Liver stiffness and thrombin generation in compensated cirrhosis

Abstract

Background Decompensated cirrhosis is associated with coagulation abnormalities that can increase the risk of thrombosis and bleeding. It is unclear precisely when these abnormalities arise and whether they are exacerbated as compensated cirrhosis progresses. Transient elastography using FibroScan generates liver stiffness measurements ( LSM ) that associate with portal hypertension, clinical outcomes and provides prognostic information at an earlier stage than traditional liver function scores eg, MELD score. Objective To characterize thrombin generation in patients with compensated cirrhosis and to determine whether parameters of coagulation change throughout compensated cirrhosis, staged using LSM . Patients/Methods Blood samples were collected from well‐compensated cirrhotic patients n = 61, All Child Pugh A stage) attending the Mater Misericordiae University Hospital, Ireland. Comprehensive clinical staging of liver disease, including LSM , was performed. Tissue Factor‐stimulated thrombin generation was measured by calibrated automated thrombography. Results Using LSM to stage well‐compensated cirrhotic patients, we demonstrate a significant decrease in the rate of propagation, the rate of attenuation, and total thrombin generation as LSM increase. LSM correlated with endogenous thrombin potential, peak thrombin generation, the rate of propagation, and the rate of attenuation. This association between thrombin generation and LSM was still evident in sub‐analyses excluding patients with ongoing alcohol use, active HCV infection, or a history of decompensation. In contrast, there was no significant correlation between thrombin generation, prothrombin times, Child‐Pugh scores, or MELD scores. Conclusion Liver stiffness measurements identify differences in parameters of thrombin generation within a cohort of compensated cirrhotic patients before changes in clotting times occur.

Resistance to thrombomodulin correlates with liver stiffness in chronic liver disease a prospective single-center cohort study

“…Since the measurement of the liver stiffness is a reliable method for the staging of CLD [29,36], LSM was used to stage the patients included in the CLD cohort. We used a cut-off of 21 kPa to subgroup the patients' sample, as a LSM ≥21 kPa is currently considered the best non-invasive surrogate marker of clinically significant portal hypertension [22]. STG is the first fully automated TG analyzer that could be suitable for the accurate measurement of TG parameters in patients.…”

“…Conventional coagulation tests do not reflect the hemostatic balance in patients with CLD [1]. In patients with CLD, TG and TM-modified TG are currently considered a more accurate measure of the in vivo coagulation, because it can assess both pro-and anticoagulant forces [15,[19][20][21][22][38][39][40]. There is evidence of a procoagulant imbalance in patients with CLD.…”

“…Disease severity was staged based on LSM according to the EASL-ALEH guidelines [29]. A cut-off of 21 kPa was used to identify patients with a high likelihood of bearing clinically significant portal hypertension [22,26,34,35].…”

“…Using a modified TG assay that adds soluble TM, it has been shown that the coagulation potential observed in patients with liver disease is preserved indicating that the deficiency of anticoagulant proteins compensates for the deficiency of procoagulant proteins [15]. Even in CLD patients with prolonged coagulation times, TM-modified TG is normal or even increased compared to healthy individuals [16,17].Global hemostatic tests such as TG assays provide currently the most accurate representation of the coagulation phenotype at the individual level [18] and have been used for investigating coagulopathy in CLD in several studies due to their ability to taking into account the protein C pathway [9,15,[19][20][21][22][23]. Using this methodologic approach, La Mura et al have shown that TM resistance is associated with portal vein thrombosis and might predict an adverse outcome in patients with CLD [24].…”

“…A recent meta-analysis demonstrated for diagnosis clinically significant portal hypertension (CSPH) in patients with CLD, that the most sensitive validated cut-off is 13 kPa and the most specific cut-off is 21 kPa [25][26][27]. Recently, Dillon et al reported that liver stiffness measurements (LSM) identify differences in parameters of TG measured by the calibrated automated thrombogram (CAT) assay in patients with cirrhosis before changes in coagulation times occur [22].…”