Elevated TAT in COVID-19 Patients with Normal D-Dimer as a Predictor of Severe Respiratory Failure: A Retrospective Analysis of 797 Patients

Abstract

Although previous studies have revealed that elevated D-dimer in the early stage of coronavirus 2019 (COVID-19) indicates pulmonary intravascular coagulation, the state of coagulation/fibrinolysis disorder with normal D-dimer is unknown. The study aimed to investigate how coagulation/fibrinolysis markers affect severe respiratory failure in the early stage of COVID-19. Among 1043 patients with COVID-19, 797 patients were included in our single-center retrospective study. These 797 patients were divided into two groups, the normal D-dimer and elevated D-dimer groups and analyzed for each group. A logistic regression model was fitted for age, sex, body mass index (BMI) ≥ 30 kg/m2, fibrinogen ≥ 617 mg/dL, thrombin-antithrombin complex (TAT) ≥ 4.0 ng/mL, and plasmin-alpha2-plasmin inhibitor-complex (PIC) > 0.8 µg/mL. A multivariate analysis of the normal D-dimer group demonstrated that being male and TAT ≥ 4.0 ng/mL significantly affected severe respiratory failure. In a multivariate analysis of the elevated D-dimer group, BMI ≥ 30 kg/m2 and fibrinogen ≥ 617 mg/dL significantly affected severe respiratory failure. The elevated PIC did not affect severe respiratory failure in any group. Our study demonstrated that hypercoagulation due to SARS-CoV-2 infection may occur even during a normal D-dimer level, causing severe respiratory failure in COVID-19.

Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation

“…Disruption to the functions of endogenous anticoagulants has also been observed in these patients. Based on the research evidence, activities and plasma levels of AT, PC, and protein S (PS) have been reduced in patients with the critical COVID-19 under the influence of the factors involved in the uncontrolled immunothrombosis and have negatively been associated with the disease exacerbation and mortality [2] , [57] , [87] , [88] , [98] , [99] , [100] , [102] , [104] , [105] , [106] , [107] , [108] , [109] , [110] , [111] , [112] , [113] , [114] , [115] , [116] . Furthermore, the increased soluble form (inefficient/attenuated form) of thrombomodulin (TM) (known as an anticoagulant and anti-inflammatory molecule) and its decreased tissue expression level were reported in patients with the critical COVID-19 accompanied by the disease severity [3] , [97] , [102] , [105] , [111] , [117] .…”

Antithrombin as Therapeutic Intervention against Sepsis-Induced Coagulopathy and Disseminated Intravascular Coagulation: Lessons Learned from COVID-19-Associated Coagulopathy

“…Referring to a possibly specific role of AT in COVID-19-associated coagulopathy, TAT complexes are known to increase with D-dimer remaining normal [ 69 ]. Testing for AT levels in patients with COVID-19 revealed a significant difference between ICU and non-ICU patients, showing a significant decrease in AT activity in patients with severe COVID-19, 89.65% in all patients, and significantly lower AT activity in the non-survivor group (87.52%) than in the survivor group (92.38%) [ 70 ].…”