Association Between Fibrinolysis Products and Platelet Activity in Patients with Acute Type A Aortic Dissection: A single-centre observational study

Association Between Fibrinolysis Products and Platelet Activity in Patients with Acute Type A Aortic Dissection: A single-centre observational 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 Association Between Fibrinolysis Products and Platelet Activity in Patients with Acute Type A Aortic Dissection: A single-centre observational study Zhe Chen, Shaoheng Chen, Zehua Zhang, Jianxin Yuan, Hao Peng, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8718591/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Acute type A aortic dissection (ATAAD) is a highly lethal cardiovascular emergency in which platelet dysfunction plays a pivotal role; however, the underlying mechanisms of this dysfunction remain poorly understood. Methods In the present study, we investigated the relationship between fibrinolytic products at admission and platelet function. We retrospectively analysed the data of patients with ATAAD from July 2020 to July 2025 at Delta Health Hospital (Shanghai, China). Pearson’s chi-square test was used to analyse the correlations between platelet aggregation and fibrinolysis parameters. The risk factors affecting postoperative in-hospital death and massive blood transfusion (MBT) were analysed using multivariate logistic regression analysis. Results A total of 154 patients with ATAAD, with a mean age of 52.40 ± 15.02 years, were selected for the study. In patients with ATAAD, the peripheral blood fibrinogen (FIB) concentration was negatively correlated with both adenosine diphosphate (ADP)-induced and arachidonic acid (AA)-induced platelet inhibition rates, whereas elevated D-dimer and fibrinogen degradation product (FDP) levels were associated with increased platelet inhibition rates in response to both agonists. We further found that fibrinolysis products derived from healthy human blood samples enhanced both ADP- and AA-induced platelet inhibition in a dose-dependent manner. Multivariate logistic regression analysis revealed elevated levels of D-dimer and FDP, along with increased ADP-induced and AA-induced platelet inhibition rates, as independent predictors of MBT and in-hospital major adverse events (MAEs). Conclusions In summary, our study elucidates the association between fibrinolysis products and platelet activity in patients with ATAAD and highlights the clinical value of platelet function monitoring in predicting perioperative transfusion requirements and patient prognosis. ATAAD FIB FDP D-dimer Platelet dysfunction Figures Figure 1 Figure 2 Figure 3 Introduction Acute type A aortic dissection (ATAAD) is a highly lethal cardiovascular emergency in which mortality risk increases by 1% to 2% per hour in the absence of timely surgical intervention[ 1 , 2 ]. Refractory perioperative bleeding, a complication typically due to significant underlying coagulopathy, and the substantial allogeneic transfusion required after refractory bleeding are formidable challenges for clinicians. The coagulation state in ATAAD is characterized by a distinct paradox. An initial hypercoagulable thrust, driven by systemic endothelial damage, promotes microthrombosis and ischaemic complications. However, this consumptive process, augmented by flow-induced platelet dysfunction in the false lumen, swiftly depletes haemostatic reserves, culminating in secondary haemorrhagic diathesis upon surgical trauma[ 3 ]. Patients with ATAAD frequently present with a pathophysiological state in which the coagulation and fibrinolytic systems are simultaneously activated, resulting in profound coagulopathy[ 4 ]. A hallmark of ATAAD is a significant decrease in fibrinogen, resulting from concurrent thrombosis and degradation by hyperfibrinolysis. This condition is strongly associated with major perioperative bleeding and is an independent predictor of both transfusion demand and surgical complications. As a marker of hyperfibrinolysis, the D-dimer level is drastically elevated in the peripheral blood after the onset of ATAAD, and the D-dimer level is positively correlated with the extent of dissection, disease severity, and clinical prognosis[ 5 , 6 ]. Within this complex network of coagulation disorders, platelet dysfunction plays a pivotal hub role. These patients exhibit significantly reduced platelet counts, suggesting substantial consumption during thrombosis, with thrombocytopenia being an independent predictor of postoperative mortality[ 7 – 9 ]. Beyond the quantitative deficiency in platelet count, evidence shows that platelet aggregation function is also qualitatively impaired in patients with ATAAD. Platelet aggregation function is compromised in patients with ATAAD. Tanaka et al. used laser scattering spectrometry to evaluate 20 patients with ATAAD and reported a significant reduction in platelet aggregation rates during the acute phase, particularly in the formation of medium (25–50 µm) and large (50–70 µm) aggregates[ 10 ]. This complex platelet dysfunction directly contributes to refractory perioperative bleeding, increased transfusion requirements, and subsequent multiple organ failure. Additionally, a prior investigation using laser scatterometry revealed inhibited platelet aggregation in patients with ATAAD, resulting in systemic platelet dysfunction and the production of relatively small microaggregates. However, the precise mechanisms responsible for platelet dysfunction in ATAAD remain poorly understood. Therefore, in this study, we explored the relationship between the levels of these fibrinolysis products (fibrinogen degradation products [FDP] and D-dimer) and platelet aggregation in early ATAAD. We also used in vitro assays to investigate how they modulate platelet activation and function. This study provides a more in-depth understanding of platelet dysfunction mechanisms in ATAAD. Materials and Methods Study Design and Study Population This study involved a cohort of patients with ATAAD admitted to Delta Health Hospital (Shanghai, China) from July 2020 to July 2025. A retrospective analysis was conducted using the electronic medical records and laboratory test results of these patients. However, exclusion criteria for the study included known preexisting coagulation disorders, liver disease, and the use of oral anticoagulant or antiplatelet treatment. Surgical procedures were categorized into emergency surgery and elective surgery. The indications for surgical intervention and the corresponding surgical strategy were determined by the attending surgeons in accordance with the 2010 Guidelines for the Diagnosis and Management of Thoracic Aortic Disease issued by the American Association for Thoracic Surgery (AATS). This single-centre observational study was designed to analyse the data of patients with ATAAD. The relationships between early ATAAD levels, fibrinolysis products (FDP and D-dimer), calcium levels and platelet aggregation were clarified. The protocol was approved by the Institutional Review Board of Delta Health Hospital (Approval No. SDH (2025) KYSL001). Written informed consent was obtained from each participant or legal proxy. The investigation conforms to the principles of the Declaration of Helsinki. Data collection The plasma levels of D-dimer, PT, APTT, FIB, TT, and FDP were measured using an automated coagulation analyser (ACL TOP 70; Werfen/Instrumentation Laboratory, Bedford, MA, USA) in patients with suspected ATAAD immediately following admission. Baseline haematological parameters (platelet count, haemoglobin level, and red blood cell count) were measured using an automated haematology analyser (XS-9001; Sysmex Corporation, Kobe, Japan). Thromboelastography (TEG) results were analysed using a TEG® 5000 Hemostasis Analyzer (Haemonetics Corporation, Braintree, MA, USA). Previous medical histories, including hypertension, diabetes mellitus, coronary artery disease, stroke, and hyperlipidaemia, were extracted from the electronic medical records (EMRs). Massive blood transfusion (MBT) was defined as the need for ≥ 8 units of packed red blood cells within any 24-hour period. Major adverse events (MAEs), defined in accordance with the International Aortic Arch Surgery Study Group consensus statement, included in-hospital mortality, gastrointestinal bleeding, paraplegia, acute kidney injury, re-exploration for bleeding, low cardiac output syndrome, stroke, respiratory failure, multiple organ dysfunction syndrome (MODS), and severe infection[ 11 ]. Preparation of fibrinolytic products Plasma samples from routine clinical blood tests were used as the starting material. To induce coagulation, kaolin (200 mg/L) and CaCl₂ (0.2 M) were added at a ratio of 1 unit kaolin and 20 µL CaCl₂ per 1 mL plasma. The clot was centrifuged to separate it from the other plasma components, after which it was repeatedly washed with normal saline to remove residual impurities. The purified clots were homogenized using a glass grinder to increase the surface area for subsequent enzymatic reactions. Fibrinogenase for injection (100 U/mL), supplied by *** Pharmaceutical Co., Ltd., was stored at 2–8°C until use. Fibrinogenase was added to the homogenized mixture, and the mixture was incubated overnight at 37°C to ensure complete enzymatic hydrolysis of fibrin into FDP. The supernatant of the fibrin-digested fibrin was collected, and the concentration and purity of the prepared FDP solution were verified using an ACL TOP 750 automated coagulation analyser. Different concentrations of fibrinolytic products were added to normal blood donor samples. Platelet function was examined using the TEG method. Statistical analysis All the statistical analyses were performed using GraphPad Prism version 10.0. Normally distributed continuous data are presented as the mean ± standard deviation (SD), whereas nonnormally distributed continuous data are presented as the median value and interquartile range. Simple linear regression was used to assess the association between platelet aggregation and fibrinolysis parameters. For comparisons among multiple groups, one- or two-way analysis of variance (ANOVA) was used for data analysis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of factors identified as significant for in-hospital MAEs and MBTs based on the literature and on the results of the univariate analysis ( p < 0.05), with a parallel line test performed for the variables. All analyses were performed using SPSS 26 (SPSS, IBM Corp. Armonk, USA), with p < 0.05 considered to indicate statistical significance. Results Demographic characteristics A total of 352 patients with ATAAD were enrolled via an inpatient electronic information system. A total of 65 patients with coagulation disorders, 47 patients with liver disease, 71 patients who received oral anticoagulant or antiplatelet treatment and 15 patients whose baseline data were missing were excluded from the study. Finally, 154 patients with ATAAD were selected for the study, with a mean age of 52.40 ± 15.02 years (29–75 years). This study included 117 male and 37 female patients. A total of 98 (63.64%) patients had a history of hypertension, 5 (3.25%) had a history of diabetes mellitus, 31 (20.13%) had a history of acute renal failure, 31 (20.13%) had a history of hypoproteinaemia, and 15 (9.74%) had a history of cerebral apoplexy. Preoperative complete blood tests, coagulation profiles, and TEG results were also collected. Correlations between platelet aggregation and fibrinolysis parameters The plasma levels of fibrinogen (FIB), FDP, D-dimer, and calcium ions were measured separately in patients with ATAAD. A Pearson correlation analysis was then performed to evaluate their associations with the AA-induced and ADP-induced platelet inhibition rates. First, the peripheral blood FIB concentration in patients with ATAAD was negatively correlated with both AA-induced and ADP-induced platelet inhibition rates (R 2 = 0.091, p < 0.001; R 2 = 0.171, p < 0.001) (Fig. 2A and B). Conversely, increased FDP levels were positively correlated with increases in the AA-induced platelet inhibition rate and the ADP-induced platelet inhibition rate (R 2 = 0.082, p < 0.001; R 2 = 0.113, p < 0.001) (Fig. 2C and D). A parallel correlation was observed, whereby elevated D-dimer levels corresponded to increased platelet inhibition rates for both agonists (R 2 = 0.057, p = 0.003; R 2 = 0.076, p = 0.001) (Fig. 2E and F). However, our analysis revealed no discernible association between the Ca 2+ concentration in peripheral blood and platelet inhibition rates among patients with ATAAD (R 2 = 0.014, p = 0.136; R 2 = 0.000, p = 0.923) (Fig. 2G and H). Effects of in vitro fibrinolysis products on platelet aggregation Following the initial correlation observed between early fibrinolysis product concentrations and platelet aggregation levels, an in vitro system was established to further investigate this relationship. To this end, the fibrinolytic state in the setting of ATAAD was modelled by introducing plasmin to preformed clots from healthy human blood samples. The direct effects of these fibrinolysis products on platelet aggregation function were subsequently evaluated. First, in the control group (plasma from healthy volunteers), the AA-induced and ADP-induced platelet inhibition rates were 48.0 ± 9.4% and 49.3 ± 10.6%, respectively. With increasing concentrations of added fibrinolysis products (reflected by increasing final FDP concentrations), both the ADP-induced and AA-induced platelet inhibition rates increased in a dose-dependent manner. Notably, a saturation point was reached at an FDP concentration of approximately 80 µg/mL, beyond which no further increase in inhibition was detected. Postoperative outcomes of patients with ATAAD Multivariate logistic regression analysis was subsequently conducted on variables with a p value < 0.1. Based on the backward-stepwise regression method, factors with a p value ≥ 0.1 were removed from the regression model at each step. After adjustment for confounders, the results are shown in Table 2 . Multivariate logistic regression analysis revealed that age > 65 years (OR = 1.093; 95% confidence interval [CI] 0.984–3.659; p = 0.053) and ADP-induced and AA-induced platelet inhibition rates (OR = 2.531; 95% CI 1.451–34.866; p = 0.021; OR = 1.903; 95% CI 1.071–42.547; p = 0.041) and a D-dimer concentration ≥ 5.00 mg/L (OR = 2.629; 95% CI 1.654–9.675; p = 0.029) were independent risk factors for postoperative MBT. Table 1 Baseline characteristics of acute type A aortic dissection. Characteristics, n 154 Demographics, n Age (years), mean (SD) 52.40 (15.02) Sex, Male, n (%) 117 (75.97) Comorbidities and medical history Hypertension, n (%) 98 (63.64) Diabetes, n (%) 5 (3.25) Prior bypass surgery, n (%) 15 (9.74) Prior valve replacement surgery, n (%) 4 (2.60) Atrial fibrillation, n (%) 6 (3.90) Cardiac insufficiency, n (%) 11(7.14) Arrhythmia, n (%) 15 (9.74) Cerebral apoplexy, n (%) 15 (9.74) COPD, n (%) 19 (12.34) CRI, n (%) 4 (2.60) Acute renal failure, n(%) 31(20.13) Anemia, n(%) 9 (5.84) Pericardial effusion, n(%) 27(17.53) Pleural effusion, n(%) 32 (20.78) Hypoproteinemia, n(%) 31 (20.13) Paraplegia, n(%) 6 (3.90) Laboratory tests on admission Pre-Op PLT (×10 9 /L), mean (SD) 174.00 (65.33) Pre-Op HGB (g/L), mean (SD) 125.20 (22.98) Pre-Op RBC (×10 12 /L), mean (SD) 4.21 (0.73) PT (second), mean (SD) 12.96 (2.99) APTT (second), mean (SD) 31.77 (5.14) INR, mean (SD) 1.10 (0.24) FIB (g/L), mean (SD) 2.83 (1.38) TT (second), mean (SD) 17.98 (8.31) D-Dimer (µg/mL), mean (SD) 8.63 (20.35) FDP (µg/mL), mean (SD) 57.69 (82.20) AT (%), mean (SD) 90.71 (16.00) R (min), mean (SD) 5.10 (1.82) K (min), mean (SD) 1.99 (1.44) Angle (degree), mean (SD) 63.57 (9.62) MA (mm), mean (SD) 64.30 (9.76) AA (%), mean (SD) 63.64 (32.60) ADP (%), mean (SD) 62.56 (29.90) CRP (mg/L), mean (SD) 28.47 (48.40) Ca 2+ (mmol/L), mean (SD) 2.14 (0.12) K+ (mmol/L), mean (SD) 3.75 (0.65) RBC transfusion, n (%) 120 (77.92) RBC (U) transfusion, mean (SD) 11.22 (16.16) RBC, > 8U, n (%) 59 (38.31) Platelet transfusion(U), mean(SD) 1.36 (2.25) Plasma transfusion(U), mean(SD) 14.97 (27.47) Postoperative in-hospital mortality, n(%) 2 (1.30) a. Abbreviations: COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; PLT, platelet; HGB, hemoglobin; RBC, red blood cells, PT, Prothrombin Time; APTT, activated partial thromboplastintime; INR, international normalized ratio; FIB, fibrinogen; TT, thrombin time; FDP,fibrin(ogen) degradation products; AT, antithrombin time; R, reaction; K, kinetics time; MA, maximum amplitude; AA, arachidonic acid; ADP, adenosine diphosphate; CRP, c-reactive protein b. Data are reported as number (percent), mean (SD), or median (Q1- Q3). Table 2 Risk factors in multivariate logistic regression analysis of postoperative in-hospital MAEs and MBT in patients with ATAAD Variables OR 95% CI P value MBT Age > 65 years 1.093 0.984–3.659 0.053 ADP-induced platelet inhibition rates 2.531 1.451–34.866 0.021 AA-induced platelet inhibition rates 1.903 1.071–42.547 0.041 D-dimer ≥ 5.00 mg/L 2.629 1.654–9.675 0.029 In-hospital MAEs Age > 65 years 1.423 1.234–3.598 0.036 D-dimer ≥ 5.00 mg/L 2.546 1.211–8.898 0.465 MBT 3.543 1.102–54.873 0.013 ADP-induced platelet inhibition rates 2.634 1.654–34.675 0.035 AA-induced platelet inhibition rates 1.655 1.765–56.938 0.019 Abbreviations: MBT, massive blood transfusion; MAEs, major adverse events; ATAAD, acute type A aortic dissectio. ADP, adenosine diphosphate; AA, arachidonic acid. In addition, the analysis revealed preoperative ADP-induced and AA-induced platelet inhibition rates (OR = 2.634, 95% CI 1.654–34.675, p = 0.035; OR = 1.655, 95% CI 1.765–56.938, p = 0.019), D-dimer levels (OR = 2.546, 95% CI 1.211–8.898, p = 0.465), and MBT (OR = 3.543, 95% CI 1.102–54.873, p = 0.013) as independent risk factors for in-hospital MAEs. Discussion As a cornerstone effector of thrombosis and inflammation, platelet dysfunction is recognized as a key driver of ATAAD pathogenesis[ 3 , 4 , 12 ]. Recent evidence has indicated that thrombocytopenia, dysregulated platelet activation, and the subsequent thrombo-inflammatory cascade collectively influence patient outcomes, thereby critically determining surgical recovery and long-term survival[ 1 , 2 , 12 , 13 ]. This study preliminarily revealed the association between early circulating fibrinolysis product levels and platelet dysfunction in patients with ATAAD and explored its potential role in predicting patient prognosis. Mechanistically, the scale of intimal tear and subendothelial matrix exposure in patients with ATAAD inevitably triggers massive platelet activation. Through the release of procoagulant factors (including CD40 ligands) and proinflammatory mediators (such as TNF-α and IL-6), platelets contribute to vascular wall inflammation and medial degradation, ultimately accelerating dissection progression[ 14 , 15 ]. In addition to the release of inflammatory mediators, monocyte-platelet aggregates (MPAs) also serve as a pivotal mechanism driving dissection progression by enhancing monocyte adhesion and infiltration[ 16 , 17 ]. However, few studies have focused on the effects of fibrinolysis products, such as FDP and D-dimer, in the peripheral blood of patients with ATAAD on platelet function. By measuring the plasma concentrations of FIB, FDP, and D-dimer using TEG in 154 patients with ATAAD, we initially identified an inverse correlation between peripheral FIB levels and both ADP-induced and AA-induced platelet inhibition rates. Our findings are consistent with early research showing that elevated FIB is associated with a significantly reduced inhibition rate of the ADP pathway, as assessed by TEG or LTA, in patients with DAPT-treated coronary artery disease or those who underwent PCI compared with those with normal or low FIB. As platelet aggregation culminates in fibrinogen binding to the GPIIb/IIIa receptor, extremely high fibrinogen levels can counteract the effects of antiplatelet drugs that target upstream pathways such as ADP or AA. This is achieved by providing a surplus of ligand, which promotes extensive cross-linking between platelets even when a fraction of receptors remains active, bypassing pharmacological blockade. Elevated fibrinogen contributes to adverse cardiovascular risk by increasing the clot strength (MA-CFF) and fibrin polymerization rate (α-angle), serving as an indirect marker of inadequate inhibition of the AA pathway (fibrin clot strength is associated with an increased risk of major adverse cardiac events after TAVR). Furthermore, our study revealed that increased levels of FDP and D-dimer were positively associated with increased platelet inhibition rates following both ADP and AA stimulation. Early studies have also demonstrated that, in trauma patients, the plasma D-dimer levels are associated with trauma-induced platelet dysfunction, making it a potential predictor. Likewise, studies regarding the FDP-platelet relationship in disease states have concentrated on correlating peripheral blood FDP levels with platelet counts. Elevated FDP levels in patients with disseminated intravascular coagulation (DIC) frequently coincide with thrombocytopenia, reflecting platelet consumption due to excessive fibrinolytic activation[ 18 , 19 ]. Similarly, high FDP levels in trauma patients or patients with sepsis are associated with reduced platelet counts and coagulation dysfunction[ 20 , 21 ]. To definitively establish the impact of fibrinolysis products on platelet function, we generated these products from clotted healthy human blood, which contained D-dimers and fibrin degradation products (FDPs). Our results confirmed that fibrinolysis products directly inhibit platelet aggregation in a concentration-dependent manner. Early findings indicated that FDPs play a critical role in platelet activation, particularly by modulating signalling pathways. Research indicates that FDPs interfere with normal signalling mechanisms by affecting the activity of platelet surface receptors. FDPs can inhibit glycoprotein VI (GPVI) signalling, leading to impaired calcium mobilization and reducing platelet aggregation capacity[ 22 ]. Furthermore, the heterogeneity among FDP subtypes translates into diverse biological activities on platelets. It has been established that cross-linked FDPs (such as D-dimers) have a pronounced inhibitory effect on platelet aggregation and activation, in contrast to noncross-linked FDPs, which have negligible effects[ 23 ]. During trauma, D-dimers and FDPs mediate platelet inhibition through the binding of GPVI and integrin αIIbβ3, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype[ 22 ]. While our findings corroborate earlier studies regarding the inhibitory effects of FDPs and D-dimers on platelet activation, we used a preparation representing the complete mixture of fragments from plasmin-induced proteolysis of fibrinogen and fibrin. Future work will delineate the specific contributions and mechanisms of individual components of this fibrinolysis product mixture on platelet activation. Numerous studies have reported that ATAAD, D-dimers and FIB serve not only as highly sensitive diagnostic markers for initial screening but also as robust prognostic biomarkers indicating disease severity, risk of complications, and mortality[ 5 , 6 , 24 , 25 ]. Multivariate logistic regression analysis in this study revealed elevated admission D-dimer levels as an independent risk factor for in-hospital MAEs in patients with ATAAD. In addition, both ADP-induced and AA-induced platelet inhibition rates were associated with 30-day postoperative mortality in patients with ATAAD in this study. This phenomenon likely reflects underlying platelet dysfunction, where higher inhibition rates compromise haemostatic capacity, thereby predisposing patients to greater bleeding and subsequent complications during disease progression or surgical intervention[ 26 ]. We also reported a correlation between elevated ADP-induced and AA-induced platelet inhibition rates and increased blood product utilization. Previous studies have shown that preoperative thrombocytopenia or platelet dysfunction (due to antiplatelet medication) increases intraoperative blood loss and transfusion requirements[ 27 ]. The confluence of preexisting platelet dysfunction and complications associated with substantial blood transfusion is postulated to contribute to poor outcomes in patients with ATAAD. This study has several limitations. The findings of this single-centre retrospective study, which is limited by its sample size, should be considered with the potential for selection bias. Although our study focused on D-dimer levels and FDPs, the pathogenesis of platelet dysfunction likely involves additional mediators, and integrating knowledge from other disciplines remains essential. To build upon these encouraging findings, we propose that subsequent work validate our observations by examining platelet ultrastructure, receptor dynamics, and their in vivo relevance. In summary, this study has preliminarily elucidated the association between circulating D-dimer/FDP levels and platelet aggregation function in patients with ATAAD. We demonstrated the direct inhibitory effect of fibrinolysis products on platelet aggregation, a finding crucial for understanding the platelet dysfunction that occurs during ATAAD pathogenesis. Furthermore, our results highlight the clinical value of platelet function monitoring for predicting perioperative transfusion requirements and patient prognosis. Declarations AUTHOR CONTRIBUTIONS Z.C. designed and conceived this project; S.C. and Z.Z. performed experiments and generated data; J.Y. analyzed and interpreted data; H.P. and N.P. made suggestions for this project; S.C. wrote the draft; J.Z. and X.L. revised and finalized the manuscript; All authors contributed to and approved the manuscript. Zhe Chen, Shaoheng Chen and Zehua Zhang contributed equally to this work. COMPETING INTERESTS: The authors declare no competing interests. SOURCES OF FUNDING: This work was supported by Social Development (Medical and Health) Program of Science and Technology Development Fund of Qingpu District, Shanghai (Grant No. QKY2025-80); WeiGao Science Foundation of Chinese Society of Blood Transfusion (CSBT-WG-2024-08). Clinical Research Innovation Plan of Shanghai General Hospital (CCTR-2025C47). Clinical trial number: not applicable. The protocol was approved by the Institutional Review Board of Delta Health Hospital (Approval No. SDH (2025) KYSL001). Written informed consent was obtained from each participant or legal proxy. The investigation conforms to the principles of the Declaration of Helsinki. References Chen L, Pan Y, Zhang H, Chen Y, Wang C, et al. Propensity score matching analysis of valve-sparing versus aortic root replacement in type a aortic dissection patients. Nat Commun. 2025;16:1238. 10.1038/s41467-025-56509-2 . Liu H, Diao YF, Shao YF, Qian SC, Zeng ZH, et al. Prognostic implication of residual inflammatory trajectories in acute type i aortic dissection: dual-center prospective cohort study. Int J Surg. 2024;110:3346–56. 10.1097/JS9.0000000000001245 . Rylski B, Schilling O, Czerny M. Acute aortic dissection: evidence, uncertainties, and future therapies. Eur Heart J. 2023;44:813–21. 10.1093/eurheartj/ehac757 . Yuan X, Mitsis A, Nienaber CA. Current understanding of aortic dissection. Life-Basel. 2022;12. 10.3390/life12101606 . Itagaki R, Kimura N, Mieno M, Hori D, Itoh S, et al. Characteristics and treatment outcomes of acute type a aortic dissection with elevated d-dimer concentration. J Am Heart Assoc. 2018;7:e9144. 10.1161/JAHA.118.009144 . Qiu L, Ji Q, Miao H, Long M, Gong M, et al. Prognostic value of d-dimer in acute type a aortic dissection and intramural hematoma: observations from the acute aortic syndrome group of the registry of acute non‐traumatic chest pain in china. J Am Heart Assoc. 2025;14:e36843. 10.1161/JAHA.124.036843 . He X, Balati A, Wang W, Wang H, Zhang B, et al. Association of thrombocytopenia and d-dimer elevation with in-hospital mortality in acute aortic dissection. Ann Med. 2025;57:2478477. 10.1080/07853890.2025.2478477 . Smedberg C, Hultgren R, Olsson C, Steuer J. Incidence, presentation and outcome of acute aortic dissection: results from a population-based study. Open Heart. 2024;11. 10.1136/openhrt-2023-002595 . Liu G, Wang H, Luo Q, Cao L, Yang L, et al. Low postoperative blood platelet count may be a risk factor for 3-year mortality in patients with acute type a aortic dissection. J Cardiothorac Surg. 2021;16:274. 10.1186/s13019-021-01623-7 . 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. 10.1016/s0022-5223(03)00734-7 . Yan TD, Tian DH, Lemaire SA, Hughes GC, Chen EP, et al. Standardizing clinical end points in aortic arch surgery. Circulation. 2014;129:1610–6. 10.1161/CIRCULATIONAHA.113.006421 . Erdoes G, Ahmed A, Kurz SD, Gerber D, Bolliger D. Perioperative hemostatic management of patients with type a aortic dissection. Front Cardiovasc Med. 2023;10:1294505. 10.3389/fcvm.2023.1294505 . Zhu Y, Lingala B, Baiocchi M, Tao JJ, Toro AV, et al. Type a aortic dissection-experience over 5 decades: jacc historical breakthroughs in perspective. J Am Coll Cardiol. 2020;76:1703–13. 10.1016/j.jacc.2020.07.061 . Qin C, Gu J, Qian H, Liu R, Xu F, et al. Potential mechanism of post-acute aortic dissection inflammatory responses: the role of mtdna from activated platelets. Cardiology. 2016;135:228–35. 10.1159/000446870 . Zhang S, Qian H, Yang Q, Hu J, Gan C, Meng W. Relationship between the extent of dissection and platelet activation in acute aortic dissection. J Cardiothorac Surg. 2015;10:162. 10.1186/s13019-015-0351-5 . Rolling CC, Barrett TJ, Berger JS. Platelet-monocyte aggregates: molecular mediators of thromboinflammation. Front Cardiovasc Med. 2023;10:960398. 10.3389/fcvm.2023.960398 . Sun W, Zheng J, Gao Y. Targeting platelet activation in abdominal aortic aneurysm: current knowledge and perspectives. Biomolecules. 2022;12. 10.3390/biom12020206 . Yamada S, Asakura H. Therapeutic strategies for disseminated intravascular coagulation associated with aortic aneurysm. Int J Mol Sci. 2022;23. 10.3390/ijms23031296 . S OS, C, A. E., S, S. A., F, N. E., and T, P. J., et al. Bleeding disorders in bothrops atrox envenomations in the brazilian amazon: participation of hemostatic factors and the impact of tissue factor. Toxins. 2020;12. 10.3390/toxins12090554 . Capecchi M, Novembrino C, Abbattista M, Boscolo-Anzoletti M, Galbiati E, et al. Involvement of the contact pathway in covid-19 coagulopathy. Intern Emerg Med. 2025. 10.1007/s11739-025-04191-z . Wang H, Zhou H, Jiang R, Qian Z, Wang F, Cao L. Globulin, the albumin-to-globulin ratio, and fibrinogen perform well in the diagnosis of periprosthetic joint infection. Bmc Musculoskelet Disord. 2021;22:583. 10.1186/s12891-021-04463-7 . Verni CC, Davila A, Sims CA, Diamond SL. D-dimer and fibrin degradation products impair platelet signaling: plasma d-dimer is a predictor and mediator of platelet dysfunction during trauma. J Appl Lab Med. 2020;5:1253–64. 10.1093/jalm/jfaa047 . Onselaer MB, Hardy AT, Wilson C, Sanchez X, Babar AK, et al. Fibrin and d-dimer bind to monomeric gpvi. Blood Adv. 2017;1:1495–504. 10.1182/bloodadvances.2017007732 . Dong J, Duan X, Feng R, Zhao Z, Feng X, et al. Diagnostic implication of fibrin degradation products and d-dimer in aortic dissection. Sci Rep. 2017;7:43957. 10.1038/srep43957 . Liu Y, Han L, Li J, Gong M, Zhang H, Guan X. Consumption coagulopathy in acute aortic dissection: principles of management. J Cardiothorac Surg. 2017;12. 10.1186/s13019-017-0613-5 . Ho L, Lenihan M, Mcvey MJ, Karkouti K. The association between platelet dysfunction and adverse outcomes in cardiac surgical patients. Anaesthesia. 2019;74:1130–7. 10.1111/anae.14631 . Badulescu OV, Ciocoiu M, Vladeanu MC, Huzum B, Plesoianu CE, et al. The role of platelet dysfunctions in the pathogenesis of the hemostatic-coagulant system imbalances. Int J Mol Sci. 2025;26. 10.3390/ijms26062756 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 05 Mar, 2026 Reviewers invited by journal 24 Feb, 2026 Editor assigned by journal 23 Feb, 2026 Editor invited by journal 04 Feb, 2026 Submission checks completed at journal 04 Feb, 2026 First submitted to journal 04 Feb, 2026 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-8718591","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":596346404,"identity":"0b90def3-6608-406c-a09c-fe209358c4da","order_by":0,"name":"Zhe Chen","email":"","orcid":"","institution":"Department of Transfusion Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhe","middleName":"","lastName":"Chen","suffix":""},{"id":596346406,"identity":"f4d00822-5052-4adb-8ebf-1231befa2126","order_by":1,"name":"Shaoheng Chen","email":"","orcid":"","institution":"Department of Transfusion Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Shaoheng","middleName":"","lastName":"Chen","suffix":""},{"id":596346407,"identity":"aa53cc49-5346-4217-a1ca-1f8c0fd88d9f","order_by":2,"name":"Zehua Zhang","email":"","orcid":"","institution":"Department of Transfusion Medicine, Delta Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zehua","middleName":"","lastName":"Zhang","suffix":""},{"id":596346408,"identity":"b5c61f10-9d53-4410-a0bc-95fe521e6028","order_by":3,"name":"Jianxin Yuan","email":"","orcid":"","institution":"Department of Transfusion Medicine, Delta Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jianxin","middleName":"","lastName":"Yuan","suffix":""},{"id":596346409,"identity":"da72869d-a535-4c24-8208-721af952cb6c","order_by":4,"name":"Hao Peng","email":"","orcid":"","institution":"Department of Cardiovascular Surgery, Delta Health Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Peng","suffix":""},{"id":596346410,"identity":"0112a9cb-6281-4f2a-b482-052df1121194","order_by":5,"name":"Nannan Pan","email":"","orcid":"","institution":"Department of Transfusion Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Nannan","middleName":"","lastName":"Pan","suffix":""},{"id":596346411,"identity":"366eb3d1-284b-4c96-a577-ec5b7fce58a7","order_by":6,"name":"Xiang Liu","email":"","orcid":"","institution":"Department of Pharmacy, Shanghai Shareonhealth Clinic","correspondingAuthor":false,"prefix":"","firstName":"Xiang","middleName":"","lastName":"Liu","suffix":""},{"id":596346412,"identity":"a4d397e2-84fe-4045-9692-7302493bf0cd","order_by":7,"name":"Jun Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYBACNvnDBw58qGCzs29vIFILnwRb4sMZZ/iSDXgOEKlFToJH2Zi3TY5xg0QCsQ6T7mGTnHHGjNlc8vHGGww1NtGEtcicPSbxoSKNz3J2WrEFw7G03AaCWhjy0oC2HGNmuJ1jJsHYcJgYLTlm0rxt/xkbbp4hVotEjjHQ+2yMG27wEKuF5xgokNmSJXuAfkkgxi/y7c2QqORnP7zxxocaG8JakIEB0VGDpIVUHaNgFIyCUTAyAADsVj+6cIfF/gAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Transfusion Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Jun","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2026-01-28 09:43:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8718591/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8718591/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103590494,"identity":"4d39c3b4-1788-4619-abe7-8ec6c2373f8d","added_by":"auto","created_at":"2026-02-27 12:05:02","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":953214,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlow diagram of patient selection. \u003c/strong\u003eAAD, type A aortic dissection; ATAAD, acute type A aortic dissection; TEG, thromboelastography.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8718591/v1/5a4a6d90544b6bf43e916e19.jpg"},{"id":103590496,"identity":"38f52937-4c4a-4c84-b378-5eb093c127db","added_by":"auto","created_at":"2026-02-27 12:05:02","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5180015,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCorrelations of platelet aggregation and fibrinolysis parameters.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSimple linear relationship between arachidonic acid (AA) / adenosine diphosphate (ADP) platelet inhibition and laboratory parameters. Platelet inhibition (%) induced by AA and ADP is plotted against the concentration of fibrinogen (FIB) (A, B), fibrinogen degradation product (FDP) (C, D), ionised calcium (Ca²⁺) (E, F) and D-dimer (G, H). Solid lines represent best-fit regression line.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8718591/v1/b10f13ade3cfbc2bc12abc98.jpg"},{"id":103590495,"identity":"0a097cb4-131d-4383-b634-99a2e725c053","added_by":"auto","created_at":"2026-02-27 12:05:02","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1247212,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDose-response relationship between FDP concentration and platelet inhibition.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHealthy human blood samples were incubated with increasing concentrations (0, 10, 20, 40, 80 or 160 µg mL⁻¹ FDP) of fibrinolytic products, and the inhibition rate of ADP/AA-induced platelet aggregation was measured. (A) Schematic diagram of fibrinolytic product preparation; (B) AA% platelet inhibition; (C) ADP% platelet inhibition. One- or two-way analysis of variance (ANOVA) was used for data analysis. Significant differences were denoted with asterisks: *(\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05), **(\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01), ***(\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), ****(\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.0001), ns indicates not significant.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8718591/v1/aff96b3ceb7e7d17e43c6654.jpg"},{"id":104835016,"identity":"ed278c5e-de3e-4b2e-b6d1-3347f6abd98d","added_by":"auto","created_at":"2026-03-17 17:38:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8113964,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8718591/v1/2450d09d-922b-410d-a4d0-4c5e6598b6f6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association Between Fibrinolysis Products and Platelet Activity in Patients with Acute Type A Aortic Dissection: A single-centre observational study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcute type A aortic dissection (ATAAD) is a highly lethal cardiovascular emergency in which mortality risk increases by 1% to 2% per hour in the absence of timely surgical intervention[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Refractory perioperative bleeding, a complication typically due to significant underlying coagulopathy, and the substantial allogeneic transfusion required after refractory bleeding are formidable challenges for clinicians.\u003c/p\u003e \u003cp\u003eThe coagulation state in ATAAD is characterized by a distinct paradox. An initial hypercoagulable thrust, driven by systemic endothelial damage, promotes microthrombosis and ischaemic complications. However, this consumptive process, augmented by flow-induced platelet dysfunction in the false lumen, swiftly depletes haemostatic reserves, culminating in secondary haemorrhagic diathesis upon surgical trauma[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Patients with ATAAD frequently present with a pathophysiological state in which the coagulation and fibrinolytic systems are simultaneously activated, resulting in profound coagulopathy[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. A hallmark of ATAAD is a significant decrease in fibrinogen, resulting from concurrent thrombosis and degradation by hyperfibrinolysis. This condition is strongly associated with major perioperative bleeding and is an independent predictor of both transfusion demand and surgical complications. As a marker of hyperfibrinolysis, the D-dimer level is drastically elevated in the peripheral blood after the onset of ATAAD, and the D-dimer level is positively correlated with the extent of dissection, disease severity, and clinical prognosis[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWithin this complex network of coagulation disorders, platelet dysfunction plays a pivotal hub role. These patients exhibit significantly reduced platelet counts, suggesting substantial consumption during thrombosis, with thrombocytopenia being an independent predictor of postoperative mortality[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Beyond the quantitative deficiency in platelet count, evidence shows that platelet aggregation function is also qualitatively impaired in patients with ATAAD. Platelet aggregation function is compromised in patients with ATAAD. Tanaka et al. used laser scattering spectrometry to evaluate 20 patients with ATAAD and reported a significant reduction in platelet aggregation rates during the acute phase, particularly in the formation of medium (25\u0026ndash;50 \u0026micro;m) and large (50\u0026ndash;70 \u0026micro;m) aggregates[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. This complex platelet dysfunction directly contributes to refractory perioperative bleeding, increased transfusion requirements, and subsequent multiple organ failure. Additionally, a prior investigation using laser scatterometry revealed inhibited platelet aggregation in patients with ATAAD, resulting in systemic platelet dysfunction and the production of relatively small microaggregates. However, the precise mechanisms responsible for platelet dysfunction in ATAAD remain poorly understood.\u003c/p\u003e \u003cp\u003eTherefore, in this study, we explored the relationship between the levels of these fibrinolysis products (fibrinogen degradation products [FDP] and D-dimer) and platelet aggregation in early ATAAD. We also used in vitro assays to investigate how they modulate platelet activation and function. This study provides a more in-depth understanding of platelet dysfunction mechanisms in ATAAD.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Study Population\u003c/h2\u003e \u003cp\u003eThis study involved a cohort of patients with ATAAD admitted to Delta Health Hospital (Shanghai, China) from July 2020 to July 2025. A retrospective analysis was conducted using the electronic medical records and laboratory test results of these patients. However, exclusion criteria for the study included known preexisting coagulation disorders, liver disease, and the use of oral anticoagulant or antiplatelet treatment. Surgical procedures were categorized into emergency surgery and elective surgery. The indications for surgical intervention and the corresponding surgical strategy were determined by the attending surgeons in accordance with the 2010 Guidelines for the Diagnosis and Management of Thoracic Aortic Disease issued by the American Association for Thoracic Surgery (AATS).\u003c/p\u003e \u003cp\u003eThis single-centre observational study was designed to analyse the data of patients with ATAAD. The relationships between early ATAAD levels, fibrinolysis products (FDP and D-dimer), calcium levels and platelet aggregation were clarified. The protocol was approved by the Institutional Review Board of Delta Health Hospital (Approval No. SDH (2025) KYSL001). Written informed consent was obtained from each participant or legal proxy. The investigation conforms to the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eThe plasma levels of D-dimer, PT, APTT, FIB, TT, and FDP were measured using an automated coagulation analyser (ACL TOP 70; Werfen/Instrumentation Laboratory, Bedford, MA, USA) in patients with suspected ATAAD immediately following admission. Baseline haematological parameters (platelet count, haemoglobin level, and red blood cell count) were measured using an automated haematology analyser (XS-9001; Sysmex Corporation, Kobe, Japan). Thromboelastography (TEG) results were analysed using a TEG\u0026reg; 5000 Hemostasis Analyzer (Haemonetics Corporation, Braintree, MA, USA). Previous medical histories, including hypertension, diabetes mellitus, coronary artery disease, stroke, and hyperlipidaemia, were extracted from the electronic medical records (EMRs).\u003c/p\u003e \u003cp\u003eMassive blood transfusion (MBT) was defined as the need for \u0026ge;\u0026thinsp;8 units of packed red blood cells within any 24-hour period. Major adverse events (MAEs), defined in accordance with the International Aortic Arch Surgery Study Group consensus statement, included in-hospital mortality, gastrointestinal bleeding, paraplegia, acute kidney injury, re-exploration for bleeding, low cardiac output syndrome, stroke, respiratory failure, multiple organ dysfunction syndrome (MODS), and severe infection[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003ePreparation of fibrinolytic products\u003c/h3\u003e\n\u003cp\u003ePlasma samples from routine clinical blood tests were used as the starting material. To induce coagulation, kaolin (200 mg/L) and CaCl₂ (0.2 M) were added at a ratio of 1 unit kaolin and 20 \u0026micro;L CaCl₂ per 1 mL plasma. The clot was centrifuged to separate it from the other plasma components, after which it was repeatedly washed with normal saline to remove residual impurities. The purified clots were homogenized using a glass grinder to increase the surface area for subsequent enzymatic reactions. Fibrinogenase for injection (100 U/mL), supplied by *** Pharmaceutical Co., Ltd., was stored at 2\u0026ndash;8\u0026deg;C until use. Fibrinogenase was added to the homogenized mixture, and the mixture was incubated overnight at 37\u0026deg;C to ensure complete enzymatic hydrolysis of fibrin into FDP. The supernatant of the fibrin-digested fibrin was collected, and the concentration and purity of the prepared FDP solution were verified using an ACL TOP 750 automated coagulation analyser. Different concentrations of fibrinolytic products were added to normal blood donor samples. Platelet function was examined using the TEG method.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll the statistical analyses were performed using GraphPad Prism version 10.0. Normally distributed continuous data are presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD), whereas nonnormally distributed continuous data are presented as the median value and interquartile range. Simple linear regression was used to assess the association between platelet aggregation and fibrinolysis parameters. For comparisons among multiple groups, one- or two-way analysis of variance (ANOVA) was used for data analysis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of factors identified as significant for in-hospital MAEs and MBTs based on the literature and on the results of the univariate analysis (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with a parallel line test performed for the variables. All analyses were performed using SPSS 26 (SPSS, IBM Corp. Armonk, USA), with \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered to indicate statistical significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDemographic characteristics\u003c/h2\u003e \u003cp\u003eA total of 352 patients with ATAAD were enrolled via an inpatient electronic information system. A total of 65 patients with coagulation disorders, 47 patients with liver disease, 71 patients who received oral anticoagulant or antiplatelet treatment and 15 patients whose baseline data were missing were excluded from the study. Finally, 154 patients with ATAAD were selected for the study, with a mean age of 52.40\u0026thinsp;\u0026plusmn;\u0026thinsp;15.02 years (29\u0026ndash;75 years). This study included 117 male and 37 female patients. A total of 98 (63.64%) patients had a history of hypertension, 5 (3.25%) had a history of diabetes mellitus, 31 (20.13%) had a history of acute renal failure, 31 (20.13%) had a history of hypoproteinaemia, and 15 (9.74%) had a history of cerebral apoplexy. Preoperative complete blood tests, coagulation profiles, and TEG results were also collected.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eCorrelations between platelet aggregation and fibrinolysis parameters\u003c/h3\u003e\n\u003cp\u003eThe plasma levels of fibrinogen (FIB), FDP, D-dimer, and calcium ions were measured separately in patients with ATAAD. A Pearson correlation analysis was then performed to evaluate their associations with the AA-induced and ADP-induced platelet inhibition rates.\u003c/p\u003e \u003cp\u003eFirst, the peripheral blood FIB concentration in patients with ATAAD was negatively correlated with both AA-induced and ADP-induced platelet inhibition rates (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.091, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.171, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;2A and B). Conversely, increased FDP levels were positively correlated with increases in the AA-induced platelet inhibition rate and the ADP-induced platelet inhibition rate (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.082, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.113, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;2C and D). A parallel correlation was observed, whereby elevated D-dimer levels corresponded to increased platelet inhibition rates for both agonists (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.057, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003; R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.076, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) (Fig.\u0026nbsp;2E and F). However, our analysis revealed no discernible association between the Ca\u003csup\u003e2+\u003c/sup\u003e concentration in peripheral blood and platelet inhibition rates among patients with ATAAD (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.014, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.136; R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.000, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.923) (Fig.\u0026nbsp;2G and H).\u003c/p\u003e\n\u003ch3\u003eEffects of in vitro fibrinolysis products on platelet aggregation\u003c/h3\u003e\n\u003cp\u003eFollowing the initial correlation observed between early fibrinolysis product concentrations and platelet aggregation levels, an in vitro system was established to further investigate this relationship. To this end, the fibrinolytic state in the setting of ATAAD was modelled by introducing plasmin to preformed clots from healthy human blood samples. The direct effects of these fibrinolysis products on platelet aggregation function were subsequently evaluated.\u003c/p\u003e \u003cp\u003eFirst, in the control group (plasma from healthy volunteers), the AA-induced and ADP-induced platelet inhibition rates were 48.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4% and 49.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.6%, respectively. With increasing concentrations of added fibrinolysis products (reflected by increasing final FDP concentrations), both the ADP-induced and AA-induced platelet inhibition rates increased in a dose-dependent manner. Notably, a saturation point was reached at an FDP concentration of approximately 80 \u0026micro;g/mL, beyond which no further increase in inhibition was detected.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative outcomes of patients with ATAAD\u003c/h2\u003e \u003cp\u003eMultivariate logistic regression analysis was subsequently conducted on variables with a \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.1. Based on the backward-stepwise regression method, factors with a \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026ge;\u0026thinsp;0.1 were removed from the regression model at each step. After adjustment for confounders, the results are shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Multivariate logistic regression analysis revealed that age\u0026thinsp;\u0026gt;\u0026thinsp;65 years (OR\u0026thinsp;=\u0026thinsp;1.093; 95% confidence interval [CI] 0.984\u0026ndash;3.659; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.053) and ADP-induced and AA-induced platelet inhibition rates (OR\u0026thinsp;=\u0026thinsp;2.531; 95% CI 1.451\u0026ndash;34.866; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021; OR\u0026thinsp;=\u0026thinsp;1.903; 95% CI 1.071\u0026ndash;42.547; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.041) and a D-dimer concentration\u0026thinsp;\u0026ge;\u0026thinsp;5.00 mg/L (OR\u0026thinsp;=\u0026thinsp;2.629; 95% CI 1.654\u0026ndash;9.675; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.029) were independent risk factors for postoperative MBT.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of acute type A aortic dissection.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics, n\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e154\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographics, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e52.40 (15.02)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex, Male, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e117 (75.97)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComorbidities and medical history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e98 (63.64)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (3.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior bypass surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (9.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior valve replacement surgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (2.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrial fibrillation, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (3.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac insufficiency, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11(7.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArrhythmia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (9.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral apoplexy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (9.74)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOPD, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (12.34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (2.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute renal failure, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31(20.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnemia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (5.84)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePericardial effusion, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27(17.53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePleural effusion, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32 (20.78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoproteinemia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31 (20.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParaplegia, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (3.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLaboratory tests on admission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-Op PLT (\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e174.00 (65.33)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-Op HGB (g/L), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e125.20 (22.98)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePre-Op RBC (\u0026times;10\u003csup\u003e12\u003c/sup\u003e/L), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.21 (0.73)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT (second), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.96 (2.99)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPTT (second), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e31.77 (5.14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINR, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.10 (0.24)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFIB (g/L), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.83 (1.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTT (second), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e17.98 (8.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-Dimer (\u0026micro;g/mL), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.63 (20.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFDP (\u0026micro;g/mL), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57.69 (82.20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAT (%), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e90.71 (16.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR (min), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.10 (1.82)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK (min), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.99 (1.44)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAngle (degree), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.57 (9.62)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMA (mm), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64.30 (9.76)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAA (%), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.64 (32.60)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADP (%), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e62.56 (29.90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28.47 (48.40)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCa\u003csup\u003e2+\u003c/sup\u003e (mmol/L), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.14 (0.12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eK+ (mmol/L), mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.75 (0.65)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBC transfusion, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e120 (77.92)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBC (U) transfusion, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11.22 (16.16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRBC, \u0026gt; 8U, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59 (38.31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet transfusion(U), mean(SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.36 (2.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlasma transfusion(U), mean(SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.97 (27.47)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative in-hospital mortality, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (1.30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003ea. Abbreviations: COPD, chronic obstructive pulmonary disease; CRI, chronic renal insufficiency; PLT, platelet; HGB, hemoglobin; RBC, red blood cells, PT, Prothrombin Time; APTT, activated partial thromboplastintime; INR, international normalized ratio; FIB, fibrinogen; TT, thrombin time; FDP,fibrin(ogen) degradation products; AT, antithrombin time; R, reaction; K, kinetics time; MA, maximum amplitude; AA, arachidonic acid; ADP, adenosine diphosphate; CRP, c-reactive protein\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eb. Data are reported as number (percent), mean (SD), or median (Q1- Q3).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRisk factors in multivariate logistic regression analysis of postoperative in-hospital MAEs and MBT in patients with ATAAD\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMBT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;65 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.093\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.984\u0026ndash;3.659\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADP-induced platelet inhibition rates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.531\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.451\u0026ndash;34.866\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAA-induced platelet inhibition rates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.903\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.071\u0026ndash;42.547\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.041\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer\u0026thinsp;\u0026ge;\u0026thinsp;5.00 mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.629\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.654\u0026ndash;9.675\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eIn-hospital MAEs\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u0026thinsp;\u0026gt;\u0026thinsp;65 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.423\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.234\u0026ndash;3.598\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer\u0026thinsp;\u0026ge;\u0026thinsp;5.00 mg/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.211\u0026ndash;8.898\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.465\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMBT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.543\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.102\u0026ndash;54.873\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADP-induced platelet inhibition rates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.634\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.654\u0026ndash;34.675\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAA-induced platelet inhibition rates\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.655\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.765\u0026ndash;56.938\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eAbbreviations: MBT, massive blood transfusion; MAEs, major adverse events; ATAAD, acute type A aortic dissectio. ADP, adenosine diphosphate; AA, arachidonic acid.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn addition, the analysis revealed preoperative ADP-induced and AA-induced platelet inhibition rates (OR\u0026thinsp;=\u0026thinsp;2.634, 95% CI 1.654\u0026ndash;34.675, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035; OR\u0026thinsp;=\u0026thinsp;1.655, 95% CI 1.765\u0026ndash;56.938, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.019), D-dimer levels (OR\u0026thinsp;=\u0026thinsp;2.546, 95% CI 1.211\u0026ndash;8.898, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.465), and MBT (OR\u0026thinsp;=\u0026thinsp;3.543, 95% CI 1.102\u0026ndash;54.873, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013) as independent risk factors for in-hospital MAEs.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAs a cornerstone effector of thrombosis and inflammation, platelet dysfunction is recognized as a key driver of ATAAD pathogenesis[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Recent evidence has indicated that thrombocytopenia, dysregulated platelet activation, and the subsequent thrombo-inflammatory cascade collectively influence patient outcomes, thereby critically determining surgical recovery and long-term survival[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This study preliminarily revealed the association between early circulating fibrinolysis product levels and platelet dysfunction in patients with ATAAD and explored its potential role in predicting patient prognosis.\u003c/p\u003e \u003cp\u003eMechanistically, the scale of intimal tear and subendothelial matrix exposure in patients with ATAAD inevitably triggers massive platelet activation. Through the release of procoagulant factors (including CD40 ligands) and proinflammatory mediators (such as TNF-α and IL-6), platelets contribute to vascular wall inflammation and medial degradation, ultimately accelerating dissection progression[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In addition to the release of inflammatory mediators, monocyte-platelet aggregates (MPAs) also serve as a pivotal mechanism driving dissection progression by enhancing monocyte adhesion and infiltration[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, few studies have focused on the effects of fibrinolysis products, such as FDP and D-dimer, in the peripheral blood of patients with ATAAD on platelet function.\u003c/p\u003e \u003cp\u003eBy measuring the plasma concentrations of FIB, FDP, and D-dimer using TEG in 154 patients with ATAAD, we initially identified an inverse correlation between peripheral FIB levels and both ADP-induced and AA-induced platelet inhibition rates. Our findings are consistent with early research showing that elevated FIB is associated with a significantly reduced inhibition rate of the ADP pathway, as assessed by TEG or LTA, in patients with DAPT-treated coronary artery disease or those who underwent PCI compared with those with normal or low FIB. As platelet aggregation culminates in fibrinogen binding to the GPIIb/IIIa receptor, extremely high fibrinogen levels can counteract the effects of antiplatelet drugs that target upstream pathways such as ADP or AA. This is achieved by providing a surplus of ligand, which promotes extensive cross-linking between platelets even when a fraction of receptors remains active, bypassing pharmacological blockade. Elevated fibrinogen contributes to adverse cardiovascular risk by increasing the clot strength (MA-CFF) and fibrin polymerization rate (α-angle), serving as an indirect marker of inadequate inhibition of the AA pathway (fibrin clot strength is associated with an increased risk of major adverse cardiac events after TAVR).\u003c/p\u003e \u003cp\u003eFurthermore, our study revealed that increased levels of FDP and D-dimer were positively associated with increased platelet inhibition rates following both ADP and AA stimulation. Early studies have also demonstrated that, in trauma patients, the plasma D-dimer levels are associated with trauma-induced platelet dysfunction, making it a potential predictor. Likewise, studies regarding the FDP-platelet relationship in disease states have concentrated on correlating peripheral blood FDP levels with platelet counts. Elevated FDP levels in patients with disseminated intravascular coagulation (DIC) frequently coincide with thrombocytopenia, reflecting platelet consumption due to excessive fibrinolytic activation[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Similarly, high FDP levels in trauma patients or patients with sepsis are associated with reduced platelet counts and coagulation dysfunction[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo definitively establish the impact of fibrinolysis products on platelet function, we generated these products from clotted healthy human blood, which contained D-dimers and fibrin degradation products (FDPs). Our results confirmed that fibrinolysis products directly inhibit platelet aggregation in a concentration-dependent manner. Early findings indicated that FDPs play a critical role in platelet activation, particularly by modulating signalling pathways. Research indicates that FDPs interfere with normal signalling mechanisms by affecting the activity of platelet surface receptors. FDPs can inhibit glycoprotein VI (GPVI) signalling, leading to impaired calcium mobilization and reducing platelet aggregation capacity[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Furthermore, the heterogeneity among FDP subtypes translates into diverse biological activities on platelets. It has been established that cross-linked FDPs (such as D-dimers) have a pronounced inhibitory effect on platelet aggregation and activation, in contrast to noncross-linked FDPs, which have negligible effects[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. During trauma, D-dimers and FDPs mediate platelet inhibition through the binding of GPVI and integrin αIIbβ3, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. While our findings corroborate earlier studies regarding the inhibitory effects of FDPs and D-dimers on platelet activation, we used a preparation representing the complete mixture of fragments from plasmin-induced proteolysis of fibrinogen and fibrin. Future work will delineate the specific contributions and mechanisms of individual components of this fibrinolysis product mixture on platelet activation.\u003c/p\u003e \u003cp\u003eNumerous studies have reported that ATAAD, D-dimers and FIB serve not only as highly sensitive diagnostic markers for initial screening but also as robust prognostic biomarkers indicating disease severity, risk of complications, and mortality[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Multivariate logistic regression analysis in this study revealed elevated admission D-dimer levels as an independent risk factor for in-hospital MAEs in patients with ATAAD. In addition, both ADP-induced and AA-induced platelet inhibition rates were associated with 30-day postoperative mortality in patients with ATAAD in this study. This phenomenon likely reflects underlying platelet dysfunction, where higher inhibition rates compromise haemostatic capacity, thereby predisposing patients to greater bleeding and subsequent complications during disease progression or surgical intervention[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe also reported a correlation between elevated ADP-induced and AA-induced platelet inhibition rates and increased blood product utilization. Previous studies have shown that preoperative thrombocytopenia or platelet dysfunction (due to antiplatelet medication) increases intraoperative blood loss and transfusion requirements[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The confluence of preexisting platelet dysfunction and complications associated with substantial blood transfusion is postulated to contribute to poor outcomes in patients with ATAAD.\u003c/p\u003e \u003cp\u003eThis study has several limitations. The findings of this single-centre retrospective study, which is limited by its sample size, should be considered with the potential for selection bias. Although our study focused on D-dimer levels and FDPs, the pathogenesis of platelet dysfunction likely involves additional mediators, and integrating knowledge from other disciplines remains essential. To build upon these encouraging findings, we propose that subsequent work validate our observations by examining platelet ultrastructure, receptor dynamics, and their in vivo relevance.\u003c/p\u003e \u003cp\u003eIn summary, this study has preliminarily elucidated the association between circulating D-dimer/FDP levels and platelet aggregation function in patients with ATAAD. We demonstrated the direct inhibitory effect of fibrinolysis products on platelet aggregation, a finding crucial for understanding the platelet dysfunction that occurs during ATAAD pathogenesis. Furthermore, our results highlight the clinical value of platelet function monitoring for predicting perioperative transfusion requirements and patient prognosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAUTHOR CONTRIBUTIONS\u003c/p\u003e\n\u003cp\u003eZ.C. designed and conceived this project; S.C. and Z.Z. performed experiments and generated data; J.Y. analyzed and interpreted data; H.P. and N.P. made suggestions for this project; S.C. wrote the draft; J.Z. and X.L. revised and finalized the manuscript; All authors contributed to and approved the manuscript. Zhe Chen, Shaoheng Chen and Zehua Zhang contributed equally to this work.\u003c/p\u003e\n\n\u003cp\u003eCOMPETING INTERESTS: The authors declare no competing interests.\u003c/p\u003e\n\n\u003cp\u003eSOURCES OF FUNDING: This work was supported by Social Development (Medical and Health) Program of Science and Technology Development Fund of Qingpu District, Shanghai (Grant No. QKY2025-80); WeiGao Science Foundation of Chinese Society of Blood Transfusion (CSBT-WG-2024-08). Clinical Research Innovation Plan of Shanghai General Hospital (CCTR-2025C47).\u003c/p\u003e\n\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\n\u003cp\u003eThe protocol was approved by the Institutional Review Board of Delta Health Hospital (Approval No. SDH (2025) KYSL001). Written informed consent was obtained from each participant or legal proxy. The investigation conforms to the principles of the Declaration of Helsinki.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChen L, Pan Y, Zhang H, Chen Y, Wang C, et al. Propensity score matching analysis of valve-sparing versus aortic root replacement in type a aortic dissection patients. Nat Commun. 2025;16:1238. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41467-025-56509-2\u003c/span\u003e\u003cspan address=\"10.1038/s41467-025-56509-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu H, Diao YF, Shao YF, Qian SC, Zeng ZH, et al. Prognostic implication of residual inflammatory trajectories in acute type i aortic dissection: dual-center prospective cohort study. Int J Surg. 2024;110:3346\u0026ndash;56. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/JS9.0000000000001245\u003c/span\u003e\u003cspan address=\"10.1097/JS9.0000000000001245\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRylski B, Schilling O, Czerny M. Acute aortic dissection: evidence, uncertainties, and future therapies. Eur Heart J. 2023;44:813\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/eurheartj/ehac757\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehac757\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYuan X, Mitsis A, Nienaber CA. Current understanding of aortic dissection. Life-Basel. 2022;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/life12101606\u003c/span\u003e\u003cspan address=\"10.3390/life12101606\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eItagaki R, Kimura N, Mieno M, Hori D, Itoh S, et al. Characteristics and treatment outcomes of acute type a aortic dissection with elevated d-dimer concentration. J Am Heart Assoc. 2018;7:e9144. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/JAHA.118.009144\u003c/span\u003e\u003cspan address=\"10.1161/JAHA.118.009144\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQiu L, Ji Q, Miao H, Long M, Gong M, et al. Prognostic value of d-dimer in acute type a aortic dissection and intramural hematoma: observations from the acute aortic syndrome group of the registry of acute non‐traumatic chest pain in china. J Am Heart Assoc. 2025;14:e36843. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/JAHA.124.036843\u003c/span\u003e\u003cspan address=\"10.1161/JAHA.124.036843\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe X, Balati A, Wang W, Wang H, Zhang B, et al. Association of thrombocytopenia and d-dimer elevation with in-hospital mortality in acute aortic dissection. Ann Med. 2025;57:2478477. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/07853890.2025.2478477\u003c/span\u003e\u003cspan address=\"10.1080/07853890.2025.2478477\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSmedberg C, Hultgren R, Olsson C, Steuer J. Incidence, presentation and outcome of acute aortic dissection: results from a population-based study. Open Heart. 2024;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/openhrt-2023-002595\u003c/span\u003e\u003cspan address=\"10.1136/openhrt-2023-002595\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu G, Wang H, Luo Q, Cao L, Yang L, et al. Low postoperative blood platelet count may be a risk factor for 3-year mortality in patients with acute type a aortic dissection. J Cardiothorac Surg. 2021;16:274. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13019-021-01623-7\u003c/span\u003e\u003cspan address=\"10.1186/s13019-021-01623-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\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\u0026ndash;41. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/s0022-5223(03)00734-7\u003c/span\u003e\u003cspan address=\"10.1016/s0022-5223(03)00734-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYan TD, Tian DH, Lemaire SA, Hughes GC, Chen EP, et al. Standardizing clinical end points in aortic arch surgery. Circulation. 2014;129:1610\u0026ndash;6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1161/CIRCULATIONAHA.113.006421\u003c/span\u003e\u003cspan address=\"10.1161/CIRCULATIONAHA.113.006421\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErdoes G, Ahmed A, Kurz SD, Gerber D, Bolliger D. Perioperative hemostatic management of patients with type a aortic dissection. Front Cardiovasc Med. 2023;10:1294505. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fcvm.2023.1294505\u003c/span\u003e\u003cspan address=\"10.3389/fcvm.2023.1294505\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhu Y, Lingala B, Baiocchi M, Tao JJ, Toro AV, et al. Type a aortic dissection-experience over 5 decades: jacc historical breakthroughs in perspective. J Am Coll Cardiol. 2020;76:1703\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jacc.2020.07.061\u003c/span\u003e\u003cspan address=\"10.1016/j.jacc.2020.07.061\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQin C, Gu J, Qian H, Liu R, Xu F, et al. Potential mechanism of post-acute aortic dissection inflammatory responses: the role of mtdna from activated platelets. Cardiology. 2016;135:228\u0026ndash;35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1159/000446870\u003c/span\u003e\u003cspan address=\"10.1159/000446870\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang S, Qian H, Yang Q, Hu J, Gan C, Meng W. Relationship between the extent of dissection and platelet activation in acute aortic dissection. J Cardiothorac Surg. 2015;10:162. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13019-015-0351-5\u003c/span\u003e\u003cspan address=\"10.1186/s13019-015-0351-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRolling CC, Barrett TJ, Berger JS. Platelet-monocyte aggregates: molecular mediators of thromboinflammation. Front Cardiovasc Med. 2023;10:960398. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fcvm.2023.960398\u003c/span\u003e\u003cspan address=\"10.3389/fcvm.2023.960398\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun W, Zheng J, Gao Y. Targeting platelet activation in abdominal aortic aneurysm: current knowledge and perspectives. Biomolecules. 2022;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/biom12020206\u003c/span\u003e\u003cspan address=\"10.3390/biom12020206\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYamada S, Asakura H. Therapeutic strategies for disseminated intravascular coagulation associated with aortic aneurysm. Int J Mol Sci. 2022;23. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms23031296\u003c/span\u003e\u003cspan address=\"10.3390/ijms23031296\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eS OS, C, A. E., S, S. A., F, N. E., and T, P. J., et al. Bleeding disorders in bothrops atrox envenomations in the brazilian amazon: participation of hemostatic factors and the impact of tissue factor. Toxins. 2020;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/toxins12090554\u003c/span\u003e\u003cspan address=\"10.3390/toxins12090554\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCapecchi M, Novembrino C, Abbattista M, Boscolo-Anzoletti M, Galbiati E, et al. Involvement of the contact pathway in covid-19 coagulopathy. Intern Emerg Med. 2025. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s11739-025-04191-z\u003c/span\u003e\u003cspan address=\"10.1007/s11739-025-04191-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang H, Zhou H, Jiang R, Qian Z, Wang F, Cao L. Globulin, the albumin-to-globulin ratio, and fibrinogen perform well in the diagnosis of periprosthetic joint infection. Bmc Musculoskelet Disord. 2021;22:583. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12891-021-04463-7\u003c/span\u003e\u003cspan address=\"10.1186/s12891-021-04463-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVerni CC, Davila A, Sims CA, Diamond SL. D-dimer and fibrin degradation products impair platelet signaling: plasma d-dimer is a predictor and mediator of platelet dysfunction during trauma. J Appl Lab Med. 2020;5:1253\u0026ndash;64. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/jalm/jfaa047\u003c/span\u003e\u003cspan address=\"10.1093/jalm/jfaa047\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOnselaer MB, Hardy AT, Wilson C, Sanchez X, Babar AK, et al. Fibrin and d-dimer bind to monomeric gpvi. Blood Adv. 2017;1:1495\u0026ndash;504. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1182/bloodadvances.2017007732\u003c/span\u003e\u003cspan address=\"10.1182/bloodadvances.2017007732\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDong J, Duan X, Feng R, Zhao Z, Feng X, et al. Diagnostic implication of fibrin degradation products and d-dimer in aortic dissection. Sci Rep. 2017;7:43957. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/srep43957\u003c/span\u003e\u003cspan address=\"10.1038/srep43957\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Han L, Li J, Gong M, Zhang H, Guan X. Consumption coagulopathy in acute aortic dissection: principles of management. J Cardiothorac Surg. 2017;12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s13019-017-0613-5\u003c/span\u003e\u003cspan address=\"10.1186/s13019-017-0613-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHo L, Lenihan M, Mcvey MJ, Karkouti K. The association between platelet dysfunction and adverse outcomes in cardiac surgical patients. Anaesthesia. 2019;74:1130\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/anae.14631\u003c/span\u003e\u003cspan address=\"10.1111/anae.14631\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBadulescu OV, Ciocoiu M, Vladeanu MC, Huzum B, Plesoianu CE, et al. The role of platelet dysfunctions in the pathogenesis of the hemostatic-coagulant system imbalances. Int J Mol Sci. 2025;26. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/ijms26062756\u003c/span\u003e\u003cspan address=\"10.3390/ijms26062756\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"ATAAD, FIB, FDP, D-dimer, Platelet dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-8718591/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8718591/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eAcute type A aortic dissection (ATAAD) is a highly lethal cardiovascular emergency in which platelet dysfunction plays a pivotal role; however, the underlying mechanisms of this dysfunction remain poorly understood.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn the present study, we investigated the relationship between fibrinolytic products at admission and platelet function. We retrospectively analysed the data of patients with ATAAD from July 2020 to July 2025 at Delta Health Hospital (Shanghai, China). Pearson\u0026rsquo;s chi-square test was used to analyse the correlations between platelet aggregation and fibrinolysis parameters. The risk factors affecting postoperative in-hospital death and massive blood transfusion (MBT) were analysed using multivariate logistic regression analysis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 154 patients with ATAAD, with a mean age of 52.40\u0026thinsp;\u0026plusmn;\u0026thinsp;15.02 years, were selected for the study. In patients with ATAAD, the peripheral blood fibrinogen (FIB) concentration was negatively correlated with both adenosine diphosphate (ADP)-induced and arachidonic acid (AA)-induced platelet inhibition rates, whereas elevated D-dimer and fibrinogen degradation product (FDP) levels were associated with increased platelet inhibition rates in response to both agonists. We further found that fibrinolysis products derived from healthy human blood samples enhanced both ADP- and AA-induced platelet inhibition in a dose-dependent manner. Multivariate logistic regression analysis revealed elevated levels of D-dimer and FDP, along with increased ADP-induced and AA-induced platelet inhibition rates, as independent predictors of MBT and in-hospital major adverse events (MAEs).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn summary, our study elucidates the association between fibrinolysis products and platelet activity in patients with ATAAD and highlights the clinical value of platelet function monitoring in predicting perioperative transfusion requirements and patient prognosis.\u003c/p\u003e","manuscriptTitle":"Association Between Fibrinolysis Products and Platelet Activity in Patients with Acute Type A Aortic Dissection: A single-centre observational study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-27 12:04:57","doi":"10.21203/rs.3.rs-8718591/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"287837660199553376694111081277860918986","date":"2026-03-05T15:55:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-24T13:44:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-23T08:00:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-04T09:05:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-04T06:57:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2026-02-04T06:52:54+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bad61808-f2bd-402b-bcd8-9299b986f397","owner":[],"postedDate":"February 27th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-27T12:04:57+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-27 12:04:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8718591","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8718591","identity":"rs-8718591","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}