A Pediatric Case of Chronic Immune Thrombocytopenic Purpura Treated with Sirolimus

Case Report

Ann Hematol Oncol. 2014;1(1): 1004.

A Pediatric Case of Chronic Immune Thrombocytopenic Purpura Treated with Sirolimus

Wenliang Geng1 and Guillermo de Angulo2*

1Department of Pediatrics, Miami Children's Hospital, US

2Department of Pediatric Hematology and Oncology,Miami Children's Hospital, US

*Corresponding author: Winston Tan, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, FL 32224,USA

Received: August 21, 2014; Accepted: September 15, 2014; Published: September 18, 2014


Few pediatric patients with Immune Thrombocytopenic Purpura (ITP) continue to have low platelets despite treatment with pooled gamma globulin (IVIG), corticosteroids, and anti-D immunoglobulin. Sirolimus (previously known as rapamycin) is an mTOR inhibitor that may improve platelet counts for this subset of patients. Here we present a pediatric case of chronic ITP refractoryto first-line pharmacotherapy. Following treatment with sirolimus, our patient'saverage platelet count increased from 41.9 x 109/L to 264.4 x 109/L (P=6.7 x 10-6). Furthermore, she experienced resolution of her bleeding symptoms withoutencountering side-effects related to treatment.

Keywords: ITP; Pediatric; Purpura; Rapamycin; Sirolimus; Thrombocytopenia


A patient with immune thrombocytopenic purpura has chronicdisease when the platelet count remains below 150 x 109/L beyond sixmonths and is refractory to treatment [1]. This condition affects 10%to 30% of patients with ITP and is more common in females as wellas patients with detectable anti-platelet antibodies [2-4]. Despite thepersistent thrombocytopenia, current literature suggests that chronicITP is a self-limited and asymptomatic condition that rarely resultsin significant bleeding problems and often resolves with conservativemanagement alone [4]. Pharmacologic treatment may be indicatedin patients with clinically significant thrombocytopenia characterizedby severe bleeding symptoms [3].

Options for first line treatment of ITP include IVIG,corticosteroids, and (for Rh+ patients) anti-D immunoglobulin [5-7]. Prior to the past decade, those who were refractory to medicalmanagement were referred for splenectomy, which rendered theimmune system vulnerable to infection by encapsulated bacteria.More recently, Bennett, et al. pioneered the use of rituximab, an anti-CD20 monoclonal antibody, for the successful treatment of refractoryITP [8]. Other immune-modulating agents are also currently beingevaluated as viable second line treatment modalities.

Sirolimus is an immune-modulating agent that interferes withT and B cell proliferation by inhibiting the mammalian target ofrapamycin (mTOR) pathway. By an unclear mechanism, it is thoughtto promote the regulatory CD4+CD25+FoxP3+T-lymphocytes(Treg), which are responsible for energy and frequently depleted inautoimmune diseases [9,10]. Sirolimus has been used successfullyfor the treatment of thrombocytopenia in the setting of autoimmunelymphoproliferative syndrome (ALPS) [11], and we believe may beeffective for ITP as well. Although sparse evidence exists supportingits utility in the management of ITP, however there is increasing datathat hint at its effectiveness in treating ITP in the adult population[12]. Here we present our observations from a pediatric case wheresirolimus was used off-label for the treatment of chronic refractoryITP.

Case Presentation

Our patient was a 15 year old female who presented withecchymoses, petechiae, and easy bruising. Her complete blood count(CBC) revealed a platelet count of 3 x 109/L. She was diagnosed withITP and treated immediately with two rounds of IVIG. Her plateletcount improved to 121 x 109/L but steadily decreased followinghospital discharge. She also developed pseudotumorcerebri attributedto IVIG, and was subsequently treated with two doses of anti-Dimmune globulin. Despite all initial efforts her thrombocytopeniapersisted.

Three years after diagnosis, our patient was hospitalized due tomenorrhagia accompanied by a platelet count of 4.0 x 109/L. Shereceived another dose of IVIG followed by a course of low potencycorticosteroids; however, her low platelet count was again refractory.The option for immunotherapy with rituximab was considered andsubsequently refused by the patient and her family. After carefuldiscussion of risks and benefits, the patient chose to begin off-labeltreatment with a course of sirolimus, which was initiated shortly afterher hospitalization.

The treatment regimen consisted of a single 6 mg sirolimusloading dose followed by 4 mg daily. The daily dose was taperedby 1 mg every 6 weeks, totaling 24 weeks of therapy prior todiscontinuation. All doses were self-administered orally. Completeblood count and routine side effect screening was performed at eachsubsequent follow-up clinic visit.


A two-sample t-test comparison of the average platelet countusing all data available before treatment (41.9 x 109/L) and aftertreatment (264.4 x 109/L) showed a seven-fold increase in the averageplatelet count (p=6.7 x 10-6) following administration of sirolimus(Figure 1). Furthermore, the pre-treatment average includes dataduring which the patient received IVIG, anti-D immunoglobulin,and steroids, suggesting a pre-treatment baseline that is lower andthus a more prominent therapeutic response.


Management of chronic refractory ITP in the pediatricpopulation poses many challenges. Identifying a suitable treatmentoption requires a case by case assessment of illness severity, patientcomorbidities, desired outcomes, and economic cost. There is anobvious need for prospective studies and randomized controlled trialsto confirm our findings and broaden its application. Further inquirymay confirm that pediatric patients with chronic ITP refractory tofirst-line medical management may benefit from treatment withsirolimus.


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Citation: Geng W and de Angulo G. A Pediatric Case of Chronic Immune Thrombocytopenic Purpura Treated with Sirolimus. Ann Hematol Oncol. 2014;1(1): 1004. ISSN:2375-7965

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