Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapeutics, Center for Biologics Evaluation and Research, US FDA, Silver Spring, MD, USA.
Department of Cardiac Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
J Thromb Haemost. 2017 Dec;15(12):2306-2316. doi: 10.1111/jth.13860. Epub 2017 Oct 26.
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.
围手术期血栓形成是先天性心脏病患者发病率和死亡率的主要原因。前瞻性随访接受先天性心脏病变修复的新生儿和婴儿。术后期间，血管性血友病因子（VWF）与 ADAMTS-13 活性的比值升高。血栓形成与术前 VWF 活性和冷沉淀输注有关。
背景 先天性心脏畸形的手术修复常伴有不明病因的围手术期血栓形成。VWF 与 ADAMTS-13 之间的失衡是血栓形成的一个新变量。目的 描述围手术期 VWF、ADAMTS-13 和 NETosis 的变化，并评估术后血栓形成与临床和生化的关系。
方法 招募接受姑息性或确定性先天性心脏病畸形修复的新生儿和婴儿（n=133）。测定术前和术后血浆 VWF、ADAMTS-13 和 NETosis 标志物水平。对患者进行长达 30 天的随访，以观察血栓形成的发生。进行单变量和多变量逻辑回归分析，以确定与血栓形成相关的变量。
结果 我们发现 VWF 活性、VWF 水平、DNA-组蛋白复合物和无细胞 DNA 在术后显著增加，而 ADAMTS-13 活性总体下降。发生术后血栓形成事件（9%）的患者术中体温较低、术前血乳酸水平较高、术前 VWF 活性和水平较高。多变量逻辑回归模型确定术前 VWF 活性（每 IU·mL 增加 8.39 倍，95%置信区间 [CI] 1.73-40.55）和冷沉淀输注（每 mL·kg 增加 1.10 倍，95%CI 1.03-1.17）与血栓形成相关。
结论 接受先天性心脏畸形手术修复的儿科患者在术后即刻暴露于高水平的 VWF，而 ADAMTS-13 则减少或几乎没有变化。术前 VWF 活性升高与儿科先天性心脏病患者术后血栓形成有关。
