Peripheral versus central venous blood sampling does not influence the assessment of platelet activation in cirrhosis

Abstract

Cirrhotic patients have an increased risk of bleeding and thromboembolic events, with platelets being involved as key players in both situations. The impact of peripheral versus central blood sampling on platelet activation remains unclear. In 33 cirrhotic patients, we thus analyzed platelet function in peripheral (P) and central (C) blood samples. Platelet surface expression of P-selectin, activated glycoprotein (GP) IIb/IIIa, and leukocyte-platelet aggregate formation were measured by flow cytometry in response to different agonists: thrombin receptor-activating peptide-6, adenosine diphosphate, collagen-related peptide (CrP), epinephrine, AYPGKF, Pam3CSK4, and lipopolysaccharide. Unstimulated platelet surface expression of P-selectin (p = .850) and activated GPIIb/IIIa (p = .625) were similar in peripheral and central blood samples. Stimulation with various agonists yielded similar results of platelet surface expression of P-selectin and activated GPIIb/IIIa in peripheral and central samples, except for CrP-inducible expression of activated GPIIb/IIIa (median fluorescence intensity, MFI in P: 7.61 [0.00–24.66] vs. C: 4.12 [0.00–19.04], p < .001). The formation of leukocyte-platelet aggregate was similar in central and peripheral blood samples, both unstimulated and after stimulation with all above-mentioned agonists. In conclusion, peripheral vs. central venous blood sampling does not influence the assessment of platelet activation by flow cytometry in cirrhosis.

Abbreviations: ACLD: advanced chronic liver disease; ADP: adenosine diphosphate; ALD: alcoholic liver disease; AYPGKF: PAR-4 agonist AYPGKF; CrP: collagen related protein; EPI: epinephrine; FACS: fluorescence-activated cell sorting; GP: glycoprotein; HVPG: hepatic venous pressure gradient; IQR: interquartile range; LPS: lipopolysaccharide; LSM: liver stiffness measurement; MFI: median fluorescence intensity; NAFLD: nonalcoholic fatty liver disease; PAM: lipopeptide Pam3CSK4; PAR: protease-activated receptor; PBS: phosphate-buffered saline; PH: portal hypertension; TIPS: transjugular intrahepatic portosystemic stent shunt; TLR: toll-like receptor; TRAP-6: thrombin receptor-activator peptide-6; vWF: von Willebrand factor

Keywords:

• Blood sampling
• flow cytometry
• liver disease
• platelet activation
• platelet function analysis

Author contributions

Data collection: KB, BS, BE, DB, PS, MM, TR, TG

Statistical analysis: KB, MM, TR, TG

Drafting of the manuscript: KB, TR, TG

Study supervision: TR, TG

Revision for important intellectual content and approval of the final version of the manuscript: All authors.

Disclosure statement

KB/TR were supported by the Christian-Doppler Society and Boehringer-Ingelheim.

BS received travel support from AbbVie and Gilead and was supported by an International Liver Research Scholarship by Gilead Sciences awarded to TR.

DB has received travel support from Gilead and AbbVie and speaker fees from AbbVie.

PS was supported by the Medical Scientific Fund of the Mayor of the City of Vienna (Project:18070), received consulting fees from PharmaIN, and travel support from Falk and Phenex Pharmaceuticals.

MM served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Gilead, Collective Acumen, and W. L. Gore & Associates and received travel support from AbbVie, Bristol-Myers Squibb, and Gilead.

TR received grant support from Abbvie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, Intercept, MSD, Siemens; travel support from Boehringer-Ingelheim, Gilead and Roche.

TG received lecture fees from Amgen, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Novartis, and Pfizer.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.