Scientific Publications by FDA Staff

J Thromb Haemost 2017 Dec;15(12):2306-16

Elevated preoperative von Willebrand Factor is associated with perioperative thrombosis in infants and neonates with congenital heart disease.

Hunt R, Hoffman CM, Emani S, Trenor CC 3rd, Emani SM, Faraoni D, Kimchi-Sarfaty C, Ibla JC

BACKGROUND: The surgical repair of congenital heart lesions is frequently complicated by perioperative thrombosis of unclear etiology. An imbalance between von Willebrand Factor (VWF) and ADAMTS-13 is an emerging variable in thrombosis. OBJECTIVES: To describe perioperative changes to VWF, ADAMTS-13 and NETosis and evaluate clinical and biochemical associations with postoperative thrombosis. METHODS: Neonates and infants undergoing palliation or definitive repair of congenital heart disease (CHD) were recruited (n =133). Pre- and postoperative plasma levels of VWF, ADAMTS-13 and markers of NETosis were determined. Patients were followed for up to 30 days for the occurrence of thrombosis. Univariate and multivariate logistic regression analyses were conducted to identify variables associated with thrombosis. RESULTS: We identified significant postoperative increases in VWF activity, VWF concentration, DNA-histone complexes and cell-free DNA with an overall decrease in ADAMTS-13 activity. Patients experiencing postoperative thrombotic events (9%) were characterized by surgery performed at lower intraoperative temperature, higher preoperative lactic acid levels and higher preoperative VWF activity and concentration. A multivariate logistic regression model identified preoperative VWF activity (odds ratio: 8.39 per IU/mL, 95% CI: 1.73-40.55) and transfusion of cryoprecipitate (odds ratio: 1.10 per mL/kg, 95% CI: 1.03-1.17) to be associated with thrombosis. CONCLUSIONS: Pediatric patients undergoing surgical repair of congenital heart disease are exposed to high levels of VWF with diminished or minimal change to ADAMTS-13 in the immediate postoperative period. Elevated preoperative VWF activity is associated with postoperative thrombosis in pediatric CHD.