Using this newly established SRM, we determined that the plasma levels of the cleaved M1606VTGNPASDEIK peptide in samples collected 3 months after LVAD implantation varied significantly, but were mostly below the level of normal plasma pooled from 61 healthy subjects (Figure 2A). To adjust for high VWF antigen in these patients (Figure 1B), we defined VWF cleavage as the ratio of M1606VTGNPASDEIK to ILAGPAGDSNVVK. This rate varied significantly in the post-LVAD samples, accounting for 0.23–2.5% of total VWF as compared to 1.26% ± 0.36% in normal plasma, even though the loss of large VWF multimers was found in 91.3% of patients as we have recently reported.15 The findings suggest that 1) circulating VWF was minimally cleaved in normal subjects and 2) there was no drastic increase in VWF cleavage in post-LVAD samples. These findings raise a possibility that VWF was cleaved by ADAMTS-13 primarily to be released from its anchorage to endothelial cells as we previously shown.17 Although further experiments are required to determine whether such small changes in VWF cleavage are sufficient to alter VWF reactivity, a subgroup analysis did find that VWF cleavage in post-LVAD samples was increased in patients in whom bleeding was developed and was mostly reduced in patients in whom thrombosis was developed (Figure 2B). Because this study was primarily focused on developing a quantitative method to measure VWF cleavage, it had a limited number of patients. This small patient cohort is not powered to determine the association of VWF cleavage with the development of hemostatic complications in patients on LVAD support.
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