Synchronous Hepatic Artery and Portal Vein Thrombosis in COVID-19 infection- A case report

Synchronous Hepatic Artery and Portal Vein Thrombosis in COVID-19 infection- A case report | 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 Case Report Synchronous Hepatic Artery and Portal Vein Thrombosis in COVID-19 infection- A case report Himsikhar Khataniar, Ashni Dharia, Harshad Devarbhavi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5150256/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: COVID-19, which primarily affects the respiratory system, can also lead to systemic complications, including thrombotic events. Althoughthromboses in the hepatic and portal systems are rare, they mayresult in serious complications. This case report presents a unique scenario of concomitant hepatic artery and portal vein thrombosis in a patient with previously undiagnosed essential thrombocytosis who also tested positive for COVID-19. It underscores the importance of early identification of thrombotic complications and underlying hematologic disorders. Case Presentation: A 38-year-old female presented with fever, abdominal pain, cough, and shortness of breath. She tested positive for COVID-19 and was found to have hepatic artery thrombosis and multiple liver infarcts on a contrast-enhanced CT scan. Further imaging revealed complete thrombosis of the celiac artery and its branches, portal vein thrombosis, and splenic infarction. Initial management included intravenous fluids and enoxaparin. During hospitalization, persistent thrombocytosis led to a diagnosis of essential thrombocytosis. Hydroxyurea was initiated for cytoreductive therapy. The patient’s condition improved, and she was discharged on dabigatran. At an eight-month follow-up, she remained asymptomatic, with normal liver function and no recurrence of thrombosis. Conclusions: This case demonstrates the crucial need torecognize unusual thrombotic patterns in COVID-19, especially in individuals harboring undiagnosed hematologic disorders like essential thrombocytosis. Prompt diagnosis and aggressive treatment, including anticoagulation and cytoreductive therapy, are important to avert serious outcomes and support successful recovery. COVID-19 hepatic artery thrombosis portal vein thrombosis essential thrombocytosis thromboembolic complications myeloproliferative neoplasms anticoagulation therapy case report Figures Figure 1 Figure 2 Introduction SARS-CoV-2, the pathogen responsible for COVID-19, generally presents as a respiratory illness but can also affect multiple organ systems. Extrapulmonary manifestations, including thrombotic events, occur in an estimated 20–43% of patients [ 1 ]. These complications can affect multiple systems such as cardiac, renal, gastrointestinal, liver, neurologic, and cutaneous functions [ 2 ]. High rates of thrombotic events, particularly in critical care settings, were initially noted in China and the Netherlands, with roughly 30% of severely ill COVID-19 patients developing thromboses [ 3 , 4 ]. While deep vein thrombosis and pulmonary embolism are prevalent, arterial and venous thromboses in the gastrointestinal system, although uncommon, have been documented [ 5 ]. This case was presented at the American College of Physicians (ACP) Annual Meeting in April 2022 (Chicago), where it received the Best Medical Student Oral Presentation Award. Case Report A 38-year-old female presented with fever for four days and abdominal pain for three days. Her symptoms also included a cough, shortness of breath, and episodes of vomiting. COVID-19 was confirmed at a local hospital. A contrast-enhanced CT scan of the abdomen revealed hepatic artery thrombosis and associated infarcts, prompting transfer to a specialized facility for further treatment. Upon arrival at the COVID-19 emergency department, the patient exhibited tachypnea, tachycardia, and bilateral crackles on chest auscultation. Abdominal examination showed tenderness in the right hypochondrium and epigastrium, but no signs of guarding or rigidity were present, and bowel sounds were normal. There was no family history of thrombotic disorders. Vital signs at admission included a heart rate of 102 beats per minute, respiratory rate of 20 breaths per minute, blood pressure of 110/70 mmHg, and a temperature of 98°F. Laboratory findings revealed elevated inflammatory markers, including a d-dimer level of 3630 µg/mL, C-reactive protein (CRP) at 24.26 mg/L, erythrocyte sedimentation rate (ESR) of 120 mm/hr, and ferritin at 1782 ng/L. Liver enzymes were significantly elevated, with aspartate transaminase (AST) at 3227 U/L and alanine transaminase (ALT) at 1871 U/L. Bilirubin levels remained near normal. Coagulation parameters were within normal ranges [Table 1 ]. A CT scan re-evaluation revealed complete thrombosis of the celiac artery, its branches (including the hepatic and splenic arteries), and multiple liver infarcts across both lobes [Figure 1 ].There was evidence of portal vein thrombosis and complete infarction of the spleen [Figure 2 ].Small bowel mesenteric vessels were engorged, but there were no signs of bowel wall abnormalities, obstruction, or dilation. Table 1 Laboratory Values Parameters Result Normal value Blood/Serum Investigations Hemoglobin (g/dl) 12.10 12–16 Leucocyte count, cells per mm 3 16,850 4000–11 000 Platelets (x10 5 ) 10.1 1.5- 4 Prothrombin time (seconds) 12.8 10–13 Activated partial thromboplastin time (seconds) 23.4 21–38 Albumin (g/dl) 3.2 3.5- 5 Alanine aminotransferase (U/L) 1871 7–55 Aspartate aminotransferase (U/L) 3227 8–48 Alkaline phosphatase (U/L) 136 40–129 Gamma glutamyl transferase (U/L) 144 8–61 Bilirubin (mg/dl) 1.07 0.1–1.2 Lactate dehydrogenase (U/L) 5054 230–460 C- Reactive Protein (mg/L) 24.26 0–5 D-dimer (µg/mL) 3630 < 0·25 Ferritin (ng/L) 1782 10–291 Procalcitonin (µg/L) 0.84 0.5 ESR (mm/hr) 120 0–29 Microbiological Investigation COVID-19 RT-PCR Positive Negative MPN Panel Mutation Test MPL gene Mutation Negative Negative CALR gene Mutation Negative Negative JAK2 gene Mutation Negative Negative ESR, Erythrocyte sedimentation rate; COVID-19, coronavirus disease 2019; RT-PCR, Reverse transcriptase polymerase chain reaction. The vascular surgery and hematology teams recommended further investigation for prothrombotic conditions, including testing for antiphospholipid antibodies (APLA), antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), and the BCR-ABL mutation. Conservative management was initiated, including intravenous fluids and enoxaparin, a low molecular weight heparin. Over the next seven days, the patient’s abdominal pain subsided, and liver enzyme levels gradually returned to normal. Dabigatran, a novel oral anticoagulant, replaced enoxaparin at discharge, which the patient continued for eight months. During hospitalization, the patient exhibited persistent thrombocytosis, initially attributed to a reactive process. However, a thorough hematologic workup revealed essential thrombocytosis, as tests for myeloproliferative neoplasms (MPN), including MPL, JAK2, and CALR gene mutations, were negative. Hydroxyurea was initiated at 500 mg twice daily and later increased to 1000 mg twice daily. A follow-up contrast-enhanced CT scan two months later showed partial resolution of hepatic artery and portal vein thrombosis with a decrease in collateral circulation. The patient remained asymptomatic at an eight-month follow-up, with normal platelet counts and no further episodes of thrombosis. Dabigatran was discontinued due to the absence of recurrent thrombosis. Conclusion Thromboembolic episodes are well recognized in COVID-19, frequently involving the venous system. This report describes a highly unusual occurrence of simultaneous hepatic arterial and portal venous thrombosis. COVID-19-related thrombosis stems from systemic inflammation, hypoxia, prolonged immobilization, and direct endothelial injury attributed to the virus, all of which heighten the risk of clot formation [ 6 – 8 ]. In this patient, a previously undetected myeloproliferative disorder likely worsened the prothrombotic state, causing severe ischemic injury to the liver and spleen. Dual blood supply to the liver typically guards against major infarction, but simultaneous occlusion of both arterial and venous inflow can lead to large infarcts, as seen in this case. The elevated liver enzymes were reflective of ischemic damage due to hepatic artery and portal vein obstruction. Although venous clots are more prevalent in COVID-19, arterial obstructions including strokes and heart attacks have also been reported prior [ 9 – 11 ]. Gastrointestinal thrombosis, while infrequent, has been documented in critically ill COVID-19 population, presenting with abdominal symptoms similar to this case [ 12 ]. Doppler ultrasonography is a typical first-line method to detect splanchnic vein thrombosis, boasting high sensitivity and specificity. More detailed imaging such as CT, MRI, or angiography can clarify the extent of vascular involvement [ 13 ]. Here, the contrast-enhanced CT was crucial for diagnosing both arterial and venous thromboses. Given the observed links between COVID-19 and thrombotic complications, anticoagulation for three to six months is generally advised [ 14 , 15 ]. Our patient also received hydroxyurea to mitigate platelet-related risks associated with essential thrombocytosis, which often demands long-term management. One limitation of this report is the single-patient scope, restricting the ability to generalize. Although this case demonstrates a severe thrombotic phenomenon, more comprehensive research is needed to confirm incidence, possible risk factors, and best management. In conclusion, although episodes of thrombosis are well-known in COVID-19 infections, our case highlights the unique effects of COVID-19 infection that caused both hepatic artery and portal vein thrombosis in an undiagnosed MPN. Aggressive hydration together with anticoagulation and cytoreductive therapy resulted in improved flow in the hepatosplenic system with normalization of liver biochemical profile and resolution of symptoms. Declarations Ethical Approval A written informed consent was obtained from the patient to publish her medical details and accompanying images. Ethical approval for this case report was granted by the Institutional Ethics Committee at St. Johns Medical College, Bengaluru (IEC No. 05/2021). Conflict of Interest Statement The authors have no conflicts of interest to declare. Funding Sources The authors have no funding sources to declare. Author Contribution H.D. was actively involved in the acute care and follow-up of the patient. He was also involved in critical revision of the manuscript and approved the final version for submission.H.K. and A.D. were involved in literature review, drafting of the initial manuscript, follow-up care of the patient and in creation of the final version of the manuscript for submission. H.K. is the article guarantor. Acknowledgement Department of Gastroenterology, St. Johns Medical College and Hospital and Department of Hematology, St. Johns Medical College and Hospital. References da Rosa Mesquita R, Francelino Silva Junior LC, Santos Santana FM et al (2021) Clinical manifestations of COVID-19 in the general population: systematic review. Wien Klin Wochenschr 133:377–382. 10.1007/s00508-020-01760-4 Levi M, Thachil J, Iba T, Levy JH (2020) Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol 7301459. 10.1016/S2352-3026(20)30145-9 Cui S, Chen S, Li X, Liu S, Wang F (2020) Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost 18:1421–1424. 10.1111/jth.14830 Klok FA, Kruip MJHA, van der Meer NJM et al (2020) Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res 191:145–147. 10.1016/j.thromres.2020.04.013 Kolli S, Oza VM SARS-CoV-2 and Portal Vein Thrombosis: A Rare Gastrointestinal Manifestation of COVID-19. 2021134, 14340 – 2021. 10.7759/cureus.14340 Helms J, Tacquard C, Severac F et al (2020) High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med 46:1089–1098. 10.1007/s00134-020-06062-x Avila J, Long B, Holladay D, Gottlieb M (2021) Thrombotic complications of COVID-19. Am J Emerg Med 39:213–218. 10.1016/j.ajem.2020.09.065 Gupta A, Madhavan MV, Sehgal K et al (2020) Extrapulmonary manifestations of COVID-19. Nat Med 26:1017–1032. 10.1038/s41591-020-0968-3 Fournier M, Faille D, Dossier A et al (2021) Arterial Thrombotic Events in Adult Inpatients With COVID-19. Mayo Clin Proc. 96:295–303. 10.1016/j.mayocp.2020.11.018 Wu T, Zuo Z, Yang D et al Venous thromboembolic events in patients. 19:284–293. 10.1093/ageing/afaa259 Cantador E, Núñez A, Sobrino P et al (2020) Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients. J Thromb Thrombolysis 50:543–547. 10.1007/s11239-020-02176-7 Sultan S, Altayar O, Siddique SM et al (2020) AGA Institute Rapid Review of the Gastrointestinal and Liver Manifestations of COVID-19, Meta-Analysis of International Data, and Recommendations for the Consultative Management of Patients with COVID-19. Gastroenterology 159:320–334. 10.1053/j.gastro.2020.05.001 Kumar S, Sarr MG, Kamath PS (2001) Mesenteric venous thrombosis. N Engl J Med 345:1683–1688. 10.1056/NEJMra010076 Kaptein FHJ, Stals MAM, Huisman MV, Klok FA (2021) Prophylaxis and treatment of COVID-19 related venous thromboembolism. Postgrad Med 133:27–35. 10.1080/00325481.2021.1891788 Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L The hypercoagulable state in COVID-. 19:101–115. 10.1016/j.thromres.2020.06.029 Additional Declarations No competing interests reported. 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. 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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-5150256","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":445310195,"identity":"c8c1f99e-f6b5-4be8-addb-6c18ea4423f5","order_by":0,"name":"Himsikhar Khataniar","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYBACA2YgkXDgAAMDewOIa0GKFp4DIK4EEVrAJEiLRAKIRYQWc3bu5A8PztyRN5/5/OqGHwUSDPzt3Ql4tVg2826TSLjxzHDO7Zyymz1Ah0mcObsBv8MO825jSPhwmHGGdE7aDR6gFgOJXIJaNn8AarGfIXkm7eYfIrVsADrscOIMCfZjt4m1BeiXM4eTZ/DksN2WMZDgIeyX82c3f/xx7LDtDPbjz26++WMjx9/ei18LEuABxxEPscpBgP0BKapHwSgYBaNgBAEARKtPH+Ky5uMAAAAASUVORK5CYII=","orcid":"","institution":"Allegheny General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Himsikhar","middleName":"","lastName":"Khataniar","suffix":""},{"id":445310196,"identity":"f93f4f0e-0d85-4c04-9c7c-36d4d9eca6ba","order_by":1,"name":"Ashni Dharia","email":"","orcid":"","institution":"Allegheny General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ashni","middleName":"","lastName":"Dharia","suffix":""},{"id":445310197,"identity":"37073fb2-23de-4695-af71-83b628a9dece","order_by":2,"name":"Harshad Devarbhavi","email":"","orcid":"","institution":"St.John's Medical College Hospital","correspondingAuthor":false,"prefix":"","firstName":"Harshad","middleName":"","lastName":"Devarbhavi","suffix":""}],"badges":[],"createdAt":"2024-09-25 08:24:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5150256/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5150256/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":81504743,"identity":"69ea17d0-c5cf-429b-95be-042b22aa40be","added_by":"auto","created_at":"2025-04-28 05:11:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":128491,"visible":true,"origin":"","legend":"\u003cp\u003eComputed Tomography (CT) scan showing hypoattenuated areas (Red Arrow) in the liver suggestive of liver infarction and hypoattenuation in spleen from hepatic artery and portal vein thrombosis.\u003c/p\u003e","description":"","filename":"enhancedimage1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5150256/v1/7e977096f2cc91276929bc62.jpg"},{"id":81507546,"identity":"5c769dcd-db23-4dd1-8260-60ba41a3fab5","added_by":"auto","created_at":"2025-04-28 05:35:27","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":967638,"visible":true,"origin":"","legend":"\u003cp\u003eComputed Tomography (CT) scan showing filling defect in the left portal vein (Red arrow).\u003c/p\u003e","description":"","filename":"enhancedimage2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5150256/v1/49a9e6093ff97f7cb01500b5.jpg"},{"id":82435674,"identity":"dcfe25df-3ee7-49f2-afed-74d6db99571e","added_by":"auto","created_at":"2025-05-10 20:01:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1465355,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5150256/v1/ed59fac2-0404-4bf8-80e9-da5fcf8b9d3a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Synchronous Hepatic Artery and Portal Vein Thrombosis in COVID-19 infection- A case report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSARS-CoV-2, the pathogen responsible for COVID-19, generally presents as a respiratory illness but can also affect multiple organ systems. Extrapulmonary manifestations, including thrombotic events, occur in an estimated 20\u0026ndash;43% of patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These complications can affect multiple systems such as cardiac, renal, gastrointestinal, liver, neurologic, and cutaneous functions [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. High rates of thrombotic events, particularly in critical care settings, were initially noted in China and the Netherlands, with roughly 30% of severely ill COVID-19 patients developing thromboses [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. While deep vein thrombosis and pulmonary embolism are prevalent, arterial and venous thromboses in the gastrointestinal system, although uncommon, have been documented [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This case was presented at the American College of Physicians (ACP) Annual Meeting in April 2022 (Chicago), where it received the Best Medical Student Oral Presentation Award.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 38-year-old female presented with fever for four days and abdominal pain for three days. Her symptoms also included a cough, shortness of breath, and episodes of vomiting. COVID-19 was confirmed at a local hospital. A contrast-enhanced CT scan of the abdomen revealed hepatic artery thrombosis and associated infarcts, prompting transfer to a specialized facility for further treatment.\u003c/p\u003e \u003cp\u003eUpon arrival at the COVID-19 emergency department, the patient exhibited tachypnea, tachycardia, and bilateral crackles on chest auscultation. Abdominal examination showed tenderness in the right hypochondrium and epigastrium, but no signs of guarding or rigidity were present, and bowel sounds were normal. There was no family history of thrombotic disorders.\u003c/p\u003e \u003cp\u003eVital signs at admission included a heart rate of 102 beats per minute, respiratory rate of 20 breaths per minute, blood pressure of 110/70 mmHg, and a temperature of 98\u0026deg;F. Laboratory findings revealed elevated inflammatory markers, including a d-dimer level of 3630 \u0026micro;g/mL, C-reactive protein (CRP) at 24.26 mg/L, erythrocyte sedimentation rate (ESR) of 120 mm/hr, and ferritin at 1782 ng/L. Liver enzymes were significantly elevated, with aspartate transaminase (AST) at 3227 U/L and alanine transaminase (ALT) at 1871 U/L. Bilirubin levels remained near normal. Coagulation parameters were within normal ranges [Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e]. A CT scan re-evaluation revealed complete thrombosis of the celiac artery, its branches (including the hepatic and splenic arteries), and multiple liver infarcts across both lobes [Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e].There was evidence of portal vein thrombosis and complete infarction of the spleen [Figure \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e].Small bowel mesenteric vessels were engorged, but there were no signs of bowel wall abnormalities, obstruction, or dilation.\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\u003eLaboratory Values\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eResult\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNormal value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eBlood/Serum Investigations\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12\u0026ndash;16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeucocyte count, cells per mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16,850\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4000\u0026ndash;11 000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets (x10\u003csup\u003e5\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5- 4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProthrombin time (seconds)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u0026ndash;13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActivated partial thromboplastin time (seconds)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u0026ndash;38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5- 5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlanine aminotransferase (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1871\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u0026ndash;55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspartate aminotransferase (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3227\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u0026ndash;48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlkaline phosphatase (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e136\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026ndash;129\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGamma glutamyl transferase (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e144\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8\u0026ndash;61\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin (mg/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u0026ndash;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate dehydrogenase (U/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e230\u0026ndash;460\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC- Reactive Protein (mg/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eD-dimer (\u0026micro;g/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3630\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0\u0026middot;25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (ng/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1782\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u0026ndash;291\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcalcitonin (\u0026micro;g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR (mm/hr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u0026ndash;29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMicrobiological Investigation\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCOVID-19 RT-PCR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMPN Panel Mutation Test\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 \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPL gene Mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCALR gene Mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJAK2 gene Mutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eESR, Erythrocyte sedimentation rate; COVID-19, coronavirus disease 2019;\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eRT-PCR, Reverse transcriptase polymerase chain reaction.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe vascular surgery and hematology teams recommended further investigation for prothrombotic conditions, including testing for antiphospholipid antibodies (APLA), antinuclear antibodies (ANA), antineutrophil cytoplasmic antibodies (ANCA), and the BCR-ABL mutation. Conservative management was initiated, including intravenous fluids and enoxaparin, a low molecular weight heparin. Over the next seven days, the patient\u0026rsquo;s abdominal pain subsided, and liver enzyme levels gradually returned to normal. Dabigatran, a novel oral anticoagulant, replaced enoxaparin at discharge, which the patient continued for eight months.\u003c/p\u003e \u003cp\u003eDuring hospitalization, the patient exhibited persistent thrombocytosis, initially attributed to a reactive process. However, a thorough hematologic workup revealed essential thrombocytosis, as tests for myeloproliferative neoplasms (MPN), including MPL, JAK2, and CALR gene mutations, were negative. Hydroxyurea was initiated at 500 mg twice daily and later increased to 1000 mg twice daily. A follow-up contrast-enhanced CT scan two months later showed partial resolution of hepatic artery and portal vein thrombosis with a decrease in collateral circulation. The patient remained asymptomatic at an eight-month follow-up, with normal platelet counts and no further episodes of thrombosis. Dabigatran was discontinued due to the absence of recurrent thrombosis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThromboembolic episodes are well recognized in COVID-19, frequently involving the venous system. This report describes a highly unusual occurrence of simultaneous hepatic arterial and portal venous thrombosis. COVID-19-related thrombosis stems from systemic inflammation, hypoxia, prolonged immobilization, and direct endothelial injury attributed to the virus, all of which heighten the risk of clot formation [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In this patient, a previously undetected myeloproliferative disorder likely worsened the prothrombotic state, causing severe ischemic injury to the liver and spleen.\u003c/p\u003e \u003cp\u003eDual blood supply to the liver typically guards against major infarction, but simultaneous occlusion of both arterial and venous inflow can lead to large infarcts, as seen in this case. The elevated liver enzymes were reflective of ischemic damage due to hepatic artery and portal vein obstruction. Although venous clots are more prevalent in COVID-19, arterial obstructions including strokes and heart attacks have also been reported prior [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Gastrointestinal thrombosis, while infrequent, has been documented in critically ill COVID-19 population, presenting with abdominal symptoms similar to this case [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Doppler ultrasonography is a typical first-line method to detect splanchnic vein thrombosis, boasting high sensitivity and specificity. More detailed imaging such as CT, MRI, or angiography can clarify the extent of vascular involvement [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Here, the contrast-enhanced CT was crucial for diagnosing both arterial and venous thromboses. Given the observed links between COVID-19 and thrombotic complications, anticoagulation for three to six months is generally advised [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Our patient also received hydroxyurea to mitigate platelet-related risks associated with essential thrombocytosis, which often demands long-term management. One limitation of this report is the single-patient scope, restricting the ability to generalize. Although this case demonstrates a severe thrombotic phenomenon, more comprehensive research is needed to confirm incidence, possible risk factors, and best management.\u003c/p\u003e \u003cp\u003eIn conclusion, although episodes of thrombosis are well-known in COVID-19 infections, our case highlights the unique effects of COVID-19 infection that caused both hepatic artery and portal vein thrombosis in an undiagnosed MPN. Aggressive hydration together with anticoagulation and cytoreductive therapy resulted in improved flow in the hepatosplenic system with normalization of liver biochemical profile and resolution of symptoms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthical Approval\u003c/h2\u003e \u003cp\u003e A written informed consent was obtained from the patient to publish her medical details and accompanying images. Ethical approval for this case report was granted by the Institutional Ethics Committee at St. Johns Medical College, Bengaluru (IEC No. 05/2021).\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflict of Interest Statement\u003c/h2\u003e \u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding Sources\u003c/h2\u003e \u003cp\u003eThe authors have no funding sources to declare.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eH.D. was actively involved in the acute care and follow-up of the patient. He was also involved in critical revision of the manuscript and approved the final version for submission.H.K. and A.D. were involved in literature review, drafting of the initial manuscript, follow-up care of the patient and in creation of the final version of the manuscript for submission. H.K. is the article guarantor.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eDepartment of Gastroenterology, St. Johns Medical College and Hospital and Department of Hematology, St. Johns Medical College and Hospital.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eda Rosa Mesquita R, Francelino Silva Junior LC, Santos Santana FM et al (2021) Clinical manifestations of COVID-19 in the general population: systematic review. Wien Klin Wochenschr 133:377\u0026ndash;382. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s00508-020-01760-4\u003c/span\u003e\u003cspan address=\"10.1007/s00508-020-01760-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLevi M, Thachil J, Iba T, Levy JH (2020) Coagulation abnormalities and thrombosis in patients with COVID-19. 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Postgrad Med 133:27\u0026ndash;35. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/00325481.2021.1891788\u003c/span\u003e\u003cspan address=\"10.1080/00325481.2021.1891788\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L The hypercoagulable state in COVID-. 19:101\u0026ndash;115. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.thromres.2020.06.029\u003c/span\u003e\u003cspan address=\"10.1016/j.thromres.2020.06.029\" 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":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":"COVID-19, hepatic artery thrombosis, portal vein thrombosis, essential thrombocytosis, thromboembolic complications, myeloproliferative neoplasms, anticoagulation therapy, case report","lastPublishedDoi":"10.21203/rs.3.rs-5150256/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5150256/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eBackground:\u003c/em\u003e\u003cbr\u003e\nCOVID-19, which primarily affects the respiratory system, can also lead to systemic complications, including thrombotic events. Althoughthromboses in the hepatic and portal systems are rare, they mayresult in serious complications. This case report presents a unique scenario of concomitant hepatic artery and portal vein thrombosis in a patient with previously undiagnosed essential thrombocytosis who also tested positive for COVID-19. It underscores the importance of early identification of thrombotic complications and underlying hematologic disorders.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCase Presentation:\u003c/em\u003e\u003cbr\u003e\nA 38-year-old female presented with fever, abdominal pain, cough, and shortness of breath. She tested positive for COVID-19 and was found to have hepatic artery thrombosis and multiple liver infarcts on a contrast-enhanced CT scan. Further imaging revealed complete thrombosis of the celiac artery and its branches, portal vein thrombosis, and splenic infarction. Initial management included intravenous fluids and enoxaparin. During hospitalization, persistent thrombocytosis led to a diagnosis of essential thrombocytosis. Hydroxyurea was initiated for cytoreductive therapy. The patient’s condition improved, and she was discharged on dabigatran. At an eight-month follow-up, she remained asymptomatic, with normal liver function and no recurrence of thrombosis.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConclusions:\u003c/em\u003e\u003cbr\u003e\nThis case demonstrates the crucial need torecognize unusual thrombotic patterns in COVID-19, especially in individuals harboring undiagnosed hematologic disorders like essential thrombocytosis. Prompt diagnosis and aggressive treatment, including anticoagulation and cytoreductive therapy, are important to avert serious outcomes and support successful recovery.\u003c/p\u003e","manuscriptTitle":"Synchronous Hepatic Artery and Portal Vein Thrombosis in COVID-19 infection- A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-28 05:11:01","doi":"10.21203/rs.3.rs-5150256/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":"1856d898-7671-4459-95f8-ea36eb9bc5ca","owner":[],"postedDate":"April 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-10T19:53:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-28 05:11:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5150256","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5150256","identity":"rs-5150256","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}