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.
Highlights
ADAMTS is an abbreviation for a desintegrin and metalloprotease with thrombospondin type 1 motif, and corresponds to a family of zinc metalloproteases with desintegrin and protease domains (ADAM-related), cystein-rich regions and a thrombospondin 1 repeat
We determined the level of these proteins in the plasma of children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment
ADAMTS13 consumption was further confirmed by decreased ADAMTS-13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 mg/mL, P, 0.0001) and persistent proteolysis of von Willebrand factor concentration (VWF) multimers
Summary
ADAMTS is an abbreviation for a desintegrin and metalloprotease with thrombospondin type 1 motif, and corresponds to a family of zinc metalloproteases with desintegrin and protease domains (ADAM-related), cystein-rich regions and a thrombospondin 1 repeat. Lower ADAMTS-13:Ag and ADAMTS-13 activity in patients compared to controls (Table 1) were associated with a loss of high molecular mass VWF multimeric protein complexes, resulting in increased density of low molecular mass fractions (Table 1 and Figure 1), which might be interpreted as proteolytic degradation with enzyme consumption.
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