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      Serum Thrombopoietin Levels and Its Relationship With Thrombocytopenia in Patients With Cirrhosis

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          Abstract

          Background:

          Patients with cirrhosis usually have thrombocytopenia in discrete levels. The mechanism of thrombocytopenia is thought as splenic sequestration and destruction of platelets, impaired bone marrow generation and diminished hepatic thrombopoietin synthesis.

          Objectives:

          The aim of this study was to evaluate serum thrombopoietin levels and its relationship with thrombocytopenia at patients with cirrhosis.

          Patients and Methods:

          Ninety–two cirrhotic patients and 45 healthy controls without history or findings of pathologies that can effect thrombopoietin levels were enrolled by simple random sampling to patient and control groups of this case control study performed at Eskisehir-Turkey. Thrombopoietin was measured in serum samples with a solid phase enzyme-linked immune absorbent assay. Additionally, spleen size and volume index were determined.

          Results:

          Platelet counts were lower in patients with cirrhosis (97000 ± 8000/mm 3) than in healthy subjects (240000 ± 51000/mm 3, P < 0.001). Significant difference was determined for platelet counts among child A, B and C stages (Child A vs. Child B P < 0.05 Child A vs. Child C P < 0.001–Child B vs. Child C P < 0.05). Serum TPO concentration was higher (69 ± 12 pg/mL) in cirrhotic group than healthy controls (49 ± 9 pg/ml) (P < 0.05). No significant difference in TPO levels were found among the Child A, B and C stages (64 ± 11 pg/mL, 75 ± 13 pg/mL and 68 ± 10 pg/mL, respectively). Spleen size and SVI was significantly higher in the cirrhotic patients than healthy controls (148 ± 14 mm vs. 98 ± 11 mm, P < 0.001-9167 ± 287 cm 2 vs. 4118 ± 123 cm 2). Significant difference was determined for spleen size and spleen index among child A, B and C stages (Child A vs. Child B P < 0.05 Child A vs. Child C P < 0.001–Child B vs. Child C P < 0.05). TPO levels were significantly different between cirrhotic patients with platelet levels below 50.000/mm 3 (n = 16, plt-count: 41000 ± 8300/mm 3, TPO levels: 73 ± 7 pg/mL) and above 50.000/mm 3 (n = 76, plt-count: 105000 ± 9500/mm 3, TPO levels: 65 ± 10 pg/mL) (P < 0.01). In correlation analysis, there was a strong negative correlation between platelet count-spleen size (P < 0.001, r = -0.74) and platelet count–serum TPO levels (P < 0.001, r = -0.71).

          Conclusions:

          Our results suggest that liver cirrhosis does not cause impaired thrombopoietin production even in the late stage of disease. Thrombopoietin has no contribution for the occurrence of thrombocytopenia in cirrhosis; splenic sequestration seems to be the main factor.

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          Most cited references29

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          Transection of the oesophagus for bleeding oesophageal varices.

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            Management of thrombocytopenia due to liver cirrhosis: a review.

            Thrombocytopenia is a common complication in liver disease and can adversely affect the treatment of liver cirrhosis, limiting the ability to administer therapy and delaying planned surgical/diagnostic procedures because of an increased risk of bleeding. Multiple factors, including splenic sequestration, reduced activity of the hematopoietic growth factor thrombopoietin, bone marrow suppression by chronic hepatitis C virus infection and anti-cancer agents, and antiviral treatment with interferon-based therapy, can contribute to the development of thrombocytopenia in cirrhotic patients. Of these factors, the major mechanisms for thrombocytopenia in liver cirrhosis are (1) platelet sequestration in the spleen; and (2) decreased production of thrombopoietin in the liver. Several treatment options, including platelet transfusion, interventional partial splenic embolization, and surgical splenectomy, are now available for severe thrombocytopenia in cirrhotic patients. Although thrombopoietin agonists and targeted agents are alternative tools for noninvasively treating thrombocytopenia due to liver cirrhosis, their ability to improve thrombocytopenia in cirrhotic patients is under investigation in clinical trials. In this review, we propose a treatment approach to thrombocytopenia according to our novel concept of splenic volume, and we describe the current management of thrombocytopenia due to liver cirrhosis.
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              Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia.

              This study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sysmex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 × 10⁹/L, P < .01), whereas IPF percentage was greater (29.2% vs 3.2%, P < .01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-FcγRIII antibody, had corresponding A-IPF responses. Seven of 7 patients responding to RhoD immuneglobulin (anti-D) and 6 of 8 responding to intravenous immunoglobulin (IVIG) did not have corresponding increases in A-IPF, but 2 with IVIG and 1 with IVIG anti-D did. This supports inhibition of platelet destruction as the primary mechanism of intravenous anti-D and IVIG, although IVIG may also enhance thrombopoiesis. Plasma glycocalicin, released during platelet destruction, normalized as glycocalicin index, was higher in ITP patients than controls (31.36 vs 1.75, P = .001). There was an inverse correlation between glycocalicin index and A-IPF in ITP patients (r² = -0.578, P = .015), demonstrating the relationship between platelet production and destruction. Nonresponders to thrombopoietic agents had increased megakaryocytes but not increased A-IPF, suggesting that antibodies blocked platelet release. In conclusion, A-IPF measures real-time thrombopoiesis, providing insight into mechanisms of treatment effect.
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                Author and article information

                Journal
                Hepat Mon
                Hepat Mon
                10.5812/hepatmon
                Kowsar
                Hepatitis Monthly
                Kowsar
                1735-143X
                1735-3408
                05 May 2014
                May 2014
                : 14
                : 5
                : e18556
                Affiliations
                [1 ]Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
                [2 ]Department of Internal Medicine, Division of Rheumotology, Faculty of Medicine, Eskişehir Osmangazi University, Eskisehir, Turkey
                [3 ]Biochemistry Department, Pharmacy Faculty, Anadolu University, Eskisehir, Turkey
                Author notes
                [* ]Corresponding Author: Tuncer Temel, Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey. Tel: +90-2222392979, Fax: +90-2222393772, E-mail: ttemel@ 123456ogu.edu.tr
                Article
                10.5812/hepatmon.18556
                4071317
                20464e3b-2055-4f23-87e5-ab7509c8fb6d
                Copyright © 2014, Kowsar Corp.; Published by Kowsar Corp.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 February 2014
                : 22 March 2014
                : 13 April 2014
                Categories
                Research Article

                Infectious disease & Microbiology
                liver cirrhosis,thrombocytopenia,thrombopoietin
                Infectious disease & Microbiology
                liver cirrhosis, thrombocytopenia, thrombopoietin

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