Increased VWF antigen levels and decreased ADAMTS13 activity in preeclampsia

Abstract

This study aimed to assess the von Willebrand factor (VWF) antigen levels and its proteolytic enzyme ADAMTS13 activity in preeclampsia. The study includes 10 non-pregnant women, 50 normal pregnancy, and 110 preeclamptic (PE) women at the same period of pregnancy. For all studied groups plasma ADAMTS13 activities were determined with the FRETs-VWF 73 assay, while VWF antigen levels with an immunoturbometric assay. The plasma ADAMTS13 activity was significantly reduced in PE as compared with normal pregnancy and non-pregnant women (P < 0.01 for both). In contrast, plasma VWF antigen and VWF RCO were significantly elevated in PE, as compared with normal pregnancy group as well as non-pregnant women (P < 0.01 for both). In conclusion, reduction of plasma ADAMTS13 and elevation in VWF might have a role in the pathogenesis of PE.

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

“…Inhibitors of VEGF function such as sFlt-1 are known to cause endothelial activation 42 and release of VWF. 11,43 In the ADAMTS13…”

“…52,53 Likewise, small studies have reported a decrease in ADAMTS13 activities in patients with severe preeclampsia, with ADAMTS13 activity #70% being associated with early-onset preeclampsia, independent of VWF-Ag levels. 11,54 However, it is not known if these alterations antedate clinical symptoms. Future studies should evaluate whether low ADAMTS13 activity is a determinant of HELLP syndrome among patients with preeclampsia who have high sFlt-1 levels.…”

“…10 Both preeclampsia/HELLP syndrome and atypical hemolytic uremic syndrome can be associated with a decrease in ADAMTS13 concentration or activity, implying a more general role of this enzyme in TMAs. 11,12 Chemotherapies that inhibit vascular endothelial growth factor (VEGF) or VEGF signaling-e.g., bevacizumab, 13 sunitinib, 14,15 and aflibercept 16 -have been shown to induce TMA. 10 While TMA is the most severe adverse consequence of anti-VEGF therapy, the spectrum of toxicities includes proteinuria and hypertension, issues that are believed to arise from renal microvascular injury.…”

Endothelial Dysfunction

“…1 Although sFLT-1 is almost certainly one of the key factors driving preeclampsia, there are also reports that ADAMTS13 activity is commonly reduced in patients with preeclampsia. 8,9 ADAMTS13 is a protease that cleaves large vWf multimers that are released from activated endothelial cells, thereby blocking local platelet aggregation and thrombosis. Erpenbeck et al 6 show that overexpression of sFLT-1 in control mice induced mild manifestations of TMAs, which has been previously reported, whereas a lack of ADAMTS13 resulted in no manifestations of TMAs.…”

The Dynamics of the Hemostatic Parameters in Physiological Pregnancy and After Delivery

“…ADAMTS13 activity often falls below threshold level in antiphospholipid syndrome [27]. Besides, the connection between the decrease of ADAMTS-13 activity and the increase of RCoA and vWF antigen in pregnant women with pre-eclampsia has recently been shown [28]. In general, it can be assumed that the increase of RCoA and vWF level is not that significant for pregnancy as the decrease of ADAMTS-13 activity and antigen potentially contributing to the increase of this factor multimerization and increase of platelet activation reaching delivery.…”