Experience in the treatment of immune thrombocytopenia in the Department of Oncohematology of the Voronezh Regional Children’s Clinical Hospital № 1

Abstract

Introduction. Immune thrombocytopenia (ITP) is a benign hematological disease characterized by an isolated decrease in platelet count, with different course options requiring both an urgent therapeutic decision and clinical observation of patients. At the present stage in the treatment of children with immune thrombocytopenia, especially with the chronic form, significant success has been achieved. Therapeutic options are determined by an individual approach to the patient and are based on the experience of a hematologist. Materials and methods. For the period from 01.01.2013 to 12.31.2017, in the Oncohematological Department of Chemotherapy of the Voronezh Regional Children’s Clinical Hospital № 1, 153 children with various forms of ITP, aged between 1 and 6 months to 17 years, received treatment. Diagnosis and stage of the disease were carried out on the basis of modern clinical guidelines and ITP classification. The analysis of the severity of hemorrhagic syndrome in the diagnosis of ITP was carried out. The principles of patient therapy were based on the pathogenetic aspects of ITP, the stage of the disease. Patients with newly diagnosed ITP (n = 106; 69.4 %), persistent form (n = 26; 16.9 %) received different lines of therapy, provided for by clinical guidelines, some patients were only under the supervision of a hematologist. The chronic form of the course of the disease was formed in 21 (14 %) children out of 153, regardless of the type of treatment. Children with the chronic form received various lines of therapy, including thrombopoietin agonists. The decision to manage such patients was based on a joint discussion with specialists from the largest federal centers. Splenectomy for the above period was performed for 1 child with a pronounced and chronic “wet” component of the disease. Discussion. Treatment of ITP in children, despite the emergence of a new class of drugs with a targeted effect, in some cases is a difficult task for a hematologist. The adoption of a specific therapeutic decision is based on the severity of the clinical and hematological data of the patient, the search for a possible cause of the thrombocytopenic condition, as well as the individual experience of the doctor. Prevention and prevention of bleeding in patients with different ITP, in particular with chronic ITP, with the absence or minimal manifestation of hemorrhagic syndrome according to the principle “0 bleeding per year” is the ultimate therapeutic task. Conclusion. ITP in children, in particular its chronic form, belongs to orphan diseases, therefore, the experience of managing such patients may be useful in determining the overall tactics of treating patients.

Thrombopoietin receptor agonists in pharmacotherapy of pediatric immune thrombocytopenia

“…The standard first-line drugs for newly diagnosed ITP treatment are glucocorticoids (GC) and intravenous immunoglobulins (IVIG) (Petrov 2016;Zotova et al 2017;Yasser et al 2020). First-line therapy for chronic ITP (cITP) treatment includes IVIG or anti-Rh-D immunoglobulin, second-line therapy includes GCs (Prednisolone, Dexamethasone, Methylprednisolone), immunosuppressants (Mycophenolate mofetil, Azathioprine, Cyclosporine, Cyclophosphamide, Vinblastine, etc.…”

“…The incidence of ITP in the world is 1.6-3.9 per 100,000 adults per year, in childrenfrom 1.9 to 6.4 per 100,000 (Payandeh et al 2018), which makes it possible to classify as a rare (orphan) disease (Krysanov et al 2017). At the same time, newly diagnosed acute ITP (up to 3 months from the moment of diagnosis) in 30% of cases turns into persistent (prolonged, lasting 3-12 months), and in 5-10% into chronic (lasting more than 12 months) (Zotova et al 2017).…”

“…Immune thrombocytopenia (ITP), until 2009 called idiopathic thrombocytopenic purpura, is a rare disease characterized by isolated immune-mediated thrombocytopenia (platelet count less than 100×10 9 /L) with or without hemorrhagic syndrome of varying severity. A decrease in the platelet number occurs due to their autoimmune destruction, as well as impaired proliferation of megakaryocytes and the formation of platelets from them (Krysanov et al 2017;Zotova and Sergeev 2018;Vishnu and Aboulafia 2020). Up to 10% of patients with ITP suffer from major bleeding, including 0.1% to 0.9% of cases with life-threatening intracranial hemorrhages (Nolla et al 2020).…”

“…The main mechanism for the ITP development is an intensive platelet destruction by macrophages as a result of specific autoantibodies to platelet membrane receptors (recognition is carried out by glycoproteins GP IIb/IIIa and GP Ib/IX) and megakaryocytes (MKC), which subsequently disturbs megakaryocytopoiesis (Zotova et al 2017;Kontievsky and Golenkov 2019;Singh et al 2021). The platelet destruction is caused by the binding of sensitized platelets to the Fc receptors (FcyRIIA and FcyRIIIA) of phagocytes, followed by their uptake by spleen macrophages (less often by liver and lymph node macrophages), as well as platelet destruction by complement-mediated lysis, especially in the presence of anti-GPIb /IX antibodies (Rumyancev and Maschan 2015).…”

“…Disbalance of T helper cells (Th1/Th2), which leads to an increase in the number and activity of cytotoxic T cells, plays an important role in ITP pathogenesis. An increased number of cytotoxic CD8+ and CD3+ T-lymphocytes inhibits platelet activity and induces their apoptosis through cell-mediated reactions (Zotova et al 2017;Zotova and Sergeev 2018). In addition, a potent decrease in the activity of regulatory T-cells (Tregs) leads to dysregulation of T-helpermediated B-cell activation.…”