多参数变化可能有助于诱导TA-TMA循环中的微血栓。
■通过进行VWF多聚体分析并测量VWF降解产物(DP),我们揭示了循环VWF多聚体变化与TA-TMA发病机制之间的关系。
■这项研究分析了来自14名患者的135份血浆样本,这些患者在一家机构接受了异基因造血干细胞移植。与VWF关联的标记,即VWF:抗原(VWF:Ag),VWF-DP/VWF:Ag比值,VWF:瑞斯托霉素辅因子活性,VWF:瑞斯托霉素辅因子活性/VWF:Ag比率,和ADAMTS13活性,在每7天收集的这些样品中进行分析。
■有2例明确的血栓性微血管病(TMA)和6例可能的TMA未进展为明确的TMA。每个血浆样本分为3组:明确的TMA,可能的TMA,非TMAVWF多聚体分析显示可能的TMA中不存在高分子量VWF多聚体,而在明确的TMA中观察到异常大的VWF多聚体的出现。可能的TMA中VWF-DP/VWF:Ag比率的中值升高至4.17,表明VWF切割酶对VWF多聚体的过度切割,ADAMTS13导致高分子量VWF多聚体的损失。
■在从可能的TMA过渡到确定的TMA期间,VWF多聚体的急剧变化意味着从出血转变为血栓形成倾向。广泛的VWF-DP和VWF多聚体分析提供了新颖的见解。
UNASSIGNED: Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of hematopoietic stem cell transplantation and is characterized by severe thrombocytopenia, hemolytic anemia, and organ dysfunction. In response to several possible triggers, dynamic multimetric change in von Willebrand factor (VWF) may contribute to inducing microthrombi in circulation in TA-TMA.
UNASSIGNED: By performing VWF multimer analysis and measuring VWF-degradation product (DP), we unraveled the relationship between multimeric changes in circulating VWF and the pathogenesis of TA-TMA.
UNASSIGNED: This study analyzed 135 plasma samples from 14 patients who underwent allogeneic hematopoietic stem cell transplantation at a single institute. VWF-associated markers, namely VWF:antigen (VWF:Ag), VWF-DP/VWF:Ag ratio, VWF:ristocetin cofactor activity, VWF:ristocetin cofactor activity/VWF:Ag ratio, and ADAMTS13 activity, were analyzed in these samples collected every 7 days.
UNASSIGNED: There were 2 patients with definite thrombotic microangiopathy (TMA) and 6 patients who presented with probable TMA that did not progress to definite TMA. Each plasma sample was classified into 3 groups: definite TMA, probable TMA, and non-TMA. VWF multimer analysis showed the absence of high-molecular-weight VWF multimers in probable TMA, whereas the appearance of unusually large VWF multimers was observed in definite TMA. The median value of the VWF-DP/VWF:Ag ratio in probable TMA was elevated to 4.17, suggesting that excessive cleavage of VWF multimers by VWF cleaving enzyme, ADAMTS13, resulted in the loss of high-molecular-weight VWF multimers.
UNASSIGNED: During the transition from probable to definite TMA, drastic VWF multimer changes imply a switch from bleeding to thrombotic tendencies. Extensive VWF-DP and VWF multimer analyses provided novel insights.