Heparinase-Native Thromboelastometry Detects Hypercoagulability in COVID-19 Disease

ABSTRACT

Study Objectives: COVID-19 disease is associated with elevated risk of thrombosis, but lab assessment of hypercoagulability of fibrinolysis using conventional clotting assays is challenging. Rotational thromboelastometry (ROTEM) can detect subtle changes in clotting activity and has been used to demonstrate longitudinal coagulopathy in COVID over time. However, typical ROTEM channels including EXTEM and INTEM are affected by anticoagulant use. Un-activated native ROTEM with addition of heparinase (NaHEPTEM) should be a more accurate marker given the multiple anticoagulant protocols in use during COVID-19 treatment. Our aim is to describe coagulopathy in COVID using NaHEPTEM longitudinally in a group of patients. Methods: This multi-center prospective cohort study was conducted during the initial COVID-19 disease surge in New York City at an urban hospital system with large infected population. Adult (>18y) patients admitted with new oxygen requirement secondary to COVID-19 disease were recruited either in the emergency department or inpatient floors within 24 hours of admission. Blood samples were collected for ROTEM processing at enrollment then every 72 hours for 21 days unless discharged or deceased. The main study outcome included NaHEPTEM values for clotting time (CT), clot formation time (CFT), maximal clot firmness (MCF) and maximal lysis (ML). Additional data was collected on conventional clotting assays and inflammatory markers, disease severity, and mortality. Results: There were 39 patients with ROTEM results included in the data analysis (mean age, 66.5 years;female, 50.0%). Admission SOFA score mean was 3.88. Mortality occurred in 10/39 (25.6%) of patients and ICU admission in 13/39 (33.3%). Therapeutic anticoagulation was initiated in 28/39 (71.7%) of patients as inpatients, with the rest receiving prophylactic subcutaneous heparin. ROTEM results were grouped into three-day blocks for analysis using day of enrollment as day 0. NaHEPTEM CT median values were within manufacturer reference range at all time points. CFT median values were below reference range until the period of days 9-11 since admission. MCF median values also were above reference range until days 9-11. ML median values were highest for admission NaHEPTEM tests (4% lysis) but no values were outside the manufacturer reference range of 15% lysis. None of the admission NaHEPTEM values were significantly associated with mortality. Conclusion: Modification of standard ROTEM channels using un-activated testing with heparinase addition demonstrates the expected reduced clotting times and increased clot firmness in COVID-19 associated hypercoagulability. Use of therapeutic and prophylactic anticoagulation was common in this population, and results of heparinase to ROTEM testing eliminates this confounding effect. Longitudinal assessment shows normalization of multiple hypercoagulable effects in COVID-19 disease around days 9-11 in this moderately ill cohort. [Formula presented]