Increased soluble GPVI levels in cirrhosis: evidence for early in vivo platelet activation

Abstract

Cirrhosis is a consequence of prolonged liver injury and is characterised by extensive tissue fibrosis: the deposition of collagen-rich extracellular matrix. The haemostatic balance is disordered in cirrhosis and coagulation activation appears to promote fibrosis. In spite of recent studies demonstrating a role for anticoagulant therapy in preventing cirrhosis progression, there has not been a change in clinical practice, suggesting that physicians are reluctant to anticoagulate patients with cirrhosis due to bleeding risks. Platelets play an important role in facilitating coagulation. Glycoprotein VI (GPVI) is a platelet-specific collagen receptor that is shed from the platelet surface in a metalloproteinase-dependent manner in response to GPVI ligation and coagulation activation. Our aim was to use soluble GPVI levels to determine whether there was evidence for collagen and coagulation-induced platelet activation in early, well-compensated cirrhosis. Plasma soluble GPVI levels were quantified in 46 patients with mixed aetiology cirrhosis and 55 healthy controls using an immunoassay. In the cirrhosis group, soluble GPVI levels were significantly increased (5.8 ± 4.4 ng/ml, n = 46) compared to healthy controls (3.3 ± 3.4 ng/ml, n = 55, p < 0.05). This increase in soluble GPVI levels was still evident when levels were adjusted for platelet count (Healthy controls; 0.015 ± 0.018 ng/10 platelets/ml vs. cirrhosis; 0.048 ± 0.04 ng/10 platelets/ml, p < 0.0001). This study provides evidence for early platelet activation in patients with well-compensated cirrhosis. This may have translational implications for prognosis, treatment, and risk stratification.

Platelet Activation Assessed by Glycoprotein VI/Platelet Ratio Is Associated With Portal Vein Thrombosis After Hepatectomy and Splenectomy in Patients With Liver Cirrhosis

“…Furthermore, since sGPVI is platelet-specific and the level of sGPVI depends on platelet counts, it is necessary to adjust sGPVI level by platelet counts to evaluate the actual platelet activation. 23,29 On the other hand, since endothelial cell injury plays an important role in thrombus formation, VWF and VWFpp have recently received much attention. von Willebrand factor and VWFpp are mainly synthesized by vascular endothelial cells and megakaryocytes and mediate the adhesion of platelets to sites of vascular damage by binding to specific platelet membrane glycoproteins Ib in primary thrombus formation.…”

“…22 Recently, Egan et al reported that sGPVI levels were significantly higher in patients with LC than those in healthy patients. 23 To the best of our knowledge, there have been no reports on the relationship between sGPVI levels and PVT.…”

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

“…(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.…”

“…Increased β-TG, PF-4, P-selectin, circulating CD40L (40)(41)(42)(43) No increase of these biomarkers, (35) hypothetical decreased clearance…”

Hemostatic function and inflammatory activation after weaning from cardio pulmonary bypass

“…The blood samples were either sent for clinical routine examinations, or were centrifuged within one hour, aliquoted in cryotubes and stored in -70 for subsequent biomarker measurements During study III analysis of plasmin-antiplasmin complex (PAP), thrombin-antithrombin complex (TAT), soluble fibrin, and soluble P-selectin was performed at the Department of Clinical Chemistry, University Hospital, Linköping. Soluble glycoprotein VI (GPVI) was analyzed by a newly described ELISA 130,131 . ACT was performed in the operating theater with Hemochron Jr, Signature, ICT, Edison, USA.…”