Abstract 12735: ADAMTS13 Metalloprotease and Von Willebrand Factor in Children With Cyanotic Congenital Heart Disease
In addition to congenital thrombotic thrombocytopenic purpura, plasma von Willebrand factor antigen (VWF:Ag) and ADAMTS13 activity (the metalloprotease that cleaves VWF physiologically) are altered in a number of acquired thrombotic conditions. Heightened VWF:Ag/ADAMTS13 activity ratio has been associated with worse prognosis in several disorders. We analyzed ADAMTS13 and VWF in children with cyanotic congenital heart disease (CCHD) undergoing surgical treatment. Forty-eight patients were enrolled (age 0.83 to 7.58 years). We used enzyme-linked immunoassays, collagen-binding assays and Western immunoblotting to analyze antigenic and biological activities, and the multimeric structure of VWF. At baseline (preoperatively), VWF:Ag and ADAMTS13 activity were mildly decreased (respectively, 73 and 65 percent normal) and directly related (r=0.48, p=0.0008). High molecular weight VWF multimers were lacking, suggesting abnormal interactions of VWF with biological membranes followed by proteolytic degradation. At 48 hours postoperatively, both VWF:Ag and ADAMTS13 activity were increased relative to baseline (p<0.0001). However, compared with the preoperative pattern, ADAMTS13 curve was flattened relative to VWF:Ag (p=0.0138, ANCOVA), resulting in heightened VWF:Ag/ADAMTS13 activity ratio (1.20 to 1.54, respectively pre and postoperative median values, p=0.0029). This was associated with enhancement of the proteolytic pattern of VWF multimers. The suggested enzyme consumption was further confirmed by decreased ADAMTS13 antigenic concentration (0.91 ± 0.30 to 0.70 ± 0.25 mcg/L, respectively pre and postoperative levels, p<0.0001). Finally, lower preoperative levels of ADAMTS13 activity were associated with increased risk of postoperative bleeding (12 patients, p=0.0184, logistic regression). No differences were detected between patients undergoing ON- and OFF-pump operations. We conclude that children with CCHD have pre and postoperative changes in VWF and ADAMTS13 that suggest endothelial activation, abnormal proteolysis of VWF multimers and enzyme consumption, compatible with thrombotic microangiopathy. This may be part of the complex hemostatic defect that causes postoperative bleeding in these patients.
- © 2011 by American Heart Association, Inc.