Tissue-Type Plasminogen Activator-Inhibitor Complex as an Early Predictor of Septic Shock: A Retrospective, Single-Center Study

Abstract

Background. Sepsis can progress to septic shock and death, and identifying biomarkers of this progression may permit timely intervention to prevent it. This study explored whether levels of tissue-type plasminogen activator-inhibitor complex (t-PAIC) in serum can predict septic shock early. Methods. We retrospectively analyzed 311 sepsis patients who had been admitted to the intensive care unit (ICU) at our tertiary care hospital between May 2018 and April 2021, and we divided them into those who progressed to septic shock ( <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mi>n</a:mi> <a:mo>=</a:mo> <a:mn>203</a:mn> </a:math> ) or not ( <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>n</c:mi> <c:mo>=</c:mo> <c:mn>108</c:mn> </c:math> ) based on sepsis-3 definition. After matching patients in the two groups based on propensity scoring, we screened for risk factors of septic shock using logistic regression. We assessed potential predictors of such shock based on the area under the receiver-operating characteristic curve (AUC), Kaplan-Meier survival curves, and correlation analysis. Results. After propensity score matching to generate two equal groups of 108 patients, we found that serum t-PAIC was significantly higher in septic shock patients. Uni- and multivariate logistic regression identified t-PAIC as an independent risk factor for septic shock (OR 1.14, 95% CI 1.09–1.19, <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo>&lt;</e:mo> <e:mn>0.001</e:mn> </e:math> ) and a biomarker that predicted it with an AUC up to 0.875 (95% CI, 0.829-0.920). Based on the optimal cut-off of <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mtext>t</g:mtext> <g:mo>‐</g:mo> <g:mtext>PAIC</g:mtext> <g:mo>=</g:mo> <g:mn>17.9</g:mn> <g:mtext> </g:mtext> <g:mtext>ng</g:mtext> <g:mo>/</g:mo> <g:mtext>mL</g:mtext> </g:math> , we found that patients at or above this threshold had significantly higher lactate levels and scores on the Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA). Such patients also had significantly worse survival (HR 2.4, 95% CI 1.38–4.34, <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mi>P</i:mi> <i:mo>=</i:mo> <i:mn>0.004</i:mn> </i:math> ). Spearman’s correlation coefficients were 0.66 between t-PAIC and lactate, and 0.52 between t-PAIC and SOFA. Conclusions. Serum levels of t-PAIC may be an independent risk factor for septic shock, and they may correlate with the severity of such shock.