الفهرس 
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Abstract
Immune thrombocytopenia (ITP) of childhood is characterized by isolated thrombocytopenia (platelet count <100,000/μL). The cause of ITP remains unknown in most cases, but it can be triggered by a viral infection or other immunologic or environmental trigger Primary immune thrombocytopenic purpura (ITP) is defined as an isolated thrombocytopenia, without changes of the bone marrow and in the absence of other causes of thrombocytopenia.
The term of acute ITP, recently replaced by newly diagnosed ITP, has less than 3 months from diagnosis. Persistent ITP refers to immune thrombocytopenia with 3 months to 1-year, whereas chronic ITP is the disease longer than 12 months. Refractory ITP comprises cases which did not respond to splenectomy or relapsed after surgery, with high risk of bleeding, which makes it necessary to continue therapy.
Normal platelet count in healthy individuals is defined as 150 to 450 × 109/L of blood. Typically 5 to 9 days after their production, they are eliminated via phagocytosis in the spleen and liver by Kupffer cells.
Programmed death (PD)-1 belongs to CD28/B7 family and is an important negative regulator that is mainly expressed on the surface of activated T cells, B cells, monocytes, NK cells, dendritic cells (DCs) and Treg cells.
PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells).
PD-1 has two ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2).
Activation of PD-1/PD-L1 signaling pathway inhibits the proliferation of T cells and the production of cytokines. In addition, activation of PD-1/PD-L1 signaling pathway effectively inhibits the proliferation of Th1 and Th17 cells and the secretion of IFN-γ.
ITP in children typically presents with the sudden onset of a purpura or bruising in an otherwise healthy child. In almost two thirds of pediatric patients, there is a history of a prior viral infection, mainly an upper respiratory tract infection.
Approximately 60% of children with ITP have only skin bleeding at presentation that includes petechial or purpuric rash or bruising also referred to as “dry purpura”. Mucosal bleeding (“wet purpura”) may be present in as many as 40% of children with ITP.
Mucosal bleeding (“wet purpura”) involves epistaxis, buccal and gingival bleeding, and, much less frequently, hematuria, menorrhagia, or gastrointestinal bleeding.
The diagnosis depends upon the exclusion of other causes of thrombocytopenia.
Summary and conclusion
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All patients with thrombocytopenia should undergo a thorough history-taking and physical examination to rule out other blood disorders or situations that could cause secondary thrombocytopenia.
A complete blood count (CBC) and examination of the peripheral blood smear are essential for the diagnosis. The CBC demonstrates isolated (and often profound) thrombocytopenia.
Platelets may be normal or larger in size but consistently giant platelets (approaching the size of red blood cells) are absent.
Management of childhood ITP remains controversial. Besides bleeding manifestations and platelet count, pediatric hematologists should consider a number of factors when considering treatment decisions, such as age, physical activities, health- related quality of life, potential co-morbidities and co-medications, duration of the disease, geographic distance from a tertiary care center, patient’s and parents preferences, time lost from school due to hospital visits, psychosocial impact and economic aspects.
ASH practice guidelines recommend that children with no bleeding or mild bleeding (defined as skin manifestations only), be managed with observation alone regardless of platelet count.
First-line treatment for ITP includes corticosteroids with or without intravenous IVIg.
The aim of the present study was to measure the changes in programmed death-1 (PD1) and interferon-γ (IFN-γ) on peripheral blood mononuclear cells (PBMCs) before and after one month of treatment in pediatric patients with primary immune
thrombocytopenia (ITP).
This is a prospective control study that was carried out on 40 children (20 males and 20 females) diagnosed as ITP attending Hematology oncology Unit of Pediatric Department, Menoufia University Hospitals during the period from July 2019 to August 2020 and 20 apparently healthy children of matched age and sex as control group.
The study was done on 2 groups:
Patients group: - 40 children and adolescents (20 males and 20 females) who were newly diagnosed ITP.
Control group: - 20 apparently healthy children of matched age and sex.
Inclusion criteria:
Age: - from 1 year of age to 18 years old.
Children and adolescents who were newly diagnosed ITP.
Exclusion criteria:
Children below 1 year or more than 18 years old.
chronic ITP.
Thrombocytopenia secondary to other disorders e.g. leukemia, Fanconi syndrome... etc.
Summary and conclusion
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Patients who had received specific treatment for ITP before hospital admission.
All included children were submitted to the following:
1) Careful history.
2) General examination to exclude any systemic illness.
3) Local examination: Chest, Heart and Abdomen:
With stress on spleen and liver is necessary.
4) Routine Laboratory investigations:
a. CBC and examination of the peripheral blood smear: - at diagnosis and 4 weeks after treatment as well as for the control group.
b. Platelet indices: (MPV, PDW and plateletcrit PCT).
c. Bone marrow aspiration: - Bone marrow aspiration was carried out under local anesthesia to all patients.
5) Specific Laboratory Investigations:
Assessment of programed death-1 protein level (PD1) and IFN- γ for all patients at diagnosis and after 4 weeks of treatment as well as for the control group.
Our data show that:
- No significant difference between patient group and control group regarding to age and gender.
- The most presenting symptoms were petechiae then ecchymosis and no bleeding was presented after 1 month of treatment.
- Platelets counts were significantly lower in the patients group at diagnosis than the control group and Platelets counts were significantly higher after 1 month of treatment than at diagnosis.
- The PD1level on lymphocytes in the patients group at diagnosis was a significantly higher than the control group and also The PD1 level on lymphocytes in the patients group after 1 month of treatment was a significantly higher than the control group but no significant difference between PD1 level on lymphocytes at diagnosis and after 1 month of treatment in the patients group as PD-1 level doesn’t return to normal after treatment.
- The IFN-y level in the patients group at diagnosis was a significantly higher than the control group and The IFN-γ level in the patients group at diagnosis was a significantly higher than its level after 1 month of treatment but The IFN-γ level in the patients group after 1 month of treatment was statistically non- significantly higher than the control group as IFN- γ level returns to normal after treatment.
- There was a negative significant correlation between PD1 level and platelets count at diagnosis and after 1 month of treatment among the patients group.
- There was a statistically significant negative correlation between IFN- γ level and platelets count at diagnosis and after 1 month of treatment among the patients group.
Summary and conclusion
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- There was a statistically a positive significant correlation between PD1 and IFN- γ among the patients group at diagnosis but no significant correlation after 1 month of treatment.
- At diagnosis, AUC of PD-1 was 0.930 ((P < 0.001) which means that PD-1 can be used as significant marker to discriminate patients at diagnosis from control and its Sensitivity was 85% at cut off >3.35.
- After 1 month of treatment: AUC Of PD-1 was 0.958 ((P < 0.001) which means that PD-1 can be used as significant marker to discriminate patients after 1 month of treatment from control as PD-1 level doesn’t return to normal after treatment and its Sensitivity was 90% at cut off >3.37.
- At diagnosis:AUC of IFN-γ was 0.998 ((P < 0.001) which means that IFN-γ can be used as significant marker to discriminate patients at diagnosis from control and Sensitivity was 97.50 % at cut off >8.55.
- After 1 month of treatment: AUC of IFN- γ was 0.558 ((P < 0.490) which means that IFN-γ can’t be used as significant marker to discriminate patients after 1 month of treatment from control as IFN-γ returns to normal after treatment and its Sensitivity was 52.50 % at cut off > 6.34.