Regular Article Monocyte-platelet aggregates and platelet micro-particles in patients with post-hepatitic liver cirrhosis Douaa Sayed a, ⁎, Nabila F. Amin b , Ghada M. Galal c a Flow Cytometry Lab., Clinical Pathology Department, South Egypt Cancer Institute, Assiut University, Egypt b Internal Medicine Department, Faculty of Medicine, Assiut University, Egypt c Tropical Medicine and Gastroenterology Department, Faculty of Medicine, Sohag University, Egypt abstract article info Article history: Received 8 September 2009 Received in revised form 20 October 2009 Accepted 1 December 2009 Available online 6 January 2010 Keywords: Liver cirrhosis Monocyte-platelet aggregates Platelets micro-particles Introduction: Monocytes are the cells that play a crucial role in the pathogenesis of liver damage and liver cirrhosis (LC), and as platelets, by connecting hemostasis and inflammatory processes, participate in pathogenesis of chronic liver diseases, we aimed to investigate the presence of monocyte-platelet aggregates and platelet micro-particles (PMPs) and their role in LC. Patients and methods: The study included 60 patients with post-hepatitic LC and 20 healthy controls. Activated monocytes (CD11b, HLA-DR, CD14, CD16), monocyte-platelet aggregates (CD41/CD14), activated platelets (CD41/CD62) and PMPs were analyzed by flow cytometry. Their relations to the clinical and laboratory data were assessed in the studied group. Results: Patients with LC had higher levels of activated platelets, activated monocytes and monocyte-platelet aggregations as compared to healthy controls. PMPs percentage showed no significant differences between patients and controls but significantly increased in both patients with no bleeding and patients with splenomegaly compared to patients without. All studied markers showed no significant differences between patients with thrombocytopenia and those with normal platelet counts and also between patients with different disease stages. Positive correlations between monocyte-platelet aggregates and both activated platelets and monocytes were demonstrated. There were significant negative correlations between PMPs and both age and prothrombin time among patients. Conclusions: The stage of post-hepatitic LC is not the only factor that affects the level of activated platelets, activated monocytes and monocyte-platelet aggregates. PMPs have no influence on thrombocytopenia but may have the potential to influence the progression of clotting activity in LC. © 2009 Elsevier Ltd. All rights reserved. Introduction Liver cirrhosis (LC) is a progressive process and its dynamics depend on the degree of inflammatory and immunological activity [1]. Monocytes play a crucial role in the pathogenesis of inflammation and fibrosis in chronic liver diseases. They create the system of nonspecific defense and take part, when activated, in inflammatory processes of the organism. Stimulated monocytes can accumulate selectively in the liver, thus becoming a serious link of inflammation [2]. Monocytes, besides endothelial cells, are the main cells that have a role of connecting hemostatic processes and inflammatory phenomena [3]. Blood platelets, besides hemostatic properties, have the features of inflammatory cells. Activated platelets present on their surfaces molecules CD62P and CD63 that transmit stimulation signals when in contact with other cells (platelets, monocytes and lymphocytes). Platelet interaction with inflammatory and immunological cells is intensified by the products of platelet degranulation [3]. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin in the clinical settings of stable coronary artery disease [4], percutaneous coronary intervention, and acute myocardial infarction [5]. In addition, circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction [6]. Increased circulating monocyte-platelet aggregates have also been demonstrated in peripheral venous disease [7], hemodialysis [8], sickle cell disease [9], systemic inflammatory response syndrome [10], septic multiple organ dysfunction syndrome [11], antiphospholipid syndrome, systemic lupus erythematosus, rheumatoid arthritis [12], myelopro- liferative disorders [13], and Alzheimer's disease [14]. High levels of circulating monocyte-platelet aggregates can predict rejection epi- sodes after orthotopic liver transplantation [15]. However, the function of these circulating monocyte-platelet aggregates is not well characterized. At in vivo sites of local injury, leukocyte-platelet aggregates are procoagulant [16]. Thus, the Thrombosis Research 125 (2010) e228–e233 Abbreviations: LC, liver cirrhosis; PMPs, platelet micro-particles; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INR, International Normalized Ratio; FCM, flow cytometry; PBS, phosphate buffered saline. ⁎ Corresponding author. Tel.: +20106261987; fax: +20 2 88 2348609. E-mail address: Douaa_sayed@hotmail.com (D. Sayed). 0049-3848/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2009.12.002 Contents lists available at ScienceDirect Thrombosis Research journal homepage: www.elsevier.com/locate/thromres