scholarly journals A Meta-Analysis on the Efficacy of Thrombopoietin (TPO) Agonists in Reducing the Need of Platelet Transfusion before Procedures in Chronic Liver Disease Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2108-2108
Author(s):  
Michael Jaglal ◽  
Damian A. Laber ◽  
Ankita K. Patel ◽  
Mintallah Haider ◽  
Jennifer Eatrides ◽  
...  

Introduction: Chronic liver disease (CLD) results in thrombocytopenia [1]. Depression of thrombopoietin (TPO) levels in CLD leads to thrombocytopenia. Thrombocytopenia increases the risk of bleeding in patients undergoing invasive diagnostic or therapeutic procedures [2]. TPO agonists have been depicted to be safe and efficacious in the treatment of thrombocytopenia due to idiopathic immune thrombocytopenia and aplastic anemia. Several studies have evaluated the use of TPO agonist versus placebo for pre-procedural treatment of thrombocytopenic patients with chronic liver disease. These studies were of limited sample sizes. We conducted a meta-analysis to determine if TPO agonists reduce the need of platelet transfusions before procedures in chronic liver disease patients. Methods: We performed a computerized search of Medline, Cochrane and Google Scholar databases through March 2019 for studies evaluating the efficacy of thrombopoietin (TPO) agonists versus placebo in the treatment of thrombocytopenia of chronic liver disease patients undergoing procedures. We screened 295 studies and only 5 of them met our inclusion and exclusion criteria. Inclusion criteria were studies with adults >18 years old, English literature, randomized controlled trials utilizing a TPO agonists in chronic liver disease patients. Exclusion criteria were studies with patients <18 years old, improper study design (e.g. abstract, commentary, editorials) and literature without available data. The primary study outcomes were proportion of patients responding to TPO agonists in comparison to placebo (an increase of 20000 of platelet count /ul and a value of more than 50000 count/ul). Our secondary outcomes were evaluating the proportion of patients not requiring platelet transfusion and evaluating the percentage of patients who developed a portal venous thrombosis (PVT) on study. Statistical analyses were calculated using Cumulative Meta-Analysis software (version 3.0) Results: The final analysis included 5 studies with a total of 1098 patients. Please see Image 1 for Individual Trial data. The proportion of responders for TPO agonists odds ratio was 0.060 (0.038-0.095) with P value <0.0001. The proportion of patients not requiring transfusion on TPO agonist odds ratio was 0.118 (0.077-0.182) with P value <0.0001. The portal vein thrombosis odds ratio while on TPO agonist was 0.631 (0.175-2.268) with P value of 0.480. All 5 trials demonstrated that TPO agonists compared to placebo significantly increased the platelet count and reduced the need of platelet transfusion pre-procedural with a P-value of <0.0001. The risk of developing PVT in patients receiving TPO agonists was not significantly increased when compared to those receiving placebo. Conclusion: Our analysis shows that TPO-agonists provide significant benefit compared to placebo in regard to increasing platelet count and reducing the need for platelet transfusions. The risk of developing PVT in patients receiving TPO agonists was not significantly increased when compared to those receiving placebo. More trials are needed to validate the comparison for PVT outcome. Figure Disclosures Jaglal: NOVARTIS: Consultancy.

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fred Poordad ◽  
Norah A. Terrault ◽  
Naim Alkhouri ◽  
Wei Tian ◽  
Lee F. Allen ◽  
...  

Aims. Thrombocytopenia complicates the management of patients with chronic liver disease (CLD) undergoing invasive procedures with a bleeding risk. Until recently, prophylactic platelet transfusion was the only treatment option, but has significant safety and efficacy limitations. Phase 3 data demonstrated the superiority of avatrombopag to placebo in reducing platelet transfusions for bleeding, supporting its recent approval. Methods. Integrated analyses of pooled data (N=435) from two randomized, double-blind, placebo-controlled, phase 3 studies assessed the original efficacy endpoints. Additional analyses included subgroup analyses, alternate Baseline platelet count definitions, and another efficacy endpoint. Results. Avatrombopag was superior to placebo in increasing patients not requiring a platelet transfusion or rescue procedure, those achieving a platelet count ≥50 × 109/L on Procedure Day, and the change in platelet counts from Baseline. The avatrombopag treatment effect was consistently positive across clinically important disease and Baseline clinical characteristic subgroups, and using alternate Baseline platelet count cohort definitions. Similarly, more avatrombopag-treated patients achieved ≥50 × 109/L platelets with an increase of ≥20 × 109/L from Baseline. The incidence and severity of adverse events were similar between avatrombopag and placebo. Further, safety data demonstrated a low risk for thromboembolic events and hepatotoxicity. Conclusion. These integrated analyses confirmed the superiority of avatrombopag to placebo in reducing platelet transfusions or rescue procedures for bleeding in patients with thrombocytopenia and CLD scheduled to undergo an invasive procedure, and its tolerable safety profile. Importantly, these data warrant reconsideration of clinical decision making regarding the need to treat thrombocytopenia in patients with CLD. This trial was registered with NCT01972529 and NCT01976104.


2018 ◽  
Vol 6 ◽  
pp. 205031211774522 ◽  
Author(s):  
Arash Akhavan Rezayat ◽  
Malihe Dadgar Moghadam ◽  
Mohammad Ghasemi Nour ◽  
Matin Shirazinia ◽  
Hamidreza Ghodsi ◽  
...  

Background/aims: Non-alcoholic fatty liver disease is one of the most common chronic liver diseases. Some risk factors are known to influence the development of non-alcoholic fatty liver disease, but the effect of tobacco smoking on the progression of non-alcoholic fatty liver disease is controversial. The main goal of this systematic review and meta-analysis is to investigate the association between smoking and non-alcoholic fatty liver disease. Method: Electronic databases (PubMed, Scopus, and ISI Web of Science) were searched to find published articles on non-alcoholic fatty liver disease and smoking until December 2016. All relevant studies were screened by inclusion and exclusion criteria and compatible studies were chosen. The Newcastle–Ottawa Scale was used to assess the methodological quality of eligible articles. Subsequently, information was gathered based on the following: author, publication year, keywords, country, inclusion and exclusion criteria, main results, study design, conclusion, and confounder variables (age, body mass index, gender, ethnicity, and diabetes). Finally, analyses were performed using Comprehensive Meta-Analysis Software. Results: Data were extracted from 20 observational studies (9 cross-sectional, 6 case-control, 4 cohort studies, and 1 retrospective cohort study). A significant association was observed between smoking and non-alcoholic fatty liver disease with a pooled odds ratio of 1.110 (95% confidence interval, 1.028–1.199), p-value = 0.008. The statistical heterogeneity was medium with an I2 of 40.012%, p-heterogeneity = 0.074. Also there was a significant relation between non-alcoholic fatty liver disease and passive smoking with a pooled odds ratio of 1.380 (95% confidence interval, 1.199–1.588; p-value = 0.001; I2 = 59.41; p-heterogeneity = 0.117). Conclusion: Our meta-analysis demonstrated that smoking is significantly associated with non-alcoholic fatty liver disease. Further prospective studies exploring the underlying mechanisms of this association should be pursued. Also passive smoking increases the risk of non-alcoholic fatty liver disease about 1.38-fold. The effects of smoking cigarettes on active smokers (current smoker, former smoker, and total smoker) are less than passive smokers. Further studies are needed to compare the of effects of passive and active smoking on non-alcoholic fatty liver disease.


2021 ◽  
Vol 17 (2) ◽  
pp. 174-179
Author(s):  
Muhammad Javaid Iqbal ◽  
Muhammad Usman ◽  
Mubarak Ali Anjum ◽  
Yasir Yaqoob ◽  
Ghulam Mujtaba Nasir ◽  
...  

Objective: To evaluate the role of Immature platelet fraction in patients with chronic liver disease, a marker for evaluating cirrhotic changes. Methodology: This case control study was conducted at department of Pathology, Aziz Fatima Medical and Dental College, Faisalabad, over a period of Seven months from June 2020 to January 2021. A total of 126 participants were included in the study consisting of 63 patients with chronic liver disease in group A and 63 participants without any known disease in group B as control. The IPF master program in combination with XE-2100 multiparameter automatic hematology analyzer was used to measure the immature platelet fraction. Ethylene diamine tetraacetic acid was used to collect the blood sample for IPF measurement and was maintained till analysis on room temperature. Ten repeated analyses, immediately and after 24 hours were done for reproducibility of IPF%. Results: The mean age of liver disease patients was 52.35 ± 13.64 years and in control group the mean age was 51.62 ± 11.27 years. There was no significant (p-value > 0.05) difference between both groups based on age and gender. The hemoglobin level and red cell count was found to be significantly (p-value < 0.05) reduced in cases group. While white blood cells count was comparable in both groups. The mean platelet count was significantly (p-value < 0.05) less in cases group (163.5 ± 90.4 vs 233.4 ± 54.5 (x10*3/µl). The mean value of immature platelet fraction (IPF%) was significantly (p-value < 0.05) raised in cases group (5.62 ± 2.92 vs 3.06 ± 1.87). The multivariate discriminant analysis (MDA) score showed a significant (p-value < 0.05) association with chronic hepatis as compared to other liver related diseases. Conclusions: In chronic liver disease patients, there is an inverse relationship between platelet count and IPF% with decreased platelet count and increased IPF%. The proposed MDA function can be used to identify the cirrhotic changes in liver disease patients.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hiroaki Nomoto ◽  
Naoki Morimoto ◽  
Kouichi Miura ◽  
Shunji Watanabe ◽  
Yoshinari Takaoka ◽  
...  

Abstract Background Chronic liver disease (CLD) is often complicated by severe thrombocytopenia (platelet count < 50,000/µL). Platelet transfusion has been a gold standard for increasing the platelet count to prevent hemorrhagic events in such patients. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count in such patients when invasive procedures are scheduled. Former studies on lusutrombopag included patients with a platelet count of > 50,000/µL at baseline: the proportions of patients who did not require platelet transfusion were 84–96%, which might be overestimated. Methods The efficacy and safety of lusutrombopag were retrospectively investigated in CLD patients with platelet count of < 50,000/µL, a criterion for platelet transfusion, in real-world settings. We examined the proportion of patients who did not require platelet transfusion in 31 CLD patients, which exceeded a minimum required sample size (21 patients) calculated by 80% power at a significance level of 5%. Lusutrombopag, 3 mg once daily, was administered 8–18 days before scheduled invasive procedures. Results Among 31 patients who received lusutrombopag, 23 patients (74.2%) patients showed a platelet count of ≥ 50,000/µL (Group A) and did not require platelet transfusion. The remaining 8 patients (25.8%) did not reached platelet ≥ 50,000/µL (Group B). The means of platelet increase were 38,000/µL and 12,000/µL in groups A and B, respectively. A low platelet count at baseline was a characteristic of patients in group B. Among 13 patients who repeatedly used lusutrombopag, lusutrombopag significantly increased the platelet count as the initial treatment. When all repeated uses of lusutrombopag were counted among these 13 patients, platelet transfusion was not required in 82.1% (23/28) of treatments. Although one patient showed portal thrombosis after lusutrombopag treatment, the thrombosis was disappeared by anticoagulant treatment for 35 days. The degree of platelet increase with lusutrombopag was larger than that in their previous platelet transfusion. Conclusions The proportion of patients who did not require platelet transfusion was 74.2%, which is smaller than that in former studies which included CLD patients with a platelet count of > 50,000/µL. However, lusutrombopag is effective and safe for CLD patients with a platelet count of < 50,000/µL.


2020 ◽  
Vol 27 (03) ◽  
pp. 455-460
Author(s):  
Tahir Ullah Khan ◽  
Wali Khan ◽  
Sajjad Iqbal

Objectives: To determine the frequency of spontaneous bacterial peritonitis (SBP) in chronic liver disease patients with ascites using proton pump inhibitors (PPI). Study Design: Prospective cohort study. Setting: Medicine Unit-II, Shalamar Hospital Lahore. Period: From 1st January to 30thJune 2017. Materials & Methods: A total of 380 patients enrolled in present study were divided into two groups; PPI group and non PPI group. Each group had 190 patients. We performed an extensive matching in both groups to minimize selection bias and SBP incidence was compared in both groups. Multivariate analysis was applied to sort out the causal relationship between PPI use and SBP. Results: Applying strict exclusion criteria, SBP incidence in chronic liver disease patients with ascites was found significantly high in PPI group than non-PPI group (12.63% vs. 6.84%, P Value 0.002). Moreover, a large no of patients (39.47%) were using PPI for inappropriate indications while acid peptic disease was the most common indication for its use (60.53%). Conclusion: Use of proton pump inhibitors in chronic liver disease patients with ascites significantly increases the risk of spontaneous bacterial peritonitis.


2020 ◽  
Author(s):  
Hiroaki Nomoto ◽  
Naoki Morimoto ◽  
Kouichi Miura ◽  
Shunji Watanabe ◽  
Yoshinari Takaoka ◽  
...  

Abstract Background: Chronic liver disease (CLD) is often complicated by severe thrombocytopenia (platelet count <50,000/µL). Platelet transfusion has been a gold standard for increasing the platelet count to prevent hemorrhagic events in such patients. Lusutrombopag, a thrombopoietin receptor agonist, can increase the platelet count in such patients when invasive procedures are scheduled. However, we have little information on the effect of lusutrombopag in CLD patients with severe thrombocytopenia in real-world settings.Methods: To investigate the efficacy and safety of lusutrombopag in patients with chronic liver disease and severe thrombocytopenia, we retrospectively investigated 26 CLD patients with a platelet count of <50,000/µL. Lusutrombopag, 3 mg once daily, was administered 8-15 days before scheduled invasive procedures.Results: Among 26 patients who received lusutrombopag, 19 patients (73.1%) patients showed a platelet count of ≥50,000/µL (Group A) and did not require platelet transfusion. The remaining 7 patients (26.9%) did not reached platelet ≥50,000/µL (Group B). The means of platelet increase were 36,000/µL and 13,000/µL in groups A and B, respectively. A low platelet count at baseline was a characteristic of patients in group B. Among 13 patients who repeatedly used lusutrombopag, lusutrombopag significantly increased the platelet count as the initial treatment. No adverse events were noted during or after lusutrombopag treatment. In addition, the degree of platelet increase with lusutrombopag was larger than that in their previous platelet transfusion.Conclusions: Lusutrombopag is effective and safe for CLD patients with a platelet count of <50,000/µL.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 37-38
Author(s):  
A Zoughlami ◽  
J Serero ◽  
G Sebastiani ◽  
M Deschenes ◽  
P Wong ◽  
...  

Abstract Background Patients with compensated advanced chronic liver disease (cACLD) are at higher risk of developing complications from portal hypertension, including esophageal varices (EV). Baveno VI and expanded Baveno VI criteria, based on liver stiffness measurement (LSM) by transient elastography combined with platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for large esophageal varices needing treatment (EVNT). This approach has not been validated in patients with chronic hepatitis B virus (HBV) infection, who have etiology-specific cut-off of LSM for liver fibrosis. Aims We aimed to validate the Baveno VI and expanded Baveno VI criteria for EVNT in HBV patients with cACLD. Methods We performed a retrospective analysis of HBV patients who underwent LSM in 2014–2020. Inclusion criteria were: a) diagnosis of cACLD, defined as LSM &gt;9 kPa; b) availability of EGD and platelets within 1 year of LSM. Baveno VI (LSM &lt;20 kPa and platelets &gt;150,000) and expanded Baveno VI criteria (LSM &lt;25 kPa and platelets &gt;110,000) were tested for EGD sparing. Diagnostic performance of these criteria against gold standard (EGD) was computed and compared to patients with hepatitis C virus (HCV) infection and nonalcoholic steatohepatitis (NASH) etiologies, where these criteria have been widely validated. In these patients, the threshold for cACLD definition was &gt;10 kPa. Results A total of 287 patients (mean age 56, 95% Child A) were included, comprising of 43 HBV (58% on antiviral therapy), 134 HCV and 110 NASH patients. The prevalence of any grade EV and EVNT was 25% and 8% in the whole cohort, with 19% and 5% in HBV patients, respectively. Table 1 reports diagnostic performance, spared EGD and missed EVNT according to non-invasive criteria and cACLD etiology. Both Baveno VI and expanded Baveno VI criteria performed well in patients with HBV-related cACLD. There was no significant difference on diagnostic performance of these non-invasive criteria across the cACLD etiologies. Conclusions These results support use of non-invasive criteria based on LSM and platelets to spare unnecessary EGD in patients with HBV and cACLD. Baveno VI and expanded Baveno VI criteria can improve resource utilization and avoid invasive testing in context of screening EGD for patients with HBV-related cACLD. Funding Agencies None


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