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. 2024 Aug 1;7(8):e2427786.
doi: 10.1001/jamanetworkopen.2024.27786.

Antithrombin III Levels and Outcomes Among Patients With Trauma

David H Farrell  1 , Keeley M McConnell  1 , Jevgenia Zilberman-Rudenko  1 , Brandon Behrens  1 , Scott Mcloud  1 , Mackenzie R Cook  1 , David Martin  2 , John D Yonge  1 , Samantha J Underwood  1 , Diane E Lape  1 , Andrew Goodman  1 , Martin A Schreiber  1
Affiliations

Antithrombin III Levels and Outcomes Among Patients With Trauma

David H Farrell et al. JAMA Netw Open. .

Abstract

Importance: Patients with trauma exhibit a complex balance of coagulopathy manifested by both bleeding and thrombosis. Antithrombin III is a plasma protein that functions as an important regulator of coagulation. Previous studies have found a high incidence of antithrombin III deficiency among patients with trauma.

Objective: To assess whether changes in antithrombin III activity are associated with thrombohemorrhagic complications among patients with trauma.

Design, setting, and participants: This cohort study was conducted from December 2, 2015, to March 24, 2017, at a level I trauma center. A total of 292 patients with trauma were followed up from their arrival through 6 days from admission. Data, including quantification of antithrombin III activity, were collected for these patients. Thromboprophylaxis strategy; hemorrhage, deep vein thrombosis (DVT), and pulmonary embolism screenings; and follow-up evaluations were conducted per institutional protocols. Data analyses were performed from September 28, 2023, to June 4, 2024.

Main outcomes and measures: The primary study outcome measurements were associations between antithrombin III levels and outcomes among patients with trauma, including ventilator-free days, hospital-free days, intensive care unit (ICU)-free days, hemorrhage, venous thromboembolic events, and mortality.

Results: The 292 patients had a mean (SD) age of 54.4 (19.0) years and included 211 men (72.2%). Patients with an antithrombin III deficiency had fewer mean (SD) ventilator-free days (27.8 [5.1] vs 29.6 [1.4]; P = .0003), hospital-free days (20.3 [8.2] vs 24.0 [5.7]; P = 1.37 × 10-6), and ICU-free days (25.7 [4.9] vs 27.7 [2.3]; P = 9.38 × 10-6) compared with patients without a deficiency. Antithrombin III deficiency was also associated with greater rates of progressive intracranial hemorrhage (21.1% [28 of 133] vs 6.3% [10 of 159]; P = .0003) and thrombocytopenia (24.8% [33 of 133] vs 5.0% [8 of 159]; P = 1.94 × 10-6). Although antithrombin III deficiency was not significantly associated with DVT, patients who developed a DVT had a more precipitous decrease in antithrombin III levels that were significantly lower than patients who did not develop a DVT.

Conclusions and relevance: In this cohort study of patients with trauma, antithrombin III deficiency was associated with greater injury severity, increased hemorrhage, and increased mortality, as well as fewer ventilator-free, hospital-free, and ICU-free days. Although this was an associative study, these data suggest that antithrombin III levels may be useful in the risk assessment of patients with trauma.

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Conflict of interest statement

Conflict of Interest Disclosures: Oregon Health & Science University (OHSU) and Dr Farrell have a significant interest in Gamma Diagnostics, a company that may have a commercial interest in the results of this research; this potential individual and institutional conflict of interest has been reviewed and managed by OHSU. Ms McConnell reported receiving funding through the BUILD EXITO program and the National Institute of General Medical Sciences. Dr Zilberman-Rudenko reported receiving a Ruth L. Kirschstein Fellow grant from the National Institutes of Health. Dr Behrens and Ms Underwood reported receiving consultancy stipends from Grifols. Dr Schreiber reported receiving consultancy payments from Grifols, Haemonetics, CSL Behring, Tricol, Arsenal Medical, and Velico Medical.

Figures

Figure 1.
Figure 1.. Study Flow Diagram
Figure 2.
Figure 2.. Sampling of Antithrombin III–Deficient Patients Across Time
Data represent the breakdown of patients with antithrombin III deficiency during the study.
Figure 3.
Figure 3.. Thrombohemorrhagic Complications With Respect to Antithrombin III Deficiency Over Time
See this image and copyright information in PMC

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