{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:11:45Z","timestamp":1774123905459,"version":"3.50.1"},"reference-count":120,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypercoagulation is one of the major risk factors for ICU treatment, mechanical ventilation, and death in critically ill patients infected with SARS-CoV-2. At the same time, hypoalbuminemia is one risk factor in such patients, independent of age and comorbidities. Especially in patients with severe SARS-CoV-2-infection, albumin infusion may be essential to improve hemodynamics and to reduce the plasma level of the main marker of thromboembolism, namely, the D-dimer plasma level, as suggested by a recent report. Albumin is responsible for 80% of the oncotic pressure in the vessels. This is necessary to keep enough water within the systemic circulatory system and for the maintenance of sufficient blood pressure, as well as for sufficient blood supply for vital organs like the brain, lungs, heart, and kidney. The liver reacts to a decrease in oncotic pressure with an increase in albumin synthesis. This is normally possible through the use of amino acids from the proteins introduced with the nutrients reaching the portal blood. If these are not sufficiently provided with the diet, amino acids are delivered to the liver from muscular proteins by systemic circulation. The liver is also the source of coagulation proteins, such as fibrinogen, fibronectin, and most of the v WF VIII, which are physiological components of the extracellular matrix of the vessel wall. While albumin is the main negative acute-phase protein, fibrinogen, fibronectin, and v WF VIII are positive acute-phase proteins. Acute illnesses cause the activation of defense mechanisms (acute-phase reaction) that may lead to an increase of fibrinolysis and an increase of plasma level of fibrinogen breakdown products, mainly fibrin and D-dimer. The measurement of the plasma level of the D-dimer has been used as a marker for venous thromboembolism, where a fourfold increase of the D-dimer plasma level was used as a negative prognostic marker in critically ill SARS-CoV-2 hospitalized patients. Increased fibrinolysis can take place in ischemic peripheral sites, where the mentioned coagulation proteins can become part of the provisional clot (e.g., in the lungs). Although critically ill SARS-CoV-2-infected patients are considered septic shock patients, albumin infusions have not been considered for hemodynamic resuscitation and as anticoagulants. The role of coagulation factors as provisional components of the extracellular matrix in case of generalized peripheral ischemia due to hypoalbuminemia and hypovolemia is discussed in this review.<\/jats:p>","DOI":"10.3390\/ijms22137126","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T12:03:27Z","timestamp":1625141007000},"page":"7126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Albumin Infusion in Critically Ill COVID-19 Patients: Hemodilution and Anticoagulation"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7921-7186","authenticated-orcid":false,"given":"Giuliano","family":"Ramadori","sequence":"first","affiliation":[{"name":"Internal Medicine University Clinic, University of G\u00f6ttingen, G\u00f6ttingen, Germany Robert-Koch-Strasse 40, 37075 G\u00f6ttingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ref_1","first-page":"102","article-title":"Albumin Supplementation Dampens Hypercoagulability in COVID-19: A Preliminary Report","volume":"121","author":"Violi","year":"2020","journal-title":"Thromb. Haemost."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.mam.2011.12.002","article-title":"Human serum albumin: From bench to bedside","volume":"33","author":"Fanali","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2147\/IJGM.S102819","article-title":"Human serum albumin homeostasis: A new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements","volume":"9","author":"Levitt","year":"2016","journal-title":"Int. J. Gen. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1152\/jappl.2001.90.2.528","article-title":"Enhanced synthesis of albumin and fibrinogen at high altitude","volume":"90","author":"Imoberdorf","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1152\/jappl.1966.21.2.583","article-title":"Blood volume and age: Repeated measurements on normal men after 17 years","volume":"21","author":"Chien","year":"1966","journal-title":"J. Appl. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1152\/jappl.1994.76.5.2059","article-title":"Total blood volume in healthy young and older men","volume":"76","author":"Davy","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3389\/fimmu.2018.00586","article-title":"Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines","volume":"9","author":"Rea","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s12573-010-0015-y","article-title":"Influence of age and hematocrit on the coagulation of blood","volume":"23","author":"Ujie","year":"2009","journal-title":"J. Biorheol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1055\/s-2007-1007106","article-title":"Cytokines and the Hepatic Acute-Phase Response","volume":"19","author":"Ramadori","year":"1999","journal-title":"Semin. Liver Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1056\/NEJM199902113400607","article-title":"Acute-Phase Proteins and Other Systemic Responses to Inflammation","volume":"340","author":"Gabay","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"27","DOI":"10.18683\/germs.2020.1182","article-title":"Study of the diagnostic value of interleukin-6 and interleukin-8 in children with acute gastroenteritis","volume":"10","author":"Zaki","year":"2020","journal-title":"Germs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00441-011-1152-3","article-title":"Comparison of changes in gene expression of transferrin receptor-1 and other iron-regulatory proteins in rat liver and brain during acute-phase response","volume":"344","author":"Malik","year":"2011","journal-title":"Cell Tissue Res."},{"key":"ref_13","first-page":"G1163","article-title":"Interleukin-6 expression and regulation in rat enteric glial cells","volume":"280","author":"Franzke","year":"2001","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0041-3879(90)90075-J","article-title":"Changes in serum proteins (albumin, immunoglobulins and acute phase proteins) in pulmonary tuberculosis during therapy","volume":"71","author":"Wong","year":"1990","journal-title":"Tubercle"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1128\/CVI.00211-16","article-title":"Immunoglobulin M for Acute Infection: True or False?","volume":"23","author":"Landry","year":"2016","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.1172\/JCI142804","article-title":"COVID-19 survival associates with the immunoglobulin response to the SARS-CoV-2 spike receptor binding domain","volume":"130","author":"Secchi","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"6194","DOI":"10.1172\/JCI145301","article-title":"Inflammatory syndromes associated with SARS-CoV infection:dysregulation of the immune response across the age spectrum","volume":"130","author":"Weatherhead","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s12603-009-0023-z","article-title":"Preventing and treating dehydration in the elderly during periods of illness and warm weather","volume":"13","author":"Schols","year":"2009","journal-title":"J. Nutr. Health Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4210","DOI":"10.1172\/JCI45161","article-title":"Cellular pathophysiology of ischemic acute kidney injury","volume":"121","author":"Bonventre","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1161\/STROKEAHA.111.640821","article-title":"Dehydration in Hospital-Admitted Stroke Patients","volume":"43","author":"Rowat","year":"2012","journal-title":"Stroke"},{"key":"ref_21","first-page":"521","article-title":"Transient ischemic attack:Part I.Diagnosis and evaluation","volume":"86","author":"Simmons","year":"2012","journal-title":"Am. Med. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3233\/NHA-170026","article-title":"Hydration health literacy in the elderly","volume":"4","author":"Picetti","year":"2017","journal-title":"Nutr. Heal. Aging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1148\/rg.2019190033","article-title":"Ischemic Infarction in Young Adults: A Review for Radiologists","volume":"39","author":"Mccarty","year":"2019","journal-title":"RadioGraphics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e60","DOI":"10.1056\/NEJMc2009787","article-title":"Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young","volume":"382","author":"Oxley","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1001\/jamaneurol.2021.0504","article-title":"Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome","volume":"78","author":"LaRovere","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"607221","DOI":"10.3389\/fneur.2020.607221","article-title":"COVID-19 Pathophysiology Predicts That Ischemic Stroke Occurrence Is an Expectation, Not an Exception\u2014A Systematic Review","volume":"11","author":"Wijeratne","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.4049\/jimmunol.135.6.3645","article-title":"Espression and regulation oft he murine Serum Amyloid A(SAA) gene in extrahepatic sites","volume":"135","author":"Ramadori","year":"1985","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/labinvest.3700553","article-title":"Changes of gene expression of iron regulatory proteins during turpentine oil-induced acute-phase response in the rat","volume":"87","author":"Sheikh","year":"2007","journal-title":"Lab. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1159\/000163650","article-title":"Interaction of Cultured Human Kupffer Cells with H\u0393V-Infected CEM Cells: An Electron Microscopic Study","volume":"59","author":"Gendrault","year":"1991","journal-title":"Pathobiology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1093\/oxfordjournals.bja.a013407","article-title":"Measurement of blood volume in surgical and intensive care practice","volume":"84","author":"Jones","year":"2000","journal-title":"Br. J. Anaesth."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1136\/bmj.319.7207.427","article-title":"ABC of intensive care.Recovery from intensive care","volume":"319","author":"Griffiths","year":"1999","journal-title":"BMJ"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1164\/rccm.201602-0257ED","article-title":"Long-term outcomes after critical illness.The best predictor of the future ist he past","volume":"194","author":"Cuthbertson","year":"2016","journal-title":"Am. J. Resp. Crit. Care Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S2213-2600(18)30076-6","article-title":"The long road to recovery after the ICU","volume":"6","author":"Feetham","year":"2018","journal-title":"Lancet Respir. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1111\/jocs.14963","article-title":"The long-term effects of prolonged intensive care stay postcardiac surgery","volume":"35","author":"Lathlean","year":"2020","journal-title":"J. Card. Surg."},{"key":"ref_35","first-page":"53","article-title":"Long-term outcomes from critical care","volume":"39","author":"Morgan","year":"2020","journal-title":"Surgery"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S2213-2600(20)30111-9","article-title":"Surviving the ICU is only the beginning of a long road ahead","volume":"8","author":"Morgan","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1007\/s12603-020-1497-y","article-title":"COVID-19. The Long Road to Recovery","volume":"24","author":"Morley","year":"2020","journal-title":"J. Nutr. Health Aging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1007\/s11357-020-00272-3","article-title":"Sarcopenia during COVID-19 lockdown restrictions: Long-term health effects of short-term muscle loss","volume":"42","author":"Kirvan","year":"2020","journal-title":"GeroScience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1136\/thoraxjnl-2016-208835","article-title":"Recovery from ICU-acquired weakness; do not forget the respiratory muscles!","volume":"71","author":"Gosselink","year":"2016","journal-title":"Thorax"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/00075197-200201000-00009","article-title":"Liver protein synthesis in physiology and in disease states","volume":"5","author":"Lucidi","year":"2002","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.jada.2004.05.213","article-title":"Hepatic proteins and Nutrition assessment","volume":"104","author":"Fuhrman","year":"2004","journal-title":"J. Am. D Ass."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1042\/CS20050222","article-title":"Synthesis rates of total liver protein and albumin are both increased in patients with acute inflammatory response","volume":"110","author":"Barle","year":"2006","journal-title":"Clin. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1002\/ajh.23303","article-title":"Hypoalbuminemia is an independent prognostic factor for overall survival in myelodysplastic syndromes","volume":"87","author":"Komrokji","year":"2012","journal-title":"Am. J. Hematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1111\/jth.15267","article-title":"Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response","volume":"19","author":"Townsend","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1182\/blood.2020010529","article-title":"Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: The CORE-19 registry","volume":"137","author":"Giannis","year":"2021","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e213990","DOI":"10.1001\/jamanetworkopen.2021.3990","article-title":"Mortality and Readmission Rates Among Patients With COVID-19 After Discharge From Acute Care Setting With Supplemental Oxygen","volume":"4","author":"Banerjee","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100793","DOI":"10.1016\/j.eclinm.2021.100793","article-title":"Pre-existing conditions are associated with COVID-19 patients\u2019 hospitalization, despite confirmed clearance of SARS-CoV-2 virus","volume":"7","author":"Pawlowski","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1164\/rccm.202008-3265OC","article-title":"Tissue specific immunopathology in fatal COVID-19","volume":"203","author":"Dorward","year":"2021","journal-title":"Am. J. Resp. Crit. Care Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Schurink, B., Roos, E., Radonic, T., Barbe, E., Bouman, C.S.C., de Boer, H.H., de Bree, G.J., Bulle, E.B., Aronica, E.M., and Florquin, S. (2020). Viral presence and immunopathology in patients with lethal COVID-19: A prospective autopsy cohort study. Lancet Microbe.","DOI":"10.1016\/S2666-5247(20)30144-0"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"100850","DOI":"10.1016\/j.eclinm.2021.100850","article-title":"An autopsy study of the spectrum of severe COVID-19 in children: From SARS to different phenotypes of MIS-C","volume":"35","author":"Caldini","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"104204","DOI":"10.1016\/j.archger.2020.104204","article-title":"Clinical course and prognostic factors of COVID-19 infection in an elderly hospitalized population","volume":"91","author":"Mostaza","year":"2020","journal-title":"Arch. Gerontol. Geriatr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-73962-9","article-title":"A novel severity score to predict inpatient mortality in COVID-19 patients","volume":"10","author":"Altschul","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"100765","DOI":"10.1016\/j.eclinm.2021.100765","article-title":"Estimating risk of mechanical ventilation and in-hospital mortality among adult COVID-19 patients admitted to Mass General Brigham: The VICE and DICE scores","volume":"33","author":"Nicholson","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Izcovich, A., Ragusa, M.A., Tortosa, F., Marzio, M.A.L., Agnoletti, C., Bengolea, A., Ceirano, A., Espinosa, F., Saavedra, E., and Sanguine, V. (2020). Prognostic factors for severity and mortality in patients infected with COVID-19: A systematic review. PLoS ONE, 15.","DOI":"10.1101\/2020.04.08.20056598"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"33","DOI":"10.7326\/M20-3905","article-title":"Patient Trajectories Among Persons Hospitalized for COVID-19","volume":"174","author":"Garibaldi","year":"2021","journal-title":"Ann. Intern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kheir, M., Saleem, F., Wang, C., Mann, A., and Chua, J. (2021). Higher albumin levels on admission predict better prognosis in patients with confirmed COVID-19. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248358"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/d41586-021-01246-x","article-title":"How Covid broke the evidence pipeline","volume":"593","author":"Pearson","year":"2021","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.cmi.2020.12.018","article-title":"Antibiotic prescribing in patients with COVID-19: Rapid review and meta-analysis","volume":"27","author":"Langford","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1681\/ASN.2020050744","article-title":"Postmotem Kidney Pathology Findings in Patients with COVID-19","volume":"31","author":"Santoriello","year":"2020","journal-title":"JASN"},{"key":"ref_61","first-page":"E1023","article-title":"Age effect on fibrinogen and albumin synthesis in humans","volume":"275","author":"Fu","year":"1998","journal-title":"Am. J. Physiol. Content"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1186\/1475-2891-9-69","article-title":"Pretreatment serum albumin as a predictor of cancer survival: A systematic review of the epidemiological literature","volume":"9","author":"Gupta","year":"2010","journal-title":"Nutr. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1172\/JCI101514","article-title":"Chemical, clinical and immunological studies on the products of human plasma fractionation:VII.Concentrated Human Serum Albumin","volume":"23","author":"Janeway","year":"1944","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1001\/archinte.1951.03810060002001","article-title":"Intravenous use of salt-poor human albumin","volume":"87","author":"Post","year":"1951","journal-title":"A.M.A. Arch. Intern. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1016\/S0140-6736(61)92479-5","article-title":"Intravenous albumen in the treatment","volume":"278","author":"Losowsky","year":"1961","journal-title":"Lancet"},{"key":"ref_66","first-page":"153","article-title":"Mechanism of ascites formation in chronic liver disease","volume":"30","author":"Atkinson","year":"1961","journal-title":"Quaterly J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/S0140-6736(62)90895-4","article-title":"The effect of repeated albumin infusions in patients with cirrhosis","volume":"280","author":"Wilkinson","year":"1962","journal-title":"Lancet"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/00000441-196610000-00009","article-title":"Furosemide therapy in \u201cintractable ascites\u201d","volume":"252","author":"Steigman","year":"1966","journal-title":"Am. J. Med. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/0016-5085(83)90198-1","article-title":"Randomized Comparative Study of efficacy of Furosemide versus Spironolactone in Nonazotemic Cirrhosis With Ascites. Relattionship between the diuretic response and the activity of the Renin-Aldosterone System","volume":"84","author":"Arroyo","year":"1983","journal-title":"Gastroenterology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/00005792-197105000-00002","article-title":"Spontaneous bacterial peritonitis in cirrhosis: Variations on a theme","volume":"50","author":"Conn","year":"1971","journal-title":"Medicine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJM199908053410603","article-title":"Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis","volume":"341","author":"Sort","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1056\/NEJM199912023412317","article-title":"Intravenous Albumin in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis","volume":"341","author":"Patch","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_73","first-page":"941","article-title":"Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: Results of a prospective, nonrandomized study","volume":"36","author":"Ortega","year":"2002","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S0168-8278(99)80194-9","article-title":"Albumin improves the response to diuretics in patients with cirrhosis and ascites: Results of a randomized, controlled trial","volume":"30","author":"Gentilini","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/S0140-6736(18)30840-7","article-title":"Long-term albumin administration in decompensated cirrhosis (ANSWER): An open-label randomised trial","volume":"391","author":"Caraceni","year":"2018","journal-title":"Lancet"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/S0168-8278(99)80329-8","article-title":"Albumin substitution improves urinary sodium excretion and diuresis in patients with liver cirrhosis and refractory ascites","volume":"31","author":"Schindler","year":"1999","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1016\/j.gastro.2003.02.003","article-title":"Albumin for refractory ascites","volume":"125","author":"Nolte","year":"2003","journal-title":"Gastroenterology."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.3748\/wjg.v20.i9.2374","article-title":"Procalcitonin, and cytokines document a dynamic inflammatory state in non-infected cirrhotic patients with ascites","volume":"20","author":"Attar","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1056\/NEJMoa1305727","article-title":"Albumin Replacement in Patients with Severe Sepsis or Septic Shock","volume":"370","author":"Caironi","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1056\/NEJMc1405675","article-title":"Albumin Replacement in Severe Sepsis or Septic Shock","volume":"371","author":"Wiedermann","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_81","first-page":"JC6","article-title":"Commentary","volume":"161","author":"Thompson","year":"2014","journal-title":"Am. College Phys."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/0049-3848(89)90317-4","article-title":"Von Willebrand factor is an acute phase reactant in man","volume":"53","author":"Pottinger","year":"1989","journal-title":"Thromb. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"4591","DOI":"10.1038\/s41598-017-04843-x","article-title":"Age-related diagnostic value of D-dimer testing and the role of inflammation in patients with suspected deep vein thrombosis","volume":"7","author":"Prochaska","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s11739-019-02216-y","article-title":"D-dimer testing, with gender-specific cutoff levels, is of value to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: A post hoc analysis of the DULCIS study","volume":"15","author":"Palareti","year":"2020","journal-title":"Intern. Emerg. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2125","DOI":"10.1056\/NEJMoa1909159","article-title":"Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability","volume":"381","author":"Kearon","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Lin, C., Chen, Y., Chen, B., Zheng, K., Luo, X., and Lin, F. (2020). D-Dimer Combined with Fibrinogen Predicts the Risk of Venous Thrombosis in Fracture Patients. Emerg. Med. Int.","DOI":"10.1155\/2020\/1930405"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e914","DOI":"10.1161\/CIR.0000000000000769","article-title":"Call to action to prevent venous Thromboembolism in hospitalized patients.A policy statment from the american heart association","volume":"141","author":"Henke","year":"2020","journal-title":"Circulation"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1002\/jmv.26003","article-title":"Hypoalbuminemia predicts the outcome of COVID-19 independent of age and co-morbidity","volume":"92","author":"Huang","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ajem.2020.12.076","article-title":"Inflammatory and hematologic markers as predictors of severe outcomes in COVID-19 infection: A systematic review and meta-analysis","volume":"41","author":"Hariyanto","year":"2021","journal-title":"Am. J. Emerg. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2001201","DOI":"10.1183\/13993003.01201-2020","article-title":"Venous thromboembolism in SARS-CoV-2 patients: Only a problem in ventilated ICU patients, or is there more to it?","volume":"56","author":"Criel","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1080\/17474086.2020.1831383","article-title":"D-dimer level in COVID-19 infection: A systematic review","volume":"13","author":"Rostami","year":"2020","journal-title":"Expert Rev. Hematol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6648199","DOI":"10.1155\/2021\/6648199","article-title":"Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy","volume":"2021","author":"Popadic","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Goyal, A., Prasad, R., Goel, P., Pal, A., Prasad, S., and Rani, I. (2021). An Integrated Approach of the Potential Underlying Molecular Mechanistic Paradigms of SARS-CoV-2-Mediated Coagulopathy. J. Clin. Biochem.","DOI":"10.1007\/s12291-021-00972-3"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1055\/s-0040-1715798","article-title":"Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology\/Vascular Medicine","volume":"120","author":"Gerotziafas","year":"2020","journal-title":"Thromb. Haemost."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1038\/s41598-021-81300-w","article-title":"The poor prognosis and influencing factors of high D-dimer levels for COVID-19 patients","volume":"11","author":"He","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Tan, B.K., Mainbourg, S., Friggeri, A., Bertoletti, L., Douplat, M., Dargaud, Y., Grange, C., Lobbes, H., Provencher, S., and Lega, J.-C. (2021). Arterial and venous thromboembolism in COVID-19: A study-level meta-analysis. Thorax.","DOI":"10.1136\/thoraxjnl-2020-215383"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/bja\/aeh174","article-title":"Updates in perioperative coagulation: Physiology and management of thromboembolism and haemorrhage","volume":"93","author":"Bombeli","year":"2004","journal-title":"Br. J. Anaesth."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Iba, T., Warkentin, T.E., Thachil, J., Levi, M., and Levy, J.H. (2021). Proposal of the Definition for COVID-19-Associated Coagulopathy. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020191"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S2213-2600(21)00218-6","article-title":"The COVID-19 puzzle: Deciphering pathophysiology and phenotypes of a new disease entity","volume":"9","author":"Osuchowski","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"103215","DOI":"10.1016\/j.ebiom.2021.103215","article-title":"Direct or indirect endothelial damage? An unresolved question","volume":"64","author":"Basta","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Kaptein, F., Stals, M., Huisman, M., and Klok, F. (2021). Prophylaxis and treatment of COVID-19 related venous thromboembolism. Postgrad. Med.","DOI":"10.1080\/00325481.2021.1891788"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1055\/s-0040-1721664","article-title":"Pharmacologic Thromboprophylaxis and Thrombosis in Hospitalized Patients with COVID-19: A Pooled Analysis","volume":"121","author":"Patell","year":"2021","journal-title":"Thromb. Haemost."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1182\/blood.2020006000","article-title":"COVID-19 and its implications for thrombosis and anticoagulation","volume":"135","author":"Connors","year":"2020","journal-title":"Blood"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"INSPIRATION Investigators (2021). Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care UnitThe INSPIRATION Randomized Clinical Trial. JAMA, 325, 1620\u20131630.","DOI":"10.1001\/jama.2021.4152"},{"key":"ref_105","first-page":"1","article-title":"Pulmonary embolism, pulmonary microvascular thrombosis, or both in COVID-19?","volume":"26","author":"Paramo","year":"2020","journal-title":"Cin. Appl. Thromb\/Haemost."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e255","DOI":"10.1515\/cclm-2020-1038","article-title":"Hypoalbuminemia and elevated D-dimer in COVID-19 patients: A call for result harmonization","volume":"58","author":"Aloisio","year":"2020","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1161\/CIRCRESAHA.120.317173","article-title":"Hypoalbuminemia, Coagulopathy, and Vascular Disease in COVID-19","volume":"127","author":"Violi","year":"2020","journal-title":"Circ. Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"e364","DOI":"10.1097\/CCM.0000000000002996","article-title":"Is Heparin-Binding Protein Inhibition a Mechanism of Albumin\u2019s Efficacy in Human Septic Shock?","volume":"46","author":"Fisher","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1080\/03007995.2020.1840970","article-title":"Phases of fluid management and the roles of human albumin solution in perioperative and critically ill patients","volume":"36","author":"Wiedermann","year":"2020","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_110","first-page":"a005132","article-title":"Extracellular Matrix Proteins in Homostasis and Thrombosis","volume":"4","author":"Bergmeier","year":"2012","journal-title":"Cold Spring HarbPerspect Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/S2352-4642(20)30257-1","article-title":"SARS-CoV-2 in cardiac tissue of a child with COVID-19-related multisystem inflammatory syndrome","volume":"4","author":"Dolhnikoff","year":"2020","journal-title":"Lancet Child Adolesc. Health"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1001\/jamacardio.2020.7308","article-title":"Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction","volume":"6","author":"Blasco","year":"2021","journal-title":"JAMA Cardiol."},{"key":"ref_113","first-page":"470","article-title":"Expression of Von Willebrand Factor in Normal and Diseased Rat Livers and in cultivated Liver Cells","volume":"21","author":"Knittel","year":"1995","journal-title":"Hepatology"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/0016-5085(95)90211-2","article-title":"Accumulation and cellular localisation of fibrinogen\/fibrin during short-term and long-term rat liver injury","volume":"108","author":"Neubauer","year":"1995","journal-title":"Gastroenterology"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0168-8278(02)00215-5","article-title":"Von Willebrand factor in plasma and in liver tissue after partial hepatectomy","volume":"37","author":"Baruch","year":"2002","journal-title":"J. Hepatol."},{"key":"ref_116","first-page":"684","article-title":"Von Willebrand gene expression in damaged human liver","volume":"51","author":"Baruch","year":"2004","journal-title":"Hepatogastroenterology"},{"key":"ref_117","first-page":"525","article-title":"Entactin gene-expression in normal and fibrotic rat liver and in rat liver cells","volume":"70","author":"Schwoegler","year":"1994","journal-title":"Lab. Investig."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"6485","DOI":"10.1073\/pnas.1404809111","article-title":"Secretion of von Willebrand factor by endothelial cells links sodium to hypercoagulability and thrombosis","volume":"111","author":"Dimitrieva","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1053\/j.seminhematol.2004.09.009","article-title":"Von Willebrand Factor and Factor VIII as Risk factors for arterial and venous thrombosi","volume":"42","author":"Martinelli","year":"2005","journal-title":"Sem. Hematol."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Pandey, E., Nour, A.S., and Harris, E.N. (2020). Prominent receptors of liver Sinusoidal endothelial cells in liver homeostasis and disease. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00873"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7126\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:24:42Z","timestamp":1760163882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/13\/7126"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,1]]},"references-count":120,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22137126"],"URL":"https:\/\/doi.org\/10.3390\/ijms22137126","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,1]]}}}