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Thromb Haemost 2020; 120(08): 1173-1181
DOI: 10.1055/s-0040-1713169
Coagulation and Fibrinolysis

Endothelial Damage of the Portal Vein is Associated with Heparin-Like Effect in Advanced Stages of Cirrhosis

Sarah Shalaby‡   *
1   Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Paolo Simioni‡   *
2   Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), University of Padua Medical School, Padua, Italy
,
Elena Campello
2   Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), University of Padua Medical School, Padua, Italy
,
Luca Spiezia
2   Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), University of Padua Medical School, Padua, Italy
,
Sabrina Gavasso
2   Hemorrhagic and Thrombotic Diseases Unit, Department of Medicine (DIMED), University of Padua Medical School, Padua, Italy
,
Debora Bizzaro
1   Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Romilda Cardin
1   Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Francesco D'Amico
3   Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Enrico Gringeri
3   Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Umberto Cillo
3   Hepatobiliary Surgery and Liver Transplantation Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Giulio Barbiero
4   Institute of Radiology, Department of Medicine, Padua University Hospital, Padua, Italy
,
Michele Battistel
4   Institute of Radiology, Department of Medicine, Padua University Hospital, Padua, Italy
,
Alberto Zanetto
1   Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Alessandro Ruzzarin
1   Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Patrizia Burra
1   Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
,
Marco Senzolo
1   Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, Padua, Italy
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Abstract

Background Portal vein thrombosis (PVT) is the most common thrombotic complication in cirrhosis; however, local risk factors involved in its pathogenesis are still not fully investigated. The aim of the study was to evaluate hemostasis and endothelial damage in the portal vein in patients with cirrhosis and portal hypertension.

Methods Adult cirrhotics undergoing transjugular intrahepatic portosystemic shunt were consecutively enrolled. Rotational thromboelastometry (ROTEM), dosage of total circulating glycosaminoglycans (GAGs), and endotoxemia levels (lipopolysaccharide [LPS]), along with evaluation of endothelial dysfunction by quantification of circulating endothelial microparticles (MPs), were performed on citrated peripheric and portal venous blood samples from each enrolled patient.

Results Forty-five cirrhotics were enrolled. ROTEM analysis revealed the presence of a significant heparin-like effect in portal blood (median ɑ angle NATEM 50° vs. HEPTEM 55°, p = 0.027; median coagulation time NATEM 665 s vs. HEPTEM 585 s, p = 0.006), which was not detected in peripheral blood, and was associated with a higher concentration of circulating GAGs. Even though total annexin V-MP circulating MPs were less concentrated in the splanchnic district, the proportion of MPs of endothelial origin, with respect to annexin V-MP, was significantly increased in the portal district (p = 0.036). LPS concentration was higher in portal (197 pg/mL) compared with peripheral blood (165 pg/mL) (p < 0.001).

Conclusion Evidences of a damage of glycocalyx along with increased concentration of endothelial MPs suggest the presence of a significant endothelial alteration in the portal vein with respect to peripheral veins. Portal site-specific endothelial damage could hamper its antithrombotic properties and may represent an important local risk factor in the pathogenesis of PVT.

Keywords

heparin-like effect - microparticles - glycosaminoglycans - endotoxemia - portal hypertension

* Equally contributed and share first authorship.


Supplementary Material



Publication History

Received: 27 January 2020

Accepted: 05 May 2020

Article published online:
30 June 2020

Georg Thieme Verlag KG
Stuttgart · New York

 

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