Von Willebrand factor and ADAMTS13: a candidate couple for preeclampsia pathophysiology

Abstract

Objective: The goal of this study was to search for an association between a desintegrin-like and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13) levels and the occurrence of preeclampsia, its characteristics (time-onset and severity), and its consequences (occurrence of fetal growth restriction or preterm delivery).

Methods and results: We studied 140 pairs of women in a case-control study with 3 matching criteria: maternal age, gestational age, and ethnic origin. We measured ADAMTS13 activity using a fluorescence resonance energy transfer assay with the fluorescence resonance energy transfer-VWF73 peptide. ELISA was used to assess protein antigen levels: ADAMTS13, von Willebrand Factor (VWF), interleukin-6, C-reactive protein, P-selectin, and thrombospondin-1. The lowest levels of ADAMTS13 (activity ≤ 70% or antigen ≤ 592 ng/mL) were significantly associated with preeclampsia (odds ratios [OR] [95% confidence interval] of 4.2 [1.1 to 15] and 14.3 [1.7 to 123], respectively). This association was independent of VWF levels and preeclampsia risk factors but dependent on interleukin-6 and C-reactive protein levels for ADAMTS13 activity. Levels of ADAMTS13 activity (≤ 57%) were significantly associated with early-onset preeclampsia (OR = 2.5 [1.1 to 5.8]). Severe preeclampsia was associated with the highest levels of P-selectin (>57 ng/mL) (OR = 3.4 [1.2 to 9.7]).

Conclusions: Preeclampsia is associated with decreased levels of ADAMTS13, independently of VWF. This decrease is quantitative, occurs early, and seems to be dependent on inflammation. Our results suggest that ADAMTS13 could participate in the pathophysiology of preeclampsia.