Use of the international normalized ratio for the diagnosis of sepsis in thrombocytopenic blood cancer patients

Lyanguzov AV, Bulanov AY, Ignatyev SV, et al. Use of the international normalized ratio for the diagnosis of sepsis in thrombocytopenic blood cancer patients. Russian Journal of Anesthesiology and Reanimatology. 2025;(6):21‑27. (In Russ., In Engl.)
https://doi.org/10.17116/anaesthesiology202506121

Использование инфографики авторами научных работ

Close metadata

Abstract:

OBJECTIVE

To investigate the role of international normalized ratio (INR) as a marker of sepsis-related clotting disorders in blood cancer patients with thrombocytopenia.

MATERIAL AND METHODS

A retrospective analysis included 279 patients with hematologic malignancies admitted to ICU due to infectious complications or sepsis. Clinical and laboratory data, specifically those required for calculating Sequential Organ Failure Assessment (SOFA) scores, were extracted. Predictive value of individual SOFA parameters for mortality was evaluated. We analyzed predictive role of coagulation parameters in sepsis to find the most suitable alternative to platelet count.

RESULTS

Sepsis, as defined by the Sepsis-3 criteria, was diagnosed in 256 (91.7%) out of 279 patients. The overall mortality rate was 34.7%. Thrombocytopenia (platelet count <150·10⁹/L) was present in 236 (84.5%) of patients. In 58 (23.0%) patients, diagnosis of sepsis was due to infectious complication with acute multiple organ dysfunction (SOFA score ≥2) and thrombocytopenia <100·10⁹/l. Comparison of survival in these patients with survival of patients with complex homeostasis disorders according to SOFA scale revealed significant differences (Logrank χ²=12.8; p=0.0003). Platelet count was not a predictor of unfavorable outcome (OR 0.996; 95% CI 0.992—1.0001; p=0.058). Multivariate analysis revealed that the most significant predictor of mortality associated with hemostasis disorders in sepsis in patients with blood diseases was INR (OR 2.14; 95% CI 1.168—3.921; p=0.014).

CONCLUSION

Elevated INR in patients with blood diseases and thrombocytopenia preceding infectious complications and sepsis is associated with higher risk of mortality and may be used as indicator of hemostasis disorders according to SOFA score in diagnosis of sepsis.

Keywords:

sepsis diagnosis

SOFA score

thrombocytopenia

international normalized ratio

Authors:

Lyanguzov A.V.

Kirov Research Institute of Hematology and Blood Transfusion

ORCID: 0000-0001-5509-5308

Bulanov A.Y.

N.V. Sklifosovsky Research Institute of Emergency Medicine

ORCID: 0000-0001-6999-8145

Ignatyev S.V.

Kirov Research Institute of Hematology and Blood Transfusion

ORCID: 0000-0002-8457-2967

Zorina N.A.

Kirov Research Institute of Hematology and Blood Transfusion

ORCID: 0000-0003-1948-209X

Khorobrykh M.N.

Kirov Research Institute of Hematology and Blood Transfusion

ORCID: 0000-0003-0357-5136

Lagunova M.V.

Kirov Research Institute of Hematology and Blood Transfusion

ORCID: 0009-0006-3097-5230

Kovtunova M.E.

Kirov Research Institute of Hematology and Blood Transfusion

ORCID: 0000-0003-1065-9709

Paramonov I.V.

Kirov Research Institute of Hematology and Blood Transfusion

ORCID: 0000-0002-7205-912X

Received:

20.02.2025

Accepted:

11.03.2025

Close metadata

References:

Rhee C, Klompas M. Sepsis trends: increasing incidence and decreasing mortality, or changing denominator? Journal of Thoracic Disease. 2020; 12(Suppl 1):S89-S100. https://doi.org/10.21037/jtd.2019.12.51
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-810. https://doi.org/10.1001/jama.2016.0287
Jones AE, Trzeciak S, Kline JA. The Sequential Organ Failure Assessment score for predicting outcome in patients with severe sepsis and evidence of hypoperfusion at the time of emergency department presentation. Critical Care Medicine. 2009;37(5):1649-1654. https://doi.org/10.1097/CCM.0b013e31819def97
Gonzalez DA, Kumar R, Asif S, Bali A, Dang AK. Sepsis and Thrombocytopenia: A Nowadays Problem. Cureus. 2022;14(5):e25421. https://doi.org/10.7759/cureus.25421
Lopatin AF, Redkin IV, Samoylenko VV, Petrovskaya EL, Molchanov IV. The role of antithrombin in diagnosis and treatment of sepsis. Russian Journal of Anesthesiology and Reanimatology. 2018;(3):19-24. (In Russ.). https://doi.org/10.17116/anaesthesiology201803119
Kim YJ, Ko BS, Park SY, Oh DK, Hong SB, Jang S, Kim WY. Effect of High-dose Antithrombin Supplementation in Patients with Septic Shock and Disseminated Intravascular Coagulation. Scientific Reports. 2019;9(1):16626. https://doi.org/10.1038/s41598-019-52968-y
Tsuchida T, Makino Y, Wada T, Ushio N, Totoki T, Fujie N, Yasuo S, Matsuoka T, Koami H, Yamakawa K, Iba T. Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta-analysis, and meta-regression. Acute Medicine and Surgery. 2024;11(1):e950. https://doi.org/10.1002/ams2.950
Martí-Carvajal AJ, Solà I, Gluud C, Lathyris D, Cardona AF. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients. The Cochrane Database of Systematic Reviews. 2012;12(12): CD004388. https://doi.org/10.1002/14651858.CD004388.pub6
Osovskikh VV, Vasileva MS, Bautin AE, Kiseleva LN. Prognostic value of selected hypercoagulabilitymarkers in sepsis. A prospective study. Annals of Critical Care. 2020;3:66-73. (In Russ.). https://doi.org/10.21320/1818-474X-2020-3-66-73
Han YQ, Yan L, Zhang L, Ouyang PH, Li P, Lippi G, Hu ZD. Performance of D-dimer for predicting sepsis mortality in the intensive care unit. Biochemia Medica. 2021;31(2):020709. https://doi.org/10.11613/BM.2021.020709
Lungu N, Popescu DE, Gorun FI, Nan G, Popa ZL, Manea A, Brandibur TE, Jura AC, Costescu S, Belovan B, Boia M. D-dimer as a Useful Biomarker in Early Diagnosis of Neonatal Sepsis: A Single-Center Study From Romania. Cureus. 2024;16(7):e65213. https://doi.org/10.7759/cureus.65213
Zheng R, Pan H, Wang JF, Yu XS, Chen ZQ, Pan JY. The association of coagulation indicators with in-hospital mortality and 1-year mortality of patients with sepsis at ICU admissions: A retrospective cohort study. Clinica Chimica Acta. 2020;504:109-118. https://doi.org/10.1016/j.cca.2020.02.007
Liu B, Du H, Zhang J, Jiang J, Zhang X, He F, Niu B. Developing a new sepsis screening tool based on lymphocyte count, international normalized ratio and procalcitonin (LIP score). Scientific Reports. 2022;12(1):20002. https://doi.org/10.1038/s41598-022-16744-9
Verma A, Kole T. International normalized ratio as a predictor of mortality in trauma patients in India. World Journal of Emergency Medicine. 2014; 5(3):192-195. https://doi.org/10.5847/wjem.j.issn.1920-8642.2014.03.006
Peltan ID, Vande Vusse LK, Maier RV, Watkins TR. An international normalized ratio-based definition of acute traumatic coagulopathy is associated with mortality, venous thromboembolism, and multiple organ failure after injury. Critical Care Medicine. 2015;43(7):1429-1438. https://doi.org/10.1097/CCM.0000000000000981
Kander T, Larsson A, Taune V Schött U, Tynngård N. Assessment of haemostasis in disseminated intravascular coagulation by use of point-of-care assays and routine coagulation tests, in critically ill patients; a prospective observational study. PLoS One. 2016;11(3):e0151202. https://doi.org/10.1371/journal.pone.0151202
Benediktsson S, Frigyesi A, Kander T. Routine coagulation tests on ICU admission are associated with mortality in sepsis: an observational study. Acta Anaesthesiologica Scandinvica. 2017;61(7):790-796. https://doi.org/10.1111/aas.12918
Czempik PF, Herzyk J, Wilczek D, Krzych ŁJ. Hematologic system dysregulation in critically ill septic patients with anemia — a retrospective cohort study. International Journal of Environmental Research and Public Health. 2022;19(11):6626. https://doi.org/10.3390/ijerph19116626
Benediktsson S, Hansen C, Frigyesi A, Kander T. Coagulation tests on admission correlate with mortality and morbidity in general ICU patients: An observational study. Acta Anaesthesiologica Scandinvica. 2020;64(5):628-634. https://doi.org/10.1111/aas.13545
Ling XW, Lin K, Jiang XQ Wu Q, Liu ZJ, Li S, Zhao S, Lin C. International normalised ratio as an independent predictor of mortality in limb necrotising fasciitis with sepsis. Annals of the Royal College of Surgeons of England. 2021;103(1):35-40. https://doi.org/10.1308/rcsann.2020.0189
Zhang J, Du HM, Cheng MX, He FM, Niu BL. Role of international normalized ratio in nonpulmonary sepsis screening: An observational study. World Journal of Clinical Cases. 2021;9(25):7405-7416. https://doi.org/10.12998/wjcc.v9.i25.7405
Liu J, Bai C, Li B Shan A, Shi F, Yao C, Zhang Y, Wang J, Chen W, Xie M, Deng D. Mortality prediction using a novel combination of biomarkers in the first day of sepsis in intensive care units. Scientific Reports. 2021;11(1):1275. https://doi.org/10.1038/s41598-020-79843-5
Jhang WK, Park SJ. Evaluation of sepsis-induced coagulopathy in critically ill pediatric patients with septic shock. Thrombosis and Haemostasis. 2021;121(4):457-463. https://doi.org/10.1055/s-0040-1718736
Thiery-Antier N, Binquet C, Vinault S Meziani F, Boisramé-Helms J, Quenot JP; EPIdemiology of Septic Shock Group. Is thrombocytopenia an early prognostic marker in septic shock? Critical Care Medicine. 2016; 44(4):764-772. https://doi.org/10.1097/CCM.0000000000001520
Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Brück LM, Hoffmann U, Kittel M, Bertsch T, Akin I, Behnes M. Diagnostic and prognostic role of platelets in patients with sepsis and septic shock. Platelets. 2023;34(1):2131753. https://doi.org/10.1080/09537104.2022.2131753
Iba T, Nisio MD, Levy JH, 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. https://doi.org/10.1136/bmjopen-2017-017046
Taylor FB, Toh CH, Hoots WK, Wada H, Levi M. Scientific Subcommittee on Disseminated Intravascular Coagulation (DIC) of the International Society on Thrombosis and Haemostasis (ISTH). Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thrombosis and Haemostasis. 2001;86(5):1327-1330.
Shapiro N, Howell MD, Bates DW, Angus DC, Ngo L, Talmor D. The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Annals of Emergency Medicine. 2006;48(5):583-590. https://doi.org/10.1016/j.annemergmed.2006.07.007
Turcato G, Zaboli A, Sibilio S, Fanni Canelles M, Rella E, Giudiceandrea A, Pfeifer N, Brigo F. Prognostic Role of Serum Albumin in Predicting 30-Day Mortality in Patients with Infections in Emergency Department: A Prospective Study. Journal of Clinical Medicine. 2023;12(10):3447. https://doi.org/10.3390/jcm12103447
Schupp T, Weidner K, Rusnak J, Jawhar S, Forner J, Dulatahu F, Brück LM, Hoffmann U, Bertsch T, Müller J, Weiß C, Akin I, Behnes M. Diagnostic and prognostic significance of the prothrombin time/international normalized ratio in sepsis and septic shock. Clinical and Applied Thrombosis/Hemostasis. 2022;28:10760296221137893. https://doi.org/10.1177/10760296221137893