Thrombopoietin-receptor agonists in perioperative treatment of patients with chronic liver disease

Abstract

Thrombocytopenia is a multifactorial disorder that is common in patients with chronic liver disease (CLD), leading to challenging perioperative planning. As thrombocytopenia in CLD is associated with thrombopoietin (TPO) deficiency, the use of TPO-receptor agonists (TPO-RAs) to increase platelet counts is a promising approach. This has led to the development of various TPO-RAs, including romiplostim, eltrombopag, avatrombopag, and lusutrombopag. Of these, only avatrombopag and lusutrombopag are approved by the United States Food and Drug Administration for the perioperative treatment of thrombocytopenia in patients with CLD. Platelet transfusion is commonly used for the clinical management of thrombocytopenia in patients with CLD undergoing invasive procedures. However, the limitations and possible risks of transfusion, including short duration of efficacy, development of antiplatelet antibodies, risk of infections and such complications as transfusion-related acute lung injury or circulatory overload, and possibility of refractoriness, limit its use. Moreover, there is no consensus among guidelines as to the platelet count at which transfusions are indicated. Results from studies using TPO-RAs perioperatively in patients with thrombocytopenia and CLD are promising and provide an alternative to platelet transfusions in the pre- and post-operative setting. These TPO-RAs are the subject of this review, with focus on their use in the perioperative setting in patients with thrombocytopenia, associated supporting clinical trials, efficacy and safety data, and their use with respect to platelet transfusions.

Keywords: Chronic liver disease; Thrombocytopenia; Thrombopoietin; Receptor agonist; Avatrombopag; Lusutrombopag; Romiplostim; Perioperative

Core tip: Thrombocytopenia in patients with chronic liver disease complicates perioperative planning. Platelet transfusions are typically used as periprocedural treatment in these patients, but their use is complicated due to risk factors such as the development of infections and refractoriness. This has led to the development of thrombopoietin-receptor agonists, such as avatrombopag and lusutrombopag, that can increase platelet counts in patients with compromised thrombopoietin production and chronic liver disease. These thrombopoietin-receptor agonists can provide physicians with a safe and effective alternative to platelet transfusions and their use in clinical practice is the focus of this review.