Dynamic dosing of romiplostim in patients with immune thrombocytopenia purpura: Two case reports

Abstract

Romiplostim is a thrombopoietin receptor agonist approved for the treatment of immune thrombocytopenia purpura. When following FDA-approved romiplostim prescribing recommendations to withhold treatment for platelet counts above 400k/µL, some patients exhibit a precipitous decline in their platelet count potentially causing patient harm. We present two cases where stable platelet counts were achieved only through persistent weekly dosing of romiplostim despite platelet counts above 400k/µL on the day of administration. Therefore, continuous weekly dosing of romiplostim despite platelet count being above 400k/µL combined with twice weekly vigilant monitoring is an alternative method of romiplostim dosing that mitigates severe fluctuations in platelets. We also discuss important details, postulated mechanisms, and evidence-based mitigation strategies.

Keywords

Immune thrombocytopenic purpura romiplostim benign hematology thrombopoietin receptor agonist

Get full access to this article

View all access options for this article.

References

Broudy

Lin

Sabath

. Human platelets display high-affinity receptors for thrombopoietin. Blood 1997; 89: 1896–1904.

Xia

Kuter

. Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics. Br J Haematol 1999; 106: 345–356.

Grozovsky

Begonja

Liu

et al.

The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling. Nat Med 2015; 21: 47–54.

Yang

Kuter

. The physiological response of thrombopoietin (c-Mpl ligand) to thrombocytopenia in the rat. Br J Haematol 1999; 105: 478–485.

Kuter

Beeler

Rosenberg

. The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production. Proc Natl Acad Sci U S A 1994; 91: 11104–11108.

Kuter

. The biology of thrombopoietin and thrombopoietin receptor agonists. Int J Hematol 2013; 98: 10–23.

Makar

Zhukov

Sahud

et al.

Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists. Am J Hematol 2013; 88: 1041–1044.

Kuter

Bussel

Lyons

et al.

Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008; 371: 395–403.

Wang

Nichol

Sullivan

. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther 2004; 76: 628–638.

10.

Choe

Packer

. Severe romiplostim-induced rebound thrombocytopenia after splenectomy for refractory ITP. Ann Pharmacother 2015; 49: 140–144.

11.

Shinohara

Kambara

. Highly Fluctuating Thrombocytopenia Developing in a patient with immune thrombocytopenia (ITP) while Administering romiplostim. Intern Med 2012; 51: 1399–1401.

12.

Bussel

Kuter

George

et al.

AMG 531, a Thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 2006; 355: 1672–1681.

13.

Tefferi

Hanson

Inwards

. How to interpret and pursue an abnormal complete blood cell count in adults. Mayo Clin Proc 2005; 80: 923–936.

14.

NPLATE- romiplostim injection, powder, lyophilized, for solution, www.dailymed.nlm.nih.gov (2013, accessed 16 March 2017); http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c45f9a58-37c1-4f76-8e36-97d38c577037 (accessed 5 January 2018).

15.

Cuker

. Toxicities of the thrombopoietic growth factors. Semin Hematol 2010; 47: 289–298.

16.

Chalmers

Tarantino

. Romiplostim as a treatment for immune thrombocytopenia: a review. JBM 2015; 6: 37–44.

17.

Bussel

Kuter

Pullarkat

et al.

Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP. Blood 2009; 113: 2161–2171.

18.

Zeller

Heddle

Kelton

et al.

Effect of a thrombopoietin receptor agonist on use of intravenous immune globulin in patients with immune thrombocytopenia. Transfusion 2016; 56: 73–79.