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

Deepti Joshi,Garima Goel,Abhishek Goyal,Sarat Manohar,Abhijit P Pakhare,Saurabh Saigal

doi:10.7759/cureus.18538

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.

Highlights

Coronavirus disease 2019 (COVID-19) has emerged as a major global health crisis and has so far affected millions of individuals all across the globe and resulted in more than 3.5 million deaths [1,2]
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 Antithrombin III (ATIII), anti-factor Xa assay and other routine coagulation parameters
We restricted the study to only those patients who had serial measurements of ATIII assay, antifactor Xa assay, prothrombin time (PT)/international normalised ratio (INR), activated partial thromboplastin time (APTT), platelets and fibrin degradation products (FDP) done on the first three days of Intensive Care Unit (ICU) admission

Summary

Introduction

Coronavirus disease 2019 (COVID-19) has emerged as a major global health crisis and has so far affected millions of individuals all across the globe and resulted in more than 3.5 million deaths [1,2]. Endothelial dysfunction and thrombosis have emerged as dominant pathophysiological features that determine the course of this disease [3]. Thrombosis is a dominant phenomenon in COVID-19 infection rather than bleeding [5]. This phenomenon has led most guidelines to recommend the use of anti-coagulants, either unfractionated heparin (UH) or low molecular weight heparin (LMWH), for all moderate to severely ill patients with COVID19. Inflammation can significantly reduce the levels of ATIII resulting in decreased efficacy of heparin. Both reduced ATIII levels and the phenomenon of heparin resistance in COVID-19 patients have been reported in few studies [7,8]. The exact relationship between ATIII titres and other markers of disease progression is not yet established [7]

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Discussion

Conclusion