Liver cirrhosis, an advanced stage of chronic liver disease, involves fibrosis, liver dysfunction, and altered coagulation [
1]. Traditionally viewed as coagulopathic, cirrhosis is now seen through the lens of rebalanced hemostasis. The functional quality of platelets—in terms of adhesion, activation, and aggregation—emerges as a critical component that may indicate the severity of portal hypertension, the course of the disease, and the probability of complications [
2].
Platelets play essential roles in hemostasis. Upon vascular injury, they adhere via GPVI-collagen and GPIb-vWF interactions, triggering activation. This leads to granule release, shape change, and expression of markers like Pselectin and GPIIb/IIIa, promoting aggregation. The resulting plug supports secondary hemostasis through the coagulation cascade [
3].
Thrombocytopenia in liver cirrhosis is brought on by a combination of bone marrow suppression (especially in alcohol-related liver disease), decreased thrombopoietin synthesis by the liver, and splenic sequestration due to portal hypertension [
4]. Recent studies suggest platelet function may be preserved or enhanced despite low counts, reflecting complex, variable compensatory mechanisms across functional dimensions [
5]. We herein discuss through a snapshot about the aspect of platelet functions in cirrhosis based on recent literature.
Platelet adhesion in cirrhosis, as assessed by the Platelet Function Analyzer (PFA-100) [
6]. The test measures platelet occlusion time under high shear conditions. Platelet adhesion, assessed via PFA-100 in cirrhosis, increases with disease severity, likely due to elevated vWF and reduced ADAMTS13. This may compensate for thrombocytopenia. However, it doesn’t correlate with decompensation or mortality, and prognostic tools like Model for End-Stage Liver Disease (MELD) score and hepatic venous pressure gradient remain more reliable for assessing clinical outcomes [
6]. Thus, while the molecular mechanism of enhanced adhesion is noteworthy, its independent therapeutic usefulness is unknown.
The second functional feature, platelet activation, is increasingly being investigated using flow cytometry, which analyzes the expression of surface markers such as P-selectin and activated GPIIb/IIIa following stimulation with agonists such as PAR-1 and PAR-4. Platelet activation is often reduced in cirrhosis, especially in alcohol-related cases, possibly due to platelet depletion or marrow suppression. This reduction, evident through decreased MFI in flow cytometry, correlates with hepatic decompensation but not with bleeding risk—suggesting bleeding is usually mechanical, not hemostatic. While flow cytometry offers valuable insights, its technical complexity and variability limit routine clinical use, though it remains useful in research and select clinical contexts. Thus, platelet activation may serve more as a biomarker than a bleeding predictor [
7]. Furthermore, flow cytometry, while informative, is technically difficult and vulnerable to variation based on the agonist type, concentration, and incubation methods.
Light transmission or whole-blood aggregometry can be used to assess platelet aggregation, which is a crucial stage in primary hemostasis and is brought on by agonists such as adenosine diphosphate, collagen, or arachidonic acid. In cirrhosis, aggregation is impaired by thrombocytopenia and inhibitors. Yet, a high platelet aggregation-to-count ratio (>0.75) independently predicts portal vein thrombosis, regardless of MELD score or platelet count [
8]. In compensated cirrhosis, Turon et al. found platelet function markers lacked prognostic value, suggesting platelet activity may be preserved or elevated [
9].
Thrombin generation tests in whole blood and plateletrich plasma show that thrombin production markedly declines in Child C cirrhosis in whole blood, despite remaining stable in plasma—suggesting impaired overall coagulation and a higher procedural bleeding risk [
10].
Platelet function in cirrhosis reflects adaptive changes influenced by disease severity, cause, inflammation, and vascular status. The “rebalanced hemostasis” model highlights a fragile balance between bleeding and thrombosis. Thus, platelet function tests offer insight but must be interpreted with platelet count and clinical context.
In summary, thrombocytopenia remains key in cirrhosis, but platelet function is influenced by multiple factors. Advanced disease shows reduced aggregation and activation, with paradoxically increased adhesion. Though underused clinically, functional tests may aid risk assessment and treatment decisions. Standardized research integrating clinical data is needed to unlock their full potential.
FOOTNOTES
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Authors’ contribution
VJ: drafted the manuscript. SB: drafted and revised. CB: conceptualizing, reviewing and revision.
-
Conflicts of Interest
The authors have no conflicts to disclose.
Abbreviations
hepatic vein pressure gradient
light transmission aggregometry
model of end stage liver disease
mean fluoroscent intensity
platelet function analyzer
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