Coagulopathy of COVID-19 correlates with liver injury
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The coagulopathy of COVID-19 driven by endothelial Factor VIII correlated with liver injury, according to a presenter at The Liver Meeting Digital Experience.
“Our study illuminates a mechanism of injury in COVID-19 that was previously unknown,” Matthew McConnell, MD, from the department of internal medicine/digestive diseases at Yale School of Medicine, said during his presentation. “Our study therefore provides a first step toward understanding how patients will be affected long-term after suffering from this liver injury. Our study centers around the global coagulopathy of COVID-19 and defines a mechanism for increased coagulation and factor levels that may be future targets for treatment.”
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At Yale New Haven Hospital, McConnell and colleagues measured coagulation parameters and liver tests in 68 patients with PCR-confirmed COVID-19. They assessed liver tests 5 days prior and 5 days after coagulation paraments and recorded peak values if no liver tests were gathered within the time window.
Investigators cultured the primary human liver sinusoidal endothelial cells (LSEC) with interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) for the in vitro studies to mimic IL-6 trans signaling thought to occur in COVID-19.
The study comprised three cohorts based on ALT three times over the upper limit of normal or ALT three times under the upper limit of normal.
Results showed a higher percentage of patients with ALT three times over the upper limit of normal also had a hypercoagulable TEG profile (P < .05). In the plasma of patients with ALT three times the upper limit of normal, investigators saw an elevation of factor VIII, fibrinogen and factor II (P < .05).
“We focused on determining whether the liver sinusoidal endothelial cells may be stimulated by the inflammatory markers of COVID-19 to adopt a hyper coagulable phenotype by producing excessive Factor VIII,” he said. “Because the complex of the IL-6 and sIL-6R has gained increasing importance as a pathologic inflammatory signal for endothelial cells in COVID-19, we treated sinusoidal endothelial cells with this complex and found significantly elevated gene expression of Factor VIII and its stabilizing protein factor.”
McConnell and colleagues also found the IL-6/IL-6R complex induced activation of STAT1 (P < .01) transcription factors that are known to induce Factor VIII expression.
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