Abstract
Background and aimsThrombocytopenia occurs frequently in patients with cirrhosis. The immature platelet fraction (IPF%) is measured to differentiate the causes of thrombocytopenia. To date the relevance of thrombopoietin (TPO) in the context of cirrhosis is unknown. The aim of our study was to investigate the cause of thrombocytopenia in patients with liver cirrhosis by measuring IPF%, TPO and spleen size. In addition we examined the use of IPF% to evaluate the severity of cirrhosis and its complications.MethodsOverall, we included 88 in-patients with cirrhosis in our study. The collected data comprises current health status, blood parameters, severity of cirrhosis evaluated by Child-Pugh score and MELD score, spleen diameter, ascites and esophageal varices. The IPF% was measured using an automatic hematology analyzer. TPO was measured with ELISA.ResultsIPF% (p = 0.003) and spleen diameter (p = 0.001) were significantly higher in patients with thrombocytopenia. There was no significant difference in TPO between patients with and without thrombocytopenia. The mean values of IPF% varied significantly (p = 0.044) in Child-Pugh stages. IPF% was significantly (p = 0.005) elevated in patients with esophageal varices. Moreover, IPF% higher than 3.85% displayed sensitivity of 76.6% and specificity of 52.4% with an area under receiver operating curve characteristics of 0.669 for the presence of esophageal varices.ConclusionOn closer examination of the three compartments known to have an influence on platelet count splenomegaly seems to be the major cause of thrombocytopenia in patients with cirrhosis according to current knowledge. Higher IPF% in patients with thrombocytopenia indicates peripheral consumption of platelets. The relation between spleen diameter and platelet count indicates the spleen to be the major place of platelets’ consumption. TPO did not differ between patients with and without thrombocytopenia. Furthermore, we cannot exclude an influence of impaired thrombopoietin synthesis on platelet counts. The association between IPF% and platelet count suggests that there is physiological regulation of platelets in patients with cirrhosis. In our study IPF% is associated with esophageal varices and the stage of cirrhosis. Further studies are needed to confirm these results.
Highlights
On closer examination of the three compartments known to have an influence on platelet count splenomegaly seems to be the major cause of thrombocytopenia in patients with cirrhosis according to current knowledge
We cannot exclude an influence of impaired thrombopoietin synthesis on platelet counts
In our study IPF% is associated with esophageal varices and the stage of cirrhosis
Summary
Thrombocytopenia is a common complication in patients with liver cirrhosis and its pathogenesis is multifactorial. [1,2] Previous studies have reported the splenic sequestration of platelets to be a consequence of an enlarged spleen due to portal hypertension. [3] recent studies propose that decreased TPO production in the liver and an impaired platelet production in the bone marrow are additional factors. [4,5] Increasing TPO levels and platelet recovery after orthotopic liver transplantation confirm these results as well as the availability of the TPO receptor agonist eltrombopag, which increases platelet counts in patients with liver cirrhosis caused by chronic hepatitis c virus infection. [6,7,8,9] In contrast, other studies have not been able to verify the associations between liver cirrhosis and decreased TPO production. [10,11,12] There are further factors that have an influence on platelet counts, such as anti platelet autoantibodies leading to shortened lifespan by removal via the reticuloendothelial system or chronic alcoholism, leading to the suppression of platelet production in the bone marrow. [13,14] the exact pathogenesis of thrombocytopenia in patients with liver cirrhosis is still unclear.The interpretation of serum TPO levels is complex. [4,12,15,16] The term reticulated platelets describes immature platelets that contain remnants of RNA. [17] In analogy to reticulocytes that are a valid marker of erythropoesis in bone marrow, reticulated platelets, measured as immature platelet fraction using an automated blood cell analyzer, reflect thrombopoesis. [18] The immature platelet fraction is low when there is impaired bone marrow function and is high in case of peripheral consumption or destruction of platelets. [19] it can be used to differentiate between the etiologies of thrombocytopenia. [20] Reticulated platelets have been reported to be lower in patients with liver cirrhosis and thrombocytopenia as compared to patients without. [21] the stage of chronic liver disease can be assessed by measuring the immature platelet fraction. [22] In addition, the development of complications in patients with cirrhosis such as variceal bleeding, ascites, spontaneous bacterial peritonitis or hepatorenal syndrome is associated with poor prognosis. [3] recent studies propose that decreased TPO production in the liver and an impaired platelet production in the bone marrow are additional factors. [21] the stage of chronic liver disease can be assessed by measuring the immature platelet fraction. The aim of our study was to investigate the cause of thrombocytopenia by measuring immature platelet fraction, thrombopoietin and spleen size. We assessed whether immature platelet fraction could be used to evaluate the severity of cirrhosis and its complications. The immature platelet fraction (IPF%) is measured to differentiate the causes of thrombocytopenia. The aim of our study was to investigate the cause of thrombocytopenia in patients with liver cirrhosis by measuring IPF%, TPO and spleen size. In addition we examined the use of IPF% to evaluate the severity of cirrhosis and its complications
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