Potential Biomarkers for Early Diagnosis, Evaluation, and Prognosis of Sepsis-Induced Coagulopathy

Overview

Journal Clin Appl Thromb Hemost

Publisher Sage Publications

Specialty Cardiology & Vascular Diseases

Date 2023 Aug 22

PMID 37605466

Authors

Yuting Li

Hongxiang Li

Youquan Wang

Jianxing Guo

Dong Zhang

Affiliations

Soon will be listed here.

Abstract

Sepsis-induced coagulopathy (SIC) is a life-threatening complication characterized by the systemic activation of coagulation in sepsis. The diagnostic criteria of SIC consist of three items, including Sequential Organ Failure Assessment (SOFA) score, platelet count, and prothrombin time (PT)-international normalized ratio (INR). SIC has a high prevalence and it can lead to a higher mortality rate and longer length of hospital and ICU stay. Thus, the early detection of SIC is extremely important. It is unfortunate that there is still no precise biomarker for early diagnosis and assessment of the prognosis of SIC. We reviewed the current literature and discovered that some potential biomarkers, such as soluble thrombomodulin (sTM), thrombin-antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), α2-plasmin inhibitor-plasmin complex (PIC), C-type lectin-like receptor 2 (CLEC-2), neutrophil extracellular traps (NETs), prothrombin fragment 1.2 (F1.2), Angiopoietin-2 (Ang-2), plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be useful for early diagnosis, evaluation, and prognosis of SIC. Early initiation of treatment without missing any therapeutic opportunities may improve SIC patients' prognosis. Further large-scale clinical studies are still needed to confirm the role of these biomarkers in the diagnosis and prognosis assessment of SIC.

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References

Iba T, Levy J, Raj A, Warkentin T . Advance in the Management of Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation. J Clin Med. 2019; 8(5). PMC: 6572234. DOI: 10.3390/jcm8050728. View

Boehme M, Deng Y, Raeth U, Bierhaus A, Ziegler R, Stremmel W . Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: in vivo and in vitro studies. Immunology. 1996; 87(1):134-40. PMC: 1383979. View

Matsuo T, Kario K, Matsuo M . [Thrombin.antithrombin III complex]. Rinsho Byori. 1991; 39(7):701-6. View

Wexels F, Seljeflot I, Pripp A, Dahl O . D-Dimer and prothrombin fragment 1 + 2 in urine and plasma in patients with clinically suspected venous thromboembolism. Blood Coagul Fibrinolysis. 2015; 27(4):396-400. DOI: 10.1097/MBC.0000000000000461. View

Li J, Zhou J, Ren H, Teng T, Li B, Wang Y . Clinical Efficacy of Soluble Thrombomodulin, Tissue Plasminogen Activator Inhibitor complex, Thrombin-Antithrombin complex,α2-Plasmininhibitor-Plasmin complex in Pediatric Sepsis. Clin Appl Thromb Hemost. 2022; 28:10760296221102929. PMC: 9134456. DOI: 10.1177/10760296221102929. View

Rybak M, Lau H, Tomkins B, Rosenberg R, Handin R . Relationship between platelet secretion and prothrombin cleavage in native whole blood. J Clin Invest. 1981; 68(2):405-12. PMC: 370812. DOI: 10.1172/jci110269. View

Semeraro N, Ammollo C, Semeraro F, Colucci M . Coagulopathy of Acute Sepsis. Semin Thromb Hemost. 2015; 41(6):650-8. DOI: 10.1055/s-0035-1556730. View

Fleischmann C, Scherag A, Adhikari N, Hartog C, Tsaganos T, Schlattmann P . Assessment of Global Incidence and Mortality of Hospital-treated Sepsis. Current Estimates and Limitations. Am J Respir Crit Care Med. 2015; 193(3):259-72. DOI: 10.1164/rccm.201504-0781OC. View

Gibson N, Sohne M, Gerdes V, Meijers J, Buller H . Clinical usefulness of prothrombin fragment 1+2 in patients with suspected pulmonary embolism. Thromb Res. 2009; 125(1):97-9. DOI: 10.1016/j.thromres.2009.03.002. View

10.

Serrano-Gomez S, Burgos-Angulo G, Nino-Vargas D, Nino M, Cardenas M, Chacon-Valenzuela E . Predictive Value of Matrix Metalloproteinases and Their Inhibitors for Mortality in Septic Patients: A Cohort Study. J Intensive Care Med. 2017; 35(1):95-103. DOI: 10.1177/0885066617732284. View

11.

Martinod K, Wagner D . Thrombosis: tangled up in NETs. Blood. 2013; 123(18):2768-76. PMC: 4007606. DOI: 10.1182/blood-2013-10-463646. View

12.

Massberg S, Grahl L, von Bruehl M, Manukyan D, Pfeiler S, Goosmann C . Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med. 2010; 16(8):887-96. DOI: 10.1038/nm.2184. View

13.

Hoshino K, Nakashio M, Maruyama J, Irie Y, Kawano Y, Ishikura H . Validating plasminogen activator inhibitor-1 as a poor prognostic factor in sepsis. Acute Med Surg. 2020; 7(1):e581. PMC: 7642588. DOI: 10.1002/ams2.581. View

14.

Bauer K, Humphries S, Smillie B, Li L, Cooper J, Barzegar S . Prothrombin activation is increased among asymptomatic carriers of the prothrombin G20210A and factor V Arg506Gln mutations. Thromb Haemost. 2000; 84(3):396-400. View

15.

Singer M, Deutschman C, Seymour C, Shankar-Hari M, Annane D, Bauer M . The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016; 315(8):801-10. PMC: 4968574. DOI: 10.1001/jama.2016.0287. View

16.

Lubis B, Lelo A, Amelia P, Prima A . The Effect of Thiamine, Ascorbic Acid, and the Combination of Them on the Levels of Matrix Metalloproteinase-9 (MMP-9) and Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) in Sepsis Patients. Infect Drug Resist. 2022; 15:5741-5751. PMC: 9531617. DOI: 10.2147/IDR.S378523. View

17.

Sivula M, Hastbacka J, Kuitunen A, Lassila R, Tervahartiala T, Sorsa T . Systemic matrix metalloproteinase-8 and tissue inhibitor of metalloproteinases-1 levels in severe sepsis-associated coagulopathy. Acta Anaesthesiol Scand. 2014; 59(2):176-84. DOI: 10.1111/aas.12423. View

18.

Takano S, Kimura S, Ohdama S, Aoki N . Plasma thrombomodulin in health and diseases. Blood. 1990; 76(10):2024-9. View

19.

Zhang J, Xue M, Chen Y, Liu C, Kuang Z, Mu S . Identification of soluble thrombomodulin and tissue plasminogen activator-inhibitor complex as biomarkers for prognosis and early evaluation of septic shock and sepsis-induced disseminated intravascular coagulation. Ann Palliat Med. 2021; 10(10):10170-10184. DOI: 10.21037/apm-21-2222. View

20.

Iba T, Di Nisio M, Levy J, Kitamura N, Thachil J . New criteria for sepsis-induced coagulopathy (SIC) following the revised sepsis definition: a retrospective analysis of a nationwide survey. BMJ Open. 2017; 7(9):e017046. PMC: 5623518. DOI: 10.1136/bmjopen-2017-017046. View