Excessive cleavage of von Willebrand factor multimers by ADAMTS13 may predict progression of transplant-associated thrombotic microangiopathy

Abstract

Abstract Transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Since little is known about multimer changes of von Willebrand factor (VWF) in TA-TMA, VWF-degradation product (DP) was analyzed to unravel the mechanism of change in the VWF multimer and disease course. This study enrolled 14 patients who underwent allogeneic HSCT at a single institute. VWF-associated markers were measured in blood samples collected every 7 days. There were two patients of definite TMA, and six patients that presented with probable TMA that did not progress to definite TMA. Each plasma sample was classified into three groups: definite TMA, probable TMA, and non-TMA. VWF multimer analysis showed the absence of high-molecular-weight (HMW)-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:antigen 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 HMW-VWF multimers. 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.