Comparison of the TEG 6s thrombelastograph with conventional coagulation parameters in infants and toddlers during craniosynostosis surgery - a prospective observational clinical study

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The Thrombelastograph Coagulation Analyzer TEG 6s is a modern point of care (POC) device for rapid detection of perioperative coagulation disorders and for the guidance of coagulation factor substitution. By now little is known about changes in TEG 6s values in infants and toddlers with perioperative coagulopathies. The aim of this study was to monitor, compare and relate TEG 6s parameters with conventional coagulation parameters (CCP) during pediatric CS. Methods: In this prospective clinical observational study 29 infants and toddlers (median age 6 months, median weight 8.5 kg) undergoing CS were enrolled. Blood was sampled pre- and perioperatively. Samples were analyzed by TEG 6s and using CCP (prothrombin time, aPTT, INR, fibrinogen, factor XIII, and antithrombin III). The TEG 6s parameters (reaction time “R”, coagulation time “K”, maximum amplitude “MA”) and CCP were related using linear regression analyses. Results: Regarding the linear relationship of “R”, “MA”, and “K” of the TEG 6s assays CK, CRT, CKH, and CFF with CCP highest R 2 values were obtained for the CK-R – aPTT relationship (R 2 = 0.448), for the CK-MA – fibrinogen relationship (R 2 = 0.47) and for the CK-K - aPTT relationship (R 2 =0.631). Conclusions: The relationship between TEG 6s and conventional coagulation assays is rather low in the perioperative setting of CS in infants. This may be explained by the fact that TEG 6s and conventional coagulation assays do not employ identical methods and do not measure the same coagulatory substrates and dynamics. Our results may contribute to the establishment of reference ranges for TEG6s parameters. Further studies should evaluate which method may be preferred and should establish algorithms and treatment thresholds to guide coagulation management in the pediatric population. Trial registration: not applicable (observational data only, no trial interventions) craniosynostosis surgery coagulation pediatric population Figures Figure 1 Figure 2 Background The Thrombelastograph Coagulation Analyzer TEG 6s (Haemonetics, Munich, Germany) is a modern automated point of care (POC) device that can be used for the detection of perioperative coagulation deficiencies. It has the potential to accelerate and broaden the investigation of coagulatory function as viscoelastic tests allow for fast analysis of clot initiation, amplification, strengthness and lysis in whole blood samples. As rather small amounts of whole blood (0.3ml) are needed per sample the TEG 6s may contribute to save blood at the same time and is especially suitable for the pediatric setting. Conventional coagulation tests require rather high volumes of blood (at least 1 ml) and due to logistic issues and the need for specialized laboratories it takes roundabout 45–60 minutes until results are available. After this time frame these results may no longer reflect the current coagulation status. Additionally, these results do not investigate fibrin polymerization, test for a potential hyperfibrinolysis nor investigate platelet function. Premature fusion of one or more cranial sutures occurs in one out of 2000–3000 live births. In 80% of cases such craniosynostosis occurs as an isolated condition, the majority probably being caused by intrauterine fetal head constraint. Compensatory growth occurs at other suture sites and results in a characteristic abnormal head shape.[ 1 , 2 ] Craniosynostosis surgery (CS) is a method to correct such an abnormal head shape and to allow the growing brain to expand normally. However, severe diffuse perioperative bleeding is quite common during CS and can lead to a significant coagulopathy which is characterized by prolongations of conventional coagulation assays including prothrombin times (PT), international normalized ratios (INR), partial thromboplastin times (PTT) and thrombin times.[ 3 ] Targeted coagulation therapy is therefore often required during CS. The majority of pediatric craniofacial patients have normal coagulation preoperatively.[ 4 ] The perioperative course of CS is suitable for analyzing and comparing the functionality and benefits of different coagulation tests. By now little is known about changes in thrombelastography (TEG) values in infants and toddlers with perioperative coagulopathies. [ 5 ] The aim of this study was to monitor, compare and relate the TEG 6s parameters reaction time (R), coagulation time (K), maximum amplitude (MA) with conventional coagulation parameters (prothrombin time, aPTT, INR, fibrinogen, factor XIII levels, and antithrombin III levels) under perioperative conditions in pediatric CS. Methods Study population and protocol Patients In this prospective clinical observational study 29 successive infants and toddlers undergoing elective CS were enrolled from July 2020 to July 2022. Inclusion criteria were age < 4 years, singular CS and no concomitant diseases including syndromic diseases. Exclusion criteria were diagnosis of hepatitis B / C or HIV, age ≥ 4 years or refusal for study participation. The study was conducted in compliance with the Declaration of Helsinki. Written parental respectively legal guardian consent was obtained in all patients in advance. Demographic data comprised age at surgery, preoperative weight, height and sex. Perioperative monitoring included S p O 2 , electrocardiogram, invasive arterial blood pressure, end tidal CO 2 and body temperature. Information on primary diagnosis, medication, former treatments and laboratory values were obtained from patient charts. No additional catheter placements or other invasive procedures were performed for study purposes. Reference ranges for TEG 6s were determined in compliance with the Clinical and Laboratory Standards Institute (CLSI) C28A3 guideline. [ 6 ] Anesthesia / perioperative course Anesthesia was performed by experienced pediatric anesthesiologists using total intravenous anesthesia with continuous weight-adjusted infusion of propofol and remifentanil. All patients received endotracheal intubation and an arterial catheter. Maintenance of vital parameters as well as fluid and volume substitution were performed according to common anesthesia standards and institutional standard operating procedures. Blood gas analyses were taken when required. All patients received tranexamic acid (TXA) with a bolus of 20 mg/kgBW and a perioperative perfusion rate of 2 mg/kg/h. Blood sampling Blood was sampled from study patients either from the arterial canula using routine standards of hygienic catheter handling: one ethylendiamintetraacetate (EDTA)-anticoagulated blood sample for whole blood and cell count (0.7 ml) and one citrate-anticoagulated blood sample for analysis with the thrombelastograph TEG 6s as well as analysis of conventional coagulation markers (Quick, INR, aPTT, fibrinogen, factor XIII levels, and antithrombin III levels) (1 ml). 0.3 ml of the citrated blood sample was taken out of the tube and analyzed in the TEG 6s. 0.7 ml of the citrated blood sample were sent to the central laboratory for analysis of conventional coagulation parameters (CCP). As all coagulation parameters were analyzed from the same citrated tube, no additional blood had to be taken for study and sampling-related differences could be excluded. Altogether on each sampling time-point 1.7 ml of whole blood were taken. In accordance with the WHO guideline on blood collection from children, the amount of patient blood collected for study purposes up to a body weight of 15 kg did not exceed 12 ml. [ 7 ] The first sample was taken preoperatively after induction of general anesthesia to analyze baseline coagulation parameters. Further samples were taken perioperatively as ordered by the attending anesthesiologist in the case of relevant bleeding. All results that were obtained from coagulation analyses were immediately made available so that treatment could be adjusted if necessary. Coagulation analyses Laboratory analysis of conventional coagulation markers was performed using the Atellica COAG 360 System (Siemens Healthineers, Munich, Germany). aPTT was detected using the Dade Actin FS assay (Siemens, Erlangen, Germany using ellagic acid activation. The prothrombin time was analyzed using the Dade Innovin assay (Siemens) using activation with recombinant human tissue factor. Factor XIII levels were analyzed using the Dade Berichrom FXIII assay (Siemens). Antithrombin III levels using the Berichrom Antithrombin III assay (Siemens) and fibrinogen levels using a respective anti human fibrinogen antiserum assay (Siemens). The TEG 6s system is a fully automated, FDA approved, point of care (POC) thrombelastograph. It assesses whole blood coagulation properties due to activation with specific agonists using the resonance method.[ 8 ] A blood sample of 0.3 ml is pipetted into the entry port in the four-channel self-contained microfluidics. For analysis we used these four channels: the CK-channel (“citrated kaolin”), CKH-channel (“citrated kaolin and heparinase”), the CFF-channel (“citrated functional fibrinogen”) and the CRT channel (“citrated rapid TEG”).[ 5 ] Each assay incorporates distinct activators, such as kaolin, which activates the intrinsic coagulation pathway. The CKH additionally incorporates heparinase to neutralize the influence of heparin in the blood sample. In CRT, both kaolin and tissue factor are included, thereby activating the intrinsic and extrinsic coagulation pathways. CFF is an assay in which the extrinsic coagulation pathway is activated, and it employs a potent GPIIb/IIIa platelet inhibitor to inhibit platelet function and determine the fibrin contribution to clot strength. It is utilized in conjunction with Kaolin TEG to assess the relative contribution of platelets and fibrin to the overall strength of the clot. [ 9 ] Approximately 20 µl of blood is delivered to each cell where it is exposed to a sinusoidal motion range (20–500 Hz). As clotting proceeds, clot-strength-specific resonance frequencies are detected by a photodetector and converted into TEG-equivalent units in millimeters. The latter are used to generate TEG tracings, which are illustrating the viscoelastic change of the blood sample in real time.[ 10 ] [ 8 ] TEG 6s allows statements on the primary hemostasis, plasmatic coagulation, thrombin formation, clot stability and lysis as well as the effect of heparin and describes the clot resistance as a function of the measuring duration. The TEG 6s is faster than conventional coagulation analysis. First conclusions are possible after 7–10 min. [ 11 ] The test parameter "MA" is of particular importance: It allows statements to be made about the strength of the clot and thus supports the indication for treatment with fibrinogen, platelets and possibly other coagulation factor preparations.[ 11 ] Statistical analysis Categorical data are presented as frequencies and percentages. Continuous data are presented as median, range and interquartile range (IQR). The relationship between TEG 6s parameters and conventional laboratory parameters was analyzed using linear regression. To detect a deterministic relationship between respective parameters, the coefficient of determination R 2 and its respective standard error (SE) were calculated. All charts and analyses were created with the software SPSS® Statistics version 28 (SPSS, Chicago, IL, USA). Results Patient history, intraoperative bleeding and blood product administration. Patient parameters including the demographic parameters age, sex, body weight and height, as well as duration of surgery, the amount of administered red blood cell concentrates (RBC), fresh frozen plasma (FFP) and tranexamic acid (TXA) are given in Table 1 . In the case of clinically relevant blood loss we administered a combination of RBC and FFP to replace intravascular volume as well as coagulation factors. Fibrinogen concentrates, prothrombin complex concentrate (PPSB) as well as FXIII preparations were not administered. Exact amount of intraoperative bleeding could not be determined reliably mainly due to blood loss in surgical gauzes. Preoperative and intraoperative coagulation analyses Conventional coagulation tests The inconspicuous coagulation history in our patients was accompanied by relatively widely distributed conventional coagulation values which are mainly within normal ranges (Fig. 1 a-f). TEG 6s parameters Medians with 2.5th and 97.5th percentiles derived from preoperative TEG 6s measurements are depicted in Table 2 , which serves as an initial basis for reference ranges of these parameters in this age group. Correlations of TEG 6s results and conventional coagulation tests are depicted in Fig. 2 a-d. Table 2 Medians with 2.5th and 95th percentils derived from preoperative TEG 6s measurements Pre Op reference (95% interval) median 2.5th percentile 95th percentile CK (n = 28) R (min) 8.8 5.3 14.0 K (min) 1.4 1.0 2.8 MA (mm) 60.0 46.9 67.8 CKH (n = 29) R (min) 9.1 5.0 13.9 K (min) 1.4 0.9 2.8 MA (mm) 59.5 47.8 67.7 CFF (n = 29) MA (mm) 18.7 14.6 26.4 A10 (mm) 17.7 13.7 23.7 Determination of linear relationships of conventional coagulation tests and TEG 6s parameters. All linear relationship analyses with associated R 2 values are given in table 3a (preoperative analyses) and table 3b (intraoperative analyses). For determination of the linear relationship of “R” of the TEG 6s assays CK, CRT, CKH, and CFF with conventional coagulation parameters the largest R 2 was obtained for the CK-R – aPTT relationship (R 2 = 0.448; Fig. 2 a). For linear relationship of “MA” of the respective TEG 6s assays with conventional coagulation parameters the highest R 2 was obtained for the CK-MA – fibrinogen level relationship (R 2 = 0.47; Fig. 2 b). Except CK-ACT vs aPTT, R 2 values of all other linear relationships were smaller (table 3a and table 3b). Of note, linear relationship analyses for which clear relations may be expected (CFF-MA – fibrinogen levels and CK-MA – aPTT) revealed preoperative R 2 values which were in the range of 0.25 and lower (Figs. 2 c and 2 d). The relation of FXIII levels and the CFF-MA revealed a R 2 of 0.291. The relation of preoperative CK-K and aPTT values revealed R 2 = 0.631. However intraoperative data of the CK-K / aPTT relationship revealed R 2 = 0.273. Discussion Our present study depicts perioperative coagulation data from a pediatric patient population, which were measured during CS using conventional coagulation assays and the TEG 6s POC device. Of note the linear relationship of TEG 6s derived data and conventional coagulation tests was rather low, even where clear relations might have been expected. Relevant correlations may especially be present for the CFF-MA – fibrinogen level relationship and also for the CK-R – aPTT relationship as similar substrates are effective in the respective assays. However, in our pediatric patient group both relationships still revealed a R 2 below of 0.5. Until now, published evidence in the youngest age group for bleeding management strategies in neonates and children is scarce.[ 12 ] Therefore, it needs to be evaluated which of the test procedures employed in our study should be preferred and could be potential parameters to guide individual coagulation therapy. Thromboelastography contributes to the investigation of coagulopathies and goal-directed management of bleeding by providing a quick and complete picture of clot formation, strength, and lysis in whole blood. The differential contribution of coagulation factors, fibrinogen, and platelets is summarized in thrombelastography results. In contrast, conventional coagulation assays have several limitations, such as their lack of correlation with bleeding and hypercoagulability; their inability to reflect the contribution of platelets, factor XIII, and plasmin during clot formation and lysis, and their slow turnaround times. [ 13 ] The coagulation history in our patients was inconspicuous and the majority of values derived from conventional coagulation tests were within normal ranges but varied considerably and therefore influenced the relationship to the TEG 6s results. Reference ranges for the TEG 6s have been reported previously and indicate a relevant data spread within respective percentiles.[ 14 ] TEG 6s and conventional coagulation tests do not necessarily evaluate the same components of coagulation. Of note, the TEG 6s does not contain an assay which is specific for the extrinsic pathway of plasmatic coagulation. It is therefore unable to indicate a specific extrinsic factor deficit and thus the indication for the administration of the factor concentrate PPSB.[ 11 ] Both the traditional aPTT assay as well as the TEG6s CK assay aim to analyze the intrinsic pathway of plasmatic coagulation. However, in these assays different activators are used (ellagic acid versus kaolin). Also, aPTT can be prolonged by nonspecific inhibitors like lupus anticoagulants due to bacterial or viral infections without any evident clinical impairment of coagulation. These factors may further influence a clear relationship between conventional analyses and thrombelastography measurements.[ 15 ] This may explain why we observed two completely different relationships between CK-K and aPTT preoperatively (R 2 = 0.631) and perioperatively (R 2 = 0.273). Influences of the vascular endothelium or subendothelial matrix, potential hypocalcemia and hypothermia escape viscoelastic diagnosis but also conventional coagulation tests. They should therefore not influence a possible relation in our patient correlation. Thrombelastography-derived R-times are known to be affected by artificial colloids. As indicated in Table 1 1 2 patients in our study received albumin 5% but no artificial colloid was given. According to Kheirabadi et al. in rats albumin maintains coagulation function, decreases blood loss, and improves survival time compared to synthetic colloids.[ 16 ] Whether the TEG results of our study in a pediatric population are influenced by albumin administration remains unclear. However, a potential effect cannot be excluded. The findings of our study are supported by previous reports in adult patients, indicating that the agreement between conventional laboratory tests and TEG is poor. [ 17 ] This statement is clearly supported also for infants by the results of our study. It has already been reported that in pediatric patients undergoing cardiac surgery using cardiopulmonary bypass (CPB) there is no association of conventional coagulation tests and heparin-specific TEG-derived results.[ 18 ] For pediatric cardiac patients thresholds and predictive values for the use of TEG 6s in guiding cryoprecipitate transfusion have been reported and indicated an optimal cut-off of 9.5 mm of TEG‐FF‐MA.[ 12 ] Maximal clot formation (MCF)/MA has proven to reliably guide transfusion of platelets. The results of the FIBTEM/functional fibrinogen assay may be applied to guide administration of fibrinogen concentrate or other coagulation factor preparations[ 12 ] as administered in our patients. The prognostic value of TEG 6s was evaluated, and cryoprecipitate transfusion was related to TEG-FF-MA values, but also CPB-time, surgical complexity, and in particular excessive intraoperative bleeding. A clear-cut threshold for TEG-FF-MA is difficult to establish in infants undergoing congenital heart surgery.[ 19 ] As Moynihan et al state, it is difficult to determine clear-cut thresholds in this heterogenic pediatric population as hemostasis differs significantly between children and adults as an evolving and dynamic process with age maturation.[ 14 ] Furthermore, coagulation parameters also differ between pediatric age groups and official reference ranges for coagulation parameters still need to be established.[ 20 – 22 ] Our results add information about coagulation related TEG changes in infants and contribute to the establishment of reference ranges for TEG6s parameters. Limitations: The results of coagulation analyses were mainly within normal limits in our study, which may decrease the discriminatory power when comparing conventional assays and TEG parameters. Also, TEG and conventional coagulation analyses were sampled simultaneously, but initiated with a time delay of 10–15 min due to logistic reasons. Due to our current study design coagulations management and respective outcomes using each method (static traditional assays versus viscoelastic testing) have not been compared. Conclusion The relationship between TEG 6s and conventional coagulation assays is rather poor in the perioperative setting of CS in infants. This may be explained by the fact that TEG 6s and conventional coagulation assays do not use identical activators and do not measure same coagulatory parameters and dynamics even when similar issues seem to be evaluated. Therefore, it needs to be decided, which method and assays should be used to analyze coagulopathies and guide blood product administration. TEG 6s is more rapid and thereby offers a dynamic real time assessment of blood coagulation. Therefore TEG6s may have more potential regarding the evaluation of coagulation and substitution potential for blood products and may have an advantage compared to conventional coagulation tests in perioperative pediatric settings when quick decisions are needed. This intuitive advantage of the TEG6s has however not yet been proven in respective clinical evaluations. As a next step algorithms which incorporate TEG parameters, establish clinically meaningful tresholds and guided blood product administration in the pediatric population should be established. Such algorithms may contribute to optimize coagulation management. However, due to logistical and ethical reasons it is not realistic that this objective will be evaluated in prospective clinical studies. Respective experience will most likely be gained by personal and single center experience. Abbreviations aPTT – activated partial thromboplastin times CPB - cardiopulmonary bypass CFF - citrated functional fibrinogen CK- citrated kaolin CKH - citrated kaolin and heparinase CLSI - Clinical and Laboratory Standards Institute CCP - conventional coagulation parameters CRT - citrated rapid TEG CS - Craniosynostosis surgery EDTA - ethylendiamintetraacetate FFP - fresh frozen plasma INR – International normalized ratio IQR - interquartile range K - coagulation time MA - maximum amplitude MCF - Maximal clot formation POC - point of care PPSB - prothrombin complex concentrate PT - prothrombin times R - reaction time RBC - red blood cell concentrates SE - standard error TEG - thrombelastography TXA - tranexamic acid Declarations Ethics approval and consent to participate and consent for publication: All study procedures were approved by the ethics committee of the University of Tübingen, Germany (project number: 567/2019BO1). Legal guardians / parents consented for study participation and consented for publication of data. Availability of data and materials: Not applicable Competing interests: No conflict of interest exists for any of the authors. Funding: Study procedures were funded by institutional resources Authors' contributions: Conception and design of the work: FF, FB, YSF, BD, HM, MUS, PR, AS. Acquisition, analysis, or interpretation of data: FF, FB, YSF, BD, HM, PR, AS. Drafting the work or substantively revising it: FF, FB, YSF, AS. All authors have approved the submitted version of the present work and have agreed both to be personally accountable for the author's own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature. 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Lindhardt RB, Kronborg JR, Wanscher M, Andersen LW, Gjedsted J, Ravn HB: E valuation of Thromboelastography 6s prognostication of fibrinogen supplementation in pediatric cardiac surgery. A cta Anaesthesiol Scand 2 022, 6 6( 10):1166-1173. Di Felice G, Vidali M, Parisi G, Pezzi S, Di Pede A, Deidda G, D'Agostini M, Carletti M, Ceccarelli S, Porzio O: R eference Intervals for Coagulation Parameters in Developmental Hemostasis from Infancy to Adolescence. D iagnostics (Basel) 2 022, 1 2( 10). Weidhofer C, Meyer E, Ristl R, Wiedemann H, Cadamuro J, Kipman U, Zierk J, Male C, Quehenberger P, Haschke-Becher E et al: D ynamic reference intervals for coagulation parameters from infancy to adolescence. C lin Chim Acta 2 018, 4 82: 124-135. Toulon P, Berruyer M, Brionne-Francois M, Grand F, Lasne D, Telion C, Arcizet J, Giacomello R, De Pooter N: A ge dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges. T hromb Haemost 2 016, 1 16( 1):9-16. Table 1 and 3 Table 1 and 3 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1and3.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4959349","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":350333266,"identity":"e2a9f391-76ef-45fc-9136-616d0f1a3985","order_by":0,"name":"Frank Fideler","email":"data:image/png;base64,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","orcid":"","institution":"University Hospital Tübingen","correspondingAuthor":true,"prefix":"","firstName":"Frank","middleName":"","lastName":"Fideler","suffix":""},{"id":350333267,"identity":"e1ddb72a-71d8-4519-b56e-a4248774381f","order_by":1,"name":"Franziska Beck","email":"","orcid":"","institution":"University Hospital Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Franziska","middleName":"","lastName":"Beck","suffix":""},{"id":350333268,"identity":"eec94ad4-29dd-4f41-87c0-79854d94be99","order_by":2,"name":"You-Shan Feng","email":"","orcid":"","institution":"University Hospital Tübingen","correspondingAuthor":false,"prefix":"","firstName":"You-Shan","middleName":"","lastName":"Feng","suffix":""},{"id":350333269,"identity":"88774ce5-1b69-46fc-ae9c-65aa2b14c53a","order_by":3,"name":"Berthold Drexler","email":"","orcid":"","institution":"University Hospital Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Berthold","middleName":"","lastName":"Drexler","suffix":""},{"id":350333270,"identity":"352e6d73-fd2a-47fc-9ff6-9d7c030fb15e","order_by":4,"name":"Harry Magunia","email":"","orcid":"","institution":"University Hospital Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Harry","middleName":"","lastName":"Magunia","suffix":""},{"id":350333272,"identity":"172fb558-fce2-4651-8df6-bc7e1d5dfcdd","order_by":5,"name":"Martin U Schuhmann","email":"","orcid":"","institution":"University Hospital Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"U","lastName":"Schuhmann","suffix":""},{"id":350333274,"identity":"f70aac8a-c45d-43f6-9b58-559635a8265f","order_by":6,"name":"Peter Rosenberger","email":"","orcid":"","institution":"University Hospital Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Rosenberger","suffix":""},{"id":350333277,"identity":"32a60b1e-9da4-48aa-925f-cd5f1a102540","order_by":7,"name":"Andreas Straub","email":"","orcid":"","institution":"Oberschwabenklinik Ravensburg","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Straub","suffix":""}],"badges":[],"createdAt":"2024-08-22 16:08:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4959349/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4959349/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66789973,"identity":"2bafb72b-1416-47bb-88a6-9698e81cc0a9","added_by":"auto","created_at":"2024-10-16 13:30:03","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":261301,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea) - f):\u003c/strong\u003e Boxplots of preoperative and intraoperative conventional coagulation tests. The boxplots indicate the median (black bar), interquartile range (grey box), variability outside the quartiles (whiskers) and outliers (individual points).\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-4959349/v1/c8964e2dbfd83ac953bbde23.png"},{"id":66789975,"identity":"566ede7d-1e0c-48d6-b3cc-1490597f4ba7","added_by":"auto","created_at":"2024-10-16 13:30:03","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":250551,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea) – d):\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ea): preoperative CK-R – aPTT relationship (n=27; p\u0026lt;0.001)\u003c/p\u003e\n\u003cp\u003eb): intraoperative CK-MA – fibrinogen level relationship (n=26; p\u0026lt;0.001)\u003c/p\u003e\n\u003cp\u003ec): preoperative CK-MA – aPTT relationship (n=27; p=0.011)\u003c/p\u003e\n\u003cp\u003ed): preoperative CFF-MA – fibrinogen relationship (n=28; p=0.006)\u003c/p\u003e\n\u003cp\u003eThe coefficient of deterministic relationship R\u003csup\u003e2\u003c/sup\u003e was calculated using linear regression. Inner black lines: Least squares regression line (LSRL)\u003c/p\u003e\n\u003cp\u003eOuter black lines: 95% confidence interval\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-4959349/v1/75f934d5701ebd42cf8532fb.png"},{"id":80375489,"identity":"64236e0f-c263-4f0c-9f05-966310d4117b","added_by":"auto","created_at":"2025-04-11 07:47:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2107432,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4959349/v1/af782902-6b99-4ca9-a32e-9e485aa01fcd.pdf"},{"id":66789976,"identity":"d5d1f3db-de71-4a31-bbd1-b03954194146","added_by":"auto","created_at":"2024-10-16 13:30:03","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":405051,"visible":true,"origin":"","legend":"","description":"","filename":"Table1and3.docx","url":"https://assets-eu.researchsquare.com/files/rs-4959349/v1/58fd634cbd16caf9e2ad88ec.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eComparison of the TEG 6s thrombelastograph with conventional coagulation parameters in infants and toddlers during craniosynostosis surgery - a prospective observational clinical study \u003c/p\u003e","fulltext":[{"header":"Background","content":"\u003cp\u003eThe Thrombelastograph Coagulation Analyzer TEG 6s (Haemonetics, Munich, Germany) is a modern automated point of care (POC) device that can be used for the detection of perioperative coagulation deficiencies. It has the potential to accelerate and broaden the investigation of coagulatory function as viscoelastic tests allow for fast analysis of clot initiation, amplification, strengthness and lysis in whole blood samples. As rather small amounts of whole blood (0.3ml) are needed per sample the TEG 6s may contribute to save blood at the same time and is especially suitable for the pediatric setting. Conventional coagulation tests require rather high volumes of blood (at least 1 ml) and due to logistic issues and the need for specialized laboratories it takes roundabout 45\u0026ndash;60 minutes until results are available. After this time frame these results may no longer reflect the current coagulation status. Additionally, these results do not investigate fibrin polymerization, test for a potential hyperfibrinolysis nor investigate platelet function.\u003c/p\u003e \u003cp\u003ePremature fusion of one or more cranial sutures occurs in one out of 2000\u0026ndash;3000 live births. In 80% of cases such craniosynostosis occurs as an isolated condition, the majority probably being caused by intrauterine fetal head constraint. Compensatory growth occurs at other suture sites and results in a characteristic abnormal head shape.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Craniosynostosis surgery (CS) is a method to correct such an abnormal head shape and to allow the growing brain to expand normally. However, severe diffuse perioperative bleeding is quite common during CS and can lead to a significant coagulopathy which is characterized by prolongations of conventional coagulation assays including prothrombin times (PT), international normalized ratios (INR), partial thromboplastin times (PTT) and thrombin times.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Targeted coagulation therapy is therefore often required during CS. The majority of pediatric craniofacial patients have normal coagulation preoperatively.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] The perioperative course of CS is suitable for analyzing and comparing the functionality and benefits of different coagulation tests.\u003c/p\u003e \u003cp\u003eBy now little is known about changes in thrombelastography (TEG) values in infants and toddlers with perioperative coagulopathies. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] The aim of this study was to monitor, compare and relate the TEG 6s parameters reaction time (R), coagulation time (K), maximum amplitude (MA) with conventional coagulation parameters (prothrombin time, aPTT, INR, fibrinogen, factor XIII levels, and antithrombin III levels) under perioperative conditions in pediatric CS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and protocol\u003c/h2\u003e \u003cdiv id=\"Sec4\" class=\"Section3\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eIn this prospective clinical observational study 29 successive infants and toddlers undergoing elective CS were enrolled from July 2020 to July 2022. Inclusion criteria were age\u0026thinsp;\u0026lt;\u0026thinsp;4 years, singular CS and no concomitant diseases including syndromic diseases. Exclusion criteria were diagnosis of hepatitis B / C or HIV, age\u0026thinsp;\u0026ge;\u0026thinsp;4 years or refusal for study participation. The study was conducted in compliance with the Declaration of Helsinki. Written parental respectively legal guardian consent was obtained in all patients in advance.\u003c/p\u003e \u003cp\u003eDemographic data comprised age at surgery, preoperative weight, height and sex. Perioperative monitoring included S\u003csub\u003ep\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003e, electrocardiogram, invasive arterial blood pressure, end tidal CO\u003csub\u003e2\u003c/sub\u003e and body temperature. Information on primary diagnosis, medication, former treatments and laboratory values were obtained from patient charts.\u003c/p\u003e \u003cp\u003eNo additional catheter placements or other invasive procedures were performed for study purposes.\u003c/p\u003e \u003cp\u003e Reference ranges for TEG 6s were determined in compliance with the Clinical and Laboratory Standards Institute (CLSI) C28A3 guideline. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eAnesthesia / perioperative course\u003c/h2\u003e \u003cp\u003eAnesthesia was performed by experienced pediatric anesthesiologists using total intravenous anesthesia with continuous weight-adjusted infusion of propofol and remifentanil. All patients received endotracheal intubation and an arterial catheter. Maintenance of vital parameters as well as fluid and volume substitution were performed according to common anesthesia standards and institutional standard operating procedures. Blood gas analyses were taken when required. All patients received tranexamic acid (TXA) with a bolus of 20 mg/kgBW and a perioperative perfusion rate of 2 mg/kg/h.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eBlood sampling\u003c/h2\u003e \u003cp\u003eBlood was sampled from study patients either from the arterial canula using routine standards of hygienic catheter handling: one ethylendiamintetraacetate (EDTA)-anticoagulated blood sample for whole blood and cell count (0.7 ml) and one citrate-anticoagulated blood sample for analysis with the thrombelastograph TEG 6s as well as analysis of conventional coagulation markers (Quick, INR, aPTT, fibrinogen, factor XIII levels, and antithrombin III levels) (1 ml). 0.3 ml of the citrated blood sample was taken out of the tube and analyzed in the TEG 6s. 0.7 ml of the citrated blood sample were sent to the central laboratory for analysis of conventional coagulation parameters (CCP). As all coagulation parameters were analyzed from the same citrated tube, no additional blood had to be taken for study and sampling-related differences could be excluded. Altogether on each sampling time-point 1.7 ml of whole blood were taken. In accordance with the WHO guideline on blood collection from children, the amount of patient blood collected for study purposes up to a body weight of 15 kg did not exceed 12 ml. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe first sample was taken preoperatively after induction of general anesthesia to analyze baseline coagulation parameters. Further samples were taken perioperatively as ordered by the attending anesthesiologist in the case of relevant bleeding. All results that were obtained from coagulation analyses were immediately made available so that treatment could be adjusted if necessary.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eCoagulation analyses\u003c/h2\u003e \u003cp\u003eLaboratory analysis of conventional coagulation markers was performed using the Atellica COAG 360 System (Siemens Healthineers, Munich, Germany).\u003c/p\u003e \u003cp\u003eaPTT was detected using the Dade Actin FS assay (Siemens, Erlangen, Germany using ellagic acid activation. The prothrombin time was analyzed using the Dade Innovin assay (Siemens) using activation with recombinant human tissue factor. Factor XIII levels were analyzed using the Dade Berichrom FXIII assay (Siemens). Antithrombin III levels using the Berichrom Antithrombin III assay (Siemens) and fibrinogen levels using a respective anti human fibrinogen antiserum assay (Siemens).\u003c/p\u003e \u003cp\u003e The TEG 6s system is a fully automated, FDA approved, point of care (POC) thrombelastograph. It assesses whole blood coagulation properties due to activation with specific agonists using the resonance method.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] A blood sample of 0.3 ml is pipetted into the entry port in the four-channel self-contained microfluidics. For analysis we used these four channels: the CK-channel (\u0026ldquo;citrated kaolin\u0026rdquo;), CKH-channel (\u0026ldquo;citrated kaolin and heparinase\u0026rdquo;), the CFF-channel (\u0026ldquo;citrated functional fibrinogen\u0026rdquo;) and the CRT channel (\u0026ldquo;citrated rapid TEG\u0026rdquo;).[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eEach assay incorporates distinct activators, such as kaolin, which activates the intrinsic coagulation pathway. The CKH additionally incorporates heparinase to neutralize the influence of heparin in the blood sample. In CRT, both kaolin and tissue factor are included, thereby activating the intrinsic and extrinsic coagulation pathways. CFF is an assay in which the extrinsic coagulation pathway is activated, and it employs a potent GPIIb/IIIa platelet inhibitor to inhibit platelet function and determine the fibrin contribution to clot strength. It is utilized in conjunction with Kaolin TEG to assess the relative contribution of platelets and fibrin to the overall strength of the clot. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eApproximately 20 \u0026micro;l of blood is delivered to each cell where it is exposed to a sinusoidal motion range (20\u0026ndash;500 Hz). As clotting proceeds, clot-strength-specific resonance frequencies are detected by a photodetector and converted into TEG-equivalent units in millimeters. The latter are used to generate TEG tracings, which are illustrating the viscoelastic change of the blood sample in real time.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] TEG 6s allows statements on the primary hemostasis, plasmatic coagulation, thrombin formation, clot stability and lysis as well as the effect of heparin and describes the clot resistance as a function of the measuring duration. The TEG 6s is faster than conventional coagulation analysis. First conclusions are possible after 7\u0026ndash;10 min. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] The test parameter \"MA\" is of particular importance: It allows statements to be made about the strength of the clot and thus supports the indication for treatment with fibrinogen, platelets and possibly other coagulation factor preparations.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical analysis\u003c/strong\u003e \u003cp\u003eCategorical data are presented as frequencies and percentages. Continuous data are presented as median, range and interquartile range (IQR).\u003c/p\u003e \u003c/p\u003e \u003cp\u003eThe relationship between TEG 6s parameters and conventional laboratory parameters was analyzed using linear regression. To detect a deterministic relationship between respective parameters, the coefficient of determination R\u003csup\u003e2\u003c/sup\u003e and its respective standard error (SE) were calculated.\u003c/p\u003e \u003cp\u003eAll charts and analyses were created with the software SPSS\u0026reg; Statistics version 28 (SPSS, Chicago, IL, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cem\u003ePatient history, intraoperative bleeding and blood product administration.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePatient parameters including the demographic parameters age, sex, body weight and height, as well as duration of surgery, the amount of administered red blood cell concentrates (RBC), fresh frozen plasma (FFP) and tranexamic acid (TXA) are given in Table \u003cspan\u003e1\u003c/span\u003e. In the case of clinically relevant blood loss we administered a combination of RBC and FFP to replace intravascular volume as well as coagulation factors. Fibrinogen concentrates, prothrombin complex concentrate (PPSB) as well as FXIII preparations were not administered. Exact amount of intraoperative bleeding could not be determined reliably mainly due to blood loss in surgical gauzes.\u003c/p\u003e\n\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003ePreoperative and intraoperative coagulation analyses\u003c/h2\u003e\n \u003cp\u003eConventional coagulation tests\u003c/p\u003e\n \u003cp\u003eThe inconspicuous coagulation history in our patients was accompanied by relatively widely distributed conventional coagulation values which are mainly within normal ranges (Fig.\u0026nbsp;\u003cspan\u003e1\u003c/span\u003ea-f).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003eTEG 6s parameters\u003c/h2\u003e\n \u003cp\u003eMedians with 2.5th and 97.5th percentiles derived from preoperative TEG 6s measurements are depicted in Table \u003cspan\u003e2\u003c/span\u003e, which serves as an initial basis for reference ranges of these parameters in this age group. Correlations of TEG 6s results and conventional coagulation tests are depicted in Fig. \u003cspan\u003e2\u003c/span\u003ea-d.\u0026nbsp;\u003c/p\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2 Medians with 2.5th and 95th percentils derived from preoperative TEG 6s measurements\u003c/div\u003e\n \u003cdiv\u003e\u003cbr\u003e\u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePre Op reference (95% interval)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003emedian\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e2.5th percentile\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95th percentile\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eCK (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eR (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eK (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMA (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eCKH (n\u0026thinsp;=\u0026thinsp;29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eR (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eK (min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMA (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e59.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eCFF (n\u0026thinsp;=\u0026thinsp;29)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMA (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA10 (mm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cem\u003eDetermination of linear relationships of conventional coagulation tests and TEG 6s parameters.\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003eAll linear relationship analyses with associated R\u003csup\u003e2\u003c/sup\u003e values are given in table 3a (preoperative analyses) and table 3b (intraoperative analyses).\u003c/p\u003e\n \u003cp\u003eFor determination of the linear relationship of \u0026ldquo;R\u0026rdquo; of the TEG 6s assays CK, CRT, CKH, and CFF with conventional coagulation parameters the largest R\u003csup\u003e2\u003c/sup\u003e was obtained for the CK-R \u0026ndash; aPTT relationship (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.448; Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003ea).\u003c/p\u003e\n \u003cp\u003eFor linear relationship of \u0026ldquo;MA\u0026rdquo; of the respective TEG 6s assays with conventional coagulation parameters the highest R\u003csup\u003e2\u003c/sup\u003e was obtained for the CK-MA \u0026ndash; fibrinogen level relationship (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.47; Fig.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003eb).\u003c/p\u003e\n \u003cp\u003eExcept CK-ACT vs aPTT, R\u003csup\u003e2\u003c/sup\u003e values of all other linear relationships were smaller (table 3a and table 3b). Of note, linear relationship analyses for which clear relations may be expected (CFF-MA \u0026ndash; fibrinogen levels and CK-MA \u0026ndash; aPTT) revealed preoperative R\u003csup\u003e2\u003c/sup\u003e values which were in the range of 0.25 and lower (Figs.\u0026nbsp;\u003cspan\u003e2\u003c/span\u003ec and \u003cspan\u003e2\u003c/span\u003ed). The relation of FXIII levels and the CFF-MA revealed a R\u003csup\u003e2\u003c/sup\u003e of 0.291.\u003c/p\u003e\n \u003cp\u003eThe relation of preoperative CK-K and aPTT values revealed R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.631. However intraoperative data of the CK-K / aPTT relationship revealed R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.273.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur present study depicts perioperative coagulation data from a pediatric patient population, which were measured during CS using conventional coagulation assays and the TEG 6s POC device. Of note the linear relationship of TEG 6s derived data and conventional coagulation tests was rather low, even where clear relations might have been expected. Relevant correlations may especially be present for the CFF-MA \u0026ndash; fibrinogen level relationship and also for the CK-R \u0026ndash; aPTT relationship as similar substrates are effective in the respective assays. However, in our pediatric patient group both relationships still revealed a R\u003csup\u003e2\u003c/sup\u003e below of 0.5.\u003c/p\u003e \u003cp\u003eUntil now, published evidence in the youngest age group for bleeding management strategies in neonates and children is scarce.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Therefore, it needs to be evaluated which of the test procedures employed in our study should be preferred and could be potential parameters to guide individual coagulation therapy.\u003c/p\u003e \u003cp\u003eThromboelastography contributes to the investigation of coagulopathies and goal-directed management of bleeding by providing a quick and complete picture of clot formation, strength, and lysis in whole blood. The differential contribution of coagulation factors, fibrinogen, and platelets is summarized in thrombelastography results. In contrast, conventional coagulation assays have several limitations, such as their lack of correlation with bleeding and hypercoagulability; their inability to reflect the contribution of platelets, factor XIII, and plasmin during clot formation and lysis, and their slow turnaround times. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe coagulation history in our patients was inconspicuous and the majority of values derived from conventional coagulation tests were within normal ranges but varied considerably and therefore influenced the relationship to the TEG 6s results. Reference ranges for the TEG 6s have been reported previously and indicate a relevant data spread within respective percentiles.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTEG 6s and conventional coagulation tests do not necessarily evaluate the same components of coagulation. Of note, the TEG 6s does not contain an assay which is specific for the extrinsic pathway of plasmatic coagulation. It is therefore unable to indicate a specific extrinsic factor deficit and thus the indication for the administration of the factor concentrate PPSB.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Both the traditional aPTT assay as well as the TEG6s CK assay aim to analyze the intrinsic pathway of plasmatic coagulation. However, in these assays different activators are used (ellagic acid versus kaolin). Also, aPTT can be prolonged by nonspecific inhibitors like lupus anticoagulants due to bacterial or viral infections without any evident clinical impairment of coagulation. These factors may further influence a clear relationship between conventional analyses and thrombelastography measurements.[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] This may explain why we observed two completely different relationships between CK-K and aPTT preoperatively (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.631) and perioperatively (R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.273).\u003c/p\u003e \u003cp\u003eInfluences of the vascular endothelium or subendothelial matrix, potential hypocalcemia and hypothermia escape viscoelastic diagnosis but also conventional coagulation tests. They should therefore not influence a possible relation in our patient correlation.\u003c/p\u003e \u003cp\u003eThrombelastography-derived R-times are known to be affected by artificial colloids. As indicated in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e2 patients in our study received albumin 5% but no artificial colloid was given. According to Kheirabadi et al. in rats albumin maintains coagulation function, decreases blood loss, and improves survival time compared to synthetic colloids.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] Whether the TEG results of our study in a pediatric population are influenced by albumin administration remains unclear. However, a potential effect cannot be excluded.\u003c/p\u003e \u003cp\u003eThe findings of our study are supported by previous reports in adult patients, indicating that the agreement between conventional laboratory tests and TEG is poor. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] This statement is clearly supported also for infants by the results of our study. It has already been reported that in pediatric patients undergoing cardiac surgery using cardiopulmonary bypass (CPB) there is no association of conventional coagulation tests and heparin-specific TEG-derived results.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eFor pediatric cardiac patients thresholds and predictive values for the use of TEG 6s in guiding cryoprecipitate transfusion have been reported and indicated an optimal cut-off of 9.5 mm of TEG‐FF‐MA.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Maximal clot formation (MCF)/MA has proven to reliably guide transfusion of platelets. The results of the FIBTEM/functional fibrinogen assay may be applied to guide administration of fibrinogen concentrate or other coagulation factor preparations[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] as administered in our patients.\u003c/p\u003e \u003cp\u003eThe prognostic value of TEG 6s was evaluated, and cryoprecipitate transfusion was related to TEG-FF-MA values, but also CPB-time, surgical complexity, and in particular excessive intraoperative bleeding. A clear-cut threshold for TEG-FF-MA is difficult to establish in infants undergoing congenital heart surgery.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAs Moynihan et al state, it is difficult to determine clear-cut thresholds in this heterogenic pediatric population as hemostasis differs significantly between children and adults as an evolving and dynamic process with age maturation.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] Furthermore, coagulation parameters also differ between pediatric age groups and official reference ranges for coagulation parameters still need to be established.[\u003cspan additionalcitationids=\"CR21\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Our results add information about coagulation related TEG changes in infants and contribute to the establishment of reference ranges for TEG6s parameters.\u003c/p\u003e \u003cp\u003eLimitations:\u003c/p\u003e \u003cp\u003eThe results of coagulation analyses were mainly within normal limits in our study, which may decrease the discriminatory power when comparing conventional assays and TEG parameters. Also, TEG and conventional coagulation analyses were sampled simultaneously, but initiated with a time delay of 10\u0026ndash;15 min due to logistic reasons.\u003c/p\u003e \u003cp\u003eDue to our current study design coagulations management and respective outcomes using each method (static traditional assays versus viscoelastic testing) have not been compared.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe relationship between TEG 6s and conventional coagulation assays is rather poor in the perioperative setting of CS in infants. This may be explained by the fact that TEG 6s and conventional coagulation assays do not use identical activators and do not measure same coagulatory parameters and dynamics even when similar issues seem to be evaluated.\u003c/p\u003e \u003cp\u003eTherefore, it needs to be decided, which method and assays should be used to analyze coagulopathies and guide blood product administration.\u003c/p\u003e \u003cp\u003eTEG 6s is more rapid and thereby offers a dynamic real time assessment of blood coagulation. Therefore TEG6s may have more potential regarding the evaluation of coagulation and substitution potential for blood products and may have an advantage compared to conventional coagulation tests in perioperative pediatric settings when quick decisions are needed. This intuitive advantage of the TEG6s has however not yet been proven in respective clinical evaluations.\u003c/p\u003e \u003cp\u003eAs a next step algorithms which incorporate TEG parameters, establish clinically meaningful tresholds and guided blood product administration in the pediatric population should be established. Such algorithms may contribute to optimize coagulation management.\u003c/p\u003e \u003cp\u003eHowever, due to logistical and ethical reasons it is not realistic that this objective will be evaluated in prospective clinical studies. Respective experience will most likely be gained by personal and single center experience.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eaPTT \u0026ndash; activated partial thromboplastin times\u003c/p\u003e\n\u003cp\u003eCPB -\u0026nbsp;cardiopulmonary bypass\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCFF - citrated functional fibrinogen\u003c/p\u003e\n\u003cp\u003eCK- citrated kaolin\u003c/p\u003e\n\u003cp\u003eCKH - citrated kaolin and heparinase\u003c/p\u003e\n\u003cp\u003eCLSI - Clinical and Laboratory Standards Institute\u003c/p\u003e\n\u003cp\u003eCCP - conventional coagulation parameters\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCRT - citrated rapid TEG\u003c/p\u003e\n\u003cp\u003eCS - Craniosynostosis surgery\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEDTA - ethylendiamintetraacetate\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFFP - fresh frozen plasma\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eINR \u0026ndash; International normalized ratio\u003c/p\u003e\n\u003cp\u003eIQR - interquartile range\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eK - coagulation time\u003c/p\u003e\n\u003cp\u003eMA - maximum amplitude\u003c/p\u003e\n\u003cp\u003eMCF - Maximal clot formation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePOC - point of care\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePPSB - prothrombin complex concentrate\u003c/p\u003e\n\u003cp\u003ePT - prothrombin times\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eR - reaction time\u003c/p\u003e\n\u003cp\u003eRBC - red blood cell concentrates\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSE - standard error\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTEG - thrombelastography\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTXA - tranexamic acid\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate and consent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll study procedures were approved by the ethics committee of the University of T\u0026uuml;bingen, Germany (project number: 567/2019BO1). Legal guardians / parents consented for study participation and consented for publication of data.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo conflict of interest exists for any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy procedures were funded by institutional resources\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception \u003cstrong\u003eand\u003c/strong\u003e design of the work:\u0026nbsp;FF, FB, YSF, BD, HM, MUS, PR, AS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcquisition, analysis, \u003cstrong\u003eor\u003c/strong\u003e interpretation of data:\u0026nbsp;FF, FB, YSF, BD, HM, PR, AS.\u003c/p\u003e\n\u003cp\u003eDrafting the work or substantively revising it:\u0026nbsp;FF, FB, YSF, AS.\u003c/p\u003e\n\u003cp\u003eAll authors have\u0026nbsp;approved the submitted version of the present work and have agreed both to be personally accountable for the author\u0026apos;s own contributions and to ensure that questions related to the accuracy or integrity of any part of the work, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements: \u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eThomas K, Hughes C, Johnson D, Das S: \u003cstrong\u003eAnesthesia for surgery related to craniosynostosis: a review. Part 1\u003c/strong\u003e. \u003cem\u003ePaediatr Anaesth \u003c/em\u003e2012, \u003cstrong\u003e22\u003c/strong\u003e(11):1033-1041.\u003c/li\u003e\n\u003cli\u003eHughes C, Thomas K, Johnson D, Das S: \u003cstrong\u003eAnesthesia for surgery related to craniosynostosis: a review. Part 2\u003c/strong\u003e. \u003cem\u003ePaediatr Anaesth \u003c/em\u003e2013, \u003cstrong\u003e23\u003c/strong\u003e(1):22-27.\u003c/li\u003e\n\u003cli\u003eZarour S, Constantini S, Roth J, Friedman S, Kirgner I, Cohen B, Ekstein M: \u003cstrong\u003ePostoperative coagulopathy among otherwise healthy pediatric patients undergoing open craniosynostosis repair: a retrospective study\u003c/strong\u003e. \u003cem\u003eEur J Pediatr \u003c/em\u003e2023, \u003cstrong\u003e182\u003c/strong\u003e(3):1341-1349.\u003c/li\u003e\n\u003cli\u003eWilliams GD, Ellenbogen RG, Gruss JS: \u003cstrong\u003eAbnormal coagulation during pediatric craniofacial surgery\u003c/strong\u003e. \u003cem\u003ePediatr Neurosurg \u003c/em\u003e2001, \u003cstrong\u003e35\u003c/strong\u003e(1):5-12.\u003c/li\u003e\n\u003cli\u003eGurbel PA, Bliden KP, Tantry US, Monroe AL, Muresan AA, Brunner NE, Lopez-Espina CG, Delmenico PR, Cohen E, Raviv G\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eFirst report of the point-of-care TEG: A technical validation study of the TEG-6S system\u003c/strong\u003e. \u003cem\u003ePlatelets \u003c/em\u003e2016, \u003cstrong\u003e27\u003c/strong\u003e(7):642-649.\u003c/li\u003e\n\u003cli\u003eHorowitz GL, Altaie S, Boyd JC, et al. CLSI Document C28-A3. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline-Third edition. Clinical and Laboratory Standards Institute, Wayne, PA, USA, 2009; Vol.28, no 30.\u003c/li\u003e\n\u003cli\u003eHowie SR: B\u003cstrong\u003elood sample volumes in child health research: review of safe limits.\u003c/strong\u003e B\u003cem\u003eull World Health Organ 2\u003c/em\u003e011, 8\u003cstrong\u003e9(\u003c/strong\u003e1):46-53.\u003c/li\u003e\n\u003cli\u003eDias JD, Haney EI, Mathew BA, Lopez-Espina CG, Orr AW, Popovsky MA: N\u003cstrong\u003eew-Generation Thromboelastography: Comprehensive Evaluation of Citrated and Heparinized Blood Sample Storage Effect on Clot-Forming Variables.\u003c/strong\u003e A\u003cem\u003erch Pathol Lab Med 2\u003c/em\u003e017, 1\u003cstrong\u003e41(\u003c/strong\u003e4):569-577.\u003c/li\u003e\n\u003cli\u003eWhiting D, DiNardo JA: T\u003cstrong\u003eEG and ROTEM: technology and clinical applications.\u003c/strong\u003e A\u003cem\u003em J Hematol 2\u003c/em\u003e014, 8\u003cstrong\u003e9(\u003c/strong\u003e2):228-232.\u003c/li\u003e\n\u003cli\u003eBliden KP, Chaudhary R, Mohammed N, Muresan AA, Lopez-Espina CG, Cohen E, Raviv G, Doubleday M, Zaman F, Mathew B \u003cem\u003eet al:\u003c/em\u003e D\u003cstrong\u003eetermination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system.\u003c/strong\u003e J\u003cem\u003e Thromb Thrombolysis 2\u003c/em\u003e017, 4\u003cstrong\u003e3(\u003c/strong\u003e4):437-445.\u003c/li\u003e\n\u003cli\u003eWeber CF, Zacharowski K: [\u003cstrong\u003ePoint of Care 2.0: Coagulation Monitoring Using Rotem(R) Sigma and Teg(R) 6S].\u003c/strong\u003e A\u003cem\u003enasthesiol Intensivmed Notfallmed Schmerzther 2\u003c/em\u003e018, 5\u003cstrong\u003e3(\u003c/strong\u003e6):412-424.\u003c/li\u003e\n\u003cli\u003eHaas T, Faraoni D: V\u003cstrong\u003eiscoelastic testing in pediatric patients.\u003c/strong\u003e T\u003cem\u003eransfusion 2\u003c/em\u003e020, 6\u003cstrong\u003e0 Suppl 6:\u003c/strong\u003eS75-S85.\u003c/li\u003e\n\u003cli\u003eSelby R: \u0026quot;\u003cstrong\u003eTEG talk\u0026quot;: expanding clinical roles for thromboelastography and rotational thromboelastometry.\u003c/strong\u003e H\u003cem\u003eematology Am Soc Hematol Educ Program 2\u003c/em\u003e020, 2\u003cstrong\u003e020(\u003c/strong\u003e1):67-75.\u003c/li\u003e\n\u003cli\u003eMoynihan KM, Johnson K, Rane M, Norman A, Humphreys S, Stocker C, Gibbons K, Roy J: P\u003cstrong\u003eediatric Thromboelastograph 6s and Laboratory Coagulation Reference Values.\u003c/strong\u003e A\u003cem\u003erch Pathol Lab Med 2\u003c/em\u003e021, 1\u003cstrong\u003e45(\u003c/strong\u003e11):1413-1423.\u003c/li\u003e\n\u003cli\u003eMalbora B, Bilaloglu E: L\u003cstrong\u003eupus Anticoagulant Positivity in Pediatric Patients With Prolonged Activated Partial Thromboplastin Time: A Single-Center Experience and Review of Literature.\u003c/strong\u003e P\u003cem\u003eediatr Hematol Oncol 2\u003c/em\u003e015, 3\u003cstrong\u003e2(\u003c/strong\u003e7):495-504.\u003c/li\u003e\n\u003cli\u003eKheirabadi BS, Crissey JM, Deguzman R, Perez MR, Cox AB, Dubick MA, Holcomb JB: E\u003cstrong\u003effects of synthetic versus natural colloid resuscitation on inducing dilutional coagulopathy and increasing hemorrhage in rabbits.\u003c/strong\u003e J\u003cem\u003e Trauma 2\u003c/em\u003e008, 6\u003cstrong\u003e4(\u003c/strong\u003e5):1218-1228; discussion 1228-1219.\u003c/li\u003e\n\u003cli\u003eAgren A, Wikman AT, Holmstrom M, Ostlund A, Edgren G: T\u003cstrong\u003ehromboelastography (TEG(R)) compared to conventional coagulation tests in surgical patients--a laboratory evaluation.\u003c/strong\u003e S\u003cem\u003ecand J Clin Lab Invest 2\u003c/em\u003e013, 7\u003cstrong\u003e3(\u003c/strong\u003e3):214-220.\u003c/li\u003e\n\u003cli\u003eMagunia H, Schenk S, Schlensak C, Icheva V, Rosenberger P, Straub A, Nowak-Machen M: D\u003cstrong\u003eetection of early incomplete heparin reversal following congenital cardiac surgery: A single-center retrospective observational study.\u003c/strong\u003e T\u003cem\u003ehromb Res 2\u003c/em\u003e019, 1\u003cstrong\u003e82:\u003c/strong\u003e33-38.\u003c/li\u003e\n\u003cli\u003eLindhardt RB, Kronborg JR, Wanscher M, Andersen LW, Gjedsted J, Ravn HB: E\u003cstrong\u003evaluation of Thromboelastography 6s prognostication of fibrinogen supplementation in pediatric cardiac surgery.\u003c/strong\u003e A\u003cem\u003ecta Anaesthesiol Scand 2\u003c/em\u003e022, 6\u003cstrong\u003e6(\u003c/strong\u003e10):1166-1173.\u003c/li\u003e\n\u003cli\u003eDi Felice G, Vidali M, Parisi G, Pezzi S, Di Pede A, Deidda G, D\u0026apos;Agostini M, Carletti M, Ceccarelli S, Porzio O: R\u003cstrong\u003eeference Intervals for Coagulation Parameters in Developmental Hemostasis from Infancy to Adolescence.\u003c/strong\u003e D\u003cem\u003eiagnostics (Basel) 2\u003c/em\u003e022, 1\u003cstrong\u003e2(\u003c/strong\u003e10).\u003c/li\u003e\n\u003cli\u003eWeidhofer C, Meyer E, Ristl R, Wiedemann H, Cadamuro J, Kipman U, Zierk J, Male C, Quehenberger P, Haschke-Becher E \u003cem\u003eet al:\u003c/em\u003e D\u003cstrong\u003eynamic reference intervals for coagulation parameters from infancy to adolescence.\u003c/strong\u003e C\u003cem\u003elin Chim Acta 2\u003c/em\u003e018, 4\u003cstrong\u003e82:\u003c/strong\u003e124-135.\u003c/li\u003e\n\u003cli\u003eToulon P, Berruyer M, Brionne-Francois M, Grand F, Lasne D, Telion C, Arcizet J, Giacomello R, De Pooter N: A\u003cstrong\u003ege dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges.\u003c/strong\u003e T\u003cem\u003ehromb Haemost 2\u003c/em\u003e016, 1\u003cstrong\u003e16(\u003c/strong\u003e1):9-16.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1 and 3","content":"\u003cp\u003eTable 1 and 3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"craniosynostosis surgery, coagulation, pediatric population","lastPublishedDoi":"10.21203/rs.3.rs-4959349/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4959349/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eBackground:\u003c/em\u003e Craniosynostosis surgery (CS) is associated with severe diffuse perioperative bleeding which can result in a significant coagulopathy. The Thrombelastograph Coagulation Analyzer TEG 6s is a modern point of care (POC) device for rapid detection of perioperative coagulation disorders and for the guidance of coagulation factor substitution. By now little is known about changes in TEG 6s values in infants and toddlers with perioperative coagulopathies. The aim of this study was to monitor, compare and relate TEG 6s parameters with conventional coagulation parameters (CCP) during pediatric CS.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMethods:\u003c/em\u003e In this prospective clinical observational study 29 infants and toddlers (median age 6 months, median weight 8.5 kg) undergoing CS were enrolled. Blood was sampled pre- and perioperatively. Samples were analyzed by TEG 6s and using CCP (prothrombin time, aPTT, INR, fibrinogen, factor XIII, and antithrombin III). The TEG 6s parameters (reaction time “R”, coagulation time “K”, maximum amplitude “MA”) and CCP were related using linear regression analyses.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eResults: \u003c/em\u003eRegarding the linear relationship of “R”, “MA”, and “K” of the TEG 6s assays CK, CRT, CKH, and CFF with CCP highest R\u003csup\u003e2 \u003c/sup\u003evalues were obtained for the CK-R – aPTT relationship (R\u003csup\u003e2 \u003c/sup\u003e=\u003csup\u003e \u003c/sup\u003e0.448), for the CK-MA – fibrinogen relationship (R\u003csup\u003e2 \u003c/sup\u003e=\u003csup\u003e \u003c/sup\u003e0.47) and for the CK-K - aPTT relationship (R\u003csup\u003e2\u003c/sup\u003e=0.631).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConclusions:\u003c/em\u003e The relationship between TEG 6s and conventional coagulation assays is rather low in the perioperative setting of CS in infants. This may be explained by the fact that TEG 6s and conventional coagulation assays do not employ identical methods and do not measure the same coagulatory substrates and dynamics. Our results may contribute to the establishment of reference ranges for TEG6s parameters.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurther studies should evaluate which method may be preferred and should establish algorithms and treatment thresholds to guide coagulation management in the pediatric population.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Trial registration: not applicable (observational data only, no trial interventions)\u003c/p\u003e","manuscriptTitle":"Comparison of the TEG 6s thrombelastograph with conventional coagulation parameters in infants and toddlers during craniosynostosis surgery - a prospective observational clinical study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-16 13:29:59","doi":"10.21203/rs.3.rs-4959349/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cb05fe68-818e-4b3a-a09b-f87dd3243350","owner":[],"postedDate":"October 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-04-11T07:38:48+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-16 13:29:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4959349","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4959349","identity":"rs-4959349","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}