The primary purpose of this study is to compare the efficacy of lusutrombopag with placebo for the treatment of thrombocytopenia in patients with chronic liver disease who are undergoing elective invasive procedures.

The study consists of 3 periods: a screening period (up to 28 days prior to randomization), a treatment period of 7 days (Days 1 to 7 during which study drug is to be administered for 4 to 7 days), and a posttreatment period (through 28 days posttreatment).

Once-daily treatment with lusutrombopag 3 mg or placebo is to commence on Day 1 and continue for up to 7 days. Platelet count is to be determined on Days 5, 6, and 7 prior to administration of study drug; if a participant meets the administration stopping criterion (ie, platelet count ≥ 50 × 10⁹/L with an increase of ≥ 20 × 10⁹/L from baseline), no additional dose of study drug is to be administered. The planned invasive procedure is to be performed in the posttreatment period between Days 9 and 14. Platelet count for determination of the need for platelet transfusion is to be determined on or after Day 8, but no more than 2 days prior to the invasive procedure; a platelet transfusion is required if the platelet count is < 50 × 10⁹/L.

Inclusion Criteria:

1. Able to understand the study and comply with all study procedures.
2. Willing to provide written informed consent prior to Screening.
3. Male or female.
4. 18 years of age or older at the time of signing informed consent.
5. Platelet count < 50 × 10^9/L at baseline on Day 1 prior to randomization.
6. Undergoing an elective invasive procedure.
7. In the opinion of the investigator, able to meet study requirements.
8. Male patients who are sterile or who agree to use an appropriate method of contraception (including use of a condom with spermicide) from Screening to completion of the Post-treatment Period.
9. Female patients who are not postmenopausal or surgically sterile need to agree to use a highly effective contraception (including contraceptive implant, injectable contraceptive, combination hormonal contraceptive [including vaginal rings], intrauterine contraceptive device or vasectomised partner) from Screening to completion of the Post-treatment Period. Barrier method with or without spermicide, double barrier contraception and oral contraceptive pill are insufficient methods on their own.

Exclusion Criteria:

1. Any of the following diseases:

   • hematopoietic tumor
   • aplastic anemia
   • myelodysplastic syndrome
   • myelofibrosis
   • congenital thrombocytopenia
   • drug-induced thrombocytopenia
   • generalized infection requiring treatment except for viral liver disease
   • immune thrombocytopenia.

2. History of splenectomy.

3. History of liver transplantation.

4. Any of the following at Screening:

   • hepatic encephalopathy uncontrolled by drugs
   • ascites uncontrolled by drugs.

5. Portal vein tumor embolism.

6. Known to be positive for the human immunodeficiency virus.

7. Past or present thrombosis or prothrombotic condition (e.g., cerebral infarction, myocardial infarction, angina pectoris, coronary artery stent placement, angioplasty, coronary artery bypass grafting, congestive heart failure [New York Heart Association Grade III/IV], arrhythmia known to increase the risk of thromboembolic events [atrial fibrillation], pulmonary thromboembolism, deep vein thrombosis, or disseminated intravascular coagulation syndrome).

8. History or evidence of any of the following diseases:

   • congenital thrombotic disease (eg, antithrombin deficiency, protein C deficiency, protein S deficiency, or coagulation factor [Factor V Leiden] mutation)
   • acquired thrombotic disease (eg, antiphospholipid antibody syndrome, paroxysmal nocturnal hemoglobinuria, hyperhomocysteinemia, or increased factor VIII)
   • Budd Chiari syndrome.

9. Portal vein thrombosis based on ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) within 28 days prior to randomization or a history of portal vein thrombosis.

10. Absence of hepatopetal blood flow in the main trunk of the portal vein as demonstrated by Doppler ultrasonography within 28 days prior to randomization.

11. History or evidence of disease associated with a risk of bleeding (e.g., coagulation factor deficiency or von Willebrand factor deficiency).

12. Bleeding score at randomization ≥ Grade 2 according to the World Health Organization (WHO) Bleeding Scale.

13. Any of the following drugs or therapies within 90 days prior to randomization:

    • anticancer drugs
    • interferon preparations
    • radiation therapy
    • exsanguination
    • other thrombopoietin receptor agonist
    • any investigational agent.

14. Any invasive procedure within 14 days prior to randomization.

15. Blood transfusion within 14 days prior to randomization.

16. Prior treatment with lusutrombopag (S-888711).

17. Pregnancy or lactation.

18. Known or suspected ongoing, active alcohol or substance abuse. Patients with a recent history who the investigator feels are able to comply with the study procedures and medications will be allowed to participate.

19. Considered ineligible by the investigator for any other reason.

From first dose of study drug until 28 days after last dose, 35 days