Evaluation of the Prothrombin Fragment 1.2 in Patients with COVID‐19

Al‐Samkari, Hanny; Song, Fei; Van Cott, Elizabeth; Kuter, David J.; Rosovsky, Rachel

INTRODUCTION: Coronavirus disease 2019 (COVID‐19) may cause a hypercoagulable state. The D‐dimer is frequently elevated in COVID‐19, but other markers of coagulation activation, including the prothrombin fragment 1.2 (PF1.2) are poorly described. METHODS: We studied hospitalized adults with COVID‐19 and PF1.2 measurement performed at any time during hospitalization. We evaluated the relationship between PF1.2 and synchronously measured D‐dimer. We utilized receiver operating characteristic (ROC) analysis to evaluate optimal thresholds for diagnosing thrombosis and multivariable logistic regression to evaluate association with thrombosis. RESULTS: 115 patients were included [110 (95.7%) critically ill]. PF1.2 and D‐dimer were moderately positively correlated (r=0.542, P<0.001) but significant discordance was observed in elevation of each marker above the laboratory reference range (59.0% elevated PF1.2 vs. 98.5% elevated D‐dimer). Median PF1.2 levels were higher in patients with thrombosis than those without (611 vs. 374 pmol/L, P=0.006). In ROC analysis, PF1.2 had superior specificity and conferred a higher positive likelihood ratio in identifying patients with thrombosis than D‐dimer (PF1.2 threshold of >523 pmol/L: 69.2% sensitivity, 67.7% specificity; >924 pmol/L: 37.9% sensitivity, 87.8% specificity). In multivariable analysis, a PF1.2 >500 pmol/L was significantly associated with VTE [adjusted odds ratio (OR) 4.26, 95% CI, 1.12‐16.21, P=0.034] and any thrombotic manifestation (adjusted OR 3.85, 95% CI, 1.39‐10.65, P=0.010); conversely, synchronously measured D‐dimer was not significantly associated with thrombosis. 90.6% of patients with a non‐elevated PF1.2 result did not develop VTE. CONCLUSIONS: PF1.2 may be a useful assay, and potentially more discriminant than D‐dimer, in identifying thrombotic manifestations in hospitalized patients with COVID‐19. This article is protected by copyright. All rights reserved.