Date Published: February 15, 2019
Publisher: Public Library of Science
Author(s): Hitomi Takada, Masayuki Kurosaki, Hiroyuki Nakanishi, Yuka Takahashi, Jun Itakura, Kaoru Tsuchiya, Yutaka Yasui, Nobuharu Tamaki, Kenta Takaura, Yasuyuki Komiyama, Mayu Higuchi, Youhei Kubota, Wann Wang, Mao Okada, Takao Shimizu, Keiya Watakabe, Nobuyuki Enomoto, Namiki Izumi, Yun-Wen Zheng.
The present study aimed to report our real-life experience of the TPO receptor agonist lusutrombopag for cirrhotic patients with low platelet counts.
We studied platelet counts in 1,760 cirrhotic patients undergoing invasive procedures at our hospital between January 2014 and December 2017. In addition, we studied 25 patients who were administered lusutrombopag before invasive procedures between June 2017 and January 2018. Effectiveness of lusutrombopag to raise platelet counts and to avoid transfusion and treatment-related adverse events were analyzed.
In 1,760 cirrhotic patients without lusutrombopag prior to invasive procedures, proportion of patients whose platelet counts <50,000/μL and needed platelet transfusions were 66% (n = 27/41) for radiofrequency ablation, 43% (n = 21/49) for transarterial chemoembolization, and 55% (n = 21/38) for endoscopic injection sclerotherapy / endoscopic variceal ligation, respectively. In 25 cirrhotic patients treated by lusutrombopag prior to the invasive procedures, platelet counts significantly increased compared with baseline (82,000 ± 26,000 vs. 41,000 ± 11,000/μL) (p < 0.01). Out of 25 patients, only 4 patients (16%) needed platelet transfusion before the invasive procedures. The proportion of patients with low platelet count and who needed platelet transfusions was significantly low in patients treated with lusutrombopag compared to those not treated with lusutrombopag (16% (4/25) vs. 54% (69/128), p = 0.001). Platelet counts after lusutrombopag treatment and prior to invasive procedures were lower in patients with a baseline platelet count ≤30,000/μL (n = 8) compared with those with a baseline platelet count >30,000/μL (n = 17) (50,000 ± 20,000 vs 86,000 ± 26,000/μL, p = 0.002). Patients with a baseline platelet count ≤30,000/μL with spleen index (calculated by multiplying the transverse diameter by the vertical diameter measured by ultrasonography) ≥40 cm2 (n = 3) had a lower response rate to lusutrombopag compared to those with spleen index <40 cm2 (n = 5) (0% vs. 100%, p = 0.02). Hemorrhagic complication was not observed. Recurrence of portal thrombosis was observed and thrombolysis therapy was required in one patient who had prior history of thrombosis. Lusutrombopag is an effective and safe drug for thrombocytopenia in cirrhotic patients, and can reduce the frequency of platelet transfusions.
In patients with chronic liver disease, thrombocytopenia is reportedly caused by decreased thrombopoietin (TPO) production in the impaired liver, accelerated platelet destruction due to an enlarged spleen, and decreased hematopoietic ability of the bone marrow as a result of alcohol use or viral infection. The frequency of thrombocytopenia tends to increase with the degree of exacerbated hepatic function. Platelet reduction (platelet count <150,000/μL) in patients with liver cirrhosis is as high as 76% compared with 6% in patients without cirrhosis[1, 2]. Complications including liver cancer, gastroesophageal varices, ascites, and hepatic encephalopathy are common and require frequent invasive procedures in patients with chronic liver disease. Therefore, thrombocytopenia is an important problem that must be treated prior to these procedures. In the present study, we confirmed that lusutrombopag treatment was safe and effective in cirrhotic patients with low platelet counts to increase the platelet count before the invasive procedure and to avoid transfusion. There have been several Japanese reports on the efficacy and safety of lusutrombopag in actual clinical use but the number of patients are small. This study is the first to summarize the characteristics of complete and non-complete response to lusutrombopag. A stratified study with baseline platelet counts and spleen index revealed that patients with a baseline platelet count ≤30,000/μL with spleen index ≥40 cm2 had a lower response rate to lusutrombopag compared to others. Spleen index was 50, 56, and 56 cm2 in these patients, respectively. The reason for the low response rates in these patients is unclear. One possible reason may be that platelet production was increased but a large fraction of platelets were sequestered in the spleen, resulting in poor platelet increments. In this subgroup of patients, optimal number of days of lusutrombopag therapy before the invasive procedure needs to be determined and more realistically, other treatments for thrombocytopenia including splenectomy, PSE, TIPS, and platelet transfusions may be considered. Source: http://doi.org/10.1371/journal.pone.0211122