Researchers in Dublin, Ireland, found links between moderate COVID-19 and endothelial damage and hypercoagulability, even in the setting of thromboprophylaxis. The study’s results were published in the Journal of Thrombosis and Haemostasis.
“SARS-CoV-2 infection elicits a unique thromboinflammatory response,” the study investigators wrote in their report. They explained this infection has been reported to have connections with endothelial dysfunction, abnormal platelet activity, and procoagulant leukocyte dysfunction, and also that thromboinflammation and immunothrombosis may be factors in disease severity. Although risks and outcomes have been studied in patients with severe COVID-19, the researchers indicated that little is known about the extent to which these disease processes occur in patients with moderate COVID-19, who are hospital inpatients who do not receive critical care.
Patients in this study were admitted to a hospital for COVID-19 management. These patients had confirmation of SARS-CoV-2 infection through reverse transcriptase-polymerase chain reaction analysis of nasopharyngeal swab samples. The study also included an age-matched control group, which consisted of patients who tested negative for SARS-CoV-2 infection, but who were also admitted for an acute infection. Only patients who were receiving low-molecular-weight heparin thromboprophylaxis were recruited for this study. Various endothelial markers and plasma thrombin generation parameters were evaluated.
The study included 14 patients with COVID-19 and 11 patients who were in the control group. Thromboprophylaxis was provided by enoxaparin (40 mg/d) in all patients. Plasma antifactor Xa activity levels were considered normal in both patient groups, and during hospitalization thrombotic events did not occur in either group.
Patients with moderate COVID-19 showed significantly higher plasma endogenous thrombin potential (1929 ± 448 nM*min) than patients in the control group did (1528 ± 460.8 nM*min; P =.04). The lag time to initiation of thrombin generation was also significantly longer for patients with COVID-19 (8.1 ± 1.8 min), than in those without COVID-19 (6.2 ± 1.8 min; P =.02).
Many markers of endothelial damage did not significantly differ between groups. However, plasma tissue plasminogen activator (tPA) levels were higher in patients with COVID-19 (8.3 ± 4.4 ng/mL) than in patients of the control group (4.9 ± 2.4 ng/mL; P =.02). Patients with COVID-19 also had greater sensitivity to neutralization of plasma tissue factor pathway inhibitor (TFPI) activity.
While most markers of endothelial damage were not significantly different between groups, the researchers considered the elevated tPA with COVID-19, in addition to sensitivity to neutralization of TFPI activity, to be evidence of endothelial damage. They noted that their findings cannot confirm a causal relationship between these markers of endothelial damage and hypercoagulability in COVID-19. However, they considered the results to be consistent with those of other studies showing endothelial damage and hypercoagulability after infection with SARS-CoV-2.
“In conclusion, in this study we have demonstrated that despite pharmacological thromboprophylaxis, plasma thrombin generation is increased among patients with COVID-19 of moderate severity in comparison to a matched control group of hospitalised patients without COVID-19,” the study investigators wrote.
Kelliher S, Weiss L, Cullivan S, et al. Non-severe COVID-19 is associated with endothelial damage and hypercoagulability despite pharmacological thromboprophylaxis. J Thromb Haemost. Accepted manuscript. Published online February 1, 2022. doi:10.1111/jth.15660