Hypocoagulable Coagulation Profile and Endogenous Heparinoids Are Associated with Invasive Ventilation and Mortality in COVID-19

Background & Aims: A procoagulant state with pulmonary micro-thrombosis has been described in COVID-19, which contributes to pathophysiology of respiratory failure along with diffuse alveolar damage. Cytokine storm and systemic inflammation in COVID-19 generates endogenous heparinoids from the endothelium which leads to secondary organ failures. We prospectively studied the dynamic association of the coagulation abnormalities with respiratory failure and mortality in patients with COVID-19.Methods: We did a prospective observational study in adults aged between 18-80 years with COVID 19 pneumonia requiring intensive care (ICU) admissions in a tertiary care hospital in North India. All patients received standard medical therapy based on best available evidence. Patients were categorized based on the oxygen support therapy into low flow, high flow and invasive ventilation groups. In patients considered to be at risk of thromboembolic or bleeding phenomena, paired coagulation tests were performed at days 1 and 3 with, Sonoclot ® (glass beaded and heparinase-treated). All patients were consecutively followed for inflammatory markers, ventilator requirements and survival. Activated clotting time (ACT) 75 units were used as the cut-off for hypercoagulable state. The heparin like effect (HLE) was considered by a correction of ≥ 40 s in hACT (heparinized treated ACT). The trial is registered with ClinicalTrials.gov (NCT04668404).Results: A total of 2324 patients with COVID-19 were screened from August 2020 to November 2020. Two hundred and fifteen patients requiring ICU admission were assessed and 74 patients with a median age of 54(42-67) years were enrolled. A procoagulant profile was seen in 45.5%, 32.4% and 20.7% in low-flow, high-flow, and invasive ventilation. Paired Sonoclot ® assays in 33 patients demonstrated HLE in 17 (51.5%) and 20 (62.5%) at days 1 and 3 respectively. In multivariate analysis, the presence of HLE (HR 1.02; CI 1.08-1.6; p < 0.05), C-reactive protein (HR 1.2; CI 1.1-1.4; p=0.014)] and platelet function (HR 0.9; CI 0.7-1.1 p < 0.05) predicted mortality. The presence of HLE at day 1 predicted the need for invasive ventilation (HR 1.4; CI 1.01-1.5; p 131 s, clot rate 96.7 mg/l at admission predicted mortality.Conclusions: HLE contributes to hypocoagulable effect, need for invasive ventilation and mortality in patients with COVID-19.Trial Registration: The trial is registered with ClinicalTrials.gov (NCT04668404).Funding Statement: NoneDeclaration of Interests: NoneEthics Approval Statement: Ethical clearance was obtained from the Institutional Review Board (PGI/IEC/2020/000997 dated 24 August 2020)