A novel description of AT deficiency in hospitalized COVID-19 patients.

Objective: Antithrombin (AT) has anti-inflammatory and anti-coagulant properties, but its role in COVID-19 and the rate of deficiency is unknown. We hypothesize that AT3 deficiency is common in COVID-19, and supplementing AT3 will impact COVID-19 coagulopathy.

Patients and methods: This is a prospective randomized control trial. Patients with plasma AT3<100% were randomized to either standard of care (SOC) or SOC+AT3 q48hr weight-based for a goal of 120% for up to 5 doses. An additional reference group with AT3>100% received SOC.

Results: 531 subjects were assessed for eligibility; 324 did not meet inclusion criteria, 151 did not consent, 6 withdrew consent, and 50 subjects completed the study. Enrollment AT3 (M±SD) was 91±13%.  AT3 levels were <100% in 38 (76%) and <80% in 11 (22%) patients. SOC+AT3, SOC only, and AT3>100% had a disseminated intravascular coagulation (DIC) score change (M±SD) of 0.4±1.5, -0.13±1.85 and 0±1.54, respectively, (p=0.63). Hospital length of stay was 11.7 [6-14], 6 [4.5-10], 8.5 [6-21] respectively, (p=0.176). Mortality occurred in 2 (11%), 3 (15%), and 3 (25%) patients, respectively (p=0.56). There was one bleeding event in a subject with AT3>100%, and no bleeding events were observed with exogenous AT3. There were no observed drug-related adverse events. Subjects received a median dose of 1,825.5 IU (IQR 794).

Conclusions: COVID-19 is associated with relative AT3 deficiency (22% of this cohort). No bleeding complications or drug-related adverse events with exogenous AT3 were observed. There were no significant differences in length of stay or mortality. Further studies should evaluate higher doses of exogenous AT3 and focus on higher-risk groups.

Clinicaltrials: gov: NCT04899232.