Impact of Anti-GPIIb/IIIa Antibody-Producing B Cells as a Predictor of the Response to Lusutrombopag in Thrombocytopenic Patients with Liver Disease

Dig Dis. 2021;39(3):234-242. doi: 10.1159/000510692. Epub 2020 Aug 6.

Abstract

Background: To make an accurate estimate of the response to thrombopoietin (TPO) receptor agonists for thrombocytopenia associated with chronic liver disease, we evaluated the influence of antiplatelet autoantibodies on the response to lusutrombopag in thrombocytopenic patients with liver disease.

Methods: A prospective study was conducted at 2 hospitals. Thrombocytopenic patients with liver disease received oral lusutrombopag 3.0 mg once daily for up to 7 days. We analyzed changes in platelet counts from baseline to the maximum platelet count on days 9-14. The definition of clinical response was a platelet count of ≥5 × 104/μL with an increased platelet count of ≥2 × 104/μL from baseline. We assessed the correlation between the response to treatment drug and antiplatelet autoantibodies measured by anti-GPIIb/IIIa antibody-producing B cells.

Results: Thirty patients received the trial drug. There were 25 responders and 5 nonresponders. The median change in platelet counts was 3.9 × 104/μL (95% CI 2.8-4.6, p < 0.0001). The correlation between change in platelet counts and the frequency of the anti-glycoprotein IIb/IIIa antibody-producing B cells was moderate (r = 0.414, 95% CI 0.064-0.674, p = 0.023). In multivariate analysis of factors affecting the change in platelet counts, the anti-GPIIb/IIIa antibody-producing B cells were identified as an independent factor (regression coefficient [B] = 0.089; CI 0.021-0.157, p = 0.013).

Conclusion: Anti-GPIIb/IIIa antibody-producing B cells may be a predictor for TPO receptor agonists in patients with chronic liver disease.

Keywords: Anti-GPIIb/IIIa antibody-producing B cells; Chronic liver disease; Lusutrombopag; Thrombocytopenia; Thrombopoietin receptor agonist.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Autoantibodies / biosynthesis*
  • Autoantibodies / immunology
  • B-Lymphocytes / immunology*
  • Blood Platelets / pathology
  • Cinnamates / administration & dosage
  • Cinnamates / therapeutic use*
  • Female
  • Humans
  • Liver Diseases / blood
  • Liver Diseases / complications*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Organ Size
  • Platelet Count
  • Platelet Glycoprotein GPIIb-IIIa Complex / immunology*
  • Prospective Studies
  • Spleen / pathology
  • Thiazoles / administration & dosage
  • Thiazoles / therapeutic use*
  • Thrombocytopenia / blood
  • Thrombocytopenia / complications
  • Thrombocytopenia / drug therapy*
  • Thrombocytopenia / immunology*

Substances

  • Autoantibodies
  • Cinnamates
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Thiazoles
  • lusutrombopag