Abbreviations
- AA
arachidonic acid
- ACLF
acute‐on‐chronic liver failure
- AD
acute decompensation
- ADP
adenosine diphosphate
- BI
bacterial infection
- DC
decompensated cirrhosis
- DC+BI
decompensated cirrhosis with bacterial infection
- vWF:Ag
von Willebrand factor antigen
- vWF:RCo
von Willebrand factor ristocetin cofactor activity
1.
We read with interest the Letter by Ferdinande et al. [1]. As we previously reported, reduced platelet (PLT) aggregation was observed in patients with decompensated cirrhosis (DC) and bacterial infection (BI) compared with patients with stable DC, and the severity of sepsis and organ failure significantly affected PLT aggregation [2]. We fully agree that comparing the current cohort of patients with DC+BI with a cohort with acute‐on‐chronic liver failure (ACLF) or acute decompensation (AD) without BI would have enabled a more accurate assessment of the independent contribution of infection.
As also highlighted by Ferdinande et al. [1], the DC+BI cohort presented in our article did not include longitudinal data of primary haemostasis parameters. We therefore provide herewith a comparison of primary haemostasis measurements obtained at baseline and after resolution of infection using the same methods and definitions as those described in the original article, in a separate cohort of patients with DC + BI. Comparisons were performed using the Wilcoxon signed‐rank test.
The cohort comprised 60 patients with DC+BI, including 14 with ACLF and 46 with AD [48 male, median (IQR) MELD score 17 (12.6–23)]. Alcohol‐associated liver disease was the most common aetiology of cirrhosis. As shown in Table 1, adenosine diphosphate (ADP)‐induced PLT aggregation and von Willebrand factor (vWF) levels were significantly lower following resolution of infection than at baseline, both in the overall cohort and in the ACLF and AD subgroups. vWF: Ristocetin‐cofactor activity and PLT aggregation in response to arachidonic acid (AA) did not change significantly. These findings demonstrate that primary haemostasis parameters either deteriorated or remained unchanged despite infection resolution, suggesting prolonged platelet dysfunction as was previously reported [3].
TABLE 1.
Comparison of PLT aggregation levels and vWF‐related parameters between baseline (T1) and after resolution of infection (T2) in overall cohort and within groups (ACLF or AD).
| Parameters | Overall (N = 60) | Acute‐on chronic liver failure (ACLF) (N = 14) | Acute decompensation (AD) (N = 46) | ||||
|---|---|---|---|---|---|---|---|
| p | p | p | |||||
| PLT aggregation (ADP) (%) | T1 | 84.9 (61.2–93.9) | 0.009 | 57.6 (47.4–79.3) | 0.136 | 88.6 (69.2–95.4) | 0.031 |
| T2 | 75.9 (42.5–91.4) | 45.2 (24.8–71) | 81.9 (56.9–96.0) | ||||
| PLT aggregation (AA) (%) | T1 | 87.5 (72.7–97.6) | 0.735 | 83.2 (70–96.8) | 0.099 | 86 (72.9–99.3) | 0.189 |
| T2 | 85.7 (73.0–98.9) | 71.9 (64.7–88.8) | 89.4 (79.5–93.4) | ||||
| vWF:Ag (%) | T1 | 381 (255–480) | < 0.001 | 480 (425–545) | 0.007 | 351 (252–420) | 0.009 |
| T2 | 324 (252–420) | 419 (256–420) | 307 (242–415) | ||||
| vWF:RCo (%) | T1 | 378 (270–492) | 0.339 | 513 (323–602) | 0.063 | 379 (251–454) | 0.869 |
| T2 | 350 (263–558) | 484 (242–601) | 350 (266–504) | ||||
Abbreviations: AA, arachidonic acid; ADP, adenosine diphosphate; PLT, platelet; vWF, von Willebrand factor; vWF:RCo, vWF Ristocetin cofactor.
During bacterial infection, PLT activation is mediated through FcγRIIA and glycoprotein IIb/IIIa receptors, as well as through Toll‐like receptor 4 in response to Gram‐positive and Gram‐negative bacteria, respectively [4]. In sepsis, endothelial dysfunction promotes PLT activation and tissue factor‐dependent coagulation. Activated PLT interact with leukocytes and contribute to excessive coagulation, ultimately resulting in PLT hyporesponsiveness. Elevated endotoxin levels, increased nitric oxide production and higher concentrations of glycosaminoglycans are common features of liver cirrhosis and may further contribute to impaired PLT aggregation [5].
Whether these alterations in primary haemostasis persist long after removal of the precipitating factor (bacterial infection) or gradually recover over time remains to be determined. Should PLT function ultimately recover following resolution of infection, both the trajectory of recovery and its clinical implications warrant further investigation.
Author Contributions
Study concept and design: F.A. and A.A. Acquisition of data: F.A. Statistical analysis: L.V. and A.A. Interpretation of data: F.A., E.N. and A.A. Drafting manuscript: F.A., E.N. and A.A. Critical revisions of the manuscript for important intellectual content: All authors.
Funding
The authors have nothing to report.
Conflicts of Interest
The authors declare no conflicts of interest.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.