Reduced platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis

Vinholt, Pernille Just; Hvas, Anne‐Mette; Nielsen, Christian; Söderström, Anna; Sprogøe, Ulrik; Fialla, Annette Dam; Nybo, Mads

doi:10.1080/09537104.2017.1349308

Cited by 38 publications

(38 citation statements)

References 30 publications

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“…78 Patients diagnosed with NAFLD/NASH commonly display increased mean platelet volume, an indicator of platelet activation, which was shown to correlate directly with the severity of inflammation and the grade of fibrosis, 79 whereas patients with alcohol-related liver disease seem to display reduced platelet activation and aggregation capacity. 80 However, in another study, patients with alcohol-related liver cirrhosis were reported to display a decreased platelet count but a significantly increased mean platelet volume compared to control patients or patients with simple alcohol-related fatty liver disease (AFLD). 81 Recent data from our laboratories indicated an increase of infiltrating platelets in hepatic tissue of pre-clinical models of diet-induced NASH and of NASH-diagnosed patients.…”

Section: Platelets In Alcohol-related and Non-alcoholic Steatohepatitismentioning

confidence: 98%

Platelets in chronic liver disease, from bench to bedside

et al. 2019

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In the last decade, numerous studies revealed physiologic and pathophysiologic roles of platelets beyond haemostasis, a process to prevent and stop bleeding. These include the activation of the immune system and the promotion of inflammation, infection and cancer. Hence, the emerging view on the role of platelets has shiftedplatelets are now seen as alert "sentinels" of the immune compartment, rather than passive bystanders. Herein, we review well-established and newly discovered features of platelets that define their natural role in maintaining blood haemostasis, but also their functional relationship with other cells of the immune system. We focus on recent studies underlining functional involvement of platelets in chronic liver diseases and cancer, as well as the effects of anti-platelet therapy in these contexts. Finally, we illustrate the potential of platelets as possible diagnostic and therapeutic tools in liver disease based on recently developed methodologies.

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Section: Platelets In Alcohol-related and Non-alcoholic Steatohepatitismentioning

confidence: 98%

Platelets in chronic liver disease, from bench to bedside

et al. 2019

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“…In LC, decreased agonist-induced platelet aggregation compatible with thrombocytopathy has also been documented. (34)(35)(36)(37)(38) The defect is intrinsic to platelets, as washed platelets exhibit decreased aggregation, too. (36) As causal anomalies, intracellular signaling/ thromboxane A2 metabolism defects and storage pool defects have been reported ( Table 2).…”

Section: Thrombocytopathymentioning

confidence: 99%

“…(34)(35)(36)(37)(38) The defect is intrinsic to platelets, as washed platelets exhibit decreased aggregation, too. (36) As causal anomalies, intracellular signaling/ thromboxane A2 metabolism defects and storage pool defects have been reported ( Table 2). (34,37,38) However, one study reported an increased percentage of platelets activated by subthreshold agonist concentrations.…”

Section: Thrombocytopathymentioning

confidence: 99%

“…(39) Moreover, data suggest in vivo platelet activation (Table 3) due to hyperactive platelets or in vivo thrombin generation (see below). (35,36,(40)(41)(42)(43)(44)(45) Low-grade endotoxemia could play a role, as bacterial lipopolysaccharides are increased in LC and correlate with in vivo platelet activation markers. (39) Differences between peripheral and portal circulation are possible, with higher platelet activation in the portal circulation.…”

Section: Thrombocytopathymentioning

confidence: 99%

“…Biomarkers on resting platelets Increased P-selectin (40,45) No difference in P-selectin (36) Increased CD63 in alcohol-associated LC (levels remain low) (36) Metabolites of thromboxane A2 Increased because of platelet activation (44) Increased because of increased platelet destruction (35) Abbreviations: β-TG, β-thromboglobulin; CD40L, CD40 ligand; CONTRA, contradicting; LC, liver cirrhosis; PF-4, platelet factor 4; PRO, in favor of.…”

Section: Soluble Biomarkersmentioning

confidence: 99%

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Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis

et al. 2020

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In the setting of liver cirrhosis (LC), profound hemostatic changes occur, which affect primary hemostasis, coagulation, and fibrinolysis. They involve prohemorrhagic and prothrombotic alterations at each of these steps. Patients with cirrhosis exhibit multifactorial thrombocytopenia and in vitro thrombocytopathy, counterbalanced by increased von Willebrand factor. The resultant shift is difficult to assess, but overall these changes probably result in a rebalanced primary hemostasis. Concerning coagulation, the reduced activity of coagulation factors is counterbalanced by an increase in factor VIII (produced by liver sinusoidal endothelial cells), a decrease of the natural anticoagulants, and complex changes, including changes in circulating microparticles, cell-free DNA, and neutrophil extracellular traps. Overall, these alterations result in a procoagulant state. As for fibrinolysis, increased tissue-type and urokinase-type plasminogen activators, a relatively decreased plasminogen activator inhibitor 1, and decreased levels of thrombin-activatable fibrinolysis inhibitor and α2-antiplasmin are counterbalanced by decreased plasminogen and a decreased fibrin clot permeability. Whether and how these changes shift fibrinolysis remains to be determined. Overall, the current consensus is that in patients with cirrhosis, the hemostasis is shifted toward a procoagulant state. We review the published evidence for the concept of LC as a prothrombotic state, discuss discordant data, and highlight the impact of the underlying cause of LC on the resultant imbalance. (Hepatology 2020;71:2135-2148). Primary HemostasisChanges of primary hemostasis in patients with LC are shown in Table 1.Abbreviations: ADAMTS13, a disintegrin and metalloprotease with thrombospondin type 1 repeats 13;Hepatology, June 2020 ZERMATTEN ET AL. 2136pRoHeMoRRHagIC CHaNgeS thrombocytopenia Thrombocytopenia (platelets <150 × 10 9 /L) occurs in up to 78% (1) of patients with LC, moderate thrombocytopenia (platelets 50-75 × 10 9 /L) occurs in approximately 13%, (2) and severe thrombocytopenia (platelets <50 × 10 9 /L) occurs in 1% to 2%. (3) Decreased production and increased clearance of platelets are both involved in LC-associated thrombocytopenia ( Fig. 1). Indeed, reticulated/immature platelets and glycocalicin (proteolytic extracellular fragment of glycoprotein 1b), which are markers of platelet production, are decreased in LC. (4) However, reticulated/ immature platelet fraction and glycocalicin index, which are markers of platelet turnover, are increased in patients with LC versus healthy donors (4,5) and in thrombocytopenic versus non-thrombocytopenic patients with LC. (4,6) Moreover, the mean platelet survival is decreased in LC, (7) indicating an increased platelet turnover. Differences across LC causes are possible. Indeed, reticulated platelets are increased in hepatitis C virus (HCV)-induced LC and decreased in alcohol-induced LC and hepatitis B virus (HBV)induced LC. (5) DeCReaSeD pRoDUCtIoN oF plateletSDecreased production is due to decre...

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Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding: A Danish population‐based cohort study

Riahi

Adelborg

Pedersen

et al. 2022

Research and Practice in Thrombosis and Haemostasis

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Objectives We examined the impact of liver cirrhosis on the risk of thromboembolic events and bleeding complications in patients with atrial fibrillation or flutter (AFF). Methods This population‐based cohort study used data from Danish health registries. We identified all patients with a first‐time diagnosis of AFF during 1995 to 2015, and followed them from their AFF diagnosis until the end of 2016. Patients were categorized according to the presence or absence of liver cirrhosis. We computed incidence rates per 1000 person‐years and hazard ratios (HRs) with 95% confidence intervals (CIs) based on Cox regression analyses, adjusting for age, CHA 2 DS 2 VASc score, and Charlson Comorbidity Index score. Results We identified 273 225 patients with AFF. Of these, 1463 (0.54%) had liver cirrhosis. During 0 to 5 years of follow‐up, compared to patients without liver cirrhosis, patients with liver cirrhosis had higher incidence rates and hazards of ischemic stroke (29.7 vs 21.6; HR, 1.3; 95% CI, 1.1‐1.6), venous thromboembolism (9.2 vs 5.5; HR, 1.5; 95% CI, 1.2‐2.3), but not myocardial infarction (10.2 vs 11.2; HR, 0.9; 95% CI, 0.7–1.2). Patients with liver cirrhosis also had higher rates of hemorrhagic stroke (5.8 vs 3.3; HR, 1.7; 95% CI, 1.1‐2.6), subdural hemorrhage (5.3 vs 1.6; HR, 3.2; 95% CI, 2.1‐4.9), hemorrhage of the lung or urinary tract (24.6 vs 15.2; HR, 1.6; 95% CI, 1.3–2.0), and gastrointestinal hemorrhage (34.5 vs 10.4; HR, 3.3; 95% CI, 2.7–3.9). Conclusion In patients with AFF, liver cirrhosis was associated with an elevated risk of ischemic stroke, venous thromboembolism, and all evaluated bleeding complications.

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Reduced platelet activation and platelet aggregation in patients with alcoholic liver cirrhosis

Cited by 38 publications

References 30 publications

Platelets in chronic liver disease, from bench to bedside

Platelets in chronic liver disease, from bench to bedside

Hemostatic Alterations in Patients With Cirrhosis: From Primary Hemostasis to Fibrinolysis

Atrial fibrillation, liver cirrhosis, thrombosis, and bleeding: A Danish population‐based cohort study

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