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

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.

Coagulopathy is not predictive of bleeding in patients with acute decompensation of cirrhosis and acute‐on‐chronic liver failure

“… 24 ROTEM ® was performed according to the standard protocols supplied by the manufacturer, as previously reported. 25 , 26 , 27 The following tests were performed: INTEM (to assess intrinsic coagulation pathway), EXTEM (to assess extrinsic coagulation pathway) and FIBTEM (to assess fibrinogen contribution to clot formation and stability). For EXTEM and INTEM tests, the following ROTEM ® parameters were collected: clotting time (CT), clotting formation time (CFT), maximum clot firmness (MCF), α‐angle and maximum lysis for EXTEM and INTEM tests.…”

Current knowledge and management of portal vein thrombosis in cirrhosis

“…32 Moreover, the observation of a significantly higher concentration of microparticles of endothelial origin (CD62E-MP) in the portal vein compared to the systemic circulation suggested greater endothelial damage at this level. 33 Although all these arguments make it possible that local inflammatory conditions could play a role in PVT development in patients with cirrhosis, this has not been demonstrated in prospective cause-effect studies.…”

Recent Advances in the Management of Acute Variceal Hemorrhage

“…Additionally, a small RCT showed that TIPS is more effective than EVL and NSBBs in preventing rebleeding in patients with cirrhosis and portal vein thrombosis, with a higher rate of thrombus resolution but without differences in mortality [61]. Patients with cirrhosis and portal vein thrombosis, which is the most common thrombotic complications in cirrhosis [86][87][88], may be a third group in which to consider TIPS earlier rather than later in the setting of secondary prophylaxis. This would be particularly important if the patient is awaiting liver transplantation, as the presence of thrombosis at time of transplantation is associated with a higher risk of post-transplant mortality [89].…”