Abstract Number: VPB0842
Meeting: ISTH 2022 Congress
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.
Patient 1 met the criteria of definite TA-TMA between day 35 and 49. The appearance of UL-VWFMs and an increase in VWF Rco/Ag ratio were observed. Before definite TA-TMA state -day 21 and 28-, a defect of HMW-VWFMs, decrease in the VWF Rco/Ag ratio, and a marked increase in VWF-DP were observed.
Patient 2 met the criteria of definite TA-TMA between day 21 and 28. UL-VWFMs were found on day 21 and 28 following the absence of HMW-VWFMs -day 14-.
VWF, von Willebrand factor; TA-TMA, transplant-associated thrombotic microangiopathy; UL-VWFM, unusually-large VWF multimers; VWF:Rco, VWF:ristocetin cofactor; VWF:Ag, VWF:antigen; VWF-DP, VWF degradation product; HMW-VWFMs, high-molecular-weight VWF multimers
To cite this abstract in AMA style:Yamada S, Kubo M, Okumura H, Matsumoto M. von Willebrand factor multimer analysis may predict the development of transplant-associated thrombotic microangiopathy [abstract]. https://abstracts.isth.org/abstract/von-willebrand-factor-multimer-analysis-may-predict-the-development-of-transplant-associated-thrombotic-microangiopathy/. Accessed September 21, 2023.
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