Eltrombopag in long‐term management of pediatric thrombocytopenia

Shah, Sanjay; Etzl, Michael

doi:10.1002/ccr3.1916

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…Two small prospective studies identified around 30% of patients who were able to completely discontinue eltrombopag for at least 12 weeks while maintaining hemostatic platelet counts [10,11]. These rates of therapy-free responses (TFRs) are in line with those reported in adult and pediatric patients treated with TPO-RA [12][13][14][15][16][17][18][19][20][21][22]. Although to date we still cannot identify on which patients this approach is likely to be most successful, a complete response to low doses of TPO-RA and a diagnosis of ITP < 1 year could lead to higher TFRs [15,23].…”

Section: Introductionmentioning

confidence: 58%

Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach

Lozano

Segú-Vergés

Coma

et al. 2021

IJMS

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Eltrombopag is a thrombopoietin receptor (MPL) agonist approved for the treatment of primary immune thrombocytopenia (ITP). Recent evidence shows that some patients may sustain platelet counts following eltrombopag discontinuation. The systemic immunomodulatory response that resolves ITP in some patients could result from an increase in platelet mass, caused either by the direct action of eltrombopag on megakaryocytes through MPL stimulation, or potential MPL-independent actions on other cell types. To uncover the possible mechanisms of action of eltrombopag, in silico analyses were performed, including a systems biology-based approach, a therapeutic performance mapping system, and structural analyses. Through manual curation of the available bibliography, 56 key proteins were identified and integrated into the ITP interactome analysis. Mathematical models (94.92% mean accuracy) were obtained to elucidate potential MPL-dependent pathways in non-megakaryocytic cell subtypes. In addition to the effects on megakaryocytes and platelet numbers, the results were consistent with MPL-mediated effects on other cells, which could involve interferon-gamma, transforming growth factor-beta, peroxisome proliferator-activated receptor-gamma, and forkhead box protein P3 pathways. Structural analyses indicated that effects on three apoptosis-related proteins (BCL2L1, BCL2, BAX) from the Bcl-2 family may be off-target effects of eltrombopag. In conclusion, this study proposes new hypotheses regarding the immunomodulatory functions of eltrombopag in patients with ITP.

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Section: Introductionmentioning

confidence: 58%

Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach

Lozano

Segú-Vergés

Coma

et al. 2021

IJMS

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“…Although eltrombopag is currently approved as a second‐line approach to achieve a hemostatic platelet count, recent studies suggest that it has value as a prophylactic and primary treatment for different thrombocytopenias 14 . As suggested by Matthys et al, higher doses of eltrombopag may be required to treat thrombocytopenia secondary to myelosuppressive therapies and for other future indications 7 .…”

Section: Discussionmentioning

confidence: 99%

Interference of eltrombopag with bilirubin measurements on the Vitros 5600 analyzer

Poventud‐Fuentes

Garnett

Despotovic

et al. 2021

Clinical Laboratory Analysis

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Background Eltrombopag is a thrombopoietin‐receptor agonist used to restore platelet count to hemostatic levels in chronic immune thrombocytopenia. The drug has shown to have hepatobiliary adverse effects, but also positive interference with the analytical measurement of bilirubin. Understanding the degree of interference of this drug with bilirubin testing becomes relevant in the clinical management of these patients. Methods Eltrombopag at concentrations ranging from 10 to 150 µg/ml was spiked into plasma samples with different baseline concentrations of bilirubin. Total bilirubin, conjugated, and unconjugated bilirubin were measured for each sample using VITROS TBILI and BuBc slides on the Vitros 5600 automated chemistry platform, and interference was assessed. Results Plasma samples spiked with eltrombopag yielded falsely elevated bilirubin measurements compared to baseline, with the degree of elevation increasing with greater concentrations of eltrombopag. Bilirubin values were increased relative to baseline across all groups, except in conjugated bilirubin measurements in samples with low baseline conjugated bilirubin. For samples with low total bilirubin at baseline, >100 µg/ml of eltrombopag resulted in an error of >+0.6 mg/dl on the measured total bilirubin. For samples with low unconjugated bilirubin at baseline, the error for the same concentrations was >+0.7 mg/dl. Conclusion Our results show that, at supra‐physiologically high concentrations, eltrombopag can positively interfere with bilirubin measurements on Vitros 5600 platform.

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“…Approximately 10 years after its initial approval for adult chronic ITP, eltrombopag was approved to treat pediatric patients with chronic ITP [ 2 , 3 ]. Long-term safety data on the use of eltrombopag in children are limited, and studies in adults have not revealed a clinically significant increase in the incidence of thrombosis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment-Free Remission in Chronic Idiopathic Thrombocytopenic Purpura

Ahmed¹,

Yassin²

2020

Cureus

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Idiopathic thrombocytopenic purpura (ITP) is a disease in which the immune system attacks platelets and causes a decrease in their number, exposing the patient to bleeding risk. It is a diagnosis by exclusion. ITP usually presents as acute disease and is self-limiting in pediatric patients, while it tends to be chronic in adults. Eltrombopag is a thrombopoietin receptor agonist used as a second-line treatment for ITP. This drug is approved for use in adults as second-line therapy, but little is known about its use in the pediatric patient population. We report the case of a 14-year-old girl with chronic steroid-dependent ITP who responded well to eltrombopag and maintained treatment-free remission after stopping the drug.

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Eltrombopag in long‐term management of pediatric thrombocytopenia

Cited by 5 publications

References 16 publications

Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach

Elucidating the Mechanism of Action of the Attributed Immunomodulatory Role of Eltrombopag in Primary Immune Thrombocytopenia: An In Silico Approach

Interference of eltrombopag with bilirubin measurements on the Vitros 5600 analyzer

Treatment-Free Remission in Chronic Idiopathic Thrombocytopenic Purpura

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