CD62P (P-selectin) expression as a platelet activation marker in patients with liver cirrhosis with and without cholestasis

Abstract

Aim of the study: P-selectin (CD62P) is a platelet activation marker that was claimed to mediate the accumulation of platelets induced by cholestasis. The nature of platelet dysfunction and hemostasis abnormalities in cholestatic liver disease needs to be more explored. The aim of this study was to assess platelet CD62P expression in cirrhotic patients with and without cholestasis, and to evaluate its relationship with a bleeding tendency.

Material and methods: 150 patients were included in this case-control study. Participants were divided into 84 patients with liver cirrhosis (group I), 44 of whom had cholestasis (Group Ia) and 40 patients were without cholestasis (group Ib); 36 patients who were cholestatic without liver cirrhosis (group II); and 30 healthy subjects who formed the control group (group III). Platelet CD62P expression was assessed by a flow cytometer.

Results: Platelets expressing CD62P were significantly increased in all patient groups compared to controls (p < 0.001). Platelets expressing CD62P were significantly increased in gastrointestinal (GIT) bleeders compared to non-bleeders in cirrhotic and cholestatic groups (p < 0.001 each). Among group I patients at cut-off > 12.4, up-regulation of platelet CD62P yielded 72% sensitivity and 44.1% specificity to discriminate bleeders from non-bleeders (p = 0.01), while among group II at cut-off > 12.9, it yielded 90% sensitivity and 80.8% specificity (p < 0.001). In cirrhotic patients, platelet CD62P expression was significantly increased in patients with an advanced Child-Pugh class (p < 0.001). Platelet expressing CD62P was shown as an independent risk factor for bleeding among cirrhotic cases with an odds ratio of 1.07 and CI 0.99-1.15.

Conclusions: Up-regulation of platelet CD62P expression can serve as a GIT bleeding predictor in liver cirrhosis.

Keywords: CD62P; bleeding; cholestasis; cirrhosis; gastrointestinal; liver; marker; overexpression; platelet activation; selectin.

Fig. 1

Gating strategy to detect percentage of positivity of CD62P expressed on platelets using a single histogram gated on CD 41a +ve cells and CD62P +ve cells MFI which was measured in area under M1 marker

Fig. 2

Correlation between percentage of platelets expressing CD62P with total bilirubin (r = 0.67, p < 0.001) and direct bilirubin r = 0.65, p < 0.001)

Fig. 3

Scatter dot figure of correlation between CD62P% and platelet count and PCT in cirrhosis groups (with and without cholestasis). A) Percentage of platelets expressing CD62P was negatively correlated with platelet count (r = –0.39, p < 0.001). B) Percentage of platelets expressing CD62P was negatively correlated with plateletcrit (PCT) (r = –0.35, p < 0.001)

Fig. 4

ROC curve analysis of CD62P% to predict bleeding among cases of cirrhosis with and without cholestasis (Group I) (A) and among cases of cholestasis (Group II) (B)