ПОРЕМЕЋАЈИ ФИБРИНОЛИЗЕ У СЕПСИ: ЗНАЧАЈ РАНОГ ОТКРИВАЊА АБНОРМАЛНОСТИ У СЕПСОМ ИЗАЗВАНОЈ КОАГУЛОПАТИЈИ И ДОСТУПНИ ЛАБОРАТОРИЈСКИ МАРКЕРИ ФИБРИНОЛИЗЕ
Ključne reči:
сепсом изазвана коагулопатија, фибринолиза, оштећење фибринолизе, вискоеластични тестови
Sažetak
Сепса представља животно угрожавајућу дисфункцију органа узроковану неефикасним одговором домаћина на инфекцију. Неки од најзаступљенијих поремећаја у сепси су хемостазни поремећаји. Код сепсе се често развија стање поремећене антикоагулантне активности и супресије фибринолизе, које се назива сепсом изазвана коагулопатија. Оштећење фибринолитичког система се све више сматра кључним фактором у коагулопатији изазваној сепсом. Оштећена фибринолиза у сепси може допринети нежељеним исходима као што су микроваскуларна тромбоза, дисфункција органа и повећан морталитет. Обзиром да је један од постулата везан за сепсу, да су неопходни брза дијагностика и брзо збрињавање, од великог би значаја било, да се различити облици коагулопатија у сепси, дијагностикују на самом почетку њиховог настанка, ради адекватног терапијског приступа. У том смислу, неопходни су лако доступни, рутински дијагностички тестови. Досадашњи конвенционални лабораторијски тестови коагулопатија не успевају да у потпуности дефинишу сепсом изазвану коагулопатију. Посебно изазовно је тестирање хипофибринолизе у рутинској пракси. Циљеви нашег истраживања били су, да прегледом доступне научне литературе, истражимо везу између запаљења и коагулације у сепси, поремећаје фибринолизе у сепсом изазваној коагулопатији, утврдимо значај раног препознавања ових поремећаја у сепси, и да истражимо доступне лабораторијске маркере фибринолизе и коагулопатија.
Кључне речи: сепсом изазвана коагулопатија, фибринолиза, оштећење фибринолизе, вискоеластични тестови
Reference
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2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017; 43: 304-77.
3. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020; 395: 200-11.
4. Dimić N, Đurić M, Nenadić I, et al. Razvoj definicije sepse. Srpski medicinski časopis Lekarske komore 2023; 4: 75-81.
5. Kell DB, Pretorius E. To What Extent Are the Terminal Stages of Sepsis, Septic Shock, Systemic Inflammatory Response Syndrome, and Multiple Organ Dysfunction Syndrome Actually Driven by a Prion/Amyloid Form of Fibrin? Semin Thromb Hemost 2018; 44: 224-38.
6. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 801-10.
7. Kim HI, Park S. Sepsis: Early Recognition and Optimized Treatment. Tuberc Respir Dis (Seoul) 2019; 82: 6-14.
8. Larsen JB, Aggerbeck MA, Larsen KM, Hvas CL, Hvas AM. Fibrin Network Formation and Lysis in Septic Shock Patients. Int J Mol Sci 2021; 22: 9540.
9. Schmitt FCF, Manolov V, Morgenstern J, et al. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 2019; 9: 19.
10. Helms J, Iba T, Connors JM, et al. How to manage coagulopathies in critically ill patients. Intensive Care Med 2023; 49: 273-90.
11. Iba T, Helms J, Levi M, Levy JH. Thromboinflammation in acute injury: infections, heatstroke, and trauma. J Thromb Haemost 2024; 22: 7-22.
12. Iba T, Helms J, Maier CL, Levi M, Scarlatescu E, Levy JH. The role of thromboinflammation in acute kidney injury among patients with septic coagulopathy. J Thromb Haemost 2024; 22: 1530-40.
13. Delano MJ, Ward PA. The immune system's role in sepsis progression, resolution, and long-term outcome. Immunol Rev 2016; 274: 330-53.
14. Medcalf RL, Keragala CB. Fibrinolysis: A Primordial System Linked to the Immune Response. Int J Mol Sci 2021; 22: 3406.
15. Bergmann S, Hammerschmidt S. Fibrinolysis and host response in bacterial infections. Thromb Haemost 2007; 98: 512-20.
16. Williams B, Zou L, Pittet JF, Chao W. Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesth Analg 2024; 138: 696-711.
17. Hvas CL, Larsen JB. The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment. International Journal of Molecular Sciences 2023; 24: 14179.
18. Rijken DC, Uitte de Willige S. Inhibition of fibrinolysis by coagulation factor XIII. Biomed Res Int 2017; 2017: 1209676.
19. Spasić, I. Specifičnosti hemostaznog mehanizma kod obolelih od SARS-CoV-2 virusne infekcije. Doktorska disertacija, Novi Sad: Medicinski fakultet, 2022.
20. Gando S. Role of Fibrinolysis in Sepsis. Semin Thromb Hemost 2013; 39: 392-99.
21. Degen JL, Bugge TH, Goguen JD. Fibrin and fibrinolysis in infection and host defense. J Thromb Haemost 2007; 5: 24–31.
22. Brewer JS, Hvas CL, Hvas AM, Larsen JB. Impaired Whole-Blood Fibrinolysis is a Predictor of Mortality in Intensive Care Patients. TH Open 2024; 08: 164-74.
23. Coupland LA, Rabbolini DJ, Schoenecker JG, et al. Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study. Crit Care 2023; 27: 55.
24. Singhal S, Ranga S, Chawla AS, Kamra R. Role of Antithrombin III, Plasminogen, Protein C and Protein S in Deep Vein Thrombosis in Indian Population. IJSHR 2019; 4: 54-9.
25. Levi M, Van Der Poll T. Thrombomodulin in sepsis. Minerva Anestesiol 2013; 79: 294-8.
26. Kato H, Hagihara M, Asai N. Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-induced disseminated intravascular coagulation - A meta-analysis. Thromb Res 2023; 226: 165-72.
27. Wang G, Hao C, Yao S, Wang Y, Xu Z, Zhao H, et al. Exploring the Mediating Role of Multiple Organ Dysfunction in Sepsis-Induced Disseminated Intravascular Coagulation and Its Impact on Worsening Prognosis. Clin Appl Thromb Hemost 2024; 30: 10760296241271358.
28. Iba T, Helms J, Levy JH. Sepsis-induced coagulopathy (SIC) in the management of sepsis. Ann Intensive Care 2024; 14: 148.
29. Egi M, Ogura H, Yatabe T, et al. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020). Acute Med Surg 2021; 8: e659.
30. Larsen JB, Aggerbeck MA, Granfeldt A, Schmidt M, Hvas AM, Adelborg K. Disseminated intravascular coagulation diagnosis: Positive predictive value of the ISTH score in a Danish population. Res Pract Thromb Haemost 2021; 5: e12636.
31. Hartmann J, Hermelin D, Levy JH. Viscoelastic testing: an illustrated review of technology and clinical applications. Res Pract Thromb Haemost 2022; 7:100031.
32. Govil D, Pal D. Point-of-care testing of coagulation in intensive care unit: Role of thromboelastography. Indian J Crit Care Med 2019; 23: S202-6.
33. Zátroch I, Dinya E, Fazakas J. New under the sun: ClotPro's ECA-test detects hyperfibrinolysis in a higher number of patients, more frequently and 9 min earlier. Blood Coagul Fibrinolysis 2023; 34: 99-104.
34. Bui-Thi HD, Kien To Gia, Le Minh K. Coagulation profiles in patients with sepsis/septic shock identify mixed hypo-hypercoagulation patterns based on rotational thromboelastometry: A prospective observational study. Thromb Res 2023; 227: 51-9.
35. Zheng Z, Mukhametova L, Boffa MB, et al. Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis. J Thromb Haemost 2023; 21: 1043-54.
36. Mavrommatis AC, Theodoridis T, Economou M, et al. Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med 2001; 27: 1853-59.
37. Ghansah H, Orban-Kalmandi R, Debreceni IB, et al. Low factor XIII levels and altered fibrinolysis in patients with multiple myeloma. Thromb Res 2024; 234: 12-20.
38. Cohen T, Haas T, Cushing MM. The strengths and weaknesses of viscoelastic testing compared to traditional coagulation testing. Transfusion 2020; 6 :S21-8.
39. Ostrowski SR, Windeløv NA, Ibsen M, Haase N, Perner A, Johansson PI. Consecutive thrombelastography clot strength profiles in patients with severe sepsis and their association with 28-day mortality: A prospective study. J Crit Care 2013; 28: 317.
40. Kim SM, Kim SI, Yu G, et al. Role of thromboelastography in the evaluation of septic shock patients with normal prothrombin time and activated partial thromboplastin time. Sci Rep 2021; 11: 11833.
41. Enk NM, Kutter APN, Kuemmerle-Fraune C, Sigrist NE. Correlation of plasma coagulation tests and fibrinogen (Clauss) with rotational thromboelastometry parameters and prediction of bleeding in dogs. J Vet Intern Med 2019; 33: 132-40.
42. Moore HB. Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States. Semin Thromb Hemost 2023; 49: 433-43.
43. Mohapatra P, Kumar A, Singh RK, et al. The Effect of Sepsis and Septic Shock on the Viscoelastic Properties of Clot Quality and Mass Using Thromboelastometry: A Prospective Observational Study. Indian J Crit Care Med 2023; 27: 625-34.
44. Hans GA, Besser MW. The place of viscoelastic testing in clinical practice. Br J Haematol 2016; 173: 37-48.
45. Borawski J, Myśliwiec M. Plasma fibrinogen level is an important determinant of prolonged euglobulin clot lysis time in hemodialysis patients. Clin Appl Thromb Hemost 2001; 7: 296-9.
2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017; 43: 304-77.
3. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet 2020; 395: 200-11.
4. Dimić N, Đurić M, Nenadić I, et al. Razvoj definicije sepse. Srpski medicinski časopis Lekarske komore 2023; 4: 75-81.
5. Kell DB, Pretorius E. To What Extent Are the Terminal Stages of Sepsis, Septic Shock, Systemic Inflammatory Response Syndrome, and Multiple Organ Dysfunction Syndrome Actually Driven by a Prion/Amyloid Form of Fibrin? Semin Thromb Hemost 2018; 44: 224-38.
6. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 801-10.
7. Kim HI, Park S. Sepsis: Early Recognition and Optimized Treatment. Tuberc Respir Dis (Seoul) 2019; 82: 6-14.
8. Larsen JB, Aggerbeck MA, Larsen KM, Hvas CL, Hvas AM. Fibrin Network Formation and Lysis in Septic Shock Patients. Int J Mol Sci 2021; 22: 9540.
9. Schmitt FCF, Manolov V, Morgenstern J, et al. Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study. Ann Intensive Care 2019; 9: 19.
10. Helms J, Iba T, Connors JM, et al. How to manage coagulopathies in critically ill patients. Intensive Care Med 2023; 49: 273-90.
11. Iba T, Helms J, Levi M, Levy JH. Thromboinflammation in acute injury: infections, heatstroke, and trauma. J Thromb Haemost 2024; 22: 7-22.
12. Iba T, Helms J, Maier CL, Levi M, Scarlatescu E, Levy JH. The role of thromboinflammation in acute kidney injury among patients with septic coagulopathy. J Thromb Haemost 2024; 22: 1530-40.
13. Delano MJ, Ward PA. The immune system's role in sepsis progression, resolution, and long-term outcome. Immunol Rev 2016; 274: 330-53.
14. Medcalf RL, Keragala CB. Fibrinolysis: A Primordial System Linked to the Immune Response. Int J Mol Sci 2021; 22: 3406.
15. Bergmann S, Hammerschmidt S. Fibrinolysis and host response in bacterial infections. Thromb Haemost 2007; 98: 512-20.
16. Williams B, Zou L, Pittet JF, Chao W. Sepsis-Induced Coagulopathy: A Comprehensive Narrative Review of Pathophysiology, Clinical Presentation, Diagnosis, and Management Strategies. Anesth Analg 2024; 138: 696-711.
17. Hvas CL, Larsen JB. The Fibrinolytic System and Its Measurement: History, Current Uses and Future Directions for Diagnosis and Treatment. International Journal of Molecular Sciences 2023; 24: 14179.
18. Rijken DC, Uitte de Willige S. Inhibition of fibrinolysis by coagulation factor XIII. Biomed Res Int 2017; 2017: 1209676.
19. Spasić, I. Specifičnosti hemostaznog mehanizma kod obolelih od SARS-CoV-2 virusne infekcije. Doktorska disertacija, Novi Sad: Medicinski fakultet, 2022.
20. Gando S. Role of Fibrinolysis in Sepsis. Semin Thromb Hemost 2013; 39: 392-99.
21. Degen JL, Bugge TH, Goguen JD. Fibrin and fibrinolysis in infection and host defense. J Thromb Haemost 2007; 5: 24–31.
22. Brewer JS, Hvas CL, Hvas AM, Larsen JB. Impaired Whole-Blood Fibrinolysis is a Predictor of Mortality in Intensive Care Patients. TH Open 2024; 08: 164-74.
23. Coupland LA, Rabbolini DJ, Schoenecker JG, et al. Point-of-care diagnosis and monitoring of fibrinolysis resistance in the critically ill: results from a feasibility study. Crit Care 2023; 27: 55.
24. Singhal S, Ranga S, Chawla AS, Kamra R. Role of Antithrombin III, Plasminogen, Protein C and Protein S in Deep Vein Thrombosis in Indian Population. IJSHR 2019; 4: 54-9.
25. Levi M, Van Der Poll T. Thrombomodulin in sepsis. Minerva Anestesiol 2013; 79: 294-8.
26. Kato H, Hagihara M, Asai N. Efficacy and safety of recombinant human soluble thrombomodulin in patients with sepsis-induced disseminated intravascular coagulation - A meta-analysis. Thromb Res 2023; 226: 165-72.
27. Wang G, Hao C, Yao S, Wang Y, Xu Z, Zhao H, et al. Exploring the Mediating Role of Multiple Organ Dysfunction in Sepsis-Induced Disseminated Intravascular Coagulation and Its Impact on Worsening Prognosis. Clin Appl Thromb Hemost 2024; 30: 10760296241271358.
28. Iba T, Helms J, Levy JH. Sepsis-induced coagulopathy (SIC) in the management of sepsis. Ann Intensive Care 2024; 14: 148.
29. Egi M, Ogura H, Yatabe T, et al. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020). Acute Med Surg 2021; 8: e659.
30. Larsen JB, Aggerbeck MA, Granfeldt A, Schmidt M, Hvas AM, Adelborg K. Disseminated intravascular coagulation diagnosis: Positive predictive value of the ISTH score in a Danish population. Res Pract Thromb Haemost 2021; 5: e12636.
31. Hartmann J, Hermelin D, Levy JH. Viscoelastic testing: an illustrated review of technology and clinical applications. Res Pract Thromb Haemost 2022; 7:100031.
32. Govil D, Pal D. Point-of-care testing of coagulation in intensive care unit: Role of thromboelastography. Indian J Crit Care Med 2019; 23: S202-6.
33. Zátroch I, Dinya E, Fazakas J. New under the sun: ClotPro's ECA-test detects hyperfibrinolysis in a higher number of patients, more frequently and 9 min earlier. Blood Coagul Fibrinolysis 2023; 34: 99-104.
34. Bui-Thi HD, Kien To Gia, Le Minh K. Coagulation profiles in patients with sepsis/septic shock identify mixed hypo-hypercoagulation patterns based on rotational thromboelastometry: A prospective observational study. Thromb Res 2023; 227: 51-9.
35. Zheng Z, Mukhametova L, Boffa MB, et al. Assays to quantify fibrinolysis: strengths and limitations. Communication from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee on fibrinolysis. J Thromb Haemost 2023; 21: 1043-54.
36. Mavrommatis AC, Theodoridis T, Economou M, et al. Activation of the fibrinolytic system and utilization of the coagulation inhibitors in sepsis: comparison with severe sepsis and septic shock. Intensive Care Med 2001; 27: 1853-59.
37. Ghansah H, Orban-Kalmandi R, Debreceni IB, et al. Low factor XIII levels and altered fibrinolysis in patients with multiple myeloma. Thromb Res 2024; 234: 12-20.
38. Cohen T, Haas T, Cushing MM. The strengths and weaknesses of viscoelastic testing compared to traditional coagulation testing. Transfusion 2020; 6 :S21-8.
39. Ostrowski SR, Windeløv NA, Ibsen M, Haase N, Perner A, Johansson PI. Consecutive thrombelastography clot strength profiles in patients with severe sepsis and their association with 28-day mortality: A prospective study. J Crit Care 2013; 28: 317.
40. Kim SM, Kim SI, Yu G, et al. Role of thromboelastography in the evaluation of septic shock patients with normal prothrombin time and activated partial thromboplastin time. Sci Rep 2021; 11: 11833.
41. Enk NM, Kutter APN, Kuemmerle-Fraune C, Sigrist NE. Correlation of plasma coagulation tests and fibrinogen (Clauss) with rotational thromboelastometry parameters and prediction of bleeding in dogs. J Vet Intern Med 2019; 33: 132-40.
42. Moore HB. Fibrinolysis Shutdown and Hypofibrinolysis Are Not Synonymous Terms: The Clinical Significance of Differentiating Low Fibrinolytic States. Semin Thromb Hemost 2023; 49: 433-43.
43. Mohapatra P, Kumar A, Singh RK, et al. The Effect of Sepsis and Septic Shock on the Viscoelastic Properties of Clot Quality and Mass Using Thromboelastometry: A Prospective Observational Study. Indian J Crit Care Med 2023; 27: 625-34.
44. Hans GA, Besser MW. The place of viscoelastic testing in clinical practice. Br J Haematol 2016; 173: 37-48.
45. Borawski J, Myśliwiec M. Plasma fibrinogen level is an important determinant of prolonged euglobulin clot lysis time in hemodialysis patients. Clin Appl Thromb Hemost 2001; 7: 296-9.
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2026/06/18
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