Plasma and Urinary FGF-2 and VEGF-A Levels Identify Children at Risk for Severe Bleeding after Pediatric Cardiopulmonary Bypass: A Pilot Study.

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Anthony A. Sochet, MD, MSc Elizabeth A. Wilson, MD, MSHS Jharna R. Das, PhD John T. Berger, MD Patricio E Ray, MD


Severe bleeding after cardiothoracic surgery with cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality in adults and children. Fibroblast Growth Factor-2 (FGF-2) and Vascular Endothelial Growth Factor-A (VEGF-A) induce hemorrhage in murine models with heparin exposure. We aim to determine if plasma and urine levels of FGF-2 and VEGF-A in the immediate perioperative period can identify children with severe bleeding after CPB. We performed a prospective, observational biomarker study in 64 children undergoing CPB for congenital heart disease repair from June 2015 - January 2017 in a tertiary pediatric referral center. Primary outcome was severe bleeding defined as ≥ 20% estimated blood volume loss within 24-hours. Independent variables included perioperative plasma and urinary FGF-2 and VEGF-A levels. Analyses included comparative (Wilcoxon rank sum, Fisher’s exact, and Student’s t tests) and discriminative (receiver operator characteristic [ROC] curve) analyses.

Forty-eight (75%) children developed severe bleeding. Median plasma and urinary FGF-2 and VEGF-A levels were elevated in children with severe bleeding compared to without bleeding (preoperative: plasma FGF-2 = 16[10-35] vs. 9[2-13] pg/ml; urine FGF-2= 28[15-76] vs. 14.5[1.5-22] pg/mg; postoperative: plasma VEGF-A = 146[34-379] vs. 53[0-134] pg/ml; urine VEGF-A = 132[52-257] vs. 45[0.1-144] pg/mg; all p < 0.05). ROC curve analyses of combined plasma and urinary FGF-2 and VEGF-A levels discriminated severe postoperative bleeding (AUC: 0.73-0.77) with mean sensitivity and specificity above 80%.  We conclude that the perioperative plasma and urinary levels of FGF-2 and VEGF-A discriminate risk of severe bleeding after pediatric CPB.

Keywords: Cardiopulmonary bypass surgery, heparin, Fibroblast Growth Factor 2, bleeding

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SOCHET, Anthony A. et al. Plasma and Urinary FGF-2 and VEGF-A Levels Identify Children at Risk for Severe Bleeding after Pediatric Cardiopulmonary Bypass: A Pilot Study.. Medical Research Archives, [S.l.], v. 8, n. 6, june 2020. ISSN 2375-1924. Available at: <>. Date accessed: 16 july 2024. doi:
Research Articles


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