Abstract Ref Number = APCP134
Clinical practice in Management of Childhood Immune Thrombocytopenia(ITP)
Hematology Oncology Division Child Health Departement
Medical Faculty University of Sumatera Utara HAdam Malik Hospital
Immune Thrombocytopenia(ITP) is an autoimmune mediated condition that results from antibody-mediated destruction of platelets and impaired or suppression of platelet production by the bone marrow megakaryocytes, that may be a risk for significant hemorrhage. International Working Group (IWG) 2007 recommendations has replaced “Idiopathic thrombocytopenic purpura” with “Immune Thrombocytopenia”.
The IWG 2007 suggested the definition of the disease: Primary ITP is an autoimmune disorder characterized by isolated thrombocytopenia (peripheral blood platelet count < 100 x 109̸ L in the absence of other causes or disorders that may be associated with thrombocytopenia) and secondary ITP ( all forms of immune-mediated thrombocytopenia except primary ITP ).
Phases of the disease: Newly diagnosed ITP (occurs within 3 months from diagnosis) , persistent ITP (from 3 to 12 months from diagnosis), Chronic ITP (lasts for more than 12 months) and severe ITP (presence of bleeding symptoms at presentation sufficient to mandate treatment or occurrence of new bleeding symptoms requiring additional therapeutic intervention with a different platelet-enhancing agent or an increased dose).
The diagnosis of ITP bases on the history of isolated bleeding symptoms which is consistent with thrombocytopenia without constitutional symptoms, and hepatosplenomegaly, lymphadenopathy were not found in physical examination,and the complete blood count (platelet < 100x109̸ L, normal red cell indices and white blood count and differential) and the morphology of peripheral blood smear: red blood cell, white blood cell, and platelet are normal. Bone marrow examination is unnecessary, however, it is suggested in children with typical ITP prior to initiation of treatment with corticosteroids, splenectomy or patient who fails with IVIG therapy.
Immature Platelet Fraction (IPF) is used to evaluate the thrombopoeitic state withthe cut-off point is 7.7% (sensitivity 86.8% and specificity 92.6%) for differential diagnosis of ITP and Bone Marrow Failure (BMF) syndrome or malignancy .Thrombocytopenia with an increased IPF may indicate an increased destruction in peripheral blood cells, loss of platelets or a hereditary macrothrombocytopenia . Thrombocytopenia with a normal or decreased IPF may indicate a decreased platelet production in bone marrow.
Management of ITP remains controversial.
The main goal of treatment strategies for ITP is to rapidly increase the platelet count which is associated with adequate hemostatic level and prevent the occurrence of severe bleeding events.
Followings are the description of the different therapeutic options:
1.Watch and wait policy is safe if the platelet count is above 10x109̸ L and the patient has no bleeding manifestation.
2.Therapeutic agents are generally divided into three types based on the mechanism of action:
(1) Inhibiting antibody production, (2) Inhibiting Fc & Receptors (Fc & R) function and (3) Stimulating platelet production.There are three main options for the initial pharmacological treatment:Corticosteroid , Intra-venous Immunoglobulin (IVIG), Anti-D immunoglobulin.
A. Treatment of newly diagnosed children with ITP:
Prednison (1 – 2 mg ̸ Kg ̸ day) for 2 weeks and discontinued by the third week ,
High-dose oral Prednisone(4 mg ̸ Kg ̸ day) for four days only (without tapering-off)
High-dose intravenous Methylprednisolone (30 mg ̸ Kg ̸ day) for 3 days
2.Intravenous Immunoglobulin G (IVIG) : 0.8- 1 g ̸ Kg for 2 days to be infused over 6 – 10 hours
3.Anti-D immunoglobulin : it has not yet to be available in all countries and for first line treatment of newly diagnosed ITP in children remains controversial.
B. Treatment of persistent ITP, Chronic ITP and non-responder
1.Rituximab : Chimeric monoclonal antibody directed against CD20, an antigen expressed on the surface of B lymphocytes. Dosage regimen : 375 mg ̸ m2once weekly/ intravenous for 4 weeks.
2.Recombinant thrombopoietin and thrombopoietin –receptor agonist
Study in children are very limited but ongoing .
Rominplostim 2 mcg-5mcg ̸ Kg once a week
Eltrombopag : there is no published study in pediatric study.
3.Splenectomy is indicated in paediatric chronic ITP with troublesome or persistent bleeding who failed other options of medical therapy.
4. Other immune suppressive therapies : ITP patients who do not respond to the above first and second line therapies.There is no enough data for evidence based recommendations.Examples of such drugs: vincristine,vinblastine, cyclophosphamide, azathioprine, cyclosporine
Keywords: Immune Thrombocytopenia (ITP),