ArticleFrontiers in medicine2026
Admission antithrombin III activity as a risk-enrichment marker for septic shock below the ISTH overt-DIC threshold.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: International Society on Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) scoring is a standard bedside framework for infection-associated coagulopathy but does not capture anticoagulant-pathway markers. The study examined whether admission antithrombin III (AT-III) activity provided risk-enrichment information for septic shock among adults admitted with infection below the ISTH 2001 overt-DIC threshold. Methods: The study retrospectively analyzed 1,286 adults admitted with infection. AT-III activity was evaluated in the ISTH-complete and below-threshold subsets and compared with ISTH 2001 and 2025 SSC overt-DIC scores. Retrospective temporal adjudication compared first valid AT-III report availability with operational septic-shock onset. In a clinically indicated lactate-measured subset, the study assessed whether AT-III added discrimination beyond age, sex, and lactate. Firth-penalized regression evaluated the conditional association of AT-III with septic shock beyond age, sex, and raw ISTH components. Results: Among 1,027 ISTH-complete patients, 974 (94.8%) were below the ISTH 2001 overt-DIC threshold, including 44 of 60 septic-shock cases. In this subgroup, 43 of 44 shock cases had AT-III activity <80%; the area under the curve (AUC) was 0.844 and the positive predictive value was 9.37% (43/459). Of 82 septic-shock admissions, 74 were temporally adjudicable: 62 were incident and 12 were prevalent or concurrent at AT-III report availability. In incident cases, AT-III report availability preceded operational shock onset by a median of 7.6 h (interquartile range (IQR) 5.0-9.6); sampling therefore also preceded onset. In the lactate-measured subset ( Conclusion: Admission AT-III activity was associated with septic shock within the large ISTH below-threshold infection subgroup and provided high-sensitivity, low-positive-predictive-value enrichment information. Retrospectively reconstructed temporal ordering demonstrated a report-release-to-operational-onset interval in incident cases but does not establish prospective prediction, prospective workflow performance, or clinical benefit. AT-III should not be used as a standalone trigger for escalation decisions. Prospective, time-stamped validation is required.
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