Changes of ADAMTS13 Activity and VWF Level in the Plasma of Patients Undergoing Hematopoietic Stem-Cell Transplantation (HSCT)
Authors: Han Yue , HU Luping , Zhu Qian , Xu Yang , Hu Xiaohui , Su Jian , Ma Zhenni , Zhang Wei , Sun Aining , Qiu Huiying , Wang Zhaoyue , Ruan Changgeng , Depei Wu 
Published: October 2019

Abstract
Abstract 3329

BACKGROUND:
Thrombotic disorders are common and potentially fatal complications in patients undergoing hematopoietic stem-cell transplantation (HSCT). Plasma ADAMTS13, a von willebrand factor (VWF)–cleaving protease, may play a role in the pathogenesis of HSCT related thrombosis by cleaving the prothrombotic ultralarge VWF into less active VWF multimers. Our aim in this study was to investigate the alterations of plasma ADAMTS13 and VWF in HSCT recipients during the course of transplantation, and to evaluate their clinical significance in the transplantation-related thrombotic complications.

METHODS:
A total of 113 hematologic patients receiving allogeneic-HSCT were enrolled in this study, the sodium citrate anticoagulated plasma was collected in -2, 0, 2 and 4 weeks following HSCT. Fluorescence resonance energy transfer substrate VWF73 (FRETS-VWF73) assay was established to detect the plasma ADAMTS13 activity while VWF antigen was measured by ELISA. Of all the patients recruited for his study, 8 patients were diagnosed to have the thrombotic disorders and 49 patients were classified to have acute graft-versus-host disease (aGVHD). Twenty healthy donors were recruited as control subjects. The alterations of ADAMTS13 activity and VWF level in the plasma of patients were analyzed during transplantation, and the correlation between ADAMTS13/VWF and transplantation-related thrombosis was evaluated using the SAS program (version 9.3).

RESULTS:
The average plasma ADAMTS13 activity in 113 cases following HSCT at each period were less than the healthy controls (P<0.05), while the VWF antigen level in each period were higher than the controls (P<0.05). Among all the patients after pretreatment, 69 showed decreased plasma ADAMTS13 activities (69/113, 59.3%), including 9 patients with more than 60% (9/113, 8.0%) decrease, while the average plasma VWF antigen level of these 69 patients was significantly increased in patients after pretreatment (P<0.05). Considering thrombotic complications, the data showed that 8 patients with thrombotic complications had decreased plasma ADAMTS13 activity (P<0.01) and increased VWF antigen level after pretreatment (P<0.01) as compared with the non-thrombotic patients; three out of 8 (37.5%) showed more than 60% decrease in plasma ADAMTS13 activity. The level of ADAMTS13 activity dropped in the 49 patients with aGVHD as compared with healthy controls (P<0.01), but there was no significant difference between patients with and without aGVHD. Twenty-five patients showed decreased plasma ADAMTS13 activities only at the onset of aGVHD occurrence (P<0.01), in which two of them decreased more than 60% (6%). Logistic regression analysis showed that the ADAMTS13 activity declined by more than 60% was the risk of thrombosis (P<0.01), while decreased ADAMTS13 activity after pretreatment was not the risk factor for aGVHD.

CONCLUSIONS:
We observed decreased plasma ADAMTS13 activity and increased plasma level of VWF antigen in patients following HSCT after pretreatment, especially in the patients with thrombotic complications. Regression analysis showed a decrease more than 60% in plasma ADAMTS13 activity is the risk factor of thrombotic complications, which was not correlated to the development of aGVHD although ADAMTS13 activity reduced in the patients when aGVHD occurred. Therefore, the plasma ADAMTS13 activity could be an important parameter for the development of vascular disorder, which has a potential role for the early diagnosis and therapy of thrombotic complications.

Disclosures:
No relevant conflicts of interest to declare.