Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases

Lisman, Ton; Porte, Robert J.

doi:10.1002/rth2.12028

Cited by 107 publications

(139 citation statements)

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“…However, PT and APTT are only sensitive to changes in the procoagulant pathways, therefore reflecting only the abnormalities of the pro‐coagulant proteins in cirrhosis, but providing little information about the anticoagulant pathways including antithrombin and proteins of the protein C pathway. Anticoagulant pathways may also be impaired in cirrhosis . Clinical data show that cirrhotic patients are not “auto‐anticoagulated,” but rather have equal or even higher thrombotic risk than patients without liver disease .…”

Section: Introductionmentioning

confidence: 99%

“…Anticoagulant pathways may also be impaired in cirrhosis . Clinical data show that cirrhotic patients are not “auto‐anticoagulated,” but rather have equal or even higher thrombotic risk than patients without liver disease . These observations have led to the concept of rebalanced hemostasis to explain the complex coagulation profiles in patients with cirrhosis .…”

Section: Introductionmentioning

confidence: 99%

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Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

Wan

Roberts

Hendrix

et al. 2020

Journal of Thrombosis and Haemostasis

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Background and Aims Patients with cirrhosis have a rebalanced hemostasis, often with normal or elevated thrombin‐generating (TG) capacity in plasma. Whole blood (WB) TG allows faster determination and, importantly, includes the influence of all circulating blood cells. We aimed to study the TG profile of patients with cirrhosis in WB and in platelet poor plasma. Methods Thrombin‐generating capacity in WB and plasma were assessed with a near‐patient WB‐TG assay and the calibrated automated thrombinography assay, respectively. TG assays were tested in presence and absence of thrombomodulin. Conventional coagulation tests were also performed. Results Thirty‐four patients with cirrhosis and twenty‐two controls were analyzed. Compared with controls, patients had substantially deranged results in conventional coagulation tests. Comparable WB‐TG capacity (endogenous thrombin potential until peak, ETPp) but significantly lower peak thrombin were found in patients, and these results persisted when thrombomodulin was present. TG of the patients was more resistant to thrombomodulin than controls in both WB and plasma, although the inhibitory effect of thrombomodulin was drastically weaker in WB than in plasma. The peak of WB‐TG in patients correlated moderately with their hematocrit and platelet count. Significant correlations were found between TG results in WB and plasma. Conclusions The WB‐TG assay shows a normal to hypocoagulable state in patients with cirrhosis with a decreased anticoagulant activity of TM compared to plasma‐TG. The clinical value of this assay needs further validation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

Wan

Roberts

Hendrix

et al. 2020

Journal of Thrombosis and Haemostasis

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“…Patients with cirrhosis, particularly decompensated cirrhosis, are prone to both bleeding and thrombotic complications. 1 Clotting times are frequently prolonged in cirrhotic patients, but poorly predict procedure-related bleeding in cirrhosis, because these assays are insensitive to coexisting anticoagulant pathway deficiencies seen in cirrhotic patients, such as reduced levels of protein C and antithrombin. 2 Thrombin generation measured by calibrated automated thrombography (CAT) is considered a more accurate representation of an individual's coagulation phenotype.…”

Section: Introductionmentioning

confidence: 99%

Liver stiffness and thrombin generation in compensated cirrhosis

Dillon

Egan

Kevane

et al. 2019

Research and Practice in Thrombosis and Haemostasis

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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.

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“…Patients with cirrhosis frequently have complex changes in their hemostatic system. The net effect of these changes is a hemostatic system that is in a “rebalanced” status, although notable hyper‐ and hypocoagulable features may be present . Although there is increasing consensus that a decreased platelet count in patients with cirrhosis is (in part) balanced by highly elevated plasma levels of von Willebrand factor and that the thrombin‐generating capacity is normal to increased compared with healthy individuals, there is continuing controversy on the status of the fibrinolytic system .…”

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confidence: 99%

Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute‐on‐Chronic Liver Failure with Hypofibrinolysis in Those With Complications and Poor Survival

et al. 2019

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Background and Aims Patients with liver disease acquire complex changes in their hemostatic system, which results in a fragile rebalanced status. The status of the fibrinolytic system is controversial, as is the role of fibrinolytic dysfunction in bleeding and thrombosis in patients with cirrhosis. Here, we aimed to determine fibrinolytic status and its relationship with outcome in acutely ill patients with cirrhosis. Approach and Results We assessed plasma fibrinolytic potential in a large cohort of patients with acutely decompensated cirrhosis (AD, n = 52) or acute‐on‐chronic liver failure (ACLF, n = 57). Compared with 40 healthy volunteers, median clot lysis times (CLTs) were shorter in patients with AD but comparable to controls in patients with ACLF. However, the variability in CLTs in patients was much larger than in healthy controls, and in both patient groups, a proportion of patients had clearly prolonged or shortened CLTs. The variability in CLTs in patients was not readily explained by variations in plasma levels of key fibrinolytic proteins. However, CLTs were clearly related to clinical characteristics, with longer CLTs in patients with sepsis and patients with any organ failure (as defined by the European Foundation for the Study of Chronic Liver Disease organ failure scores). CLTs were not different between patients that did or did not experience bleeding or a thrombotic event during follow‐up. Baseline CLTs were substantially longer in patients that died within 30 days of admission. Conclusions Our study demonstrates a mixed fibrinolytic phenotype in acutely ill patients with cirrhosis with baseline hypofibrinolysis associated with sepsis, organ failure, and short‐term mortality. These associations may be explained by defective clearance of intraorgan microthrombi that have been proposed to drive organ failure.

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Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases

Cited by 107 publications

References 123 publications

Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

Whole blood thrombin generation profiles of patients with cirrhosis explored with a near patient assay

Liver stiffness and thrombin generation in compensated cirrhosis

Mixed Fibrinolytic Phenotypes in Decompensated Cirrhosis and Acute‐on‐Chronic Liver Failure with Hypofibrinolysis in Those With Complications and Poor Survival

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