Protracted fibrinolysis resistance following cardiac surgery with cardiopulmonary bypass: A prospective observational study of clinical associations and patient outcomes

Lucy A Coupland; Kieran G Pai; Sidney J Pye; Mark T Butorac; Jennene J Miller; Philip J Crispin; David J Rabbolini; Antony H L Stewart; Anders Aneman

doi:10.1111/aas.14409

Protracted fibrinolysis resistance following cardiac surgery with cardiopulmonary bypass: A prospective observational study of clinical associations and patient outcomes

Acta Anaesthesiol Scand. 2024 Mar 18. doi: 10.1111/aas.14409. Online ahead of print.

Authors

Lucy A Coupland^{1

2

3}, Kieran G Pai^{1

2}, Sidney J Pye¹, Mark T Butorac^{1

2}, Jennene J Miller¹, Philip J Crispin^{4

5}, David J Rabbolini^{6

7}, Antony H L Stewart¹, Anders Aneman^{1

2

3}

Affiliations

¹ Liverpool Hospital, South Western Sydney Local Health District, Liverpool, New South Wales, Australia.
² South Western Sydney Clinical School, University of New South Wales Medicine, New South Wales, Australia.
³ Ingham Institute for Applied Medical Research, New South Wales, Australia.
⁴ Haematology Department, The Canberra Hospital, Canberra, Australian Capital Territory, Australia.
⁵ The Australian National University Medical School, Canberra, Australian Capital Territory, Australia.
⁶ Kolling Institute of Medical Research, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
⁷ Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

PMID: 38497568
DOI: 10.1111/aas.14409

Abstract

Background: Surgery on cardiopulmonary bypass (CPB) elicits a pleiomorphic systemic host response which, when severe, requires prolonged intensive care support. Given the substantial cross-talk between inflammation, coagulation, and fibrinolysis, the aim of this hypothesis-generating observational study was to document the kinetics of fibrinolysis recovery post-CPB using ClotPro® point-of-care viscoelastometry. Tissue plasminogen activator-induced clot lysis time (TPA LT, s) was correlated with surgical risk, disease severity, organ dysfunction and intensive care length of stay (ICU LOS).

Results: In 52 patients following CPB, TPA LT measured on the first post-operative day (D1) correlated with surgical risk (EuroScore II, Spearman's rho .39, p < .01), time on CPB (rho = .35, p = .04), disease severity (APACHE II, rho = .52, p < .001) and organ dysfunction (SOFA, rho = .51, p < .001) scores, duration of invasive ventilation (rho = .46, p < .01), and renal function (eGFR, rho = -.65, p < .001). In a generalized linear regression model containing TPA LT, CPB run time and markers of organ function, only TPA LT was independently associated with the ICU LOS (odds ratio 1.03 [95% CI 1.01-1.05], p = .01). In a latent variables analysis, the association between TPA LT and the ICU LOS was not mediated by renal function and thus, by inference, variation in the clearance of intraoperative tranexamic acid.

Conclusions: This observational hypothesis-generating study in patients undergoing cardiac surgery with cardiopulmonary bypass demonstrated an association between the severity of fibrinolysis resistance, measured on the first post-operative day, and the need for extended postoperative ICU level support. Further examination of the role of persistent fibrinolysis resistance on the clinical outcomes in this patient cohort is warranted through large-scale, well-designed clinical studies.

Keywords: cardiopulmonary bypass surgery; clot lysis time; dysregulated host response; fibrinolysis; fibrinolysis resistance; point-of-care testing; viscoelastic testing.

Abstract

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