Case Report - (2021) Volume 13, Issue 4
Department of Internal Medicine and Rheumatology, VPS Lakeshore Hospital, Kochi, Kerala, India
Received Date: January 02, 2021; Accepted Date: April 23, 2021; Published Date: April 28, 2021
Citation: Jalal MJA, Iqbal KMM, Nusaiba K, Basheer S (2021) Eltrombopag – A Cost- Effective Single Oral Therapeutic Agent Avoiding Splenectomy in Steroid-Resistant Immune Thrombocytopenic Purpura. Arch Med Vol.13 No.4:18.
Immune Thrombocytopenic Purpura (ITP) is an autoimmune disorder with isolated thrombocytopenia marked by peripheral blood platelet count<100 × 109/L without any other etiology or disorders that may be associated with thrombocytopenia. The treatment of newly diagnosed ITP patients is steroids. However, about one-third of patients do not respond to steroids. Here, we present a 63-yearold hypothyroid, hypertensive, and diabetic female presented with a history of bruising of skin in multiple sites.
Keywords
Primary ITP; Immune thrombocytopenia; Immune thrombocytopenic purpura; TPO-RA; Eltrombopag
Introduction
Immune Thrombocytopenic Purpura (ITP) is an autoimmune disorder with isolated thrombocytopenia marked by peripheral blood platelet count <100 × 109/L without any other etiology or disorders that may be associated with thrombocytopenia. The treatment of newly diagnosed ITP patients is steroids. However, about one-third of patients do not respond to steroids. In such cases, intravenous immunoglobulin or splenectomy is indicated. Apart from the evidence of platelet destruction in ITP, certain studies have shown decreased platelet production along with destruction. Eltrombopag is an oral Thrombopoietin Receptor Agonist (TPO-RA). Eltrombopag has been shown to provide a good response in chronic ITP patients not responding to steroid therapy.
Case Report
A 63-year-old hypothyroid, hypertensive, and diabetic female presented with a history of bruising of skin in multiple sites. She denied any history of hematuria, melena, epistaxis, and bleeding gums. There was no history of fever, weight loss, and trauma. General examination showed multiple echymotic patches over the trunk and extremities. System examinations were within the normal limits and did not show any hepatosplenomegaly and generalized lymph node enlargement.
Investigations revealed a low platelet count of 8 × 109/L [Normal range 150 × 109/L - 450 × 109/L] with normal white cell count and haemoglobin. Liver functions, renal functions, and coagulation profile were normal. Thus we excluded the possibilities of leukemia, aplastic anaemia, systemic lupus erythematosus, and sepsis.
Isolated thrombocytopenia suggested the possibility of immune thrombocytopenic purpura. This was confirmed by bone marrow biopsy, which demonstrated normal megakaryocytes, whereas peripheral blood smear showed decreased platelet count which was typical of ITP.
The patient was treated with platelet transfusion, intravenous, and oral steroids to prevent dreaded complications like intracranial haemorrhage. A transient increase in platelet count was noticed but failed to maintain the optimum platelet count. Immunotherapy was initiated with azathioprine along with steroids. But the platelet count remained sub-optimal and the patient developed cutaneous symptoms.
Our patient did not respond to corticosteroids and immunosuppression. So we considered TPO-RA (Eltrombopag). It resulted in a drastic increase in platelet count and the patient was free of symptoms. Hence, Eltrombopag was continued and platelet count elevated up to 300 × 109/L. She is on our follow-up for 1 year without worsening of symptoms.
Discussion
Immune Thrombocytopenic Purpura (ITP) is a diagnosis of exclusion. There are no specific clinical markers or laboratory investigations to establish the diagnosis of ITP with accuracy. Clinically, ITP has an increased risk of bleeding. If ITP is diagnosed within 3 months of its presentation, then it is said to be ‘‘newly diagnosed’’ [1]. Chronic ITP is diagnosed if symptoms last for more than 12 months [2].
Eltrombopag is an oral Thrombopoietin Receptor Agonist (TPORA) and has been shown to provide a good response in chronic ITP patients not responding to steroid therapy as it increases the platelet counts significantly in patients with chronic ITP and reduces the morbidity and mortality associated with the ITP [3,4].
The pathogenesis of Immune thrombocytopenic purpura includes [5]:
1. Increased platelet destruction.
2. Insufficient platelet production.
3. Insufficient regulatory T-cells/B-cells activity.
4. Production of anti-platelet antibodies
Corticosteroids and intravenous immunoglobulin targets increased platelet destruction. They reduce the capacity of the immune system to remove antibody-coated platelets.
Thrombopoietin Receptor Agonist [TPO-RA] addresses reduced platelet production or the lack of a compensatory boost in platelet production. They help in the recovery of regulatory T-cells/B-cells activity and re-establish autoimmune tolerance. Rituximab [Anti- CD 20 antibody] acts by inhibiting the production of anti-platelet antibodies by depleting B-cells.
The only therapeutic option in the management of ITP which focuses on increased platelet production is TPO-RAs (Figure 1) [6]. Apart from promoting existing megakaryocytes to produce more platelets, they also enhance the proliferation of megakaryocytes in bonemarrow [7,8]. TPO-RAs reduce platelet destruction by restoring regulatory T-cells and B-cells activity, thereby attenuating the autoimmune response to platelets [9]. It also progressively decreases the auto-antibody levels in patients with ITP, thus contributing to the restoration of immune tolerance to platelets [10].
Figure 1: Pathogenesis of immune thrombocytopenic purpura and mechanisms targeting the therapy.
TPO-RAs, specifically eltrombopag acts as follows:
A. When added to standard first-line therapy (Corticosteroids/ IVIG) in newly diagnosed ITP patients
1. Increases the durability of response
2. Decreases the relapse rate
3. Reduces the need for additional courses of steroid or IVIG
B. When given for a short course during the early phase of ITP
1. Increases the regulatory T-cell activity
2. Alter the natural course of the disease without the need for continued administration.
C. In combination with immune modulation is effective in patient’s refractory to single-agent ITP medications [9].
ITP in our patient was refractory to first-line management. Hence, we considered a second-line treatment strategy. Our patient could not afford IVIG/Rituximab due to financial constraints. Our only option left was splenectomy. Considering the age of the patient, co-morbidities, increased chance of surgical morbidity, infections, and cardiovascular risk, our plan was to proceed with splenectomy after a trial of a thrombopoietin receptor agonist, eltrombopag. For adult patients with ITP, the recommended starting dose for eltrombopag is 50 mg/day, which can be increased to 75 mg/ day if a sufficient platelet count is not reached [11]. Eltrombopag increased the platelet count in our patient and she was free of symptoms.
Conclusions
From the above experience, we infer that eltrombopag:
1. Is an affordable, oral mono-therapeutic agent of ITP with a good safety profile and fewer complications?
2. Increases platelet count in patients who are refractory to the first-line management of ITP.
3. Reduces the need for invasive procedures like splenectomy in the management of ITP.
4. Useful in ITP patients where splenectomy is contraindicated.
5. Useful in elderly ITP patients where the response rate is less for splenectomy compared to younger patients.
6. Helps to maintain optimum platelet count in ill controlled thrombocytopenia in post-splenectomy patients.
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