Splanchnic hypercoagulability in cirrhosis correlates with portal hypertension and is exacerbated by bacterial infections
Sebastian Raffa1,3, Juan Carlos Reverter2, Susana Seijo3,4, Juan G. Abraldes3,4, Dolors Tassies2, Annalisa Berzigotti3,4, Juan Carlos Garcia-Pagan3,4, Jaime Bosch3,4;
1Liver transplantation unit, Fun-dación Favaloro, Buenos Aires, Argentina; 2Hemotherapy and Hemostasis Department, Hospital Clinic, Barcelona, Spain; 3Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Barcelona, Spain; 4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
Background and aims: Cirrhosis has been recently shown to be a pro-thrombotic condition. This may be due to a relative unbalance between endogenous pro- and anti-coagulants and pro-and anti-fibrinolytic factors. This may explain the high incidence of portal vein thrombosis in cirrhosis. We hypothesized that this would be particularly evident in the hepato-splanchnic vascular bed and that it might be favored by bacterial infections. Patients and methods: Sixty-nine patients (pts) with cirrhosis were prospectively studied at the time of HVPG measurements. Sixteen pts were infected and 53 were not. All pts had simultaneous measurements in hepatic venous and peripheral blood of: Procoagulant factors (I, II, V, VII, VIII, IX, X, XI, XII), von Wille-brand antigen (vWF-Ag), anticoagulant factors: Antithrombin (AT), protein C and S, Markers of coagulation activation: D-dimer, plasmin-antiplasmin complex (PAP), plasminogen activator inhibitor (PAI), prothrombin fragment F1+2 (F1+2), factor VIIa (F-VIIa), activated Factor XII (F.XIIa) and endogenous throm-bin potential (ETP) with/without thrombomodulin, Microparti-cles, tissue factor and platelet-activating factors: Soluble P-selectin and soluble CD40 ligand (CD40Ls). These measurements were also done in portal venous blood in 13 pts undergoing TIPS. To compare continuous variables, Mann-Whitney U or Wicoxon tests were used. Correlation between continuous variables was done with Spearman rank test. The level of statistical significance was set at a P < 0.05. Results: Patients had a median age of 54.3 years old, 61% were males and cirrhosis was due to HCV (45%), alcohol (33%) and others (22%). Markers of coagulation activation (PAI, F-VIIa, F1+2, XIIa), vWF-Ag and Microparticles in non-infected cirrhotic patients were significantly and linearly correlated with HVPG, MELD and Child-Pugh score. Microparticles (31.6 vs. 25.9 nM/Eq, P=0.001) and CD40Ls (144 vs. 115 pg/ml, P= 0.002) were higher in hepatic venous blood than in peripheral blood. Levels of F1 +2 (1.7 vs. 1.6 nmol/L; P= 0.03), Microparticles (47 vs. 28.8 nM/Eq; P= 0.03) and ETP with thrombomodulin (272 vs. 258 nM; P= 0.02) were significantly higher in portal venous blood than in peripheral blood. Coagulation activation markers and platelet activation markers (CD40Ls and P selectin) were significantly higher in infected cirrhotics, despite a similar Child-Pugh and HVPG. Conclusions: Markers of coagulation activation, and thus the procoagulant state of cirrhosis, increase in correlation with the degree of liver failure and portal hypertension. This is more evident in the splanchnic territory and is further exacerbated during bacterial infections.
Juan Carlos Garcia-Pagan - Grant/Research Support: GORE
Jaime Bosch -Advisory Committees or Review Panels: Intercept pharma; Consulting: Chiasma, Gilead Science, Norgine, ONO-USA; Grant/Research Support: Gore
The following people have nothing to disclose: Sebastian Raffa, Juan Carlos Reverter, Susana Seijo, Juan G. Abraldes, Dolors Tassies, Annalisa Berzigotti