Fibrinolytic Capacity and Risk of Bleeding in Intensive Care Patients with Acute Kidney Injury

Abstract

Background

Acute kidney injury (AKI) is common among intensive care unit (ICU) patients and is associated with increased bleeding risk. The impact of fibrinolysis in AKI-related bleeding has not been explored previously.

Objectives

(1) Compare fibrinolytic capacity in ICU patients with and without AKI. (2) Investigate the association between fibrinolytic capacity, as well as other laboratory and clinical variables, and bleeding within the first 7 ICU days in AKI patients.

Methods

Adult ICU patients were prospectively enrolled and stratified by AKI presence and severity at ICU admission. On the morning after admission, fibrinolytic capacity was assessed using a modified rotational thromboelastometry (ROTEM-tPA) assay. The primary outcome was the difference in ROTEM-tPA lysis time on day 1 of ICU admission between AKI and non-AKI patients.

Results

AKI patients (n = 160) had more bleedings and higher 30-day mortality than non-AKI patients (n = 99). ROTEM-tPA analysis showed progressively impaired fibrinolysis with increasing AKI severity. AKI stage 3 patients (n = 53) demonstrated significant impairment across all fibrinolysis parameters compared with non-AKI patients. Among AKI stage 2 to 3 patients (n = 106), bleeding patients (n = 61) had more pronounced fibrinolytic impairment than non-bleeding patients (n = 45). Bleeding risk in AKI stage 2 to 3 was associated with increasing severity of illness (OR: 1.21 (95%CI 1.04–1.42) per 1 point increase in non-renal Sequential Organ Failure Assessment (SOFA) score, p = 0.01).

Conclusions

AKI severity in ICU patients was associated with progressively impaired fibrinolysis. Despite this, AKI patients had more bleedings within the first 7 days of ICU admission.

Keywords

acute kidney injury - blood coagulation tests - critical care - fibrinolysis - thrombelastography

• References

• 1 Hoste EA, Bagshaw SM, Bellomo R. et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med 2015; 41 (08) 1411-1423
• 2 Levey AS, James MT. Acute kidney injury. Ann Intern Med 2017; 167 (09) ITC66-ITC80
• 3 Zarka F, Tayler-Gomez A, Ducruet T. et al. Risk of incident bleeding after acute kidney injury: a retrospective cohort study. J Crit Care 2020; 59: 23-31
• 4 Jensen JLS, Hviid CVB, Hvas CL, Christensen S, Hvas AM, Larsen JB. Platelet function in acute kidney injury: a systematic review and a cohort study. Semin Thromb Hemost 2023; 49 (05) 507-522
• 5 Hung A, Garcia-Tsao G. Acute kidney injury, but not sepsis, is associated with higher procedure-related bleeding in patients with decompensated cirrhosis. Liver Int 2018; 38 (08) 1437-1441
• 6 Wu PC, Wu CJ, Lin CJ, Wu VC. National Taiwan University Study Group on Acute Renal Failure Group. Long-term risk of upper gastrointestinal hemorrhage after advanced AKI. Clin J Am Soc Nephrol 2015; 10 (03) 353-362
• 7 Decousus H, Tapson VF, Bergmann JF. et al; IMPROVE Investigators. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest 2011; 139 (01) 69-79
• 8 Vigneron C, Devautour C, Charpentier J, Birsen R, Jamme M, Pène F. Severe bleeding events among critically ill patients with haematological malignancies. Ann Intensive Care 2024; 14 (01) 155
• 9 Barea-Mendoza JA, Chico-Fernández M, Molina-Díaz I. et al; Neurointensive Care and Trauma Working Group of the Spanish Society of Intensive Care Medicine (SEMICYUC). Risk factors associated with early and late posttraumatic multiorgan failure: an analysis from RETRAUCI. Shock 2021; 55 (03) 326-331
• 10 Zanetto A, Rinder HM, Campello E. et al. Acute kidney injury in decompensated cirrhosis is associated with both hypo-coagulable and hyper-coagulable features. Hepatology 2020; 72 (04) 1327-1340
• 11 Malyszko J, Malyszko JS, Pawlak D, Pawlak K, Buczko W, Mysliwiec M. Hemostasis, platelet function and serotonin in acute and chronic renal failure. Thromb Res 1996; 83 (05) 351-361
• 12 Wiegele M, Infanger L, Lacom C, Koch S, Baierl A, Schaden E. Thrombin generation and platelet function in ICU patients undergoing CVVHD using regional citrate anticoagulation. Front Med (Lausanne) 2021; 8: 680540
• 13 Larsson SO, Hedner U, Nilsson IM. On coagulation and fibrinolysis in acute renal insufficiency. Acta Med Scand 1971; 189 (06) 443-451
• 14 Mörtberg J, Blombäck M, Wallén Å, He S, Jacobson SH, Spaak J. Increased fibrin formation and impaired fibrinolytic capacity in severe chronic kidney disease. Blood Coagul Fibrinolysis 2016; 27 (04) 401-407
• 15 Olesen JB, Lip GY, Kamper AL. et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med 2012; 367 (07) 625-635
• 16 Kellum JA, Lameire N, Aspelin P. et al. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2 (01) 1-138
• 17 Závada J, Hoste E, Cartin-Ceba R. et al; AKI6 investigators. A comparison of three methods to estimate baseline creatinine for RIFLE classification. Nephrol Dial Transplant 2010; 25 (12) 3911-3918
• 18 Jiang J, Zhang J, Liu Y, Xu D, Peng Z. Urine output calculated using actual body weight may result in overestimation of acute kidney injury for obese patients. Shock 2021; 56 (05) 737-743
• 19 Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute Dialysis Quality Initiative workgroup. Acute renal failure—definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8 (04) R204-R212
• 20 Ali T, Khan I, Simpson W. et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol 2007; 18 (04) 1292-1298
• 21 Stevens PE, Levin A. Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members. Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013; 158 (11) 825-830
• 22 Harris PA, Taylor R, Minor BL. et al; REDCap Consortium. The REDCap consortium: building an international community of software platform partners. J Biomed Inform 2019; 95: 103208
• 23 Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42 (02) 377-381
• 24 Singer M, Deutschman CS, Seymour CW. et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315 (08) 801-810
• 25 Moreno RP, Metnitz PG, Almeida E. et al; SAPS 3 Investigators. SAPS 3—From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med 2005; 31 (10) 1345-1355
• 26 Taylor Jr 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. Thromb Haemost 2001; 86 (05) 1327-1330
• 27 Kaufman RM, Djulbegovic B, Gernsheimer T. et al; AABB. Platelet transfusion: a clinical practice guideline from the AABB. Ann Intern Med 2015; 162 (03) 205-213
• 28 Larsen JB, Hvas CL, Hvas AM. Modified rotational thromboelastometry protocol using tissue plasminogen activator for detection of hypofibrinolysis and hyperfibrinolysis. Methods Mol Biol 2023; 2663: 763-773
• 29 Scarlatescu E, Kim PY, Marchenko SP, Tomescu DR. Validation of the time to attain maximal clot amplitude after reaching maximal clot formation velocity parameter as a measure of fibrinolysis using rotational thromboelastometry and its application in the assessment of fibrinolytic resistance in septic patients: a prospective observational study: communication from the ISTH SSC Subcommittee on Fibrinolysis. J Thromb Haemost 2024; 22 (04) 1223-1235
• 30 Kuiper GJ, Kleinegris MC, van Oerle R. et al. Validation of a modified thromboelastometry approach to detect changes in fibrinolytic activity. Thromb J 2016; 14: 1
• 31 Brewer JS, Hvas CL, Hvas AM, Larsen JB. Impaired whole-blood fibrinolysis is a predictor of mortality in intensive care patients. TH Open 2024; 8 (01) e164-e174
• 32 Stravitz RT, Ellerbe C, Durkalski V. et al; Acute Liver Failure Study Group. Bleeding complications in acute liver failure. Hepatology 2018; 67 (05) 1931-1942
• 33 Thomas J, Kostousov V, Teruya J. Bleeding and thrombotic complications in the use of extracorporeal membrane oxygenation. Semin Thromb Hemost 2018; 44 (01) 20-29