Investigation of ADAMTS13 and VWF in the Patients with Thrombotic Complications Following Hematopoietic Stem-Cell Transplantation (HSCT)

OBJECTIVE: Plasma ADAMTS13 may play a role in the pathogenesis of hematopoietic stem-cell transplantation (HSCT) related thrombosis by cleaving the prothrombotic ultralarge VWF into less active VWF. This study was to investigate the alterations of ADAMTS13 and VWF in HSCT recipients during transplantation, and to evaluate their significance in transplantation-related thrombotic complications.

METHODS: Plasma ADAMTS13 activity was detected by fluorescence resonance energy transfer substrate VWF73 (FRETS-VWF73) assay in 113 hematologic patients receiving allogeneic-HSCT. 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). 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<0.01), 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 (59.3%), including 9 patients with more than 60% (8.0%) decrease, while the average plasma VWF antigen level of this 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.

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. A decrease more than 60% in plasma ADAMTS13 activity is the risk factor of thrombotic complications. 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 of thrombotic complications.