Childhood Immune Thrombocytopenia Research Articles

Idiopathic Thrombocytopenic Purpura in Patients Admitted to Benghazi Children Hospital

Introduction: Childhood immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia (peripheral blood platelet count <100 x 109/L). ITP is one of the most common bleeding disorders in children, with an incidence of approximately four per 100.000 per year. Aim: Aim is to review presenting features, response to therapy, and natural history of ITP treated at Benghazi medical center, department of pediatric. Methods: Cross-sectional descriptive study was carried out at the Pediatric Department of Benghazi medical center. Results: The study included 86 patients their mean age was 4.2±2.7years,with minimum age 11months and maximum age 12years.Male to female ratio was 1:1.15, female constitute to more than half (53.5%) .Mean duration of hospital stay was 5.2± 4.3 days , minimum duration was one day and maximum was 23 days. Bruise was presented by 84.9% of patients, 67.4% was presented by history of upper respiratory tract infection and 30.2% presented with bleeding from different site. Repeated admission was recorded in 93% of the patients. Family history of ITP was recorded in 4.7%. Respiratory manifestation was present in 4.8%, CNS manifestation present in 2.4%, hepatosplenomegaly in 2.4%, Lymphoadnopathy in 2.4%, renal manifestation in 1.2% and musculoskeletal manifestation in 1.2%. WBC count was >4 in 1.2% , 4-11 in 73.3% and 25.5% had level > 11 x103/ml, mean level was 9.7± 3.4 x103/ ml. Sever decrease of platelets was recorded in 54.7% of the patients , 36% had moderate decrease , mild recorded in 9.3% and no one had normal count .Peripheral blood smear, 26.7% of patients had normocytic normochromic. 25.5%was microcytic hypochromic 4.7% had microcytic normochromic, 1.2% had atypical lymphocyte with decrease plat, 1.2% had Normocytic hypochromic, 14% were normal and 15.5% not done. Bone marrow was normal in 68.5% of the patients, 1.2% of patients had thrombocytopenia, 1.2% of them had aplastic anemia, 1.2% of .........

Influencing Factors in the Chronicity of Immune Thrombocytopenia in Children

To explore the influencing factors in children with chronicity immune thrombocytopenia (ITP), and to provide basis for judging the prognosis and treatment in children with ITP. The clinical data of children with ITP admitted to The Second Affiliated Hospital of Anhui Medical University in the past 5 years were retrospectively analyzed and followed up for more than 1 year. According to the inclusion criteria, the eligible cases (328 cases in total) were selected and collected through medical record system retrieval, outpatient clinic and telephone follow-up. Independent influencing factors affecting the prognosis of children with ITP were obtained through single-factor and multi-factor logistic analysis, and their predictive value for the prognosis of ITP in children were evaluated. Of 328 children with ITP, 208 were newly diagnosed with ITP (64%), 54 were persistent ITP (16%), 66 were chronic ITP (20%), and the remission rate within 1 year was 79.9%. The results of univariate analysis showed that, age, pre-morbidity history of infection and vaccination, antinuclear antibodies, initial absolute lymphocyte count（ALC） and treatment options were related to the prognosis of the children (P<0.05). Multivariate analysis showed that the history of infection and vaccination before onset, initial treatment options, and ALC at the time of initial diagnosis were independent factors affecting the prognosis of children with ITP (P<0.05). The time for platelet recovery to 100×109/L in the initial treatment group combined with intravenous immunoglobulin (IVIG) was shorter than that in the single corticosteroids group (P<0.01). The receivers operating characteristic (ROC) was drawn with the development of chronic disease (course >12 months) as state variable and ALC or ALC combined with preceding infection or vaccination history as test variable. The results showed that when the absolute value of lymphocytes was 3.80×109/L, the area under the curve was the largest (0.787), the sensitivity was 80.6%, and the specificity was 65.53% (P<0.01), the combined results showed that the maximum area under the curve was 0.859, the sensitivity was 77.61%, and the specificity was 78.41%. The initial treatment plan combined with IVIG can reduce the occurrence of chronicity in children with ITP, and its efficacy is better than that of the single corticosteroids group (the platelet recovery time is shorter); history of preceding infection or vaccination, ALC at the time of initial diagnosis are independent factors affecting the prognosis of children with ITP, and the combination of the two shows a better predictive value for the prognosis.

Childhood-onset systemic lupus erythematosus and immune thrombocytopenia: Prevalence and risk factors.

There are few studies examining the prevalence and clinical risk factors for subsequent systemic lupus erythematosus (SLE) development after long-term follow-up in childhood immune thrombocytopenia (ITP). The aims of this study were to evaluate the prevalence and risk factors for subsequent SLE development in childhood ITP. The medical records of childhood ITP patients aged under 15years in a major tertiary care center in Southern Thailand were retrospectively reviewed. The Kaplan-Meier method was used to estimate the cumulative probability of subsequent SLE development after ITP. Logistic regression analysis was used to identify independent risk factors for SLE development. A total of 473 childhood ITP cases were included in the study. During a mean follow-up time of 6.1 ± 6.7years, the prevalence of subsequent SLE development was 2.96%. Older age at ITP diagnosis (odds ratio [OR]: 1.24, 95% CI: 1.07-1.45) and chronic ITP (OR: 24.67, 95% CI: 3.14-100.0) were independent risk factors. The cumulative probabilities of subsequently developing SLE at 5 and 10years after diagnosis of ITP were 3.8% (95% CI: 1.4-6.2) and 6.5% (95% CI: 2.9-9.8), respectively. Older age at ITP diagnosis and chronic ITP were risk factors for subsequent SLE developed in childhood ITP.

Platelet function and bleeding at different phases of childhood immune thrombocytopenia

Immune thrombocytopenia (ITP) is believed to be associated with platelet function defects. However, their mechanisms are poorly understood, in particular with regard to differences between ITP phases, patient age, and therapy. We investigated platelet function and bleeding in children with either persistent or chronic ITP, with or without romiplostim therapy. The study included 151 children with ITP, of whom 56 had disease duration less than 12 months (grouped together as acute/persistent) and 95 were chronic. Samples of 57 healthy children were used as controls, while 5 patients with leukemia, 5 with aplastic anemia, 4 with MYH9-associated thrombocytopenia, and 7 with Wiskott-Aldrich syndrome were used as non-ITP thrombocytopenia controls. Whole blood flow cytometry revealed that platelets in both acute/persistent and chronic ITP were increased in size compared with healthy donors. They were also pre-activated as assessed by PAC1, CD62p, cytosolic calcium, and procoagulant platelet levels. This pattern was not observed in other childhood thrombocytopenias. Pre-activation by CD62p was higher in the bleeding group in the chronic ITP cohort only. Romiplostim treatment decreased size and pre-activation of the patient platelets, but not calcium. Our data suggest that increased size, pre-activation, and cytosolic calcium are common for all ITP platelets, but their association with bleeding could depend on the disease phase.

Biological stratification of clinical disease courses in childhood immune thrombocytopenia

BackgroundIn childhood immune thrombocytopenia (ITP), an autoimmune bleeding disorder, there is a need for better prediction of individual disease courses and treatment outcomes. ObjectiveTo predict the response to intravenous immunoglobulins (IVIg) and ITP disease course using genetic and immune markers. MethodsChildren aged younger than 7 years with newly diagnosed ITP (N = 147) from the Treatment With or Without IVIG for Kids with ITP study were included, which randomized children to an IVIg or observation group. A total of 46 variables were available: clinical characteristics, targeted genotyping, lymphocyte immune phenotyping, and platelet autoantibodies. ResultsIn the treatment arm, 48/80 children (60%) showed a complete response (platelets ≥100 × 109/L) that lasted for at least 1 month (complete sustained response [CSR]) and 32 exhibited no or a temporary response (absence of a sustained response [ASR]). For a biological risk score, five variables were selected by regularized logistic regression that predicted ASR vs CSR: (1) hemoglobin; (2) platelet count; (3) genetic polymorphisms of Fc‐receptor (FcγR) IIc; (4) the presence of immunoglobulin G (IgG) anti‐platelet antibodies; and (5) preceding vaccination. The ASR sensitivity was 0.91 (95% confidence interval, 0.80‐1.00) and specificity was 0.67 (95% confidence interval, 0.53‐0.80). In the 67 patients of the observation arm, this biological score was also associated with recovery during 1 year of follow‐up. The addition of the biological score to a predefined clinical score further improved the discrimination of favorable ITP disease courses. ConclusionsThe prediction of disease courses and IVIg treatment responses in ITP is improved by using both clinical and biological stratification.

Clinical Analysis of Hospitalized Children with Primary Immune Thrombocytopenia

To investigate the factors affecting the chronicity of childhood primary immune thrombo-cytopenia (ITP) and compare the efficiency of different first-line treatment regimens. Children with ITP hospitalized in our hospital from September 2013 to October 2018 were retrospectively analyzed. Three hundred and one children (150 males and 151 females) were included in this study, with a median age of 8 (0.17-17) years old, and 110 (36.5%), 92 (30.6%), and 99 (32.9%) cases were grouped into newly diagnosed, persistent, and chronic ITP, respectively. The median of follow-up was 41.92 (1.07-74.03) months. At the end of the follow-up (October 2019), among the 202 newly diagnosed/persistent ITP children, 79 cases (59 newly diagnosed and 20 persistent ITP) achieved remission within 1 year after initial diagnosis, with a remission rate of 39.3%; 122 cases (50 newly diagnosed and 72 persistent ITP) developed chronic disease, with a chronicity rate of 60.7%; one case underwent splenectomy. In 99 cases with chronic ITP, 5 cases underwent splenectomy. Multivariable logistic regression analysis showed that, the insidious onset of symptoms (OR=3.754, 95%CI: 1.882-7.488, P=0.000) increased the risk of chronicity, while the positive antibody to anti-platelet membrane glycoprotein (OR=0.446, 95%CI: 0.224-0.888, P=0.021) might reduce the risk of chronicity. And no difference was found by the analysis of subtype of anti-platelet membrane glycoprotein (P=0.305). The efficacy of the first-line treatment of intravenous immunoglobulin (IVIG) alone or combined with steroid was better than that of steroid alone (P=0.028, 0.028), however, the efficiency was not significantly different between IVIG alone and combined with steroid (P=0.086). Insidious onset of symptoms in pediatric ITP increases the risk of chronicity, while the positive titer of anti-platelet membrane glycoprotein may reduce the risk. In the first-line treatment for the newly diagnosed/persistent children. The efficacy of IVIG alone or combined with steroid is better than that of steroid alone.

Quality of life is an important indication for second-line treatment in children with immune thrombocytopenia.

The decision to initiate second-line treatment in children with immune thrombocytopenia (ITP) is complex and involves many different factors. In this prospective, observational, longitudinal cohort study of 120 children from 21 centers, the factors contributing to the decision to start second-line treatments for ITP were captured. At study entry, clinicians were given a curated list of 12 potential reasons the patient required a second-line treatment. Clinicians selected all that applied and ranked the top three reasons. Quality of life (QOL) was the most frequently cited reason for starting a second-line therapy. Clinicians chose it as a reason to treat in 88/120 (73%) patients, as among the top three reasons in 68/120 (57%), and as the top reason in 32/120 (27%). Additional factors ranked as the top reason to start second-line treatment included severity of bleeding (22/120, 18%), frequency of bleeding (19/120, 16%), and severity of thrombocytopenia (18/120, 15%). Patients for whom QOL (p=.006) or sports participation (p=.02) were ranked reasons were more likely to have chronic ITP, whereas those for whom severity (p=.003) or frequency (p=.005) of bleeding were ranked reasons were more likely to have newly diagnosed or persistent ITP. Parental anxiety, though rarely the primary impetus for treatment, was frequently cited (70/120, 58%) as a contributing factor. Perceived QOL is the most frequently selected reason pediatric patients start second-line therapies for ITP. It is critical that studies of treatments for childhood ITP include assessments of their effects on QOL.

Occurrence of autoimmune pancreatitis after chronic immune thrombocytopenia in a Caucasian adolescent

Autoimmune pancreatitis is a rare, distinct and increasingly recognized form of chronic inflammatory pancreatic disease secondary to an underlying autoimmune mechanism. We report on a 14-year-old boy who developed autoimmune pancreatitis, while he was under treatment with eltrombopag for chronic immune thrombocytopenia. Therapy with corticosteroids resulted in complete remission of both. This is the first report on the co-occurrence of autoimmune pancreatitis and chronic immune thrombocytopenia in childhood, and clinicians should be aware of this rare association, because early diagnosis and therapy of autoimmune pancreatitis may prevent severe complications.

Secondary immune thrombocytopenia in children: Characteristics and outcome of a large cohort from two Spanish centres.

To evaluate the incidence and outcome of secondary immune thrombocytopenia (ITP) in a large cohort of paediatric Spanish patients. A retrospective observational study was conducted in two paediatric University hospitals in Spain between 2009 and 2019, which included children from 4months to 18years old diagnosed with ITP. Data were recorded from clinical charts: gender, age at diagnosis, coexisting condition and associated characteristics, outcome and treatment. Secondary ITP was diagnosed in 87 out of 442 patients (19.6%). Post-immunisation ITP was seen in younger children. The onset of secondary ITP to autoimmune diseases (AD) and immunodeficiencies (ID) was at an older age and had more tendency to be insidious, and platelet level was higher than primary ITP. Mean time from ITP onset to AD diseases or ID diagnosis was 1.2 and 2.6years, respectively. Whereas the cumulative incidence of remission was significantly higher in post-immunisation and post-viral infection (compared with primary ITP patients), it was worse in AD and ID patients. Identification of secondary ITP is important as it predicts outcome. Most of them are diagnosed at ITP onset, but AD diseases and ID should be ruled out periodically as they are usually identified later.

Intravenous immunoglobulins (IVIg) in childhood immune thrombocytopenia: towards personalized medicine—a narrative review

: In childhood immune thrombocytopenia (ITP), the morbidity is significant due to the risk of bleeding and a reduced health-related quality of life (HRQoL). Current management guidelines indicate that treatment is considered for children with moderate to severe bleeding, or a reduced HRQoL. Intravenous immunoglobulin (IVIg) treatment has been introduced in childhood ITP in 1981. IVIg treatment speeds up the remission of thrombocytopenia in newly diagnosed ITP and reduces bleeding symptoms, but this has the disadvantage of side effects and costs. Some data indicated that IVIg may modulate the late disease outcomes of ITP, but our recent randomized controlled trial (RCT) showed that IVIg does not affect the development of chronic ITP. Overall, 60% of children with newly diagnosed ITP show a sustained response to IVIg. Such a sustained response after IVIg treatment is strongly associated with long-term remission from ITP. Recent molecular and clinical data show that treatment responders could be identified before IVIg is administered. The same molecular and clinical characteristics that identify treatment responders are otherwise associated with a transient, self-limiting ITP disease course, suggesting the identification of a distinct subgroup of ITP patients. Thus, the development of multivariate clinical and molecular prediction scores could allow to individualize treatment decisions, i.e., target IVIg to those who benefit the most. These prediction scores may also be used to design studies aimed at identifying children who benefit from adjunctive or alternative treatments, such as thrombopoietin receptor agonists (TPO-Ra).

Increased Expression of IL-17A and IL-17F Is Correlated With RUNX1 and RORγT in Pediatric Patients With Primary Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is characterized by dysregulated cellular immunity. Interleukin 17 (IL-17) and its secreting cells (Th17) are involved in the pathogenesis of ITP. Retinoic acid receptor-related orphan receptor γt (RORγt) is the chief regulator of Th17 development. The interaction among Runt-related transcription factor 1 (RUNX1) and IL-17-related genes in ITP remains questionable. The study aimed to evaluate the expression of RUNX1 and RORγt together with IL-17A and IL-17F genes in childhood ITP to investigate their contribution to disease pathogenesis and clinical presentation. Ninety children were included, 30 primary active ITP patients, 30 ITP patients in remission after treatment, and 30 healthy controls. The expression levels of RUNX1, RORγt, IL-17A, and IL-17F genes were measured. Significant overexpression of RUNX1, RORγt, IL-17A, and IL-17F genes was observed in active ITP patients, which was restored to normal levels in both ITP patients in remission and controls (P<0.001 for the 4 genes). Positive correlations between RUNX1, RORγt, IL-17A, and IL-17F expression levels were observed in active ITP patients (P=0.001 for RUNX1 with RORγt, P<0.001 for RUNX1 with both IL-17A and IL-17F, regarding RORγtP<0.001 with IL-17A and P=0.002 with IL-17F, P=0.001 for IL-17A with IL-17F). In conclusion, RUNX1 is possibly involved in the molecular pathogenesis of ITP upregulating the expression of Th17-secreted cytokines, IL-17A and IL-17F, through RORγt at the transcriptional level. Thus, targeting RUNX1 or RORγt may be new alternative therapeutic strategies.

Can we Predict the Clinical Course of Immune Thrombocytopenia in Children by The Mean Platelet Volume? A Preliminary Study.

Mean platelet volume (MPV) is considered a marker of platelet function and is known to increase in immune thrombocytopenia (ITP). We aimed to investigate the predictive value of MPV for predicting the clinical course of ITP in children. We retrospectively analyzed children aged < 18 years with ITP (n = 36) and healthy controls (n = 36) from June 2010 to November 2018. The subjects were stratified into: (i) Healthy controls [group I, n = 36]; (ii) Newly diagnosed ITP (nITP) and persistent ITP (pITP) [group II, n = 24]; and (iii) Chronic ITP (cITP) [group III, n = 12]. Hematological indices including MPV were measured and compared between the three groups. The median MPV values at diagnosis in group I, II, and III were 7.20, 8.15, and 8.65 fL, respectively (p = 0.0004). Cutoff value of MPV at diagnosis differentiating group I from group II + III was 7.6 fL, and group II from group III was 8.7 fL. MPV change (ΔMPV after three months minus MPV at diagnosis) in children with nITP and pITP (n = 22) was greater than in those with cITP (n = 6) (-2.18 fL vs. 0.66 fL, p = 0.0059). This study revealed that group III had a higher MPV than group II at diagnosis. Therefore, an initial MPV value more than 8.7 fL may be used as a predictive factor for chronicity in children with ITP. The change in MPV over time as well as MPV at diagnosis, may be regarded as a prognostic marker to predict the course of ITP in children.

Role of circulating myeloid-derived suppressor cells in pathogenesis of immune thrombocytopenia in children and adolescents

Context Regulatory T cells have an immunosuppressive function on T-cell activation. They are involved in pathophysiology and treatment of immune thrombocytopenia (ITP). Circulating myeloid-derived suppressor cells (MDSCs) are involved in immune dysregulation in ITP. Aim To determine the mean level of MDSCs in acute, persistent, and chronic ITP and its effect on treatment modalities and prognosis. Patients and methods A total of 41 patients with ITP were recruited from the pediatric hematology clinic of Ain Shams University. They were classified into acute, persistent, and chronic and were compared with 20 age-matched and sex-matched healthy controls. All patients were subjected to history taking with emphasis on age of presentation, disease duration, and treatment modalities, as well as thorough clinical examination. Mean values of C-reactive protein, alanine aminotransferase, and serum creatinine were collected from the patients’ files. All study participants underwent complete blood count (Coulter) and MDSCs by flow cytometry. Secondary thrombocytopenia was excluded. Results Acute ITP was detected in 29%, 24% had persistent, and 46% had chronic ITP. Their age ranged from 1 to 16 years at the study entry, and 51.2% were male. Active disease was found in 58.5%, whereas 41.4% in remission. No treatment was offered to 53%, whereas 24% of patients were on steroids. MDSCs decreased significantly in patients with ITP compared with the control group (P&lt;0.001), whereas there was no significant difference among the patient groups regarding MDSCs level (P=0.325) or with different treatment modalities. Conclusion Reduced numbers of MDSCs play a role in pathogenesis of ITP. Yet, MDSCs did not differ according to disease duration or treatment modalities.

Primary immune thrombocytopenia in children

Primary immune thrombocytopenia in children

A clinical prediction score for transient versus persistent childhood immune thrombocytopenia

Unlabelled Box AbstractBackgroundChildhood immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The prognosis (transient, persistent, or chronic ITP) remains difficult to predict. The morbidity is most pronounced in children with persistent and chronic ITP. Clinical characteristics are associated with ITP outcomes, but there are no validated multivariate prediction models. ObjectiveDevelopment and external validatation of the Childhood ITP Recovery Score to predict transient versus persistent ITP in children with newly diagnosed ITP. MethodsPatients with a diagnosis platelet count ≤ 20 × 109/L and age below 16 years were included from two prospective multicenter studies (NOPHO ITP study, N = 377 [development cohort]; TIKI trial, N = 194 [external validation]). The primary outcome was transient ITP (complete recovery with platelets ≥100 × 109/L 3 months after diagnosis) versus persistent ITP. Age, sex, mucosal bleeding, preceding infection/vaccination, insidious onset, and diagnosis platelet count were used as predictors. ResultsIn external validation, the score predicted transient versus persistent ITP at 3 months follow‐up with an area under the receiver operating characteristic curve of 0.71. In patients predicted to have a high chance of recovery, we observed 85%, 90%, and 95% recovered 3, 6, and 12 months after the diagnosis. For patients predicted to have a low chance of recovery, this was 32%, 46%, and 71%. The score also predicted cessation of bleeding symptoms and the response to intravenous immunoglobulins (IVIg). ConclusionThe Childhood ITP Recovery Score predicts prognosis and may be useful to individualize clinical management. In future research, the additional predictive value of biomarkers can be compared to this score. A risk calculator is available (http://www.itprecoveryscore.org).

Pathophysiology and clinical challenges of childhood immune thrombocytopenia and future directions

Pathophysiology and clinical challenges of childhood immune thrombocytopenia and future directions

Risk Factors and Psychological Analysis of Chronic Immune Thrombocytopenia in Children.

ObjectiveTo study the risk factors and psychological changes in children with chronic immune thrombocytopenia (CITP).MethodsThis was a retrospective analysis of 234 children with ITP diagnosed and treated in the Affiliated Hospital of Southwest Medical University from January 2016 to December 2018. The clinical characteristics and related laboratory factors of all patients were collected, and their impact on the chronicity of ITP was analyzed. The Eysenck Personality Questionnaire-Children’s Version (7–15 years old) is a psychological assessment of children with chronic ITP (CITP).ResultsUnivariate analysis found that the course of the initial diagnosis (χ2 =6.879, P<0.05), the age of onset (χ2 =13.846, P<0.05) and the absolute value of the initial diagnosis of peripheral blood lymphocytes (χ2 =6.436, P<0.05) had statistical differences in the chronicity of ITP in children; a multivariate analysis of the course of the first diagnosis, the age of onset and absolute lymphocyte count (ALC) revealed that ALC is an independent factor in children’s chronic ITP (P<0.05). Compared with normal children, children with CITP had statistical significance in extraversion (t=−3.476, P<0.05); compared with newly diagnosed children, they had statistical significance in extraversion (E) and lying (L) (P<0.05); and there was no statistical difference compared with persistent children (P>0.05).ConclusionThe age of onset, the absolute value of lymphocytes at the initial diagnosis, and the course of the initial diagnosis are important for predicting the chronicity of ITP in children. ALC is an independent predictor; children with chronic ITP have psychological problems.

PTPN22 gene polymorphism as a genetic risk factor for primary immune thrombocytopenia in Egyptian children

ABSTRACT Objectives Several genetic and non-genetic risk factors are implicated in the etiology and pathogenesis of primary immune thrombocytopenia (ITP). Protein tyrosine phosphatase non-receptor 22 gene (PTPN22) plays an important role in regulation of signal transduction through the T-cell receptors. PTPN22 1858 C > T single nucleotide polymorphism was reported to be associated with increased risk of autoimmune diseases. There are very few studies investigating the role of PTPN22(SNP) 1858 C > T in childhood ITP. Methods This case-control study was designed for assessing the contribution of PTPN22 1858 C > T polymorphism to the risk of ITP in Egyptian children. Eighty children with newly diagnosed ITP were recruited from pediatric hematology out-patient clinic. Also, eighty age and sex-matched healthy children were enrolled as a control group. PTPN22 1858 C/T SNP gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results Frequency of PTPN22 1858 C/T genotypes CT, CC, and TT were 32.5,55, and 12.5% in patients versus 10, 90, and 0% in controls (p < 0.05).TT genotype was significantly associated with higher risk of ITP (OR = 17.8(0.94–333.35), 95% CI, and P = 0.02). Conclusion PTPN22 gene polymorphism may play a pivotal role in genetic predisposition to ITP and disease progress in Egyptian children.

Primary immunodeficiencies, autoimmune hyperthyroidism, coeliac disease and systemic lupus erythematosus in childhood immune thrombocytopenia.

To evaluate the cumulative prevalence of coeliac disease, systemic lupus erythematosus, autoimmune hyperthyroidism and primary immunodeficiencies in children with either newly diagnosed/persistent or chronic immune thrombocytopenia (ITP). Monocentric retrospective analysis of the clinical and biochemical features of 330 consecutive patients with ITP referred to our Pediatric Hematology Unit between January 2009 and December 2018. The prevalence of systemic lupus erythematosus (0.3%), coeliac disease (0.3%) and autoimmune hyperthyroidism (0.6%) was not increased compared to general paediatric population. Of note, the prevalence of underlying primary immunodeficiencies was 2.4%, remarkably higher than the general paediatric population (P=.005). All the patients diagnosed with immunodeficiency developed either bi-/trilinear cytopenia or splenomegaly. Whilst autoimmune and immunological screening is already recommended at the onset of immune thrombocytopenia, we recommend that primary immunodeficiencies be regularly screened during follow-up, especially in case of additional cytopenia or lymphoproliferation.

Features of pathogenetic mechanisms of the interaction of viruses and platelets in patients with immune thrombocytopenia (review of literature)

Annotation. One of the urgent interdisciplinar problems of modern medicine is to study the mechanisms of development of virus-induced thrombocytopenia in patients. The aim is to sum up current knowledge of viruses and platelets interaction, how viruses affect platelet and modulate adaptive immune response. A systematic review of the articles in the Pub Med database was conducted between 2007 and 2020, using search terms: platelets, thrombocytopenia, viral infection. Current data on the study of the mechanisms of platelet interaction with different types of viruses in immune thrombocytopenia in children were analyzed. We studied activation of platelets by a viral infection and how the immune response works. We know that the immune response is a cyclic multistage process involving T-lymphocytes, B-lymphocytes, macrophages, cytokines, Nk-cells. Antiplatelet antibodies are increase platelet clearance from the blood. The combination of antibodies with platelets leads to phagocytosis. In patients with immune thrombocytopenia ІgG antibodies are produced against GP/ІІ b/ІІІ or GP/І b/ІХ glycoproteins located on the platelet surface. In this situation it is possible to produce antibodies of other subclasses of ІgG, also a complement of fixing Іg G, rarelyІg А to other glycoprotein, or to other complexes Іb ІХ, Іа/ІІа. Since megakaryocytes express glycoprotein ІІb/ІІІа, Ів as well as other platelet antigens, they become a target for autoantibodies. Viruses can interact directly with platelets and megakaryocytes. In addition, platelets can be activated by viral antigen-antibody complexes and B- lymphocytes can produce antiplatelet antibodies. All of these processes are activate platelets and lead to increased consumption and remove of platelets, this causes hemorrhagic manifestation in patients.