Platelet Transfusion Improves Liver Function in Patients with Chronic Liver Disease and Cirrhosis

Maruyama, Takehito; Murata, Soichiro; Takahashi, Kazuhiro; Tamura, Takafumi; Nozaki, Reiji; Ikeda, Naoya; Fukunaga, Kiyoshi; Oda, Tatsuya; Sasaki, Ryoko; Ohkohchi, Nobuhiro

doi:10.1620/tjem.229.213

Cited by 47 publications

(43 citation statements)

References 40 publications

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“…This clinical trial was a non-controlled, non-randomized study, in which only 6 patients were eventually analyzed. 14 …”

Section: 54mentioning

confidence: 99%

“…10 We also reported that platelets have a preventive effect on the progression of liver fibrosis in vitro and in vivo and that the increase in platelets induced by platelet transfusion can improve the liver function of patients with CLD and cirrhosis in a clinical setting. [11][12][13][14] In addition, it was reported that splenectomy, which is a platelet increment therapy, contributes to improvement of liver function. 15 However, there are many contradictory reports that platelets have harmful effects on liver fibrosis.…”

Section: Introductionmentioning

confidence: 99%

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Novel functions of platelets in the liver

Kurokawa

Zheng

Ohkohchi

2016

J of Gastro and Hepatol

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Platelets contain not only proteins needed for hemostasis but also many growth factors that are required for organ development, tissue regeneration, and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, is due to various causes, such as decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis and the role of platelets in CLD are poorly understood. Thus, in this paper, the experimental evidence for platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. Platelets improve liver fibrosis by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cAMP is increased by adenosine through its receptors on hepatic stellate cells, thereby resulting in inactivation of these cells. Adenosine is produced by degradation of adenine nucleotides, which are stored in abundance within the dense granules of platelets. The regenerative effect of platelets in the liver consists of three mechanisms: a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these experiments, a clinical trial suggested that the increase in platelets induced by platelet transfusion improved liver function in patients with CLD in a clinical setting.We highlight the current knowledge concerning the role of platelets in CLD and expect to open a novel avenue for application of these clinical therapies to treat liver disease.

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“…This clinical trial was a non-controlled, non-randomized study, in which only 6 patients were eventually analyzed. 14 …”

Section: 54mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel functions of platelets in the liver

Kurokawa

Zheng

Ohkohchi

2016

J of Gastro and Hepatol

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“…19 In 10 patients with chronic liver disease, platelet transfusion improved distinct parameters of liver function, although adverse events related to platelet transfusion could be seen as well. 20 One major achievement in the understanding of platelets and their defects in terms of tissue repair has been made in the field of liver pathophysiology. In a mouse model, Lesurtel et al 21 identified platelet-derived serotonin as the key player for hepatic regeneration.…”

mentioning

confidence: 99%

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Gawaz

Vogel

2013

Blood

167

129

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Besides mediating primary hemostasis and thrombosis, platelets play a critical role in tissue repair and regeneration. They regulate fundamental mechanisms involved in the healing process including cellular migration, proliferation, and angiogenesis. Control of apoptosis/cell survival and interaction with progenitor cells, which are clinically relevant but poorly understood aspects of platelets in tissue repair, will be highlighted in this review. Gaining deeper insight into the less well-characterized molecular mechanisms is necessary to develop new therapeutic platelet-based options.

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“…However, platelet increment therapies, such as splenectomy and platelet transfusion, have been reported to have adverse effects, although they have ameliorating effects for CLD and cirrhosis. In a previous clinical study, we revealed the direct effect of platelet transfusion on the improvement of indicators of liver function (Maruyama et al 2013). However, platelet transfusion often causes adverse events, such as PTR and pruritus.…”

Section: Discussionmentioning

confidence: 91%

“…We hypothesized that platelet transfusion therapy would improve liver function in humans (Murata et al 2007). In a previous clinical study, we revealed the direct effect of platelet transfusion on the improvement of indicators of liver function, i.e., albumin and cholinesterase, in patients with CLD and LC (Maruyama et al 2013). The platelet counts in the transfused patients returned to the predose counts one week after the transfusion.…”

Section: Introductionmentioning

confidence: 95%

Stable Liver Function during Long-Term Administration of Eltrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease

Kurokawa

Murata

Ohkohchi

2016

Tohoku J. Exp. Med.

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Liver cirrhosis is the end stage of chronic liver disease, but no definitive pharmacological treatment is currently available. It has been reported that thrombopoietin (TPO) promotes liver regeneration and improves liver cirrhosis by increasing platelet count. We have shown the direct effect of platelet transfusion on the improvement of liver function in patients with chronic liver disease. However, platelet transfusion often causes adverse events, such as platelet transfusion refractoriness and pruritus. Therefore, we conducted an exploratory clinical trial and administered eltrombopag, an orally bioavailable, small-molecule, non-peptide TPO receptor agonist that has been approved for the treatment of chronic idiopathic thrombocytopenic purpura. The study included five male patients, aged from 49 to 75 years (57.6 ± 10.4 years), with both chronic liver disease and hepatitis C virus infection, who presented with thrombocytopenia but without cancer. Eltrombopag, ranged from 6.25 to 50 mg/day (18.75 ± 18.22 mg/day), was administrated to the five patients during six months. All of the patients maintained platelet counts between 10 and 15 × 10 10 /L during the study. The indicators of liver function in patients were stable throughout the clinical trial, although we had predicted the same degree of the improvement of liver function, compared to platelet transfusion. Importantly, the liver volumes were also stable, and no cancerous lesions were observed. These results indicate the safety of long-term eltrombopag administration for patients with chronic liver disease and hepatitis C virus infection.

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Platelet Transfusion Improves Liver Function in Patients with Chronic Liver Disease and Cirrhosis

Cited by 47 publications

References 40 publications

Novel functions of platelets in the liver

Novel functions of platelets in the liver

Platelets in tissue repair: control of apoptosis and interactions with regenerative cells

Stable Liver Function during Long-Term Administration of Eltrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease

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