Oral thrombopoietin receptor agonists are used to treat thrombocytopenia in patients with chronic liver disease who are scheduled for invasive procedures. The efficacy of lusutrombopag based on the pretreatment platelet count was investigated.

Patients treated at nine hospitals from December 2015 to December 2023 were included. Efficacy was assessed by comparing the proportion of patients achieving a platelet count ≥ 50 000/μL and the change in platelet count.

Seventy patients were eligible for evaluation. Patients with a pretreatment platelet count < 40 000/μL had a significantly lower rate of achieving a platelet count of ≥ 50 000/μL than those with a pretreatment count of 40 000-50 000/μL (62.5% vs. 84.2%, p = 0.038); however, there was no significant difference in the change in platelet count (25 700 vs. 24 400/μL, p = 0.972). Patients with viral-related cirrhosis showed a significantly greater change in platelet count than the others (29 100 vs. 19 200/μL, p = 0.012). For patients receiving multiple lusutrombopag treatments, the change in platelet count was significantly lower in the second treatment than in the first treatment (26 900 vs. 20 800/μL, p = 0.041). The main adverse event observed was thrombosis (2.9%).

Lusutrombopag increases platelet count regardless of pretreatment levels, but efficacy, defined as achieving a platelet count of ≥ 50 000/μL, may be insufficient in patients with a pretreatment platelet count < 40 000/μL. Additionally, patients with non-viral liver disease responded less well to treatment compared to those with viral liver disease. Therefore, treatment strategies should be tailored based on pretreatment platelet counts and the etiology of liver disease.

A common cause of mild thrombocytopenia is chronic liver disease, the most common etiology being metabolic dysfunction-associated steatotic liver disease (MASLD). Mild thrombocytopenia is a well-defined, independent marker of hepatic fibrosis in patients with chronic liver disease. Currently, there is a paucity of information available to characterize perioperative risk in patients with MASLD; therefore, the characterization of perioperative morbidity is paramount. We used a platelet threshold of 150×10 9 as a surrogate for fibrosis in patients undergoing laparoscopic cholecystectomy to study its effect on perioperative complications and mortality.

We queried the American College of Surgeons National Surgical Quality Improvement Program database for laparoscopic cholecystectomies occurring from 2005 through 2018. Demographic differences between patients with and without thrombocytopenia were evaluated using the t test or the χ 2 test, whereas adjusted and unadjusted differences in outcome risk were evaluated using log-binomial regression models.

We identified 437,630 laparoscopic cholecystectomies of which 6.9% included patients with thrombocytopenia. Patients with thrombocytopenia were more often males, older, and with chronic disease. Patients with thrombocytopenia and higher Aspartate Aminotransferase to Platelet Ratio Index scores had 30-day mortality rates risk ratio of 5.3 (95% CI: 4.8-5.9), with higher complication rates risk ratio of 2.4 (95% CI: 2.3-2.5). The most frequent complications included the need for transfusion, renal, respiratory, and cardiac.

Perioperatively, patients with mild thrombocytopenia undergoing laparoscopic cholecystectomy had higher mortality rates and complications compared with patients with normal platelet counts. Thrombocytopenia may be a promising, cost-effective tool to identify patients with MASLD and estimate perioperative risk, especially if used in high-risk populations.

The phase 4 observational cohort study assessed the effectiveness and safety of the thrombopoietin receptor agonist avatrombopag in patients with chronic liver disease (CLD) and thrombocytopenia undergoing a procedure. Patients with CLD may have thrombocytopenia, increasing the risk of periprocedural bleeding. Prophylactic platelet transfusions used to reduce this risk have limitations including lack of efficacy and transfusion-associated reactions. Prophylactic thrombopoietin receptor agonists have been shown to increase platelet counts and decrease platelet transfusions. Effectiveness was assessed by change from baseline in platelet count and proportion of patients needing a platelet transfusion. Safety was assessed by monitoring adverse events (AEs). Of 50 patients enrolled, 48 were unique patients and 2 patients were enrolled twice for separate procedures. The mean (standard deviation) change in platelet count from baseline to procedure day was 41.1 × 109/L (33.29 × 109/L, n = 38), returning to near baseline at the post-procedure visit (change from baseline -1.9 × 109/L [15.03 × 109/L], n = 11). The proportion of patients not requiring a platelet transfusion after baseline and up to 7 days following the procedure was 98% (n = 49). Serious AEs were infrequent (n = 2 [4%]). No treatment-emergent AEs were considered related to avatrombopag. There were 2 mild bleeding events, no thromboembolic events or deaths, and no patients received rescue procedures (excluding transfusions). This study found that in a real-world setting, treatment with avatrombopag was well tolerated, increased the mean platelet count by procedure day, and reduced the need for intraoperative platelet transfusions in patients with CLD and thrombocytopenia.

Over the last decades, individualized approaches and a better understanding of coagulopathy complexity in end-stage liver disease (ESLD) patients has evolved. The risk of both thrombosis and bleeding during minimally invasive interventions or surgery is associated with a worse outcome in this patient population. Despite deranged quantitative and qualitative coagulation laboratory parameters, prophylactic coagulation management is unnecessary for patients who do not bleed. Transfusion of red blood cells (RBCs) and blood products carries independent risks for morbidity and mortality, including modulation of the immune system with increased risk for nosocomial infections. Optimal coagulation management in these complex patients should be based on the analysis of standard coagulation tests (SCTs) and viscoelastic tests (VETs). VETs represent an individualized approach to patients and can provide information about coagulation dynamics in a concise period of time. This narrative review will deliver the pathophysiology of deranged hemostasis in ESLD, explore the difficulties of evaluating the coagulopathies in liver disease patients, and examine the use of VET assays and management of coagulopathy using coagulation factors. Methods: A selective literature search with PubMed as the central database was performed with the following.

Chronic liver disease (CLD) related thrombocytopenia increases the risk of bleeding and poor prognosis. Many liver disease patients require invasive procedures or surgeries, such as liver biopsy or endoscopic variceal ligation, and most of them have lower platelet counts, which could aggravate the risk of bleeding due to liver dysfunction and coagulation disorders. Unfortunately, there is no defined treatment modality for CLD-induced thrombocytopenia. Recombinant human thrombopoietin (rhTPO) is commonly used to treat primary immune thrombocytopenic purpura and thrombocytopenia caused by solid tumor chemotherapy; however, there are few reports on the use of rhTPO in the treatment of CLD-related thrombocytopenia.

To evaluate the efficacy of rhTPO in the treatment of patients with CLD-associated thrombocytopenia undergoing invasive procedures.

All analyses were based on the retrospective collection of clinical data of patients with CLD who were treated in the Department of Infectious Diseases at The First Affiliated Hospital of Soochow University between June 2020 and December 2021. Fifty-nine male and 41 female patients with liver disease were enrolled in this study to assess the changes in platelet counts and parameters before and after the use of rhTPO for thrombocytopenia. Adverse events related to treatment, such as bleeding, thrombosis, and disseminated intravascular coagulation, were also investigated.

Among the enrolled patients, 78 (78%) showed a platelet count increase after rhTPO use, while 22 (22%) showed no significant change in platelet count. The mean platelet count after rhTPO treatment in all patients was 101.53 ± 81.81 × 109/L, which was significantly improved compared to that at baseline (42.88 ± 16.72 × 109/L), and this difference was statistically significant (P < 0.001). In addition, patients were further divided into three subgroups according to their baseline platelet counts (< 30 × 109/L, 30-50 × 109/L, > 50 × 109/L). Subgroup analyses showed that the median platelet counts after treatment were significantly higher (P < 0.001, all). Ninety (90%) patients did not require platelet transfusion partially due to an increase in platelet count after treatment with rhTPO. No serious adverse events related to rhTPO treatment were observed. Overall, rhTPO demonstrated good clinical efficacy for treating CLD-associated thrombocytopenia.

rhTPO can improve platelet count, reduce the risk of bleeding, and decrease the platelet transfusion rate, which may promote the safety of invasive procedures and improve overall survival of patients with CLD.

Probing efficacy and safety of lusutrombopag in Chinese chronic liver disease (CLD) and severe thrombocytopenia (PLT < 50 × 10⁹/L) patients undergoing elective invasive procedures.

In this double-blind, parallel-group phase 3 study, 66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days at 9 centers in China. Responders (PLT ≥ 50 × 10⁹/L that increased to ≥ 20 × 10⁹/L from the baseline and not received rescue therapy for bleeding) on Day 8 (the day after seven-day treatment) were assessed. PLT ≥ 50 × 10⁹/L on or after Day 8 and within 2 days before invasive procedure (alternative criteria for not requiring platelet transfusion) were also analyzed. Adverse events (AEs) were recorded.

The proportion of responders on Day 8 was evidently higher (p = 0.0011) in the lusutrombopag group (43.2%, 19/44) versus placebo (4.5%, 1/22). And 72.7% (32/44) patients receiving lusutrombopag met the alternative criteria for not requiring platelet transfusion, while 18.2% (4/22) in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5 × 10⁹/L, and median time to reach maximum was 14.5 days. Compared with placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% versus 13.6%), and only one patient had thrombotic-related AE. Overall, the incidence of treatment-emergent AEs was comparable between two groups.

Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement, and documented a safety profile like the placebo in CLD and severe thrombocytopenia patients in a Chinese cohort undergoing elective invasive procedures. Chinese clinical trial registration number: CTR20192384.

Thrombocytopenia is a common and unsolved problem in myelodysplastic syndrome (MDS) patients; we aimed to summarize the evidence of TPO-RA treatment for heath-related quality of life (HRQoL) and platelet transfusion burden of MDS patients. We searched Pubmed, Web of Science, EMBASE, and CENTRAL for randomized clinical trials (RCTs) comparing TPO-RA to placebo in MDS published until July 31, 2021. A random-effect model was used. Eight RCTs with 908 patients were identified. Only three RCTs involving eltrombopag reported HRQoL, and all three studies treated HRQoL as a secondary outcome. In these three RCTs, the HRQoL instruments used in each study were different. However, this outcome cannot be meta-analyzed because some studies did not provide complete data. Subsequent clinical trials should pay more attention to this. Compared to placebo, TPO-RA did not affect platelet transfusion incidence 0.83 (95% CI 0.60-1.15). There was no evidence for subgroup differences in the analyses of different types of TPO-RA, different additional agent, and different types of MDS risk groups. However, platelet transfusion units (RR = 0.68, 95% CI 0.53 to 0.84) were significantly decreased. The RR of patients who did not require platelet transfusion for 56 or more consecutive days was not different between groups (RR = 0.98, 95% CI 0.41 to 2.34). TPO-RA may decrease platelet transfusion units in MDS patients with thrombocytopenia. But the significance of this finding should be interpreted with caution, because too few studies were meta-analyzed.

Chronic liver disease is characterized by several hematological derangements resulting in a complex and barely rebalanced haemostatic environment. Thrombocytopenia is the most common abnormality observed in these patients and recent advances have led to researchers focus the attention on the multifactorial origin of thrombocytopenia and on the key role of thrombopoietin (TPO) in its physiopathology. Severe thrombocytopenia (platelet count < 50000/μL) complicates the management of patients with chronic liver disease by increasing the potential risk of bleeding for invasive procedures, which may be therefore delayed or canceled even if lifesaving. In the very last years, the development of new drugs which exceed the limits of the current standard of care (platelet transfusions, either immediately before or during the procedure) paves the way to a new scenario in the management of this population of patients. Novel agents, such as the TPO-receptor agonists avatrombopag and lusutrombopag, have been developed in order to increase platelet production as an alternative to platelet transfusions. These agents have demonstrated a good profile in terms of efficacy and safety and will hopefully allow reducing limitations and risks associated with platelet transfusion, without any delay in scheduled interventions. Altogether, it is expected that patients with chronic liver disease will be able to face invasive procedures with one more string in their bow.

Thrombocytopenia is highly prevalent in patients with chronic liver disease (CLD) and these patients often require invasive procedures that carry a risk of bleeding. To prevent bleeding, guidelines recommend increasing platelet counts in patients with CLD who have thrombocytopenia and are planned to undergo invasive procedures. There are currently two options to increase platelet counts in patients in this setting: platelet transfusion or thrombopoietin receptor agonists (TPORAs). Several treatment algorithms have been developed in the US to help physicians choose the best course of treatment for each patient; however, to date, no such algorithm has been proposed in other countries, where the choice of treatment has been based on each physician's judgment and experience. Here, we discuss the pathogenesis and treatment of thrombocytopenia in patients with CLD, we review and present current evidence of the efficacy of TPORAs for the treatment of thrombocytopenia in patients with CLD, and we present our expert opinion on a Japanese treatment algorithm for thrombocytopenia in patients with CLD who are planned to undergo invasive procedures. This algorithm aims to provide guidance for optimal decision making in the selection of TPORA therapy or platelet transfusion based on the latest evidence and according to actual clinical practice.

Second-generation thrombopoietin receptor agonists (TPO-RAs) are emerging as the new standard for managing thrombocytopenia (TCP) in patients with chronic liver diseases (CLDs) undergoing scheduled procedures. However, practical guidance for their routine use in CLD patients undergoing specific invasive procedures is lacking.

These practice guidelines were developed by the Initiative Group for Central European Hepatologic Collaboration (CEHC), composed of nine hepatologist/gastroenterologist experts from Central Europe. Using an adapted Delphi process, the CEHC group selected ten invasive procedures most relevant to the hepatology/gastroenterology setting in the region. Consensus recommendations for each invasive procedure are reported as a final percentage of expert panel responses.

A consensus was agreed that TPO-RAs should be considered for raising platelet count in CLD patients undergoing scheduled abdominal surgery, high-bleeding risk dentistry, endoscopic polypectomy, endoscopic variceal ligation, liver biopsy, liver surgery, liver transplantation and percutaneous ablation, but it was also agreed that they are less beneficial or not necessary for endoscopy without intervention and paracentesis.

Using a modified Delphi method, experts reached an agreement for TCP management in CLD patients undergoing ten invasive procedures. These practice guidelines may help with decision making and patient management in areas where clinical evidence is absent or limited.