Plasmatic ADAMTS-13 metalloprotease and von Willebrand factor in children with cyanotic congenital heart disease

Abstract

Changes in plasma von Willebrand factor concentration (VWF:Ag) and ADAMTS-13 activity (the metalloprotease that cleaves VWF physiologically) have been reported in several cardiovascular disorders with prognostic implications. We therefore determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight children were enrolled (age 0.83 to 7.58 years). Measurements were performed at baseline and 48 h after surgery. ELISA, collagen-binding assays and Western blotting were used to estimate antigenic and biological activities, and proteolysis of VWF multimers. Preoperatively, VWF:Ag and ADAMTS-13 activity were decreased (65 and 71% of normal levels considered as 113 (105-129) U/dL and 91 ± 24% respectively, P < 0.003) and correlated (r = 0.39, P = 0.0064). High molecular weight VWF multimers were not related, suggesting an interaction of VWF with cell membranes, followed by proteolytic cleavage. A low preoperative ADAMTS-13 activity, a longer activated partial thromboplastin time and the need for cardiopulmonary bypass correlated with postoperative bleeding (P < 0.05). Postoperatively, ADAMTS-13 activity increased but less extensively than VWF:Ag (respectively, 2.23 and 2.83 times baseline, P < 0.0001), resulting in an increased VWF:Ag/ADAMTS-13 activity ratio (1.20 to 1.54, respectively, pre- and postoperative median values, P = 0.0029). ADAMTS-13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 µg/mL, P < 0.0001) and persistent proteolysis of VWF multimers. We conclude that, in pediatric CCHD, changes in circulating ADAMTS-13 suggest enzyme consumption, associated with abnormal structure and function of VWF.

Traumatic injury results in prolonged circulation of ultralarge von Willebrand factor and a reduction in ADAMTS13 activity

“…Potential contributors to this consumptive process include thrombin and plasmin, which have both been shown to cleave ADAMTS13 and would intermittently increase in the period after injury . Furthermore, ADAMTS13 activity has been associated with bleeding events both in patients with sepsis and in pediatric patients with congenital heart disease undergoing surgery . Additional work, both in animals and in humans, is needed to understand the causal mechanism by which ADAMTS13 activity contributes to TIC.…”

Coagulation Profile in Neonates with Congenital Heart Disease: A Pilot Study

“…Soares et al reported lower levels of ADAMTS-13 antigen and activity in children with cyanotic CHD prior to surgical correction vs. controls. However, neonates were not included in the study [46]. Diminished ADAMTS-13 levels are probably attributed to elevated VWF levels, leading to consumption of ADAMTS-13, while liver dysfunction is an adding factor.…”

The Role of the von Willebrand Factor Collagen-Binding Assay (VWF:CB) in the Diagnosis and Treatment of von Willebrand Disease (VWD) and Way Beyond: A Comprehensive 36-Year History

“…I helped to establish and characterize a novel VWF:CB assay for the measurement of VWF activity. 223 Soares et al 224,225 employed a VWF:CB to help characterize ADAMTS13 and VWF level and activity in children with cyanotic congenital heart disease. Hugenholtz et al 226 included a VWF:CB to highlight an unbalance between VWF and ADAMTS13 in acute liver failure; in these patients, VWF:Ag was raised, but VWF:CB and VWF:RCo/Ag ratio was reduced, as was ADAMTS13 and the proportion of HMWM.…”