Markers Of Coagulation And Hemostatic Activation Identify COVID-19 Patients At High Risk For Thrombotic Events, ICU Admission and Intubation

Abstract

Background: Coronavirus disease 2019 (COVID-19) has been associated with a coagulopathy giving rise to venous and arterial thrombotic events. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events and other complications. Methods: COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent standardized admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) with abnormal MOCHA defined as ≥ 2 markers above the reference. Prespecified thrombotic endpoints included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, and access line thrombosis; other complications included ICU admission, intubation and mortality. We excluded patients on anticoagulation therapy prior to admission and those who were pregnant. Results: Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American race) who met study criteria, 45 (16%) had a thrombotic event. Each coagulation marker on admission was independently associated with a vascular endpoint (p<0.05). Admission MOCHA with ≥ 2 abnormalities (n=203, 74%) was associated with in-hospital vascular endpoints (OR 3.3, 95% CI 1.2-8.8), as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6), and admission D-dimer ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only admission MOCHA with ≥ 2 abnormalities was associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4), while admission D-dimer ≥ 2000 ng/mL and admission D-dimer ≥ 3000 ng/mL were not associated. MOCHA and D-dimer cutoffs were not associated with mortality. Admission MOCHA with <2 abnormalities (26% of the cohort) had a sensitivity of 88% and negative predictive value of 93% for a vascular endpoint. Conclusions: Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at increased risk of ICU admission and intubation during hospitalization more effectively than isolated admission D-dimer measurement. Admission MOCHA with <2 abnormalities identified a subgroup of patients at low risk for vascular events. Our results suggest that an admission MOCHA profile can be useful to risk-stratify COVID-19 patients.