In this retrospective descriptive study, data for 334 patients (neonates, children, adults) undergoing congenital heart surgery at Boston Children’s Hospital between 2015 and 2018 with postoperative fibrinogen levels greater than 400 mg/dl were reviewed. We excluded patients who did not have hyperfibrinogenemia, defined as fibrinogen levels greater than 400 mg/dl in the 48 h following surgery (Supplemental Fig. 1). We selected a range of 48 h post-surgery as most bleeding complications occur within the first two post-operative days. The cutoff of 400 mg/dl was selected for the fibrinogen level as this is the upper limit of the normal fibrinogen range. We selected patients with elevated plasma fibrinogen levels after surgery because these patients are at an elevated risk of developing thrombosis. [5,6,7, 9] Data for the study was abstracted from the institutional electronic database. Institutional Review Board approval (institutional review board approval number: P00016625, approval date: 8/15/2022) with waiver of consent was obtained for this study. The following data were collected for each patients’ index hospitalization.

Cox proportional hazards model of thrombosis and primary outcomes. Cumulative incidence curves of Cox proportional hazards models of a postoperative ventilation time, b total hospital length of stay, and c total intensive care unit length of stay. Death was classified as a competing risk. The hazards ratio, 95% confidence interval, and corresponding p-value are also displayed

Preoperative data: included demographic data such as age and sex, as well as type of procedure and ventricular anatomy (single ventricle, biventricular, etc.). We included case complexity as determined by the Society of Thoracic Surgeons-European Association of Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Categories (STAT), [10] preoperative anticoagulant medications, preoperative renal and hepatic dysfunction, baseline hypercoagulable panel testing, and preoperative laboratory measurements. Baseline hypercoagulability testing results were available for all patients, and the presence of any coagulopathies were noted in patient charts. We also collected prior history of stroke or thrombosis, prior history of open-heart surgery, and the number of prior sternotomies.

Intraoperative data: included blood product usage categorized as yes or no and quantified as ml per kg. Our approach to transfusion involves all patients receiving cell saver. A second class of patients additionally receive platelets only. A third class of patients receive cell saver, platelets, and cryoprecipitate. A fourth class of patients receive cell saver, platelets, cryoprecipitate, and any of the following: packed red blood cells, fresh frozen plasma, and/or activated factor VIIa. Our approach to transfusion has not changed significantly in the past few years [12, 13].

Postoperative data: included postoperative adverse events, total hospital, and intensive care unit (ICU) length of stay, ventilation time (days), blood product usage, and hospital and blood product costs. All hospital and blood product costs reported were adjusted for inflation at the time of data abstraction.

Outcomes included postoperative ventilation time, total ICU and hospital length of stay, and hospital and blood product cost. The primary predictor for these outcomes was postoperative thrombosis following the congenital heart surgery. Additionally, we explored preoperative factors associated with postoperative thrombosis.

Postoperative thrombosis: Postoperative thrombosis was defined as clinically significant postoperative thrombosis diagnosed with imaging (intravascular or intracardiac thrombus) and/or requiring therapy (anticoagulation, surgical re-intervention, catheterization). We included both partial and total venous thrombosis, arterial thrombosis, and shunt thrombosis in our definition. Early-stage thrombosis was defined if diagnosed on or before 14 days from index surgery, and thrombosis that diagnosed at any time after 14 days following index surgery was classified as late-stage thrombosis. Thrombosis data was collected for each surgical encounter until discharge from the hospital.

STAT Categories [10]: These categories assign the risk of mortality associated with a particular procedure based on cumulative empiric data collected in the Society of Thoracic Surgery Congenital Heart Surgery database. The risk of mortality increases as procedure complexity increases, with mortality category one having the lowest and five the highest mortality risk [14]. We further categorized these mortality categories into low risk (mortality categories 1, 2, and 3; used as reference categories in univariable and multivariable models) and high risk (mortality categories 4, 5) due to the smaller sample size studied.

Preoperative Hypercoagulable panel tests: These tests look for hypercoagulable states such as Factor V Leiden mutations, prothrombin gene mutations, low levels of anti-thrombin III, protein C, and protein S, and high levels of fasting plasma homocysteine, lupus anticoagulant antibodies, and anti-cardiolipin antibodies. Hypercoagulability panel testing was routinely done for all patients before surgery as part of clinical care. Given our small sample size, age-appropriate cutoffs were not used. If multiple values were present, the preoperative value closest to the time of surgery was used. We classified each test as categorical “yes or no variables” and defined overall hypercoagulable state as having one or more of these hypercoagulable conditions. As indicated by Deitcher and Chan et al., positivity in any one of these tests is considered a hypercoagulable state. We therefore created a variable “preoperative hypercoagulable state” that is positive if any one of these tests is positive [15, 16].

Hospital costs: were defined as the total cost amount in dollars for the hospital stay of the patient for the index hospitalization. This data was provided by the financial operations department at our institution.

Postoperative adverse events: included extracorporeal membrane oxygenation, ventricular assist device use, cardiac arrest, renal dysfunction requiring dialysis, re-exploration for bleeding, unplanned cardiac reoperation, unplanned cardiac catheterization intervention, unplanned non-cardiac operation, stroke, and death as defined by the Society of Thoracic Surgeons Congenital Heart Surgery Database.

Categorical variables are summarized as numbers and percentages (%) and continuous variables are summarized as medians and interquartile ranges. Proportions and odds ratios are presented with 95% confidence intervals.

Associations with postoperative thrombosis were examined by univariable logistic regression for categorical variables and Wilcoxon rank sum tests for continuous variables. We then used multivariable logistic regression to identify factors associated with thrombosis, using forward selection with a p < 0.1 inclusion criteria. Cox proportional hazards model with death as a competing risk was used for time-to-event analysis of length of stays and postoperative ventilation duration, using forward selection with a p < 0.1 for inclusion criteria. We also accounted for collinearity and interactions. To analyze hospital costs, we used multivariable median regression with a forward selection algorithm. A sensitivity analysis was performed to explore baseline characteristics between early and late-stage thrombosis groups as well as any differences in blood products transfused intraoperatively. Chi-square and Wilcoxon rank sum tests were used for categorical and continuous variables, respectively.

A p-value of 0.05 or less was considered to be statistically significant. We analyzed all data using SAS version 9.4 (SAS Institute Inc., Cary, NC).