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

Abstract

Essentials Perioperative thrombosis is a major cause of morbidity and mortality in congenital heart disease. Neonates and infants undergoing repair of congenital heart lesions were prospectively followed. Elevated von Willebrand factor (VWF) to ADAMTS-13 activity ratios typified the postoperative period. Thrombosis was associated with preoperative VWF activity and cryoprecipitate transfusion SUMMARY: Background The surgical repair of congenital heart malformations 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 surgical repair of congenital heart malformations were recruited (n = 133). Preoperative 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 level, 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 a lower intraoperative temperature, higher preoperative lactic acid levels, and higher preoperative VWF activity and level. A multivariate logistic regression model identified preoperative VWF activity (odds ratio (OR) 8.39 per IU mL , 95% confidence interval [CI] 1.73-40.55) and transfusion of cryoprecipitate (OR 1.10 per mL kg , 95% CI 1.03-1.17) as being associated with thrombosis. Conclusions Pediatric patients undergoing surgical repair of congenital heart malformations 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 congenital heart disease.

Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case‐series

“…Hunt et al . described a functional imbalance between VWF and ADAMTS‐13 in the perioperative period for neonates and infants with CHD, which also might contribute to thrombotic events because of lower postoperative levels of ADAMTS‐13 . For this reason, supplementation with VWF concentrate bears a potential risk of thrombosis and should also be considered carefully.…”

Coagulopathy and Thrombosis as a Result of Severe COVID-19 Infection: A Microvascular Focus

“…[68][69][70] Abnormal VWF-ADAMTS-13 ratios are implicated in arterial thrombosis, 71 ischemic stroke, 72,73 pediatric stroke, 74 and perioperative thrombosis in infants. 75 In addition, abnormal VWF/ADAMTS-13 metabolism has been positively associated with myocardial infarction in young women. 76 It is worth highlighting that in the case of perioperative thrombosis, elevated VWF even in the absence of significant deficiency of ADAMTS-13 was associated with thrombosis.…”

“…76 It is worth highlighting that in the case of perioperative thrombosis, elevated VWF even in the absence of significant deficiency of ADAMTS-13 was associated with thrombosis. 75 Severe hypoxia and acidosis likely caused a higher increase in VWF during cardiac surgery and were at higher risk of thrombosis. 75 Tabatabai et al 48 Relative to reference range (10) Fibrinogen, CRP, and ferritin…”

Consumptive Coagulopathy and Thrombosis during Severe COVID-19 Infection: Potential Involvement of VWF/ADAMTS13

“…In the event of vascular injury, VWF facilitates binding of platelets to sub-endothelium through its interactions with collagen, thereby inducing thrombus formation (50). Abnormal VWF-ADAMTS13 ratios are implicated in arterial thrombosis (54), ischemic stroke (55, 56) pediatric stroke (57) and perioperative thrombosis in infants (58). In this study(58), we identified an imbalance in the proportional ratio of VWF/ADAMTS13, having increased activity and concentration of VWF without a concomitant increase in plasma activity of ADAMTS13; this imbalance is associated with thrombosis.…”

“…In this study(58), we identified an imbalance in the proportional ratio of VWF/ADAMTS13, having increased activity and concentration of VWF without a concomitant increase in plasma activity of ADAMTS13; this imbalance is associated with thrombosis. Neonates exposed to severe hypoxia and acidosis demonstrated a higher increase in VWF during cardiac surgery and were at higher risk of thrombosis (58). In addition abnormal VWF/ADAMTS13 metabolism has been positively associated with myocardial infarction in young women (59).…”