Reversal of hypercoagulability in patients with <scp>HCV</scp>‐related cirrhosis after treatment with direct‐acting antivirals

Russo, Francesco Paolo; Zanetto, Alberto; Campello, Elena; Bulato, Cristiana; Shalaby, Sarah; Spiezia, Luca; Gavasso, Sabrina; Franceschet, E.; Radu, Claudia; Senzolo, Marco; Burra, Patrizia; Lisman, Ton; Simioni, Paolo

doi:10.1111/liv.13873

Cited by 43 publications

(52 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using the near patient WB‐TG assay, we observed that the endogenous thrombin generating potential (ETPp) values of patients with cirrhosis, regardless of the presence/absence of TM, were in the same range as in healthy controls, suggesting that these patients had normal thrombin‐generating capacity. The standard PPP‐TG results add to the growing literature that hypocoagulable state is suggested when TG is tested without activating the protein C pathway, whereas hypercoagulable state is found when the function of the anticoagulant protein C pathway is included in TG by adding TM into the test . These results indicate that cirrhosis does not necessarily result in a hypocoagulable state as suggested by their lower procoagulant factor levels and prolonged PT and APTT, thus reinforcing that prophylactic administration of fresh‐frozen plasma according to their PT/APTT is not required …”

Section: Discussionmentioning

confidence: 55%

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 55%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Patients' characteristics have been previously published . Briefly, 58 patients with HCV‐related cirrhosis were enrolled (M/F 38/20, mean age 59 years).…”

Section: Resultsmentioning

confidence: 99%

“…The study cohort has been recently described . Briefly, all consecutive patients with HCV‐related cirrhosis referred to the Multivisceral Transplant Unit and the Gastroenterology Unit of Padova University Hospital for anti‐HCV treatment with DAAs between September 2015 and March 2016 were eligible for enrolment.…”

Section: Methodsmentioning

confidence: 99%

“…Aliquots (0.5 mL) were immediately frozen and then stored at −80°C until use. Traditional coagulation parameters and thrombin generation test (calibrated automated thrombogram method [Thrombinoscope BV]) were performed as previously described …”

Section: Methodsmentioning

confidence: 99%

“…In 2014, the introduction of direct‐acting antiviral (DAAs) agents has changed the picture . Although it is still not clear the long‐term impact of sustained virological response (SVR) after DAAs in the history of compensated and decompensated cirrhosis, eradication of HCV has been associated with the reduction of hepatic and systemic inflammation, regression of liver fibrosis, improvement of liver synthetic function and reduction of portal pressure …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Changes in plasma circulating microvesicles in patients with HCV‐related cirrhosis after treatment with direct‐acting antivirals

Campello

Radu

Zanetto

et al. 2019

Liver International

Self Cite

View full text Add to dashboard Cite

Background & Aims The eradication of Hepatitis C (HCV) infection by direct‐acting antiviral (DAAs) agents has been linked to an amelioration of liver synthesis and regression of fibrosis. Although changes in number and type of circulating microvesicles (MVs) have been reported in cirrhosis, conclusive data on the effect of DAAs treatment on MVs profile in HCV cirrhotic patients remain scarce. Methods We measured the levels of endothelial, platelet and hepatocyte MVs, as well as MVs‐expressing versican core protein (VCAN+) in patients with HCV‐related cirrhosis at baseline, end of treatment (EOT), at 12, 24 and 48 weeks (W) after EOT by new generation flow cytometry. Results Fifty‐eight patients were enrolled (86% Child's A). MVs were increased at EOT vs baseline, though only platelet MVs revealed a statistically significant difference (P < .01). MV levels did not change significantly after EOT notwithstanding a steady downward trend towards baseline levels. Conversely, VCAN + MVs dropped significantly at EOT (P < .001) and remained low throughout the follow‐up. Hepatocyte MVs significantly correlated with liver stiffness (r = .40, P = .0021). Eight composite outcomes occurred during the 1‐year follow‐up: three portal vein thromboses (PVTs), two hepatocellular carcinomas (HCCs) and three liver decompensation. Child's B, the presence of F2 oesophageal varices (OR for interaction 19.2 [95% CI 1.45‐253.7], P = .023) and platelet MVs (OR 1.026 [95% CI 1.00‐1.05, P = .023) correlated significantly with clinical outcomes. Conclusions VCAN + MVs appear to mirror the profibrotic status of the cirrhotic disease; hepatocyte MVs correlate with liver stiffness and increased platelet MV levels could be associated with a worse clinical outcome.

show abstract

Acute Kidney Injury in Decompensated Cirrhosis Is Associated With Both Hypo‐coagulable and Hyper‐coagulable Features

et al. 2020

Self Cite

View full text Add to dashboard Cite

BaCKgRoUND aND aIMS: Recent evidence suggests that acute kidney injury (AKI) is the main predictor of postparacentesis bleeding in patients with cirrhosis. To assess the factors responsible for bleeding tendency in AKI, we performed a prospective study comparing all three aspects of hemostasis (platelets, coagulation, and fibrinolysis) in patients with decompensated cirrhosis with and without AKI. appRoaCH aND ReSUltS: Primary hemostasis assessment included platelet aggregation and secretion (platelet function markers) and von Willebrand factor. Secondary hemostasis assessment included pro-coagulant (factor VIII and factor XIII) and anti-coagulant (protein C, protein S, and antithrombin) factors and thrombin generation. Tertiary hemostasis assessment included fibrinolytic factors and plasmin-antiplasmin complex. Eighty patients with decompensated cirrhosis were recruited (40 each with and without AKI). Severity of cirrhosis and platelet count were comparable between groups. Median serum creatinine was 1.8 mg/dL and 0.8 mg/dL in patients with and without AKI, respectively. At baseline, patients with cirrhosis and AKI had lower platelet aggregation and secretion, indicative of impaired platelet function (increased bleeding tendency), without differences in von Willebrand factor. Regarding coagulation factors, factor VIII was higher, whereas protein C, protein S, and antithrombin were all lower, which, together with increased thrombin generation, indicate hypercoagulability. In contrast, factor XIII was lower in AKI (increased bleeding tendency). Finally, while both hypofibrinolytic and hyperfibrinolytic changes were present in AKI, a higher plasmin-antiplasmin complex indicated a hyperfibrinolytic state. After AKI resolution (n = 23 of 40), platelet function and coagulation improved to levels observed in patients with cirrhosis patients without AKI; however, fibrinolysis remained hyperactivated. CoNClUSIoNS: In patients with decompensated cirrhosis, AKI is associated with both hypocoagulable and hypercoagulable features that can potentially increase the risk of both bleeding and thrombosis. (Hepatology 2020;72:1327-1340). P atients with decompensated cirrhosis have multiple and complex alterations of hemostasis that predispose them to both bleeding and thrombotic complications. (1) Although patients with cirrhosis are traditionally considered to be at high risk of bleeding from procedures, data regarding the correlation between hemostatic

show abstract

Reversal of hypercoagulability in patients with HCV‐related cirrhosis after treatment with direct‐acting antivirals

Abstract: DAAs therapy in HCV-related cirrhotic patients is associated with significant changes in thrombin generation suggesting a reversal of hypercoagulability particularly in Child's A patients.

Cited by 43 publications

References 31 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

Changes in plasma circulating microvesicles in patients with HCV‐related cirrhosis after treatment with direct‐acting antivirals

Acute Kidney Injury in Decompensated Cirrhosis Is Associated With Both Hypo‐coagulable and Hyper‐coagulable Features

Contact Info

Product

Resources

About