Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests

Abstract

COVID-19-associated coagulopathy (CAC) identifies the coagulation changes in coronavirus disease 2019 (COVID-19) and is responsible for thrombosis. CAC has been studied in critical and severe stage COVID-19 disease through tests including the D-Dimer (DD), prothrombin time (PT), thromboplastin partial time (PTT), platelet count, fibrinogen (Fib), and platelet factor 4 (PF4) tests. However, these tests have some limitations. The aim of this study was to identify more accurate warning tests for early recognition of CAC and to prevent its deterioration to disseminated intravascular coagulation (DIC). First, we measured Interleukin-1a (IL-1a) and IL-8, and tissue factor pathway inhibitor (TFPI) as inflammation and endothelial damage markers, respectively. Second, we measured thrombin antithrombin complex (TAT), b-Thromboglobulin (b-TG), and thromboelastometric parameters including clotting time (CT), clot formation time (CFT), clot firmness (MCF), and clot lysis at 30 min (LY-30), as markers of coagulation and platelet activation. This study included 100 non-severe patients with COVID-19 that developed pulmonary embolism (PE) compared to 80 healthy patients. IL-1a and IL-8, and TFPI were higher as well as TAT and b-TG and thromboelastometric parameters, indicating hypercoagulability. If confirmed in other studies, these results could help in predicting the deterioration of non-severe COVID-19 disease, thereby reducing hospitalizations and health costs.

Plasma tissue factor pathway inhibitor levels in coronavirus disease 2019 patients: a systematic review and meta-analysis

“…Of 83 articles, 77 articles were excluded because 38 articles were duplicated, 7 did not report related data, 18 were review articles, 6 did not stratify TFPI levels according to disease severity or just reported temporal changes of TFPI levels, one was a case report, one was invitro study, one was viewpoint, four studies were without healthy controls, and the results of one study about TFPI value was correlation analysis on the reported data in Al-Tamimi et al [25] work that we had included this data in the analysis, so it was removed. Finally, with the agreement of both reviewers, six articles remained for analysis [25][26][27][28][29][30], as shown in Fig. 1.…”

“…Three of the six studies were prospective, two were cross-sectional, and one was retrospective with a total of 684 cases and healthy controls, of whom 180 were healthy controls and 504 were COVID-19 patients with different severity (76 mild, 292 moderate, and 136 severe) (Table 1). The severity classification of COVID-19 was defined according to the WHO guidelines in three studies [26,28,29] PRISMA flow diagram demonstrating the data gathering process to finding out coronavirus disease 2019 effect on tissue factor pathway inhibitor levels. Data from [31].…”

“…In agreement, the increase of TFPI levels in COVID-19 patients was accompanied by increased markers indicating inflammation, in addition to markers indicating endotheliopathy and hyper-coagulation. In this regard, Cacciola et al [26] [37] study showed that the increase of TFPI with disease worsening is also associated with the increased markers of inflammation (CRP and IL-6), endothelial damage (tPA, and VEGF), and hypercoagulation (D-dimer). Corey et al [35] observed that the increase in TFPI level accompanied by the increased severity of the ARDS has also been associated with the increased Ddimer and PAI-1.…”

“…Of these six studies, five [25][26][27][28]30] evaluated TFPI levels in patients with moderate COVID-19 severity and compared them with healthy controls [moderate (n ¼ 292), healthy controls (n ¼ 151)]. In four studies [26][27][28]30] the factor values were significantly higher in patients, and in one study, [25] the factor value was lower (nonsignificant) (Table 1).…”

“…Of these six studies, five [25][26][27][28]30] evaluated TFPI levels in patients with moderate COVID-19 severity and compared them with healthy controls [moderate (n ¼ 292), healthy controls (n ¼ 151)]. In four studies [26][27][28]30] the factor values were significantly higher in patients, and in one study, [25] the factor value was lower (nonsignificant) (Table 1). In addition to these, there is another study by Kelliher et [25,[28][29][30], which in three studies, the factor value was significantly higher in patients [28][29][30], and in one study [25], it was significantly lower (Table 1).…”