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

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

doi:10.1111/hepr.13696

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	1000-1006
Number of pages	7
Journal	Hepatology Research
Volume	51
Issue number	9
DOIs	https://doi.org/10.1111/hepr.13696
State	Published - Sep 2021

Keywords

SARS-CoV-2 virus
endotheliopathy
fibrinogen
neutrophil
platelet
vWF

ASJC Scopus subject areas

Hepatology
Infectious Diseases

Access to Document

10.1111/hepr.13696

Cite this

Kondo, R., Kawaguchi, N., McConnell, M. J., Sonzogni, A., Licini, L., Valle, C., Bonaffini, P. A., Sironi, S., Alessio, M. G., Previtali, G., Seghezzi, M., Zhang, X., Sun, Z., Utsumi, T., Strazzabosco, M., & Iwakiri, Y. (2021). Pathological characteristics of liver sinusoidal thrombosis in COVID-19 patients: A series of 43 cases. Hepatology Research, 51(9), 1000-1006. https://doi.org/10.1111/hepr.13696

Kondo, R, Kawaguchi, N, McConnell, MJ, Sonzogni, A, Licini, L, Valle, C, Bonaffini, PA, Sironi, S, Alessio, MG, Previtali, G, Seghezzi, M, Zhang, X, Sun, Z, Utsumi, T, Strazzabosco, M & Iwakiri, Y 2021, 'Pathological characteristics of liver sinusoidal thrombosis in COVID-19 patients: A series of 43 cases', Hepatology Research, vol. 51, no. 9, pp. 1000-1006. https://doi.org/10.1111/hepr.13696

@article{db319a5e7e8e40ef9d06802e765d6d01,

title = "Pathological characteristics of liver sinusoidal thrombosis in COVID-19 patients: A series of 43 cases",

abstract = "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.",

keywords = "SARS-CoV-2 virus, endotheliopathy, fibrinogen, neutrophil, platelet, vWF",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Japan Society of Hepatology.",

year = "2021",

month = sep,

doi = "10.1111/hepr.13696",

language = "English (US)",

volume = "51",

pages = "1000--1006",

journal = "Hepatology Research",

issn = "1386-6346",

publisher = "Wiley-Blackwell",

number = "9",

}

TY - JOUR

T1 - Pathological characteristics of liver sinusoidal thrombosis in COVID-19 patients

T2 - A series of 43 cases

AU - Kondo, Reiichiro

AU - Kawaguchi, Nao

AU - McConnell, Matthew J.

AU - Sonzogni, Aurelio

AU - Licini, Lisa

AU - Valle, Clarissa

AU - Bonaffini, Pietro A.

AU - Sironi, Sandro

AU - Alessio, Maria Grazia

AU - Previtali, Giulia

AU - Seghezzi, Michela

AU - Zhang, Xuchen

AU - Sun, Zhaoli

AU - Utsumi, Teruo

AU - Strazzabosco, Mario

AU - Iwakiri, Yasuko

PY - 2021/9

Y1 - 2021/9

N2 - 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.

AB - 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.

KW - SARS-CoV-2 virus

KW - endotheliopathy

KW - fibrinogen

KW - neutrophil

KW - platelet

KW - vWF

UR - http://www.scopus.com/inward/record.url?scp=85111685035&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85111685035&partnerID=8YFLogxK

U2 - 10.1111/hepr.13696

DO - 10.1111/hepr.13696

M3 - Article

C2 - 34260803

AN - SCOPUS:85111685035

SN - 1386-6346

VL - 51

SP - 1000

EP - 1006

JO - Hepatology Research

JF - Hepatology Research

IS - 9

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this