Recombinant Activated Factor VII in Aortic Surgery for Patients With Coagulation Disorders and Hypothermic Circulatory Arrest: a Single-center Retrospective Study

Recombinant Activated Factor VII in Aortic Surgery for Patients With Coagulation Disorders and Hypothermic Circulatory Arrest: a Single-center Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Recombinant Activated Factor VII in Aortic Surgery for Patients With Coagulation Disorders and Hypothermic Circulatory Arrest: a Single-center Retrospective Study Hayato Ise, Ryohei Ushioda, Hirotsugu Kanda, Fumiaki Kimura, Yasuaki Saijo, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-980459/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : We aimed to identify the risk factors of uncontrollable bleeding and investigate the safety of recombinant activated factor VII (rFVIIa) in aortic surgery under hypothermic circulatory arrest (ASHCA). Methods : The present single-center retrospective study compared the baseline characteristics of 144 patients who underwent ASHCA at our institute the total cohort. Of the 144 patients, 42 received rFVIIa (group rFVIIa), while the remaining 102 patients did not (group non-rFVIIa). Perioperative bleeding and transfusions, postoperative 30-day mortality, and adverse events (AEs) were analyzed in 29 propensity score-matched pairs. Results : Before surgery, the rFVIIa group demonstrated a greater number of shocks (p=0.019), higher JapanSCOREx II mortality rate (p=0.033), low platelet count (p=0.015), fibrinogen (p<0.001), prolonged activated partial thromboplastin time (p=0.005), prothrombin time international normalized ratio (p=0.006), and longer aortic cross cramp (ACC) time (p=0.049). Postoperative bleeding, transfusion, 30-day mortality, and AEs were comparable between the groups. Conclusions : Preoperative shock, higher JapanSCORE II mortality rates, low platelet and fibrinogen levels, prolonged aPTT and PT-INR, and longer ACC time might be risk factors for excessive bleeding and indicate the need for rFVIIa treatment. The present study suggests that rFVIIa can be safely used to address uncontrollable bleeding in ASHCA without inducing an increase in 30-day mortality and AEs. Cardiac & Cardiovascular Systems Cardiothoracic Surgery Aortic surgery under hypothermic circulatory arrest cardiac surgery recombinant activated factor VII retrospective study uncontrollable bleeding Background Management of bleeding is an important and often urgent concern for anesthesiologists and cardiac surgeons, especially during aortic surgery. Currently, hypothermic circulatory arrest (HCA) with cerebral perfusion is a safe standard strategy in thoracic aortic surgery to lower the incidence of perioperative stroke [ 1 – 4 ]. However, HCA causes coagulopathy because of both cardiopulmonary bypass (CPB) and hypothermia, which may result in life-threatening bleeding [ 5 , 6 ]. In such cases of bleeding, massive transfusion of packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelet concentrate (PC) is performed. Occasionally, the condition necessitates further administration of other hemostatic agents, such as fibrinogen concentrates, prothrombin complex, and recombinant activated factor VII (rFVIIa). However, researchers have not yet assessed the risk factors of such uncontrollable bleeding that necessitates rFVIIa treatment in aortic surgery under hypothermic circulatory arrest (ASHCA). rFVIIa was developed as a treatment agent for bleeding episodes in hemophilia. Nonetheless, its off-label use in cardiac surgery has increased since the first report in 2000 [ 7 ]. In 2008, rFVIIa was most frequently used in cardiac surgery (29%) and trauma (29%) in the USA, compared to its use foe hemophilia A and B (2.7%) [ 8 ]. Numerous studies have investigated the efficacy and safety of rFVIIa in cardiac surgery [ 9 , 10 ]. However, only few studies have focused on its off-label use in aortic surgery [ 1 , 12 ]. Furthermore, these studies only included patients with acute aortic dissection (AAD) or those who underwent aortic surgery without HCA. Therefore, the safety of rFVIIa for life-threatening bleeding in ASHCA remains unclear. Thus, we intended to identify the risk factors of uncontrollable bleeding in ASHCA and to elucidate the safety of off-label rFVIIa use for life-threatening bleeding events. Methods Study design and patient population We retrospectively analyzed 162 patients who underwent ASHCA between April 2014 and March 2019 at a single institution. Cases of redo and salvage surgeries (requiring cardiopulmonary resuscitation before surgery) were excluded. Of the remaining 144 patients, 42 patients received rFVIIa (group rFVIIa), while 102 patients did not (non-rFVIIa group). We analyzed the preoperative patient characteristics, perioperative bleeding and transfusions, postoperative AEs, and 30-day mortality. Postoperative 30-day mortality and thrombosis-related adverse events (AEs) were the primary endpoints. In contrast, postoperative bleeding and transfusions were the secondary endpoints. AEs were defined as follows: disabling stroke (postoperative persistent neurological deficits caused by thromboembolic events, confirmed by computed tomography (CT) scan or magnetic resonance imaging); minor stroke (postoperative temporary neurological deficits with recovery at discharge or at transfer to another hospital), and renal failure (serum creatinine >2.0 mg/dl and doubling of the preoperative value, or the new onset of hemodialysis). Myocardial infarction (MI), pulmonary embolism (PE), deep venous thrombosis, and other AEs were comprehensively diagnosed by physical examinations, laboratory tests, CT, electrocardiography, echocardiography, or color Doppler sonography (where appropriate). The Asahikawa Medical University Hospital approved the off-label use of rFVIIa. The Institutional Review Board of Asahikawa Medical University approved this study (No. 19078). While the need for informed consent for enrolment in this study was waived due to the retrospective study design, written informed consent to use rFVIIa had been obtained from the participants. Anesthetic Methods Once in the operating room, standard monitoring was performed using five-channel electrocardiography, pulse oximetry, and direct arterial or indirect blood pressure monitoring. General anesthesia was performed using the target-controlled intravenous infusion of propofol, continuous infusion of remifentanil, and single-dose administration of fentanyl. Propofol was infused to maintain a bispectral index within the range of 40–60. Sevoflurane or Desflurane were also administrated if the attending anesthesiologist judged it to be necessary. Rocuronium was administered to facilitate endotracheal intubation and to provide adequate muscle relaxation during surgery when necessary. After intubation, a central venous catheter and transesophageal echocardiography probe were inserted. After completing the surgical procedures, the patients were sedated using the continuous infusion of propofol and dexmedetomidine while intubated and were transported to the intensive care unit. Surgical Procedures Median sternotomy was performed in all cases. Before CPB, we administered heparin (300 U/kg) to maintain an activated clotting time of >480 s during CPB. CPB was established using bicaval venous cannulation. Arterial cannulation is generally performed at the level of the ascending aorta or femoral artery in some AAD cases. Following CPB establishment, mild (>28°C) to moderate (20.1-28°C) hypothermia was applied. Myocardial protection was achieved by antegrade or retrograde cardioplegia in cases of thoracic aortic aneurysm (TAA) or AAD, respectively. The ascending aorta was clamped and transected during systemic cooling, and proximal anastomosis of the aorta was performed. The rectal temperature upon reaching the target temperature induced HCA. Simultaneously, retrograde cerebral perfusion was initiated and eventually switched to antegrade selective cerebral perfusion by cannulation of the supra-aortic arch vessels. Moreover, the patients underwent distal anastomosis of the ascending aorta or aortic arch during the HCA. Following the end of the distal anastomosis, perfusion of the lower body was restarted from the side branch of the prosthesis, and rewarming was initiated. Moreover, anastomoses of the supra-aortic arch vessels were performed following distal anastomosis of the aorta in case of total arch replacement. Concomitant procedures were performed when required. Intraoperative and postoperative management of bleeding and transfusion Following weaning from CPB, heparin was antagonized by protamine administration (1:1 ratio to the applied heparin dosage). Subsequently, a transfusion was initiated. Hemoglobin <8 g/dL resulted in PRBC transfusion. Moreover, FFP was transfused upon detecting prolonged activated partial thromboplastin time (aPTT) or prothrombin time international normalized ratio (PT-INR). PC transfusion occurred when platelets (Plt) were <8 × 10 9 . In addition, the patients were administered cryoprecipitate when fibrinogen was <1.5 g/L. Fibrinogen <1.5 g/L following cryoprecipitate transfusion resulted in fibrinogen concentrate administration. rFVIIa was administered on observing continuous excessive bleeding despite the correction of surgical bleeding, pH, temperature, and adequate transfusion. Cryoprecipitate, fibrinogen concentrate, and rVIIa were only used in the operating room. After achieving adequate hemostasis in the operative field, as assessed by the surgeon, the patients were transferred to the intensive care unit (ICU). Re-exploration was considered in the ICU if the total bleeding amount from the chest tubes exceeded 400 mL/h regardless of adequate transfusion. Statistical analyses While the categorical variables are presented as numbers and percentages, the continuous variables are presented as medians. We performed propensity score matching (PSM) to balance the risk factors for outcomes between the groups. The propensity score (PS) was obtained from a logistic regression model, including variables presented in Table 1 , except for concomitant surgery and JapanSCORE II. JapanSCORE II was not considered for PS because it represents the risk-adjusted mortality and preoperatively expected morbidity, based on the Japan Cardiovascular Surgery Database (JCVSD) [ 13 ]. Patients were matched 1:1 using the nearest neighbor matching method without replacement, and a caliper width of 0.2 of the standard deviation of the logit of the estimated PS. This resulted in 29 out of the possible 42 pairs. We calculated standardized mean differences before and after PSM to assess the balance of variables between the groups. Unmatched sub-cohorts were compared using the Fischer’s exact test Mann-Whitney U test for categorical and continuous variables, respectively. Following PSM, we performed the McNemar test and Wilcoxon signed rank test for the categorical and continuous variables, respectively. PSM was performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) [ 14 ]. All other statistical analyses were performed using SPSS for Windows (version 26.0; IBM Corp., Armonk, NY, USA). We analyzed the baseline characteristics in an unmatched population. Perioperative bleeding, transfusion, and postoperative outcomes were analyzed in the matched population. The statistical significance was defined as p<0.05. Table 1 Baseline and operative characteristics Before matching After matching Characteristic rFVIIa (n=42) non-rFVIIa (n=102) p-value SMD rFVIIa (n=29) non-rFVIIa (n=29) p-value SMD Age (yr) 76.5 (69.5, 82.3) 73.5 (66.0, 79.0) 0.065 0.150 75.0 (65.0, 81.0) 78.0 (68.5, 80.5) 0.820 0.192 Sex (Male) 24 (57.1) 57 (55.9) 1.000 0.025 17 (58.6) 18 (62.1) 1.000 0.071 Body mass index (kg/m 2 ) 23.1 (19.8, 26.8) 22.8 (20.8, 26.3) 0.610 0.180 23.1 (20.4, 27.3) 21.5 (20.0, 24.7) 0.370 0.237 AAD / TAA 27 (64.3) / 15 (35.7) 53 (52.0) / 49 (48.0) 0.200 0.252 16 (55.2) / 13 (44.8) 16 (55.2) / 13 (44.8) 1.000 < 0.001 Emergency surgery 27 (64.3) 51 (50.0) 0.142 0.292 16 (55.2) 17 (58.6) 1.000 0.07 Malperfusion 5 (11.9) 9 (8.8) 0.550 0.101 3 (10.3) 2 (6.9) 1.000 0.123 Shock (requiring hemodynamic support) 6 (14.3) 3 (2.9) 0.019 0.413 3 (10.3) 2 (6.9) 1.000 0.123 Cardiac tamponade 8 (19.0) 8 (7.8) 0.077 0.333 5 (17.2) 6 (20.7) 1.000 0.088 GCS <8 1 (2.4) 3 (2.9) 1.000 0.035 1 (3.4) 2 (6.9) 1.000 0.156 Smoking 7 (16.7) 27 (26.5) 0.281 0.240 5 (17.2) 5 (17.2) 1.000 < 0.001 Hypertension 33 (78.6) 78 (76.5) 0.831 0.050 24 (82.8) 24 (82.8) 1.000 < 0.001 Diabetes mellitus 7 (16.7) 12 (11.8) 0.428 0.141 5 (17.2) 6 (20.7) 1.000 0.088 Liver dysfunction 6 (14.3) 8 (7.8) 0.234 0.206 3 (10.3) 4 (13.8) 1.000 0.106 Anticoagulant treatment 5 (11.9) 10 (9.8) 0.766 0.068 2 (6.9) 3 (10.3) 1.000 0.123 Antiplatelet treatment 7 (16.7) 17 (16.7) 1.000 <0.001 6 (20.7) 7 (24.1) 1.000 0.083 JapanSCORE II 30-day mortality (%) 8.4 (5.6, 14.0) 6.1 (3.9, 10.2) 0.033 0.355 6.9 (4.3, 11.1) 7.1 (4.4, 13.5) 0.665 0.088 Hemoglobin (g/dl) 11.5 (10.0, 13.6) 12.5 (10.8, 14.0) 0.092 0.285 11.9 (10.0, 13.7) 11.7 (10.2, 13.6) 0.811 0.101 Platelet count (10 9 /L) 157 (124, 188) 177 (142, 213) 0.015 0.401 158 (126, 179) 168 (130, 188) 0.787 0.074 APTT (sec) 31.2 (27.4, 37.7) 28.4 (26.2, 31.9) 0.005 0.284 31.1 (27.5, 35.2) 30.3 (27.2, 34.8) 0.795 0.190 PT-INR 1.07 (1.00, 1.24) 1.02 (0.96, 1.10) 0.006 0.314 1.05 (0.98, 1.18) 1.06 (1.00, 1.14) 0.964 0.056 Fibrinogen (g/L) 2.43 (1.62, 2.96) 2.90 (2.46, 3.91) <0.001 0.668 2.64 (1.77, 3.29) 2.45 (2.21, 2.97) 0.922 0.053 Serum creatinine (mg/dl) 0.94 (0.72, 1.11) 0.87 (0.70, 1.10) 0.427 0.149 0.94 (0.75, 1.12) 1.00 (0.78, 1.25) 0.160 0.195 Surgery Primary procedure 0.146 0.274 1.000 < 0.001 Total arch replacement 19 (45.2) 60 (58.8) 14 (48.3) 14 (48.3) Hemiarch replacement 23 (54.8) 42 (41.2) 15 (51.7) 15 (51.7) Concomitant procedure 14 (33.3) 26 (25.5) 0.413 0.173 9 (31.0) 8 (27.6) 1.000 0.076 None 28 (66.7) 76 (74.5) 20 (69.0) 21 (72.4) AVR or AVP 3 (7.1) 4 (3.9) 2 (6.9) 2 (6.9) Bentall 2 (4.8) 1 (1.0) 1 (3.4) 0 (0) David 3 (7.1) 7 (6.9) 2 (6.9) 3 (10.3) CABG 7 (16.7) 11 (10.8) 4 (13.8) 3 (10.3) Others 0 (0) 3 (2.9) 0 (0) 0 (0) CPB time (min) 169 (145, 230) 169 (142, 192) 0.136 0.437 161 (136, 227) 177 (136, 216) 0.754 0.084 ACC time (min) 110 (88, 146) 97 (79, 121) 0.049 0.376 102 (80, 141) 110 (75, 123) 0.462 0.119 Lowest rectal Temperature (°C) 27.5 (25.7, 27.9) 26.1 (25.3, 27.6) 0.043 0.421 27.4 (25.6, 27.9) 26.6 (25.4, 27.8) 0.546 0.183 HCA time (min) 40 (28, 49) 39.5 (29.0, 53.0) 0.986 0.094 40 (28, 50) 36 (25, 56) 0.829 0.039 AAD, acute aortic dissection; ACC, aortic cross clamp; APTT, activated partial thromboplastin time; AVP, aortic valvuloplasty; AVR, aortic valve replacement; CABG, coronary artery bypass grafting; CPB, cardiopulmonary bypass; GCS, Glasgow Coma Scale; HCA, hypothermic circulatory arrest; PT-INR, prothrombin time international normalized ratio; rFVIIa, recombinant activated factor VII; SMD, standardized mean difference; and TAA, thoracic aortic aneurysm. Results Baseline and operative characteristics Table 1 summarizes the baseline and operative characteristics. Before PSM, the number of shock patients (p=0.019) and JapanSCORE II 30-day mortality rates (p=0.033) were significantly higher in the rFVIIa group. While Plt (p=0.015) and fibrinogen (p<0.001) were significantly lower, aPTT (p=0.005) and PT-INR (p=0.006) were prolonged in the rFVIIa group. The rFVIIa group demonstrated longer ACC time (p=0.049) and higher lowest body temperature (p=0.043). Following PSM, none of the characteristics were significantly different between the groups. Perioperative bleeding and transfusion Table 2 summarizes the perioperative amounts of bleeding and transfusion. Intraoperative bleeding (p=0.012), PRBC transfusion (p=0.048), and FFP (p=0.021) were significantly higher in the rFVIIa group. Patients in the rFVIIa group received a significantly greater amount of fibrinogen concentrate (p<0.001). The median intraoperative dose of rFVIIa was 56 µg/kg. In addition, the postoperative amount of bleeding and transfusion was comparable between the groups. Table 2 Perioperative bleeding and blood products in the propensity-score matched populations Characteristic rFVIIa (n=29) non-rFVIIa (n=29) p-value Bleeding intra-operation (ml) 6773 (4019, 10185) 3639 (2399, 6627) 0.012 PRBC intra-operation (unit) 26 (19, 34) 20 (12, 24) 0.048 FFP intra-operation (unit) 34 (20, 46) 24 (18, 32) 0.021 PC intra-operation (unit) 55 (40, 60) 40 (40, 60) 0.472 Cryoprecipitate intra-operation (unit) 12 (12, 24) 12 (12, 12) 0.405 rFVIIa (µg/kg) 56 (32, 83) - Fibrinogen concentrate (g) 3 (0, 3) 0 (0, 0) <0.001 Bleeding until 12hr (ml) 790 (490, 1470) 740 (540, 1233) 0.071 PRBC until 12hr (unit) 2 (0, 6) 2 (0, 5) 0.370 FFP until 12hr (unit) 6 (4, 9) 6 (4, 8) 0.576 PC until 12hr (unit) 0 (0, 20) 0 (0, 10) 0.967 FFP: fresh frozen plasma, PC: platelet concentrates, and PRBC: packed red blood cells. Mortality and postoperative adverse events Table 3 outlines the postoperative outcomes. The rFVIIa group manifested significantly lower Plt (p<0.001) and shorter PT-INR (p<0.001). There were no significant differences between the groups, with regard to the primary and secondary endpoints. Thirty-day mortality rate was 3.4% in both the groups. We observed stroke in one patient (3.4%) in both groups. There were no cases of MI or PE. The re-exploration rate was comparable (13.8% vs. 10.3%). Table 3 Postoperative data and complications in the propensity-score matched populations Characteristic rFVIIa (n=29) non-rFVIIa (n=29) p-value Hemoglobin (g/dl) 10.6 (9.0, 11.5) 10.5 (9.5, 11.8) 0.381 Platelet count (10 9 /L) 97 (73, 137) 142 (106, 169) <0.001 APTT (sec) 45.2 (33.6, 55.1) 37.1 (33.4, 44.0) 0.206 PT-INR 0.86 (0.81, 1.03) 1.13 (1.08, 1.18) <0.001 Fibrinogen (g/L) 2.10 (1.79, 2.59) 2.39 (2.06, 2.69) 0.846 Serum creatinine (mg/dl) 1.21 (0.94, 1.72) 1.10 (0.83, 1.63) 0.226 Intubation time (h) 25 (12, 96) 16 (10, 42) 0.991 Deep sternal wound infection 1 (3.4) 0 (0) 1.000 Septicemia 0 (0) 1 (3.4) 1.000 Renal failure 1 (3.4) 3 (10.3) 0.500 Paraparesis 1 (3.4) 1 (3.4) 1.000 Deep venous thrombosis 0 (0) 1 (3.4) 1.000 Pulmonary embolism 0 (0) 0 (0) Myocardial infarction 0 (0) 0 (0) Stroke 1 (3.4) 1 (3.4) 1.000 Minor stroke 1 (3.4) 0 (0) 1.000 Disabling stroke 0 (0) 1 (3.4) 1.000 Cardiac tamponade 0 (0) 1 (3.4) 1.000 Re-exploration 4 (13.8) 3 (10.3) 1.000 30-day mortality 1 (3.4) 1 (3.4) 1.000 APTT, activated partial thromboplastin time; PT-INR, prothrombin time international normalized ratio; and rFVIIa, recombinant activated factor VII. Discussion Few studies have reported on the off-label use of rFVIIa in aortic surgery, with no previous study focusing on the safety of rFVIIa in ASHCA. 10,11 However, the high possibility of massive bleeding necessitates an evaluation of the safety of off-label rFVIIa use in ASHCA. The crucial findings of the present study were as follows: (i) preoperative shock, coagulopathic state in laboratory tests, higher JapanSCORE II 30-day mortality rate, and longer ACC time might be associated with excessive bleeding in ASHCA and (ii) rFVIIa application did not result in a significant increase in the postoperative 30-day mortality and AEs in ASHCA. Preoperative shock and coagulopathy increased the risk of intraoperative bleeding, which might require rFVIIa administration. Preoperative shock in our patients was primarily caused by AAD or ruptured TAA. The aforementioned pathologies cause coagulopathy. Guan et al. reported that intense prothrombin generation and excessive systemic fibrinolysis occur in AAD before surgery, thereby leading to prolonged consumption coagulopathy, excessive bleeding, and complications [ 15 ]. Researchers have also described coagulopathy in aortic aneurysms with increased intensity upon rupture [ 16 ]. The rFVIIa group demonstrated significantly lower Plt and fibrinogen levels, prolonged aPTT, and PT-INR before PSM. This resulted in a significantly greater amount of intraoperative bleeding and transfusion. JapanSCORE II is a calculated operative risk similar to EuroSCORE. However, it is based on JCVSD. JapanSCORE II more precisely reflects operative risk in Japan than EuroSCORE [ 17 ]. In the present study, the higher frequency of AAD, emergent surgery, and shock might result in higher operative risk in the rFVIIa group. Despite a lower actual mortality rate than the calculated value, JapanSCORE II appeared to be a reliable risk predictor. The clinical impact of HCA-induced coagulopathy is well known. However, the underlying mechanism is still unclear. Hypothermia and CPB are factors that cause coagulopathy. However, several studies have reported that the lowest body temperature is not associated with bleeding [ 2 , 4 ]. In the present study, the lowest temperature was significantly higher in the rFVIIa group. Nevertheless, intraoperative bleeding was significantly higher in the rFVIIa group than that in the control group. In other words, the lowest temperature was not strongly associated with coagulopathy. Meanwhile, the ACC time in the present study was significantly longer and supposedly associated with excessive bleeding. There are few reports on the relationship between coagulopathy and ACC. Moreover, longer ACC reportedly causes both fibrinogen consumption and accumulation of tissue plasminogen activator. Nonetheless, the underlying mechanism is unclear [ 18 ]. The efficacy of off-label rFVIIa use has been repeatedly reported. However, most of the latter studies involved patients who underwent cardiac surgery [ 7 – 10 ], where the efficacy was demonstrated with respect to the amount of perioperative bleeding, transfusion, and re-exploration [ 7 – 10 ]. However, a previous study on AAD surgery reported on significantly greater perioperative bleeding, transfusion, and re-exploration, following rFVIIa administration [ 11 ]. In the present study, the rFVIIa group demonstrated significantly higher intraoperative bleeding and transfusion, in addition to significantly lower postoperative Plt. The severity of coagulopathy in ASHCA is expectedly much higher than that in general cardiac surgery. Therefore, consumption coagulopathy may have persisted even after rFVIIa treatment. According to Paparella et al., intense thrombin generation in patients with AAD stimulates platelet activation and dysfunction, and promotes coagulation factor consumption and excessive fibrinolysis, which collectively result in excessive bleeding [ 19 ]. Consumption coagulopathy and platelet dysfunction have been not only reported in AAD but also in TAA [ 20 ]. Patients in the rFVIIa group in ASHCA might continue to suffer from life-threatening bleeding and require a greater amount of transfusion if not treated with rFVIIa. Therefore, rFVIIa in ASHCA plays an important role in rescue therapy. The safety of rFVIIa is still unclear and depends on several factors, such as patient characteristics, transfusion, and the dose of rFVIIa applied. A randomized trial reported on no significant increase in mortality, rather a numeric increase in AEs [ 9 ]. Alferevic et al. reported on higher mortality and renal morbidity in the rFVIIa group [ 21 ]. The aforementioned studies focused on complex cardiac surgery. Other studies on AAD or aortic surgery demonstrated no significant increase in postoperative mortality or AEs [ 11 , 12 ]. Intense thrombin generation in ASHCA causes platelet dysfunction, consumptive coagulopathy, and excessive fibrinolysis. Based on the above-mentioned factors, a low frequency of thromboembolic AEs might result from rFVIIa therapy in aortic surgery. The safety dose or optimal protocol for rFVIIa in cardiac surgery is still unknown. Researchers have reported on the safety and efficacy of a dose ranging between 35 µg/kg to 70 µg/kg in general cardiac surgery [ 22 ]. Several studies have described the efficacy of low-dose rFVIIa <20 µg/kg [ 10 ]. However, considering the severity of coagulopathy in ASHCA, a higher dose may also be acceptable. A dose <90 µg/kg is considered safe in patients without hemophilia [ 23 ]. In the present study, the median dose of rFVIIa was 56 µg/kg, and patients did not demonstrate an increase in mortality or thromboembolic AEs. We administered rFVIIa following the correction of other hemostatic parameters, which was in compliance with current recommendations [ 22 ]. Our study had several limitations. This was a single-center, retrospective, observational study with a small sample size. We performed PSM based on different characteristics before rFVIIa treatment. Nevertheless, there were several unmeasured confounders. In addition, we observed a difference in intraoperative transfusions, which might have affected the amount of intraoperative bleeding and rFVIIa administration. However, it was impossible to equalize the number of intraoperative transfusions because of the retrospective observational study design. Despite the aforementioned limitations, this is the first study to focus on the use of rFVIIa in ASHCA. Conclusion Preoperative shock, higher JapanSCORE II mortality rates, low Plt and fibrinogen, prolonged aPTT and PT-INR, and longer ACC time might be risk factors for excessive bleeding, thus necessitating rFVIIa treatment. The present study suggests that rFVIIa can be safely used for uncontrollable bleeding in ASHCA, without an increase in 30-day mortality and AEs. Further prospective randomized studies are required. List of abbreviations AAD, acute aortic dissection; AEs, adverse events; aPTT, activated partial thromboplastin time; ASHCA, aortic surgery under hypothermic circulatory arrest; CPB, cardiopulmonary bypass; CT, computed tomography; FFP, fresh frozen plasma; HCA, hypothermic circulatory arrest; ICU, intensive care unit; JCVSD, Japan Cardiovascular Surgery Database; MI, myocardial infarction; PC, platelet concentrate; PE, pulmonary embolism; Plt, platelets; PRBC, packed red blood cells; PS, propensity score; PSM, propensity score matching; PT-INR, prothrombin time international normalized ratio; rFVIIa, recombinant activated factor VII; TAA, thoracic aortic aneurysm. Declarations Ethics approval and consent to participate The Institutional Review Board of Asahikawa Medical University approved this study (No. 19078). While the need for informed consent for enrolment in this study was waived due to the retrospective study design. Consent for publication Not applicable Availability of data and materials Competing interests The authors declare that they have no competing interests. Funding None. Authors' contributions HI contributed to data collection and drafting of the manuscript. RU contributed to data collection. HK (Hirotsugu Kanda) conceived the study and revised the manuscript. FK contributed to data interpretation. YS provided expert consultation on statistical analysis. PA and AL contributed to conception of the study design and data interpretation. HK (Hiroyuki Kamiya) supervised the project. All authors read and approved the final manuscript. Acknowledgements HI is supported by a research fellowship award from the Japanese Society on Thrombosis and Haemostasis. References Gupta P, Harky A, Jahangeer S, Adams B, Bashir M. Varying evidence on deep hypothermic circulatory arrest in thoracic aortic aneurysm surgery. Tex Heart Inst J. 2018;45:70-5. Keenan JE, Wang H, Gulack BC, Ganapathi AM, Andersen ND, Englum BR, et al. Does moderate hypothermia really carry less bleeding risk than deep hypothermia for circulatory arrest? A propensity-matched comparison in hemiarch replacement. J Thorac Cardiovasc Surg. 2016;152:1559-69. Kamiya H, Hagl C, Kropivnitskaya I, Böthig D, Kallenbach K, Khaladj N, et al. The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: a propensity score analysis. J Thorac Cardiovasc Surg. 2007;133:501-9. Keeling WB, Tian DH, Leshnower BG, Ganapathi AM, Andersen ND, Englum BR, et al. Safety of Moderate Hypothermia With Antegrade Cerebral Perfusion in Total Aortic Arch Replacement. Ann Thorac Surg. 2018;105:54-61. Harrington DK, Lilley JP, Rooney SJ, Bonser RS. Nonneurologic morbidity and profound hypothermia in aortic surgery. Ann Thorac Surg. 2004;78:596-601. Ise H, Kitahara H, Oyama H, Takahashi K, Kanda H, Fujii S, et al. Hypothermic circulatory arrest induced coagulopathy: rotational thromboelastometry analysis. Gen Thorac Cardiovasc Surg. 2020;68:754-61. Al Douri M, Shafi T, Al Khudairi D, Al Bokhari E, Black L, Akinwale N, et al. Effect of the administration of recombinant activated factor VII (rFVIIa; NovoSeven®) in the management of severe uncontrolled bleeding in patients undergoing heart valve replacement surgery. Blood Coagul Fibrinolysis. 2000;11 Suppl 1:S121-7. Yank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, et al. Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care. Rockville (MD): Agency for Healthcare Research and Quality (US) May 2010; Report No.: 10-EHC030-EF. Gill R, Herbertson M, Vuylsteke A, Olsen PS, von Heymann C, Mythen M, et al. Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation. 2009;120:21-7. Hoffmann T, Assmann A, Dierksen A, Roussel E, Ullrich S, Lichtenberg A, et al. A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study. J Thorac Cardiovasc Surg. 2018;156:1564-73. Zindovic I, Sjögren J, Ahlsson A, Bjursten H, Fuglsang S, Geirsson A, et al. Recombinant factor VIIa use in acute type A aortic dissection repair: A multicenter propensity-score-matched report from the Nordic Consortium for Acute Type A Aortic Dissection. J Thorac Cardiovasc Surg. 2017;154:1852-9. Goksedef D, Panagopoulos G, Nassiri N, Levine RL, Hountis PG, Plestis KA. Intraoperative use of recombinant activated factor VII during complex aortic surgery. J Thorac Cardiovasc Surg. 2012;143:1198-204. Takamoto S, Motomura N, Miyata H, Tsukihara H. Current status of cardiovascular surgery in Japan, 2013 and 2014: A report based on the Japan Cardiovascular Surgery Database (JCVSD). 1: Mission and history of JCVSD. Gen Thorac Cardiovasc Surg. 2018;66:1-3. Kanda Y. Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant. 2013;48:452-8. Guan X, Li J, Gong M, Lan F, Zhang H. The hemostatic disturbance in patients with acute aortic dissection: A prospective observational study. Medicine 2016;95:e4710. Davies RS, Abdelhamid M, Wall ML, Vohra RK, Bradbury AW, Adam DJ. Coagulation, fibrinolysis, and platelet activation in patients undergoing open and endovascular repair of abdominal aortic aneurysm. J Vasc Surg. 2011;54:865-78. Kurazumi H, Mikamo A, Fukamitsu G, Kudou T, Sato M, Suzuki R, et al. Validation of the JapanSCORE versus the logistic EuroSCORE for predicting operative mortality of cardiovascular surgery in Yamaguchi University Hospital. Gen Thorac Cardiovasc Surg. 2011;59:599-604. Haithcock BE, Shepard AD, Raman SB, Conrad MF, Pandurangi K, Fanous NH. Activation of fibrinolytic pathways is associated with duration of supraceliac aortic cross-clamping. J Vasc Surg. 2004;40:325-33. Paparella D, Rotunno C, Guida P, Malvindi PG, Scrascia G, De Palo M, et al. Hemostasis alterations in patients with acute aortic dissection. Ann Thorac Surg. 2011;91:1364-9. Tanaka M, Kawahito K, Adachi H, Ino T. Platelet dysfunction in acute type A aortic dissection evaluated by the laser light-scattering method. J Thorac Cardiovasc Surg. 2003;126:837-41. Alfirevic A, Duncan A, You J, Lober C, Soltesz E. Recombinant factor VII is associated with worse survival in complex cardiac surgical patients. Ann Thorac Surg. 2014;98:618-24. Fitzgerald J, McMonnies R, Sharkey A, Gross PL, Karkouti K. Thrombin generation and bleeding in cardiac surgery: a clinical narrative review. Génération de thrombine et saignements en chirurgie cardiaque : un compte rendu narratif clinique. Can J Anaesth. 2020;67:746-53. Hsia CC, Chin-Yee IH, McAlister VC. Use of recombinant activated factor VII in patients without hemophilia: a meta-analysis of randomized control trials. Ann Surg. 2008;248:61-8. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-980459","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":57366757,"identity":"aedc3407-3039-4e1b-932d-954181d271b0","order_by":0,"name":"Hayato Ise","email":"","orcid":"","institution":"Asahikawa Medical University: Asahikawa Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hayato","middleName":"","lastName":"Ise","suffix":""},{"id":57366758,"identity":"d99147f0-dd89-424e-9ea2-f3a65c38d90d","order_by":1,"name":"Ryohei Ushioda","email":"","orcid":"","institution":"Asahikawa Medical University: Asahikawa Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ryohei","middleName":"","lastName":"Ushioda","suffix":""},{"id":57366759,"identity":"f67fe676-a813-4d79-9ee4-f47df936b786","order_by":2,"name":"Hirotsugu Kanda","email":"data:image/png;base64,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","orcid":"","institution":"Asahikawa Medical University: Asahikawa Ika Daigaku","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Hirotsugu","middleName":"","lastName":"Kanda","suffix":""},{"id":57366760,"identity":"75f58e3a-4881-485d-b55c-232e939bf47c","order_by":3,"name":"Fumiaki Kimura","email":"","orcid":"","institution":"Kushiro Kojinkai Memorial Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fumiaki","middleName":"","lastName":"Kimura","suffix":""},{"id":57366761,"identity":"494f7ef5-153d-4bff-a974-d25cf23a6abc","order_by":4,"name":"Yasuaki Saijo","email":"","orcid":"","institution":"Asahikawa Medical University: Asahikawa Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yasuaki","middleName":"","lastName":"Saijo","suffix":""},{"id":57366762,"identity":"8ea1c0e8-deda-41c5-a39f-1e6462df1f3e","order_by":5,"name":"Payam Akhyari","email":"","orcid":"","institution":"Heinrich Heine University Düsseldorf: Heinrich-Heine-Universitat Dusseldorf","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Payam","middleName":"","lastName":"Akhyari","suffix":""},{"id":57366763,"identity":"88ed9875-d8e7-4914-b669-aafce711d7b9","order_by":6,"name":"Artur Lichtenberg","email":"","orcid":"","institution":"Heinrich Heine University Düsseldorf: Heinrich-Heine-Universitat Dusseldorf","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Artur","middleName":"","lastName":"Lichtenberg","suffix":""},{"id":57366764,"identity":"c996322f-99cf-47e8-9467-af90fbf35cc0","order_by":7,"name":"Hiroyuki Kamiya","email":"","orcid":"","institution":"Asahikawa Medical University: Asahikawa Ika Daigaku","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hiroyuki","middleName":"","lastName":"Kamiya","suffix":""}],"badges":[],"createdAt":"2021-10-16 07:59:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-980459/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-980459/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":15983521,"identity":"bf0a5850-ff14-4ebf-b708-9e612f9cb356","added_by":"auto","created_at":"2021-11-29 21:31:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":387947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-980459/v1/7a187713-d5ab-4ee4-81e1-046f9dd8026e.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eRecombinant Activated Factor VII in Aortic Surgery for Patients With Coagulation Disorders and Hypothermic Circulatory Arrest: a Single-center Retrospective Study\u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eManagement of bleeding is an important and often urgent concern for anesthesiologists and cardiac surgeons, especially during aortic surgery. Currently, hypothermic circulatory arrest (HCA) with cerebral perfusion is a safe standard strategy in thoracic aortic surgery to lower the incidence of perioperative stroke [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, HCA causes coagulopathy because of both cardiopulmonary bypass (CPB) and hypothermia, which may result in life-threatening bleeding [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In such cases of bleeding, massive transfusion of packed red blood cells (PRBC), fresh frozen plasma (FFP), and platelet concentrate (PC) is performed. Occasionally, the condition necessitates further administration of other hemostatic agents, such as fibrinogen concentrates, prothrombin complex, and recombinant activated factor VII (rFVIIa). However, researchers have not yet assessed the risk factors of such uncontrollable bleeding that necessitates rFVIIa treatment in aortic surgery under hypothermic circulatory arrest (ASHCA).\u003c/p\u003e \u003cp\u003erFVIIa was developed as a treatment agent for bleeding episodes in hemophilia. Nonetheless, its off-label use in cardiac surgery has increased since the first report in 2000 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In 2008, rFVIIa was most frequently used in cardiac surgery (29%) and trauma (29%) in the USA, compared to its use foe hemophilia A and B (2.7%) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Numerous studies have investigated the efficacy and safety of rFVIIa in cardiac surgery [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, only few studies have focused on its off-label use in aortic surgery [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Furthermore, these studies only included patients with acute aortic dissection (AAD) or those who underwent aortic surgery without HCA. Therefore, the safety of rFVIIa for life-threatening bleeding in ASHCA remains unclear.\u003c/p\u003e \u003cp\u003eThus, we intended to identify the risk factors of uncontrollable bleeding in ASHCA and to elucidate the safety of off-label rFVIIa use for life-threatening bleeding events.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n\u003ch2\u003eStudy design and patient population\u003c/h2\u003e\n\u003cp\u003eWe retrospectively analyzed 162 patients who underwent ASHCA between April 2014 and March 2019 at a single institution. Cases of redo and salvage surgeries (requiring cardiopulmonary resuscitation before surgery) were excluded. Of the remaining 144 patients, 42 patients received rFVIIa (group rFVIIa), while 102 patients did not (non-rFVIIa group). We analyzed the preoperative patient characteristics, perioperative bleeding and transfusions, postoperative AEs, and 30-day mortality. Postoperative 30-day mortality and thrombosis-related adverse events (AEs) were the primary endpoints. In contrast, postoperative bleeding and transfusions were the secondary endpoints. AEs were defined as follows: disabling stroke (postoperative persistent neurological deficits caused by thromboembolic events, confirmed by computed tomography (CT) scan or magnetic resonance imaging); minor stroke (postoperative temporary neurological deficits with recovery at discharge or at transfer to another hospital), and renal failure (serum creatinine \u0026gt;2.0 mg/dl and doubling of the preoperative value, or the new onset of hemodialysis). Myocardial infarction (MI), pulmonary embolism (PE), deep venous thrombosis, and other AEs were comprehensively diagnosed by physical examinations, laboratory tests, CT, electrocardiography, echocardiography, or color Doppler sonography (where appropriate).\u003c/p\u003e\n\u003cp\u003eThe Asahikawa Medical University Hospital approved the off-label use of rFVIIa. The Institutional Review Board of Asahikawa Medical University approved this study (No. 19078). While the need for informed consent for enrolment in this study was waived due to the retrospective study design, written informed consent to use rFVIIa had been obtained from the participants.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003ch2\u003eAnesthetic Methods\u003c/h2\u003e\n\u003cp\u003eOnce in the operating room, standard monitoring was performed using five-channel electrocardiography, pulse oximetry, and direct arterial or indirect blood pressure monitoring. General anesthesia was performed using the target-controlled intravenous infusion of propofol, continuous infusion of remifentanil, and single-dose administration of fentanyl. Propofol was infused to maintain a bispectral index within the range of 40\u0026ndash;60. Sevoflurane or Desflurane were also administrated if the attending anesthesiologist judged it to be necessary. Rocuronium was administered to facilitate endotracheal intubation and to provide adequate muscle relaxation during surgery when necessary. After intubation, a central venous catheter and transesophageal echocardiography probe were inserted. After completing the surgical procedures, the patients were sedated using the continuous infusion of propofol and dexmedetomidine while intubated and were transported to the intensive care unit.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n\u003ch2\u003eSurgical Procedures\u003c/h2\u003e\n\u003cp\u003eMedian sternotomy was performed in all cases. Before CPB, we administered heparin (300 U/kg) to maintain an activated clotting time of \u0026gt;480 s during CPB. CPB was established using bicaval venous cannulation. Arterial cannulation is generally performed at the level of the ascending aorta or femoral artery in some AAD cases. Following CPB establishment, mild (\u0026gt;28\u0026deg;C) to moderate (20.1-28\u0026deg;C) hypothermia was applied. Myocardial protection was achieved by antegrade or retrograde cardioplegia in cases of thoracic aortic aneurysm (TAA) or AAD, respectively. The ascending aorta was clamped and transected during systemic cooling, and proximal anastomosis of the aorta was performed. The rectal temperature upon reaching the target temperature induced HCA. Simultaneously, retrograde cerebral perfusion was initiated and eventually switched to antegrade selective cerebral perfusion by cannulation of the supra-aortic arch vessels. Moreover, the patients underwent distal anastomosis of the ascending aorta or aortic arch during the HCA. Following the end of the distal anastomosis, perfusion of the lower body was restarted from the side branch of the prosthesis, and rewarming was initiated. Moreover, anastomoses of the supra-aortic arch vessels were performed following distal anastomosis of the aorta in case of total arch replacement. Concomitant procedures were performed when required.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n\u003ch2\u003eIntraoperative and postoperative management of bleeding and transfusion\u003c/h2\u003e\n\u003cp\u003eFollowing weaning from CPB, heparin was antagonized by protamine administration (1:1 ratio to the applied heparin dosage). Subsequently, a transfusion was initiated. Hemoglobin \u0026lt;8 g/dL resulted in PRBC transfusion. Moreover, FFP was transfused upon detecting prolonged activated partial thromboplastin time (aPTT) or prothrombin time international normalized ratio (PT-INR). PC transfusion occurred when platelets (Plt) were \u0026lt;8 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e. In addition, the patients were administered cryoprecipitate when fibrinogen was \u0026lt;1.5 g/L. Fibrinogen \u0026lt;1.5 g/L following cryoprecipitate transfusion resulted in fibrinogen concentrate administration. rFVIIa was administered on observing continuous excessive bleeding despite the correction of surgical bleeding, pH, temperature, and adequate transfusion. Cryoprecipitate, fibrinogen concentrate, and rVIIa were only used in the operating room. After achieving adequate hemostasis in the operative field, as assessed by the surgeon, the patients were transferred to the intensive care unit (ICU). Re-exploration was considered in the ICU if the total bleeding amount from the chest tubes exceeded 400 mL/h regardless of adequate transfusion.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n\u003ch2\u003eStatistical analyses\u003c/h2\u003e\n\u003cp\u003eWhile the categorical variables are presented as numbers and percentages, the continuous variables are presented as medians. We performed propensity score matching (PSM) to balance the risk factors for outcomes between the groups. The propensity score (PS) was obtained from a logistic regression model, including variables presented in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, except for concomitant surgery and JapanSCORE II. JapanSCORE II was not considered for PS because it represents the risk-adjusted mortality and preoperatively expected morbidity, based on the Japan Cardiovascular Surgery Database (JCVSD) [\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]. Patients were matched 1:1 using the nearest neighbor matching method without replacement, and a caliper width of 0.2 of the standard deviation of the logit of the estimated PS. This resulted in 29 out of the possible 42 pairs. We calculated standardized mean differences before and after PSM to assess the balance of variables between the groups. Unmatched sub-cohorts were compared using the Fischer\u0026rsquo;s exact test Mann-Whitney U test for categorical and continuous variables, respectively. Following PSM, we performed the McNemar test and Wilcoxon signed rank test for the categorical and continuous variables, respectively. PSM was performed using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) [\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]. All other statistical analyses were performed using SPSS for Windows (version 26.0; IBM Corp., Armonk, NY, USA). We analyzed the baseline characteristics in an unmatched population. Perioperative bleeding, transfusion, and postoperative outcomes were analyzed in the matched population. The statistical significance was defined as p\u0026lt;0.05.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eBaseline and operative characteristics\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eBefore matching\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eAfter matching\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCharacteristic\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003erFVIIa (n=42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enon-rFVIIa (n=102)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSMD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003erFVIIa (n=29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003enon-rFVIIa (n=29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSMD\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge (yr)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e76.5 (69.5, 82.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73.5 (66.0, 79.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.065\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.150\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e75.0 (65.0, 81.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e78.0 (68.5, 80.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.820\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.192\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSex (Male)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24 (57.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57 (55.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.025\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (58.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e18 (62.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.071\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.1 (19.8, 26.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22.8 (20.8, 26.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.610\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.180\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.1 (20.4, 27.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21.5 (20.0, 24.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.370\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.237\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAAD / TAA\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (64.3) / 15 (35.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53 (52.0) / 49 (48.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.200\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.252\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (55.2) / 13 (44.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (55.2) / 13 (44.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eEmergency surgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (64.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e51 (50.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.142\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.292\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (55.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (58.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.07\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMalperfusion\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (11.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (8.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.550\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.101\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.123\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eShock (requiring hemodynamic support)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (2.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.019\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.413\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.123\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCardiac tamponade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (19.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (7.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.077\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.333\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (17.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (20.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.088\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGCS \u0026lt;8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (2.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (2.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.035\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.156\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSmoking\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27 (26.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.281\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.240\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (17.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (17.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33 (78.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e78 (76.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.831\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.050\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24 (82.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24 (82.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDiabetes mellitus\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (11.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.428\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.141\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (17.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (20.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.088\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLiver dysfunction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (14.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (7.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.234\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.206\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (13.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.106\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAnticoagulant treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e5 (11.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (9.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.766\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.068\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.123\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAntiplatelet treatment\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e17 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (20.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (24.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.083\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eJapanSCORE II 30-day mortality (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8.4 (5.6, 14.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.1 (3.9, 10.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.033\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.355\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6.9 (4.3, 11.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7.1 (4.4, 13.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.665\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.088\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemoglobin (g/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.5 (10.0, 13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.5 (10.8, 14.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.092\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.285\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.9 (10.0, 13.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11.7 (10.2, 13.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.811\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.101\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePlatelet count (10\u003csup\u003e9\u003c/sup\u003e/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e157 (124, 188)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e177 (142, 213)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.015\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.401\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e158 (126, 179)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e168 (130, 188)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.787\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.074\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAPTT (sec)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.2 (27.4, 37.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.4 (26.2, 31.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.284\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e31.1 (27.5, 35.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30.3 (27.2, 34.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.795\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.190\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePT-INR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.07 (1.00, 1.24)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.02 (0.96, 1.10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.006\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.314\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.05 (0.98, 1.18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.06 (1.00, 1.14)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.964\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.056\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFibrinogen (g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.43 (1.62, 2.96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.90 (2.46, 3.91)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.668\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.64 (1.77, 3.29)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.45 (2.21, 2.97)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.922\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.053\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum creatinine (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.94 (0.72, 1.11)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.87 (0.70, 1.10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.427\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.149\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.94 (0.75, 1.12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.00 (0.78, 1.25)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.160\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.195\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSurgery\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePrimary procedure\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.146\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.274\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTotal arch replacement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19 (45.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60 (58.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14 (48.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14 (48.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemiarch replacement\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (54.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42 (41.2)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (51.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (51.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eConcomitant procedure\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14 (33.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (25.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.413\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.173\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e9 (31.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e8 (27.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.076\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28 (66.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e76 (74.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (69.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (72.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAVR or AVP\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (7.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (3.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBentall\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (4.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDavid\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (7.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (6.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCABG\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e7 (16.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e11 (10.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (13.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eOthers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (2.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCPB time (min)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e169 (145, 230)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e169 (142, 192)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.136\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.437\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e161 (136, 227)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e177 (136, 216)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.754\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.084\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eACC time (min)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e110 (88, 146)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e97 (79, 121)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.049\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.376\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e102 (80, 141)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e110 (75, 123)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.462\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.119\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLowest rectal Temperature (\u0026deg;C)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.5 (25.7, 27.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.1 (25.3, 27.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.043\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.421\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e27.4 (25.6, 27.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.6 (25.4, 27.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.546\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.183\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHCA time (min)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (28, 49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.5 (29.0, 53.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.986\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.094\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (28, 50)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e36 (25, 56)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.829\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.039\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"9\"\u003eAAD, acute aortic dissection; ACC, aortic cross clamp; APTT, activated partial thromboplastin time; AVP, aortic valvuloplasty; AVR, aortic valve replacement; CABG, coronary artery bypass grafting; CPB, cardiopulmonary bypass; GCS, Glasgow Coma Scale; HCA, hypothermic circulatory arrest; PT-INR, prothrombin time international normalized ratio; rFVIIa, recombinant activated factor VII; SMD, standardized mean difference; and TAA, thoracic aortic aneurysm.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n\u003ch2\u003eBaseline and operative characteristics\u003c/h2\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the baseline and operative characteristics. Before PSM, the number of shock patients (p=0.019) and JapanSCORE II 30-day mortality rates (p=0.033) were significantly higher in the rFVIIa group. While Plt (p=0.015) and fibrinogen (p\u0026lt;0.001) were significantly lower, aPTT (p=0.005) and PT-INR (p=0.006) were prolonged in the rFVIIa group. The rFVIIa group demonstrated longer ACC time (p=0.049) and higher lowest body temperature (p=0.043). Following PSM, none of the characteristics were significantly different between the groups.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n\u003ch2\u003ePerioperative bleeding and transfusion\u003c/h2\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e summarizes the perioperative amounts of bleeding and transfusion. Intraoperative bleeding (p=0.012), PRBC transfusion (p=0.048), and FFP (p=0.021) were significantly higher in the rFVIIa group. Patients in the rFVIIa group received a significantly greater amount of fibrinogen concentrate (p\u0026lt;0.001). The median intraoperative dose of rFVIIa was 56 \u0026micro;g/kg. In addition, the postoperative amount of bleeding and transfusion was comparable between the groups.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePerioperative bleeding and blood products in the propensity-score matched populations\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003erFVIIa (n=29)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003enon-rFVIIa (n=29)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBleeding intra-operation (ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6773 (4019, 10185)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3639 (2399, 6627)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.012\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePRBC intra-operation (unit)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26 (19, 34)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e20 (12, 24)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.048\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFFP intra-operation (unit)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e34 (20, 46)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24 (18, 32)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.021\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePC intra-operation (unit)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e55 (40, 60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40 (40, 60)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.472\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCryoprecipitate intra-operation (unit)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (12, 24)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12 (12, 12)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.405\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003erFVIIa (\u0026micro;g/kg)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56 (32, 83)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e-\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFibrinogen concentrate (g)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (0, 3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0, 0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBleeding until 12hr (ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e790 (490, 1470)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e740 (540, 1233)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.071\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePRBC until 12hr (unit)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0, 6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2 (0, 5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.370\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFFP until 12hr (unit)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (4, 9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e6 (4, 8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.576\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePC until 12hr (unit)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0, 20)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0, 10)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.967\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eFFP: fresh frozen plasma, PC: platelet concentrates, and PRBC: packed red blood cells.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003ch2\u003eMortality and postoperative adverse events\u003c/h2\u003e\n\u003cp\u003eTable \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e outlines the postoperative outcomes. The rFVIIa group manifested significantly lower Plt (p\u0026lt;0.001) and shorter PT-INR (p\u0026lt;0.001). There were no significant differences between the groups, with regard to the primary and secondary endpoints. Thirty-day mortality rate was 3.4% in both the groups. We observed stroke in one patient (3.4%) in both groups. There were no cases of MI or PE. The re-exploration rate was comparable (13.8% vs. 10.3%).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003ePostoperative data and complications in the propensity-score matched populations\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eCharacteristic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003erFVIIa (n=29)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003enon-rFVIIa (n=29)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep-value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eHemoglobin (g/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.6 (9.0, 11.5)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10.5 (9.5, 11.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.381\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePlatelet count (10\u003csup\u003e9\u003c/sup\u003e /L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e97 (73, 137)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e142 (106, 169)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAPTT (sec)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.2 (33.6, 55.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.1 (33.4, 44.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.206\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePT-INR\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.86 (0.81, 1.03)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.13 (1.08, 1.18)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFibrinogen (g/L)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.10 (1.79, 2.59)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2.39 (2.06, 2.69)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.846\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSerum creatinine (mg/dl)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.21 (0.94, 1.72)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1.10 (0.83, 1.63)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.226\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eIntubation time (h)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25 (12, 96)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e16 (10, 42)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.991\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeep sternal wound infection\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSepticemia\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRenal failure\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.500\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eParaparesis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDeep venous thrombosis\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003ePulmonary embolism\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMyocardial infarction\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eStroke\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMinor stroke\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eDisabling stroke\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eCardiac tamponade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0 (0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRe-exploration\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4 (13.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3 (10.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e30-day mortality\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e1 (3.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.000\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"4\"\u003eAPTT, activated partial thromboplastin time; PT-INR, prothrombin time international normalized ratio; and rFVIIa, recombinant activated factor VII.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eFew studies have reported on the off-label use of rFVIIa in aortic surgery, with no previous study focusing on the safety of rFVIIa in ASHCA.\u003csup\u003e10,11\u003c/sup\u003e However, the high possibility of massive bleeding necessitates an evaluation of the safety of off-label rFVIIa use in ASHCA. The crucial findings of the present study were as follows: (i) preoperative shock, coagulopathic state in laboratory tests, higher JapanSCORE II 30-day mortality rate, and longer ACC time might be associated with excessive bleeding in ASHCA and (ii) rFVIIa application did not result in a significant increase in the postoperative 30-day mortality and AEs in ASHCA.\u003c/p\u003e \u003cp\u003ePreoperative shock and coagulopathy increased the risk of intraoperative bleeding, which might require rFVIIa administration. Preoperative shock in our patients was primarily caused by AAD or ruptured TAA. The aforementioned pathologies cause coagulopathy. Guan et al. reported that intense prothrombin generation and excessive systemic fibrinolysis occur in AAD before surgery, thereby leading to prolonged consumption coagulopathy, excessive bleeding, and complications [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Researchers have also described coagulopathy in aortic aneurysms with increased intensity upon rupture [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The rFVIIa group demonstrated significantly lower Plt and fibrinogen levels, prolonged aPTT, and PT-INR before PSM. This resulted in a significantly greater amount of intraoperative bleeding and transfusion.\u003c/p\u003e \u003cp\u003eJapanSCORE II is a calculated operative risk similar to EuroSCORE. However, it is based on JCVSD. JapanSCORE II more precisely reflects operative risk in Japan than EuroSCORE [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In the present study, the higher frequency of AAD, emergent surgery, and shock might result in higher operative risk in the rFVIIa group. Despite a lower actual mortality rate than the calculated value, JapanSCORE II appeared to be a reliable risk predictor.\u003c/p\u003e \u003cp\u003eThe clinical impact of HCA-induced coagulopathy is well known. However, the underlying mechanism is still unclear. Hypothermia and CPB are factors that cause coagulopathy. However, several studies have reported that the lowest body temperature is not associated with bleeding [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the present study, the lowest temperature was significantly higher in the rFVIIa group. Nevertheless, intraoperative bleeding was significantly higher in the rFVIIa group than that in the control group. In other words, the lowest temperature was not strongly associated with coagulopathy. Meanwhile, the ACC time in the present study was significantly longer and supposedly associated with excessive bleeding. There are few reports on the relationship between coagulopathy and ACC. Moreover, longer ACC reportedly causes both fibrinogen consumption and accumulation of tissue plasminogen activator. Nonetheless, the underlying mechanism is unclear [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe efficacy of off-label rFVIIa use has been repeatedly reported. However, most of the latter studies involved patients who underwent cardiac surgery [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], where the efficacy was demonstrated with respect to the amount of perioperative bleeding, transfusion, and re-exploration [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, a previous study on AAD surgery reported on significantly greater perioperative bleeding, transfusion, and re-exploration, following rFVIIa administration [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In the present study, the rFVIIa group demonstrated significantly higher intraoperative bleeding and transfusion, in addition to significantly lower postoperative Plt. The severity of coagulopathy in ASHCA is expectedly much higher than that in general cardiac surgery. Therefore, consumption coagulopathy may have persisted even after rFVIIa treatment. According to Paparella et al., intense thrombin generation in patients with AAD stimulates platelet activation and dysfunction, and promotes coagulation factor consumption and excessive fibrinolysis, which collectively result in excessive bleeding [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Consumption coagulopathy and platelet dysfunction have been not only reported in AAD but also in TAA [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Patients in the rFVIIa group in ASHCA might continue to suffer from life-threatening bleeding and require a greater amount of transfusion if not treated with rFVIIa. Therefore, rFVIIa in ASHCA plays an important role in rescue therapy.\u003c/p\u003e \u003cp\u003eThe safety of rFVIIa is still unclear and depends on several factors, such as patient characteristics, transfusion, and the dose of rFVIIa applied. A randomized trial reported on no significant increase in mortality, rather a numeric increase in AEs [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Alferevic et al. reported on higher mortality and renal morbidity in the rFVIIa group [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The aforementioned studies focused on complex cardiac surgery. Other studies on AAD or aortic surgery demonstrated no significant increase in postoperative mortality or AEs [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Intense thrombin generation in ASHCA causes platelet dysfunction, consumptive coagulopathy, and excessive fibrinolysis. Based on the above-mentioned factors, a low frequency of thromboembolic AEs might result from rFVIIa therapy in aortic surgery.\u003c/p\u003e \u003cp\u003eThe safety dose or optimal protocol for rFVIIa in cardiac surgery is still unknown. Researchers have reported on the safety and efficacy of a dose ranging between 35 \u0026micro;g/kg to 70 \u0026micro;g/kg in general cardiac surgery [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Several studies have described the efficacy of low-dose rFVIIa \u0026lt;20 \u0026micro;g/kg [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, considering the severity of coagulopathy in ASHCA, a higher dose may also be acceptable. A dose \u0026lt;90 \u0026micro;g/kg is considered safe in patients without hemophilia [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In the present study, the median dose of rFVIIa was 56 \u0026micro;g/kg, and patients did not demonstrate an increase in mortality or thromboembolic AEs. We administered rFVIIa following the correction of other hemostatic parameters, which was in compliance with current recommendations [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study had several limitations. This was a single-center, retrospective, observational study with a small sample size. We performed PSM based on different characteristics before rFVIIa treatment. Nevertheless, there were several unmeasured confounders. In addition, we observed a difference in intraoperative transfusions, which might have affected the amount of intraoperative bleeding and rFVIIa administration. However, it was impossible to equalize the number of intraoperative transfusions because of the retrospective observational study design. Despite the aforementioned limitations, this is the first study to focus on the use of rFVIIa in ASHCA.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePreoperative shock, higher JapanSCORE II mortality rates, low Plt and fibrinogen, prolonged aPTT and PT-INR, and longer ACC time might be risk factors for excessive bleeding, thus necessitating rFVIIa treatment. The present study suggests that rFVIIa can be safely used for uncontrollable bleeding in ASHCA, without an increase in 30-day mortality and AEs. Further prospective randomized studies are required.\u003c/p\u003e"},{"header":"List of abbreviations","content":"\u003cp\u003eAAD, acute aortic dissection; AEs, adverse events; aPTT, activated partial thromboplastin time; ASHCA, aortic surgery under hypothermic circulatory arrest; CPB, cardiopulmonary bypass; CT, computed tomography; FFP, fresh frozen plasma; HCA, hypothermic circulatory arrest; ICU, intensive care unit; JCVSD, Japan Cardiovascular Surgery Database; MI, myocardial infarction; PC, platelet concentrate; PE, pulmonary embolism; Plt, platelets; PRBC, packed red blood cells; PS, propensity score; PSM, propensity score matching; PT-INR, prothrombin time international normalized ratio; rFVIIa, recombinant activated factor VII; TAA, thoracic aortic aneurysm.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe Institutional Review Board of Asahikawa Medical University approved this study (No. 19078). While the need for informed consent for enrolment in this study was waived due to the retrospective study design.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eHI contributed to data collection and drafting of the manuscript. RU contributed to data collection. HK (Hirotsugu Kanda) conceived the study and revised the manuscript. FK contributed to data interpretation. YS provided expert consultation on statistical analysis. PA and AL contributed to conception of the study design and data interpretation. HK (Hiroyuki Kamiya) supervised the project. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eHI is supported by a research fellowship award from the Japanese Society on Thrombosis and Haemostasis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eGupta P, Harky A, Jahangeer S, Adams B, Bashir M. Varying evidence on deep hypothermic circulatory arrest in thoracic aortic aneurysm surgery. Tex Heart Inst J. 2018;45:70-5.\u003c/li\u003e\n \u003cli\u003eKeenan JE, Wang H, Gulack BC, Ganapathi AM, Andersen ND, Englum BR, et al. Does moderate hypothermia really carry less bleeding risk than deep hypothermia for circulatory arrest? A propensity-matched comparison in hemiarch replacement. J Thorac Cardiovasc Surg. 2016;152:1559-69.\u003c/li\u003e\n \u003cli\u003eKamiya H, Hagl C, Kropivnitskaya I, B\u0026ouml;thig D, Kallenbach K, Khaladj N, et al. The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: a propensity score analysis. J Thorac Cardiovasc Surg. 2007;133:501-9.\u003c/li\u003e\n \u003cli\u003eKeeling WB, Tian DH, Leshnower BG, Ganapathi AM, Andersen ND, Englum BR, et al. Safety of Moderate Hypothermia With Antegrade Cerebral Perfusion in Total Aortic Arch Replacement. Ann Thorac Surg. 2018;105:54-61.\u003c/li\u003e\n \u003cli\u003eHarrington DK, Lilley JP, Rooney SJ, Bonser RS. Nonneurologic morbidity and profound hypothermia in aortic surgery. Ann Thorac Surg. 2004;78:596-601.\u003c/li\u003e\n \u003cli\u003eIse H, Kitahara H, Oyama H, Takahashi K, Kanda H, Fujii S, et al. Hypothermic circulatory arrest induced coagulopathy: rotational thromboelastometry analysis. Gen Thorac Cardiovasc Surg. 2020;68:754-61.\u003c/li\u003e\n \u003cli\u003eAl Douri M, Shafi T, Al Khudairi D, Al Bokhari E, Black L, Akinwale N, et al. Effect of the administration of recombinant activated factor VII (rFVIIa; NovoSeven\u0026reg;) in the management of severe uncontrolled bleeding in patients undergoing heart valve replacement surgery. Blood Coagul Fibrinolysis. 2000;11 Suppl 1:S121-7.\u003c/li\u003e\n \u003cli\u003eYank V, Tuohy CV, Logan AC, Bravata DM, Staudenmayer K, Eisenhut R, et al. Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care. Rockville (MD): Agency for Healthcare Research and Quality (US) May 2010; Report No.: 10-EHC030-EF.\u003c/li\u003e\n \u003cli\u003eGill R, Herbertson M, Vuylsteke A, Olsen PS, von Heymann C, Mythen M, et al. Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation. 2009;120:21-7.\u003c/li\u003e\n \u003cli\u003eHoffmann T, Assmann A, Dierksen A, Roussel E, Ullrich S, Lichtenberg A, et al. A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study. J Thorac Cardiovasc Surg. 2018;156:1564-73.\u003c/li\u003e\n \u003cli\u003eZindovic I, Sj\u0026ouml;gren J, Ahlsson A, Bjursten H, Fuglsang S, Geirsson A, et al. Recombinant factor VIIa use in acute type A aortic dissection repair: A multicenter propensity-score-matched report from the Nordic Consortium for Acute Type A Aortic Dissection. J Thorac Cardiovasc Surg. 2017;154:1852-9.\u003c/li\u003e\n \u003cli\u003eGoksedef D, Panagopoulos G, Nassiri N, Levine RL, Hountis PG, Plestis KA. Intraoperative use of recombinant activated factor VII during complex aortic surgery. J Thorac Cardiovasc Surg. 2012;143:1198-204.\u003c/li\u003e\n \u003cli\u003eTakamoto S, Motomura N, Miyata H, Tsukihara H. Current status of cardiovascular surgery in Japan, 2013 and 2014: A report based on the Japan Cardiovascular Surgery Database (JCVSD). 1: Mission and history of JCVSD. Gen Thorac Cardiovasc Surg. 2018;66:1-3.\u003c/li\u003e\n \u003cli\u003eKanda Y. Investigation of the freely available easy-to-use software \u0026apos;EZR\u0026apos; for medical statistics. Bone Marrow Transplant. 2013;48:452-8.\u003c/li\u003e\n \u003cli\u003eGuan X, Li J, Gong M, Lan F, Zhang H. The hemostatic disturbance in patients with acute aortic dissection: A prospective observational study. Medicine 2016;95:e4710.\u003c/li\u003e\n \u003cli\u003eDavies RS, Abdelhamid M, Wall ML, Vohra RK, Bradbury AW, Adam DJ. Coagulation, fibrinolysis, and platelet activation in patients undergoing open and endovascular repair of abdominal aortic aneurysm. J Vasc Surg. 2011;54:865-78.\u003c/li\u003e\n \u003cli\u003eKurazumi H, Mikamo A, Fukamitsu G, Kudou T, Sato M, Suzuki R,\u0026nbsp;et al. Validation of the JapanSCORE versus the logistic EuroSCORE for predicting operative mortality of cardiovascular surgery in Yamaguchi University Hospital. Gen Thorac Cardiovasc Surg. 2011;59:599-604.\u003c/li\u003e\n \u003cli\u003eHaithcock BE, Shepard AD, Raman SB, Conrad MF, Pandurangi K, Fanous NH. Activation of fibrinolytic pathways is associated with duration of supraceliac aortic cross-clamping. J Vasc Surg. 2004;40:325-33.\u003c/li\u003e\n \u003cli\u003ePaparella D, Rotunno C, Guida P, Malvindi PG, Scrascia G, De Palo M, et al. Hemostasis alterations in patients with acute aortic dissection. Ann Thorac Surg. 2011;91:1364-9.\u003c/li\u003e\n \u003cli\u003eTanaka M, Kawahito K, Adachi H, Ino T. Platelet dysfunction in acute type A aortic dissection evaluated by the laser light-scattering method. J Thorac Cardiovasc Surg. 2003;126:837-41.\u003c/li\u003e\n \u003cli\u003eAlfirevic A, Duncan A, You J, Lober C, Soltesz E. Recombinant factor VII is associated with worse survival in complex cardiac surgical patients. Ann Thorac Surg. 2014;98:618-24.\u003c/li\u003e\n \u003cli\u003eFitzgerald J, McMonnies R, Sharkey A, Gross PL, Karkouti K. Thrombin generation and bleeding in cardiac surgery: a clinical narrative review. G\u0026eacute;n\u0026eacute;ration de thrombine et saignements en chirurgie cardiaque : un compte rendu narratif clinique. Can J Anaesth. 2020;67:746-53.\u003c/li\u003e\n \u003cli\u003eHsia CC, Chin-Yee IH, McAlister VC. Use of recombinant activated factor VII in patients without hemophilia: a meta-analysis of randomized control trials. Ann Surg. 2008;248:61-8.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Aortic surgery under hypothermic circulatory arrest, cardiac surgery, recombinant activated factor VII, retrospective study, uncontrollable bleeding","lastPublishedDoi":"10.21203/rs.3.rs-980459/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-980459/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: We aimed to identify the risk factors of uncontrollable bleeding and investigate the safety of recombinant activated factor VII (rFVIIa) in aortic surgery under hypothermic circulatory arrest (ASHCA).\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: The present single-center retrospective study compared the baseline characteristics of 144 patients who underwent ASHCA at our institute the total cohort. Of the 144 patients, 42 received rFVIIa (group rFVIIa), while the remaining 102 patients did not (group non-rFVIIa). Perioperative bleeding and transfusions, postoperative 30-day mortality, and adverse events (AEs) were analyzed in 29 propensity score-matched pairs.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: Before surgery, the rFVIIa group demonstrated a greater number of shocks (p=0.019), higher JapanSCOREx II mortality rate (p=0.033), low platelet count (p=0.015), fibrinogen (p\u0026lt;0.001), prolonged activated partial thromboplastin time (p=0.005), prothrombin time international normalized ratio (p=0.006), and longer aortic cross cramp (ACC) time (p=0.049). Postoperative bleeding, transfusion, 30-day mortality, and AEs were comparable between the groups.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Preoperative shock, higher JapanSCORE II mortality rates, low platelet and fibrinogen levels, prolonged aPTT and PT-INR, and longer ACC time might be risk factors for excessive bleeding and indicate the need for rFVIIa treatment. The present study suggests that rFVIIa can be safely used to address uncontrollable bleeding in ASHCA without inducing an increase in 30-day mortality and AEs.\u003c/p\u003e","manuscriptTitle":"Recombinant Activated Factor VII in Aortic Surgery for Patients With Coagulation Disorders and Hypothermic Circulatory Arrest: a Single-center Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-10-20 16:58:11","doi":"10.21203/rs.3.rs-980459/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4476023b-ce3c-49f7-a071-95b0b9143c1d","owner":[],"postedDate":"October 20th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":7991398,"name":"Cardiac \u0026 Cardiovascular Systems"},{"id":7991399,"name":"Cardiothoracic Surgery"}],"tags":[],"updatedAt":"2021-11-29T21:31:23+00:00","versionOfRecord":[],"versionCreatedAt":"2021-10-20 16:58:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-980459","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-980459","identity":"rs-980459","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}