While the mechanisms for thrombocytopenia are multifactorial, platelet sequestration in the spleen and decreased thrombopoietin (TPO) production are the main mechanisms in patients with CLD.
While these trials do suggest that TPO-mimetics are efficacious at increasing platelet counts in patients with CLD and have led to several recent drug approvals in this space by the U.S. Food & Drug Administration, it remains unclear whether these results translate to the relevant clinical endpoint of reduced perioperative bleeding rate and severity.
Lusutrombopag, a small-molecule, thrombopoietin (TPO) receptor agonist, was evaluated as a treatment to raise platelet counts (PCs) in patients with thrombocytopenia and CLD undergoing invasive procedures.
The final PK and PK/PD models included statistically significant but not clinically relevant effects of body weight and CLD on apparent volume distribution and East Asian ethnicity, albumin, and thrombopoietin level on the slope parameter in the PK/PD relationship.
The thrombopoietin (TPO) receptor agonist (TPO-RA) avatrombopag has recently been Food and Drug Administration-approved for the treatment of thrombocytopenia in patients with chronic liver disease (CLD) scheduled for a procedure.