Pathological characteristics of liver sinusoidal thrombosis in COVID‐19 patients: A series of 43 cases

Kondo, Reiichiro; Kawaguchi, Nao; McConnell, Matthew J.; Sonzogni, Aurelio; Licini, Lisa; Valle, Clarissa; Bonaffini, Pietro A.; Sironi, Sandro; Alessio, Maria Grazia; Previtali, Giulia; Seghezzi, Michela; Zhang, Xuchen; Sun, Zhaoli; Utsumi, Teruo; Strazzabosco, Mario; Iwakiri, Yasuko

AIM: Coronavirus disease (COVID‐19) is characterized by pneumonia with secondary damage to multiple organs including the liver. Liver injury (elevated alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) often correlates with disease severity in COVID‐19 patients. The aim of this study is to identify pathological microthrombi in COVID‐19 patient livers by correlating their morphology with liver injury, and examine hyperfibrinogenemia and von Willebrand factor (vWF) as mechanisms of their formation. METHODS: Forty‐three post‐mortem liver biopsy samples from COVID‐19 patients were obtained from Papa Giovanni XXIII Hospital in Bergamo, Italy. Three morphological features of microthrombosis (sinusoidal erythrocyte aggregation [SEA], platelet microthrombi [PMT], and fibrous thrombi) were evaluated. RESULTS: We found liver sinusoidal microthrombosis in 23 COVID‐19 patients (53%) was associated with a higher serum ALT and AST level compared to those without (ALT: 10‐fold, p = 0.04; AST: 11‐fold, p = 0.08). Of 43 livers, PMT and SEA were observed in 14 (33%) and 19 (44%) cases, respectively. Fibrous thrombi were not observed. Platelet microthrombi were associated with increased ALT (p < 0.01), whereas SEA was not (p = 0.73). In COVID‐19 livers, strong vWF staining in liver sinusoidal endothelial cells was associated with significantly increased platelet adhesion (1.7‐fold, p = 0.0016), compared to those with weak sinusoidal vWF (2‐fold, p < 0.0001). Sinusoidal erythrocyte aggregation in 19 (83%) liver samples was mainly seen in zone 2. Livers with SEA had significantly higher fibrinogen (1.6‐fold, p = 0.031) compared to those without SEA in COVID‐19 patients. CONCLUSIONS: Liver PMT is a pathologically important thrombosis associated with liver injury in COVID‐19, while SEA is a unique morphological feature of COVID‐19 patient livers. Sinusoidal vWF and hyperfibrinogenemia could contribute to PMT and SEA formation.