VPB0842 - von Willebrand factor multimer analysis may predict the development of transplant-associated thrombotic microangiopathy

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication of allogenic hematopoietic stem cell transplantation (allo-HSCT). It has been reported that von Willebrand factor (VWF) antigen (Ag) levels are higher in TA-TMA patients; however, the relationship between VWF multimers and TA-TMA has not been elucidated in detail.

Aims: To investigate the relationship between TA-TMA and VWF multimers.

Methods: Plasma of patients was collected from day -7 to day 63 of allo-HSCT to test for VWF antigen (Ag), VWF ristocetin cofactor (VWF:Rco), ADAMTS13 activity, VWF multimers, and VWF-degradation product (VWF-DP). VWF-DP was measured using a monoclonal antibody that specifically recognizes Y1605 at the C-terminal boundary, which is exposed following ADAMTS13-mediated cleavage of the VWF A2 domain (Hayakawa et al. JTH. 2019).

Results: Fourteen patients were analyzed in this study. Six patients developed probable TA-TMA (Cho, et al.Transplantation, 2010) and two patients developed definite TA-TMA (Ho, et al. Biol Blood Marrow Trasplant, 2005). The results of VWF multimers and VWF parameters in the two definite TA-TMA cases are shown in Figure 1. At the onset of TA-TMA (Patient No.1, day 33 and No.2, day 20), unusually large VWF multimers (UL-VWFMs) appeared in the plasma. These findings were not seen in probable TA-TMA or others. Before the appearance of UL-VWFMs, a defect of high molecular weight VWF multimers (HMW-VWFMs) and increase in VWF-DP were found in both patients with definite TA-TMA. These results indicated that the defects of HMW-VWFMs might be caused by excessive cleavage of VWFMs by ADAMTS13. In addition, the defects of HMW-VWFMs were also found in patients with probable TA-TMA or in non-TA-TMA patients; however, UL-VWFMs did not appear after the defects of HMW-VWFMs.

Conclusion(s): When UL-VWFMs are found following the absence of HMWMs in VWF multimer analysis, the clinical state may shift from pre- to definite TA-TMA.