Circulating platelet derived microparticles are not increased in patients with cirrhosis
Authors: Pierre-Emmanuel Rautou, Anne-Clémence Vion, Dominique Valla, Chantal M. Boulanger
Journal: Journal of Hepatology (2013)

Coagulopathy in cirrhosis – The role of the platelet in hemostasisJournal of HepatologyVol. 59Issue 4PreviewCirrhotic patients are at increased risk of bleeding, particularly gastrointestinal bleeding, as a consequence of portal hypertension and/or coagulopathy attributed to liver synthetic dysfunction. Paradoxically, they are also at risk of thrombosis, predominantly in the splanchnic circulation, especially when platelet counts are increased by transfusion or drug therapy [1,2]. A major problem in clinical practice is the inadequacy of coagulation tests, which do not predict bleeding or thrombotic events, but may result in the inappropriate administration of therapies (e.g., plasma transfusions prior to procedures). Full-Text PDF Open AccessReply to: “Circulating platelet derived microparticles are not increased in patients with cirrhosis”Journal of HepatologyVol. 59Issue 4PreviewWe thank Dr. Rautou et al. for their interest in our Snapshot review (in which we sought to summarize the important role that platelets play in mediating coagulation and thrombosis in patients with cirrhosis) [1]. We proposed that microparticles could have important effects on coagulation and thrombosis in these clinical settings. We mentioned the possibility of circulating cell-derived, and by inference (given the current state of the field), platelet microparticles as possible mediators of inflammation. Full-Text PDF Open Access In their Snapshot, Tapper, Robson, and Malik suggest that circulating platelet-derived microparticles are increased in cirrhosis as a function of systemic inflammation [[1]Tapper E.B. Robson S.C. Malik R. Coagulopathy in cirrhosis – the role of the platelet in hemostasis.J Hepatol. 2013; 59: 889-890Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar]. Ogasawara and colleagues observed higher levels of circulating platelet microparticles in 22 patients with cirrhosis as compared to 17 healthy controls [[2]Ogasawara F. Fusegawa H. Haruki Y. Shiraishi K. Watanabe N. Matsuzaki S. Platelet activation in patients with alcoholic liver disease.Tokai J Exp Clin Med. 2005; 30: 41-48PubMed Google Scholar]. However, the results of two other independent studies assessing circulating platelet microparticle levels in patients with cirrhosis do not concur. Sayed and colleagues included 60 patients with hepatitis C related cirrhosis and 20 healthy controls [[3]Sayed D. Amin N.F. Galal G.M. Monocyte-platelet aggregates and platelet micro-particles in patients with post-hepatitic liver cirrhosis.Thromb Res. 2010; 125: e228-e233Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar]. Platelet microparticle levels, expressed as a percentage of the total platelet count, were not different between patients with cirrhosis and controls [[3]Sayed D. Amin N.F. Galal G.M. Monocyte-platelet aggregates and platelet micro-particles in patients with post-hepatitic liver cirrhosis.Thromb Res. 2010; 125: e228-e233Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar]. When calculating their circulating concentration, one can conclude that the platelet microparticle level was even lower in patients with cirrhosis than in controls (14.2 × 109/L vs. 36.5 × 109/L, respectively). Our group also did not observe any difference in circulating levels of platelet microparticles between 26 patients with cirrhosis and 30 healthy controls [[4]Rautou P.E. Bresson J. Sainte-Marie Y. Vion A.C. Paradis V. Renard J.M. et al.Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis.Gastroenterology. 2012; 143: 166-176Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar]. In addition, there was no correlation between circulating levels of platelet derived microparticles (CD41+) and inflammatory markers, either in the pilot cohort (C-reactive protein: Spearman correlation coefficient = 0.412, p = 0.071, n = 20; leukocytes: Spearman correlation coefficient = 0.272, p = 0.179, n = 26) or in the additional cohort (C-reactive protein: Spearman correlation coefficient = 0.211, p = 0.129, n = 53; leukocytes: Spearman correlation coefficient = 0.068, p = 0.597, n = 63). Therefore, the currently available data demonstrate that platelet derived microparticles are not systematically increased in patients with cirrhosis and likely do not contribute to the procoagulant imbalance associated with cirrhosis. Certain subpopulations of microparticles also express tissue factor, the primary initiator of coagulation, at their surface. These microparticles are highly procoagulant [[5]Rautou P.E. Mackman N. Microvesicles as risk markers for venous thrombosis.Exp Rev Hematol. 2013; 6: 91-101Crossref PubMed Scopus (46) Google Scholar]. Platelets are not a major source of tissue factor positive microparticles in healthy individuals and patients [[6]Owens 3rd, A.P. Mackman N. Microparticles in hemostasis and thrombosis.Circ Res. 2011; 108: 1284-1297Crossref PubMed Scopus (635) Google Scholar]. It remains to be determined whether these circulating tissue factor positive microparticles are increased in patients with cirrhosis and contribute to the procoagulant imbalance in this setting. This work was supported by the Société Nationale Française de Gastroentérologie, the Association Française pour l’Étude du Foie, and the Agence Nationale pour la Recherche (ANR-12-EMMA-0012-03). The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.