Detection of Continuous Flow Left Ventricular Assist Device -Associated Acquired Von Willebrand Factor (VWF) Abnormality by An Automated Immunoturbidimetric VWF Activity Assay

Abstract

Abstract▪2273▪This icon denotes a clinically relevant abstract Background:Continuous flow left ventricular assist device (CF-LVAD) recipients have high tendency of post-surgical gastrointestinal (GI) bleeding. We previously described the loss of high molecular weight VWF multimers (HMWM), due to either an accelerated clearance or enhanced cleavage of the HMWM, in most CF-LVAD recipients (Ann Thorac Surg. 90:1263–9). However, besides the tedious plasma VWF multimer analysis, neither VWF ristocetin cofactor nor collagen binding activity assay provides sufficient sensitivity for detecting such an acquired VWF abnormality (AVWA). In this study, we examined a new automated latex particle-enhanced immunoturbidimetric VWF activity assay (VWF:Lx) for its ability of detecting CF-LVAD-AVWA. We also analyzed the VWF pro-peptide (VWF:pp) to explored the potential mechanism of CF-LVAD-AVWA. Design:As part of an on-going prospective multicenter study, pre- and post-CF-LVAD implantation (7, 30 days and 5–7 months) blood samples were collected from 15 LVAD recipients (median age 52 years; 10 male and 5 female; 2008∼2009). Plasma VWF antigen (VWF:Ag), VWF:Lx activity, VWF:pp/Ag ratios were measured; and plasma VWF multimer analyses were performed on all available plasma samples. Standard statistical analyses were employed. Result:Loss of VWF HMWM was observed in 3 patients prior to CF-LVAD implantation and virtually all patients after surgery. VWF:Ag, VWF:Lx or VWF:pp/Ag ratios of the pre- and post-implantation samples were not significantly different (P> 0.1). However, VWF:Lx/Ag ratios of the post-implantation samples were significantly decreased (P<0.05). At a cut off of 0.8, the VWF:Lx/Ag ratio has a 90% sensitivity and specificity for detecting AVWA. Conclusions:VWF:Lx/Ag ratio has excellent sensitivity and specificity in detecting CF-LVAD-AVWA, and its impact on predicting post-surgical bleeding tendency in CF-LVAD recipients is being investigated. The distinct CF-LVAD-AVWA is most likely caused by enhanced cleavage, rather than clearance, of the HMWM.Table 1:Laboratory Characteristics of VWF in Pre- and Post-CF-LVAD Implantation Patient Plasma Samples.Laboratory Results (Mean±Standard Deviation)Pre-implantation (n=15)Day 7 Post (n=13)Day 30 Post (n=13)5–7 month Post (n=4)VWF:Ag (IU/dL)318 ± 178340 ± 136263.8 ± 122.7224 ± 78VWF:Lx (U/dL)258 ± 145246 ± 87102.5 ± 64.6165 ± 44VWF:Lx/Ag Ratio0.82 ± 0.120.74 ± 0.080.75 ± 0.060.76 ± 0.12VWF:pp/Ag Ratio1.04 ± 0.361.00 ± 0.300.99 ± 0.231.02 ± 0.10Samples with HMWM Loss (Present/Total)3/1510/1312/134/4Agreement between abnormal VWF:Lx/Ag ratio (<0.8) and VWF Multimer Analysis13/1511/1312/134/4 Disclosures:No relevant conflicts of interest to declare.