Lusutrombopag Combined With Recombinant Human Thrombopoietin for the Treatment of Thrombocytopenia in Patients With Chronic Liver Disease Destined to Undergo Elective Invasive Surgery

Inclusion criteria

• Ability to understand the study and willingness to comply with all study procedures by voluntarily signing an informed consent form prior to screening.
• Male or female, 18 years of age or older at the time of signing the informed consent form.
• Patients with chronic liver disease.
• Baseline platelet count ≤ 35 x 109/L prior to enrolment on day 1.
• Proposed elective invasive surgery that meets the following conditions: - Platelet transfusion may be required - Expected to be performed between days 9 and 15 after enrolment - Excludes extremely high-risk surgical operations such as open abdomen, open chest, open skull, and direct cardiac surgery.
• Eastern Collaborative Oncology Group (ECOG) Physical Status (PS) score of 0 or 1.
• According to the researcher, it will be able to fulfil the requirements of this study.
• Male patients who are infertile or who agree to use adequate contraception (including the use of condoms containing spermicides) from the start of screening until completion of the post-treatment phase.
• Female patients who are not menopausal or surgically sterilised need to agree to the use of highly effective contraception (including implants, injectable contraception, combined hormonal contraception [including vaginal rings], intrauterine devices, or partner-performed vasectomies) from the start of the screening until the completion of the end-of-treatment phase. The use of barrier contraception with or without spermicide, double barrier contraception and oral contraceptives alone is not adequate.

Exclusion criteria

• Presence of any of the following diseases: - Haematopoietic tumours - Aplastic anaemia - myelodysplastic syndrome - myelofibrosis - Congenital thrombocytopenia - Drug-induced thrombocytopenia - Immune thrombocytopenia - Systemic infections requiring treatment, except viral hepatitis
• Any solid malignancy with the following conditions: - Patients will require systemic chemotherapy, targeted therapy, immunotherapy, traditional herbal medicine or radiotherapy for that malignancy during the study period - Malignancy with lymph node metastasis, distant metastasis or peripheral organ invasion - Exceptions are: - Malignancy is a therapeutic target for the first invasive surgery - Non-melanoma skin cancers, intramucosal cancers, or carcinoma in situ that do not require any treatment during the study period.
• History of liver transplantation.
• Previous or current thrombosis or pre-thrombotic state (e.g., cerebral infarction, cardiac infarction, angina pectoris, coronary stenting, angioplasty, coronary artery bypass grafting, congestive heart failure [New York Heart Association {NYHA} class III/IV], cardiac arrhythmia [e.g., atrial fibrillation] known to increase the risk of thromboembolic events, pulmonary thromboembolism, deep venous thrombosis, or disseminated vascular (intravascular coagulation syndrome).
• Presence of any of the following conditions at screening: - Symptoms of hepatic encephalopathy with Child-Pugh Hepatic Encephalopathy Score 3 (occasional coma), with or without treatment for hepatic encephalopathy - Ascites uncontrolled by medications - Total bilirubin > 3 mg/dL
• Presence of history or evidence of a disease with bleeding risk (e.g. coagulation factor deficiency or vascular haemophilia factor vWF deficiency).
• History or evidence of any of the following disorders: - Congenital thrombophilia (e.g., antithrombin deficiency, protein C deficiency, protein S deficiency, or coagulation factor [coagulation factor V Leiden] mutation) - Acquired thrombophilia (e.g., antiphospholipid antibody syndrome, paroxysmal nocturnal haemoglobinuria, hyperhomocysteinemia, or elevated coagulation factor VIII) - Budd-Chiari syndrome
• Portal vein tumour embolism.
• Ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) within 28 days prior to enrolment showing portal vein thrombosis, or a history of portal vein thrombosis.
• Upper gastrointestinal endoscopy within 180 days prior to enrolment showing bleeding due to untreated gastro-oesophageal varices or the need to undergo treatment (except for patients in whom the first invasive procedure was performed to treat gastro-oesophageal varices).
• Prior to enrolment, the bleeding score was ≥ grade 2 according to the World Health Organization (WHO) Bleeding Scale.
• Use of any of the following medications or treatments within 90 days prior to enrolment: - Antineoplastic agents, excluding transcatheter arterial chemoembolisation (TACE) and oil iodide embolisation - Interferon agents - Radiotherapy - Radiotherapy - Any experimental drug
• Known hypersensitivity to the test drug or any of its excipients.
• Positive human immunodeficiency virus antigen/antibody test at screening.
• Women who are pregnant or breastfeeding.
• Patients deemed ineligible by the investigator for any other reason.