scholarly journals Thrombocytopenia and Hemostatic Changes in Acute and Chronic Liver Disease: Pathophysiology, Clinical and Laboratory Features, and Management

2021 ◽  
Vol 10 (7) ◽  
pp. 1530
Author(s):  
Rüdiger E. Scharf
Keyword(s):  
Platelet Count ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Bleeding Risk ◽  
Chronic Liver ◽  
Controversial Issues ◽  
Advanced Liver Disease ◽  
Platelet Destruction ◽  
Clinical Consequences ◽  
Hepatic Synthesis

Thrombocytopenia, defined as a platelet count <150,000/μL, is the most common complication of advanced liver disease or cirrhosis with an incidence of up to 75%. A decrease in platelet count can be the first presenting sign and tends to be proportionally related to the severity of hepatic failure. The pathophysiology of thrombocytopenia in liver disease is multifactorial, including (i) splenomegaly and subsequently increased splenic sequestration of circulating platelets, (ii) reduced hepatic synthesis of thrombopoietin with missing stimulation both of megakaryocytopoiesis and thrombocytopoiesis, resulting in diminished platelet production and release from the bone marrow, and (iii) increased platelet destruction or consumption. Among these pathologies, the decrease in thrombopoietin synthesis has been identified as a central mechanism. Two newly licensed oral thrombopoietin mimetics/receptor agonists, avatrombopag and lusutrombopag, are now available for targeted treatment of thrombocytopenia in patients with advanced liver disease, who are undergoing invasive procedures. This review summarizes recent advances in the understanding of defective but at low level rebalanced hemostasis in stable cirrhosis, discusses clinical consequences and persistent controversial issues related to the inherent bleeding risk, and is focused on a risk-adapted management of thrombocytopenia in patients with chronic liver disease, including a restrictive transfusion regimen.

Periprocedural Bleeding Risk Assessment in Chronic Liver Disease

2017 ◽  
Vol 01 (04) ◽  
pp. 306-312
Author(s):  
Brett Fortune ◽  
David Madoff ◽  
Benjamin May
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Blood Product ◽  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Chronic Liver ◽  
Alternative Methods ◽  
Advanced Liver Disease ◽  
Potential Harm ◽  
Clotting Disorder

AbstractInvasive procedures are common in the management of cirrhosis-related chronic liver disease (CLD). Assessing bleeding risk prior to these procedures is challenging because of commonly seen laboratory abnormalities among traditional testing used to evaluate bleeding risk in patients with advanced liver disease. However, this ‘coagulopathy’ seen in advanced liver disease is not a true bleeding or clotting disorder. The prothrombin time/international normalized ratio (PT/INR) test is frequently elevated in CLD patients, but has been shown to poorly correlate with bleeding risk in this population. A traditional interpretation of this laboratory test can lead to unnecessary transfusion of blood product, procedure delay, or even potential harm to the patient. An understanding of the ‘coagulopathy’ of advanced liver disease and alternative methods, to more accurately assess bleeding risk, allows clinicians to treat safely CLD patients.

scholarly journals A72 NON-INVASIVE PREDICTION OF ESOPHAGEAL VARICES BY TRANSIENT ELASTOGRAPHY AND PLATELET COUNT IN PATIENTS WITH HEPATITIS B AND ADVANCED CHRONIC LIVER DISEASE: VALIDATION OF BAVENO VI AND EXPANDED BAVENO VI CRITERIA

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 37-38
Author(s):  
A Zoughlami ◽  
J Serero ◽  
G Sebastiani ◽  
M Deschenes ◽  
P Wong ◽  
...  
Keyword(s):  
Platelet Count ◽  
Liver Disease ◽  
Hepatitis B ◽  
Chronic Liver Disease ◽  
Esophageal Varices ◽  
Diagnostic Performance ◽  
Transient Elastography ◽  
Chronic Liver ◽  
Non Invasive ◽  
Chronic Hepatitis B Virus

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

Chronic liver disease, thrombocytopenia and procedural bleeding risk; are novel thrombopoietin mimetics the solution?

Platelets ◽  
2018 ◽  
Vol 30 (6) ◽  
pp. 796-798 ◽  
Author(s):  
Sven R. Olson ◽  
Steven Koprowski ◽  
Justine Hum ◽  
Owen J.T. McCarty ◽  
Thomas G. DeLoughery ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Bleeding Risk ◽  
Chronic Liver

Immature Platelet Fraction in Patients with Chronic Liver Disease, A Marker for Evaluating Cirrhotic Changes.

2021 ◽  
Vol 17 (2) ◽  
pp. 174-179
Author(s):  
Muhammad Javaid Iqbal ◽  
Muhammad Usman ◽  
Mubarak Ali Anjum ◽  
Yasir Yaqoob ◽  
Ghulam Mujtaba Nasir ◽  
...  
Keyword(s):  
Platelet Count ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
White Blood Cells ◽  
Chronic Liver ◽  
Control Group ◽  
P Value ◽  
Master Program ◽  
Immature Platelet Fraction ◽  
The Mean

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.

Thrombopoietin Receptor Agonists in Patients with Chronic Liver Disease

2020 ◽  
Vol 46 (06) ◽  
pp. 682-692
Author(s):  
Saro Khemichian ◽  
Norah A. Terrault
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Invasive Procedure ◽  
Bleeding Risk ◽  
Chronic Liver ◽  
Bleeding Complications ◽  
Invasive Procedures ◽  
Platelet Counts ◽  
Receptor Agonists ◽  
Platelet Transfusions

AbstractThrombocytopenia is one of the most common hematologic complications in cirrhosis. Despite limited data linking platelet count and bleeding risk in patients with cirrhosis, the use of platelets transfusions for invasive procedures has been a common practice. Recently, thrombopoietin (TPO) receptor agonists have been approved for use in patients with chronic liver disease (CLD) undergoing invasive procedures. The aim of this study was to review current literature on bleeding risk in patients with cirrhosis and the use of platelet transfusions and TPO receptor agonists in the context of invasive procedures. PubMed search was conducted to find articles relating to cirrhosis, thrombocytopenia, and new novel treatments for this condition. Search terms included CLD, cirrhosis, thrombocytopenia, bleeding, thrombosis, coagulopathy, hemostasis, and TPO receptor agonists. Romiplostim, eltrombopag, avatrombopag, and lusutrombopag are approved TPO receptor agonists, with avatrombopag and lusutrombopag specifically approved for use in patients with CLD undergoing invasive procedures. In patients with platelet counts < 50,000/mm3, avatrombopag and lusutrombopag increased the platelet counts above this threshold in the majority of treated patients and reduced the frequency of platelet transfusions. At the approved doses, incidence of thrombosis was not increased and therapies were well tolerated. Studies were not powered to assess whether risk of bleeding complications was reduced and the fundamental question of whether correction of thrombocytopenia is warranted in patients undergoing invasive procedures remains unanswered. The use of TPO receptor agonists has resulted in less requirement for platelet transfusions. In patients with cirrhosis undergoing invasive procedures for whom platelet transfusion is planned, TPO receptor agonists are an alternative and avoid the risks associated with transfusions. However, there is need for a thoughtful approach to manage bleeding risk in patients with cirrhosis undergoing procedures, with the consideration of a comprehensive hemostatic profile, the severity of portal hypertension, and the complexity of the invasive procedure to guide decisions regarding transfusions or use of TPO receptor agonists.

scholarly journals Lusutrombopag is effective and safe in patients with chronic liver disease and severe thrombocytopenia: a multicenter retrospective study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hiroaki Nomoto ◽  
Naoki Morimoto ◽  
Kouichi Miura ◽  
Shunji Watanabe ◽  
Yoshinari Takaoka ◽  
...  
Keyword(s):  
Platelet Count ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Platelet Transfusion ◽  
Chronic Liver ◽  
Severe Thrombocytopenia ◽  
Invasive Procedures ◽  
Significance Level ◽  
Group A ◽  
Group B

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.

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