Multiple Cycles of Recombinant Human Thrombopoietin Therapy in a Patient with Chronic Refractory Idiopathic Thrombocytopenic Purpura.

Abstract

Thrombopoietin (TPO) is the key regulator of megakaryocytepoiesis and platelet production. TPO binds to its specific receptor, c-Mpl, on the surfaces of megakaryocytes, and may promote the proliferation, differentiation and maturation of megakaryocytes, and finally increase the circulating platelet count. The role of TPO in the pathogenesis of idiopathic thrombocytopenic purpura (ITP) is not certain. Plasma concentrations of TPO in ITP patients were similar to or little lower than that in healthy subjects. Therefore it is possible that supplemental TPO could significantly promote platelet production and increase platelet counts in ITP patients. Here, we report the result of multiple cycles of recombinant human thrombopoietin (rhTPO) therapy in a patient with refractory ITP. The patient, a 42-year-old woman, was admitted to our department on December 30, 2003. She had suffered from chronic ITP for more than 4 years. The patient had been treated with glucocorticosteroids, immunosuppressive agents and splenectomy. No sustained response could be achieved. The diagnosis of chronic refractory ITP was made. There were petechiae and gingival bleeding on admission. Liver and spleen were not palpable. Hemoglobin was 142g/L, white blood cell count 7.6×10 9/L, platelet count 15×10 9/L. Bone marrow aspiration revealed that erythroid and myeloid development were normal, megakaryocytes were increased in number and no dysplastic features. After an informed consent was obtained from the patient, rhTPO (Sunshine Pharmaceutical Corporation, China) was administrated subcutaneously at dosage of 1.0 μg/kg, daily for 14 days or until platelet count sustained more than 50×109/L. Anti-rhTPO antibodies were determined weekly by ELISA. Three cycles of rhTPO therapy was given with 6, 13 and 8 dosing for each cycle. The platelet counts before each cycle were all less than10×109/L and increased above 50×109/L on day 5, 11 and 8 of rhTPO administration, respectively. The peak platelet counts of 456, 130 and 82×109/L were reached on day 9, 15 and 13 for each cycle. Then platelet count decreased gradually. The durations of platelet count more than 50×109/L in 3 cycles were 13, 7 and 10 days respectively. No increase of WBC count and Hb level occurred. No liver and kidney function damage, abnormal coagulation functions or thrombosis developed during the treatment. rhTPO antibodies were not detectable. The result indicated that rhTPO could transiently increase peripheral platelet counts of the patient with chronic refractory ITP. It was uncertain why peak platelet counts declined and durations of platelet count more than 50×109/L shortened when multiple cycles of rhTPO were given.

Eltrombopag in immune thrombocytopenia: efficacy review and update on drug safety

“…For this reason, the use of TPO-mimetic agents was considered as promising to restore platelet counts in ITP patients. However, although recombinant TPO succeeded in increasing the number of circulating platelets, 22,23 its administration was associated with the appearance of autoantibodies able to cross-react with endogenous TPO. As a consequence, TPO activity was neutralized, which subsequently led again to a thrombocytopenic condition.…”

Recombinant Human Thrombopoietin Alleviates Infection-Associated Thrombocytopenia

“…The efficacy of rhTPO has been established for chemotherapy-induced thrombocytopenia and idiopathic thrombocytopenic purpura (ITP). 13 –16 The current study is a retrospective analysis of the potential therapeutic efficacy and adverse events of rhTPO in senile patients with infection-associated thrombocytopenia.…”

Eltrombopag, a thrombopoietin- receptor agonist in the treatment of adult chronic immune thrombocytopenia: a review of the efficacy and safety profile

“…Therefore, stimulation of megakaryopoiesis by thrombopoietin or thrombopoietin-mimetic agents may be useful in the treatment of ITP. Recombinant thrombopoietin had been shown to increased platelet counts in patients with ITP [Nomura et al 2002;Zhao et al 2004] but was associated with production of autoantibodies that crossreact with and neutralize endogenous thrombopoietin, leading to severe thrombocytopenia [Li et al 2001;Basser et al 2002]. Recently, two thrombopoietin-receptor (TPO-R) agonists, romiplostim (AMG-531, Nplate; Amgen, Thousand Oaks, CA, USA) and eltrombopag (Revolade, Promacta; GlaxoSmithKline, Brentford, UK) have been licensed for the treatment of chronic ITP [Wang et al 2004;Erickson-Miller et al 2005].…”

“…Recombinant thrombopoietin had been shown to increased platelet counts in patients with ITP [Nomura et al . 2002; Zhao et al . 2004] but was associated with production of autoantibodies that crossreact with and neutralize endogenous thrombopoietin, leading to severe thrombocytopenia [Li et al .…”