Changes in coagulation factor XII and its function during aortic arch surgery for acute aortic dissection°™a prospective observational study

Abstract

Changes in the intrinsic coagulation pathway during aortic arch surgery in patients with acute aortic dissection (AAD) have not yet been reported. The aim of this study is to describe the changes in intrinsic coagulation factor XII, explore its function and find a new target for the treatment of coagulopathy during surgery. Eighty-eight patients undergoing emergent surgery for AAD were enrolled. Changes in the intrinsic and extrinsic coagulation pathways were evaluated at 5 different timepoints during the perioperative period by measuring intrinsic coagulation factor XII, extrinsic coagulation factor VII and some intrinsic upstream stimulating factors. The 88 patients were also divided into two groups according to whether reoperation for coagulopathy was required after surgery. Both coagulation factors XII and VII demonstrated a significant and similar change during the perioperative period. These factors decreased significantly during hypothermia circulation arrest (P<0.001) and recovered to normal levels by 24 hours after surgery. Among the intrinsic upstream stimulating factors, bradykinin (BK) demonstrated a similar changing trend with coagulation factors XII and VII, while other stimulating factors did not. However, compared with factor VII, factor XII demonstrated a greater decline during surgery. The proportion of decline of factor XII from anesthesia induction to hypothermia circulation arrest was 42%, whereas the proportion of decline of factor VII during the same period was 20% (P<0.001). Moreover, factor VII recovered to preoperative levels 4 hours after surgery with a relatively faster speed (P<0.001) while factor XII had not recovered (P=0.010). The independent t-test and Wilcoxon test showed that coagulation factor XII levels during hypothermia circulation arrest (P=0.002), total dosage of fibrinogen (P=0.027), total dosage of packed red blood cells (PRBCs) (P=0.006) and total dosage of fresh frozen plasma (FFP) (P=0.022) during the perioperative period were significantly different between the patients who did or did not require reoperation for coagulopathy. Multivariable logistic regression analysis suggested that the factor XII level during hypothermia circulation arrest was an independent risk factor for reoperation for coagulopathy [odds ratio (OR): 1.342, 95% confidence interval (CI): 1.058-1.570; P=0.012]. Factor XII levels are more influenced by surgery and require a longer period of time to recover to preoperative levels compared with factor VII, and the level of factor XII during hypothermia circulation arrest might be an independent risk factor for reoperation for coagulopathy. Therefore, supplementation of coagulation factor XII and its upstream stimulating factors might be a promising therapeutic modality in the future.