Adequate Antithrombin III Level Predicts Survival in Severe COVID-19 Pneumonia

Abstract

Critically ill patients with COVID-19 are at an increased thrombotic risk, hence thromboprophylaxis with heparin is considered mandatory. Antithrombin III (ATIII) is the most potent endogenous anticoagulant and is required for the clinical efficacy of heparin. Profound hypercoagulable and inflammatory state associated with COVID-19 can result in decreased ATIII levels and ineffective heparin treatment resulting in increased mortality. The present study evaluated ATIII levels in critically ill patients of COVID-19 and correlated them with other coagulation parameters and disease outcomes. A retrospective review of those critically ill COVID-19 patients was performed who were on a therapeutic dose of low molecular weight heparin (LMWH) and had serial measurements of ATIII, anti-factor Xa (antiFXa) assay and other routine coagulation parameters. A total of 27 critically ill COVID-19 patients were identified, out of these, 12 survived and 15 had disease-induced mortality. ATIII levels were found to be significantly lower in non-survivors on the third day of serial measurement along with worsening of other coagulation parameters. AntiFXa levels were found to be higher in non-survivors as compared to survivors. Further studies are required to establish ATIII as a prognostic marker and to determine the utility of monitoring antiFXa levels in COVID-19 patients on LMWH therapy.

Antithrombin Activity Is Associated with Persistent Thromboinflammation and Mortality in Patients with Severe COVID-19 Illness

“…Anakli et al [ 12 ] showed that AT activity levels in patients with ARDS and COVID-19 could potentially serve as a prognostic marker for survival and organ failure; however, this finding was limited by a retrospective approach. In addition, Joshi et al [ 19 ] demonstrated significant reductions in AT activity among COVID-19 patients who died compared to those who survived. Finally, Ranucci et al [ 20 ] showed that time-dependent increases in AT activity were associated with coagulation normalization among recovering COVID-19 patients.…”

Antithrombin Therapy: Current State and Future Outlook

“…140 Heparin resistance has been documented in up to 80% of patients with COVID-19 in the intensive care unit, which may be explained by observed reductions in AT levels. 141 In addition, multiple studies have identified AT levels as a prognostic marker of survival in severe COVID-19. 16,141,142 In 2022, early results from a prospective randomized trial of AT therapy in participants with COVID-19 (N = 52) indicated that AT therapy was safe, with no breakthrough bleeding or other drug-related adverse events.…”

The interplay between inflammation and thrombosis in COVID-19: Mechanisms, therapeutic strategies, and challenges

“…Consistently, SARS-CoV-2 infection is also implicated with downregulation of endogenous anticoagulants including endothelial TM [ 38 ], EPCR [ 21 ] and ATIII [ 45 , 46 ]. Reduced levels of anticoagulant ATIII in COVID-19 patients have been observed to be correlated with disease severity.…”

“…Reduced levels of anticoagulant ATIII in COVID-19 patients have been observed to be correlated with disease severity. Non survivors amongst hospitalized COVID-19 patients, especially obese individuals, have lower levels of ATIII compared with survivors [ 45 , 46 ]. A soluble form of EPCR (sEPCR) shed from endothelial cells, which exists under normal conditions in plasma, has been found to be elevated in inflammatory conditions [ 47 ].…”