Prevalence of Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Subclinical Infection in Patients with Acute Immune Thrombocytopenic Purpura (ITP)

Background: Immune thrombocytopenic purpura (ITP) defined as a bleeding disorder in which the number and production of platelets reduced by the immune system; however, the destruction of peripheral blood platelets also occurs. Although its exact etiology and pathogenesis not already know, several studies have shown that Epstein-Barr virus (EBV) and cytomegalovirus (CMV) known as possible causative agents of ITP. This investigation aims to evaluate the presence of CMV and EBV in two groups of case and control by polymerase chain reaction (PCR). Materials and Methods: We considered the presence of CMV and EBV in 48 acute ITP patients and 48 healthy people. Study participants were recruited from Ahvaz Shafa Hospital between 2017 and 2018 and the presence of two viruses was investigated by (PCR). Results: Out of 48 acute ITP patients, the CMV DNA was detected from the blood of 12 (25%) patients and the EBV DNA from the blood of 2 (4.2%) other patients. In addition, only one patient was (2.1%) co-infected with CMV and EBV. In contrast, in 48 healthy subjects, 3 (6.6%) had CMV and none of the control group was infected with EBV. Conclusion: Due to the presence of both EBV and CMV in the acute ITP patients in Ahvaz, they can be considered as factors in the progression of this disease. Therefore, consideration of the methods of elimination and treatment of these two viruses in these patients may be used as a treatment strategy in ITP patients in the future.

The Role of Leptin in Childhood Immune Thrombocytopenia (ITP): An Anti-Inflammatory Agent?

To investigate the effect of leptin in childhood ITP, we measured plasma leptin in 39 children with acute ITP, after treatment and in remission, and in 33 healthy age/BMI-matched controls. We also cultured ITP and control peripheral blood mononuclear cells (PBMCs) with recombinant leptin to assess its direct effect on pro/anti-inflammatory cytokine gene expression. A significant increase in leptin was observed in children with active disease compared to controls. A significant inverse correlation of leptin with platelet count was also observed in children with acute ITP. Leptin remained high after treatment with IVIg, whereas steroid treatment lowered leptin below control levels. In remission, leptin was in the control range. Cytokine gene expression was significantly increased in children with acute ITP compared with controls, with highest expression for IFN-γ and IL-10. IVIg/steroid treatment significantly decreased IFN-γ and IL-10 expression. In remission, IFN-γ and IL-10 expression remained low. Addition of leptin to PBMCs isolated from patients in remission resulted in a significant increase in IL-10 gene expression compared to controls. Further experiments with purified T-cells and monocytes identified monocytes as the source of leptin-induced IL-10. We suggest that leptin acts as an active anti-inflammatory agent in childhood ITP by promoting IL-10 secretion by monocytes.

Acute Immune Thrombocytopenia (ITP) following Covid-19 vaccination in a patient with previously stable ITP

ITP (Immune Thrombocytopenia) is an autoimmune condition associated with multiple risk factors including viral infections (HBV/HCV/ CMV, HIV and recently SARS-CoV-2) and vaccines. Though immune mechanisms have been proposed to explain the pathogenesis of acute ITP, autoimmunity with Covid-19 vaccine is still unclear and needs further research. We report a case of acute ITP after administration of Pfizer-BioNTech mRNA Covid-19 vaccine in a patient with previously stable ITP.

Recurrence rate in patients with acute immune thrombocytopenic purpura in Ahvaz, southwest of Iran: Corticosteroids versus intravenous immunoglobulin

Introduction: Immune thrombocytopenic purpura (ITP) is known as the most important cause of sudden drop in platelet count among children. The acute form of unexpected drop in platelet count in children calls for treatment with medications such as corticosteroids, intravenous immunoglobulin (IVIg), and Rho(D) immunoglobulin (anti-DIG). Most of the previous studies have accordingly compared short-term therapeutic outcomes of steroids with those of IVIg. In some cases, IVIg has led to better results. However, there are few studies on the long-term treatment effects of both medicine categories. Objectives: This study was aimed to evaluate the therapeutic effects and recurrence rate (RR) of corticosteroids, IVIg, or both in the long-term to find the best and most effective treatment for these patients. Patients and Methods: A total of 188 children diagnosed with acute ITP were admitted to the hematology departments of Shafa and Baghaei hospitals of Ahvaz, Khuzestan, Iran. The therapeutic consequences and RRs of corticosteroids, IVIg, or both were compared within one year. Results: Comparing treatments employing corticosteroids and IVIg in children having acute ITP in terms of the long-term treatment outcomes showed no statistically significant difference. In addition, the findings revealed that 34% of the patients had experienced recurrence within one year with no remarkable difference between both drug groups. Conclusion: The long-term therapeutic outcomes in both medicine categories were not significantly different. Therefore, given the world’s current economic conditions and inadequate supply of all medicines, it seems more rational to use the least expensive drugs.

Surgical Control of Bleeding From Ovarian Torsion in the Setting of Immune Thrombocytopenic Purpura Without Splenectomy

Immune thrombocytopenic purpura (ITP) is a disorder caused by autoimmune antibodies which target glycoprotein IIb/IIIa complex or other platelet membrane antigens leading to platelet destruction. These platelets are then cleared by the spleen resulting in thrombocytopenia. Immune thrombocytopenic purpura affects about 1 to 6.4 cases in 100 000 children making it one of the most common causes of symptomatic thrombocytopenia in the pediatric population. It is rare that children or adolescents present with serious bleeding due to ITP. Common presentations include petechiae, bleeding gums, or bruising. Bleeding requiring hospitalization or transfusions is unusual and only occurs in approximately 5% of children. Even more uncommon is the presentation of severe bleeding complications requiring surgery for resolution. We present a case of a 17-year-old girl with acute ITP complicated by intraperitoneal hemorrhage and refractory thrombocytopenia due to ovarian cyst requiring oophorectomy.

Thrombopoietin receptor agonist for treatment of immune thrombocytopenia in pregnancy: a narrative review

The treatment of immune thrombocytopenia (ITP) in adults has evolved rapidly over the past decade. The second-generation thrombopoietin receptor agonists (TPO-RAs), romiplostim, eltrombopag, and avatrombopag are approved for the treatment of chronic ITP in adults. However, their use in pregnancy is labeled as category C by the United States Food and Drug Administration (FDA) due to the lack of clinical data on human subjects. ITP is a common cause of thrombocytopenia in the first and second trimester of pregnancy, which not only affects the mother but can also lead to thrombocytopenia in the neonatal thrombocytopenia secondary to maternal immune thrombocytopenia (NMITP). Corticosteroids, intravenous immunoglobulins (IVIGs) are commonly used for treating acute ITP in pregnant patients. Drugs such as rituximab, anti-D, and azathioprine that are used to treat ITP in adults, are labeled category C and seldom used in pregnant patients. Cytotoxic chemotherapy (vincristine, cyclophosphamide), danazol, and mycophenolate are contraindicated in pregnant women. In such a scenario, TPO-RAs present an attractive option to treat ITP in pregnant patients. Current evidence on the use of TPO-RAs in pregnant women with ITP is limited. In this narrative review, we will examine the preclinical and the clinical literature regarding the use of TPO-RAs in the management of ITP in pregnancy and their effect on neonates with NMITP.

Immunoglobulin Levels As Predictors of the Development of Chronic Disease in Pediatric Immune Thrombocytopenia

Background: Immune thrombocytopenia (ITP) is the most common acquired bleeding disorder in children. Although ~75% of these patients will go on to have spontaneous resolution of disease, up to 25% will develop chronic ITP, with significant and prolonged bleeding symptomatology and impaired quality of life. At this time, there is no definitive method to predict the development of chronic disease at the time of ITP diagnosis. Aims: We aim to identify clinical biomarkers predictive of the development of chronic ITP at the time of diagnosis among pediatric ITP patients. Methods: The clinical records of 280 pediatric ITP patients enrolled in a biological banking study at a large pediatric tertiary care referral center from July 1, 2015 to July 1, 2019 were reviewed in accordance with IRB-approved protocols. ITP diagnosis and chronicity of disease (vs. spontaneous resolution within 1 year of diagnosis) was confirmed by a pediatric hematologist, as defined by current international expert committee standards (Neunert et al, Blood, 2011;117(16):4190-207; Provan et al, Blood, 2010;115(2):168-186). Patients with non-classical ITP were excluded (1 child with drug-induced ITP in the setting of acyclovir therapy, and 1 neonate with passive ITP in the setting of maternal lupus); and patients who were lost to follow-up or had ongoing disease of <1 year duration were subsequently excluded. Patient characteristics including age, gender, ethnicity, presence of concurrent autoimmune disease, and time to resolution were collected. Pertinent biomarkers including immunoglobulin levels (IgG, IgA, and IgM), anti-nuclear antibody (ANA), C-reactive protein (CRP), and immature platelet fraction (IPF) which were obtained at the time of diagnosis were documented, if if obtained prior to the administration of any ITP-directed therapy, and within 2 weeks of diagnosis. Chi-squared test or Fisher's exact test was utilized to compare nonparametric categorical data. Mann-Whitney U test was used to compare nonparametric continuous data. A multivariate backwards logistic regression model was conducted to determine independent associations with the development of chronic ITP. Statistical analyses were performed using SPSS Statistics 26 (IBM, Armonk, New York). A Bonferroni correction was applied to correct for multiple comparisons. A p value < 0.05 was defined as statistically significant. Results: We identified 251 pediatric ITP patients with sufficient length of follow-up to define acute (<1 year) vs. chronic (>1 year) disease within our 4-year study period. This included 132 patients with acute ITP (53%) and 119 patients who went on to develop chronic ITP (47%). Mean age of diagnosis among those with acute ITP was 5.5 years, while mean age of diagnosis among those with chronic ITP was 7.7 years. Within the entire cohort, 126 (50%) were male, and 124 (49%) were of Hispanic ethnicity. Fifty-eight had ITP attributable to systemic autoimmune disease - 17% within the Acute ITP group, and 30% within the Chronic ITP group. Among all patients (n=251), 188 with evaluable biomarkers (immunoglobulin levels, ANA, CRP, or IPF) at the time of diagnosis were identified. These included 174 patients with Ig levels at diagnosis, 43 patients with ANA titers at diagnosis, 25 patients with CRP levels at diagnosis, and 78 patients with IPF at diagnosis. By univariate analysis, we found that abnormalities in immunoglobulin levels at diagnosis were significantly associated with the development of chronic ITP. Low IgG levels (p = 0.015) were more prevalent in chronic (10.3%) vs. acute ITP (1.9%). High IgG levels (p = 0.015) were more prevalent in chronic (6.7%) vs. acute ITP (1.9%). High IgM levels (p = 0.03) were more prevalent in chronic (26.5%) vs. acute ITP (13.3%). Of note, the presence of Evans syndrome (p = 0.0005) and other systemic autoimmune disease (p = 0.011) were also significantly associated with the development of chronic ITP. Subsequent multivariate analysis identified low IgG level at diagnosis to be independently predictive of chronic ITP (p = 0.043, with an odds ratio of 5.7). Conclusion: Although further study is needed within a larger international pediatric ITP cohort, the findings from this institutional study indicate that biomarkers obtained in routine clinical care at the time of ITP diagnosis, specifically immunoglobulin levels, can be utilized to help predict development of chronic disease among pediatric ITP patients. Disclosures Despotovic: Amgen: Research Funding; Dova: Honoraria; Novartis: Research Funding.

Cutaneous Hemorrhage Types As Supportive Factors for Predicting Chronic Immune Thrombocytopenia in Children

Our objective was to assess risk factors for developing chronic immune thrombocytopenia (ITP) in children. The charts of all consecutive children diagnosed with ITP between 2000 and 2015 at a single center were retrospectively reviewed, and clinical characteristics at initial presentation were analyzed. Sixty-two children were included in the study (mean age, 6.15 y); 44 (71%) were found to have acute ITP, and 18 (29%) developed chronic ITP (permanent or relapsing thrombocytopenia >12 mo). In a univariate analysis, cutaneous hemorrhages were observed significantly more in acute patients (90.9%) than in chronic patients (61.1%). Patients who had acute ITP were more likely to present with a combination of petechiae, purpura, and/or ecchymosis (75%) than patients with chronic disease (44.4%, P=0.010). In multivariate analysis, older age increased the risk (odds ratio=1.1; P<0.05) for chronic disease, and manifestations of combination skin hemorrhages (petechiae/purpura/ecchymosis) reduced the risk (odds ratio=0.167; P<0.05). In conclusion, the most important risk factor for chronic disease is older age. Skin hemorrhage types were found to be a supportive factor for the prediction process: the combination of petechia/purpura/ecchymosis was associated with a lower risk for developing chronic disease compared with petechiae alone. Future studies should assess the prognostic value of skin hemorrhage types that are a simple way to predict the course of ITP in children. Disclosures No relevant conflicts of interest to declare.

Successful Management of Immune Thrombocytopenia Presenting with Lethal Alveolar Hemorrhage

Immune thrombocytopenic purpura (ITP) typically presents with bleeding due to immunologic thrombocytopenia. Severe hemorrhage due to ITP is sometimes lethal, and the urgent recovery of platelets is necessary. In addition to conventional therapeutic strategies, romiplostim shows promising efficacy for chronic ITP. However, there is little evidence for the utilization of this treatment for acute ITP or acute exacerbation of chronic ITP. We report the case details of three elderly ITP patients presenting with lethal diffuse alveolar hemorrhage. These patients had the following underlying pulmonary diseases: case 1, nontuberculous mycobacterial infection and sarcoidosis; case 2, cryptogenic organizing pneumonia; case 3, pulmonary emphysema. These patients recovered following treatment with romiplostim at a higher dose (10 μg/kg), in addition to conventional therapies including corticosteroids and high-dose intravenous immunoglobulin. In summary, the addition of romiplostim resulted in earlier recovery of thrombocytopenia than has been previously reported. Our three cases suggest that early romiplostim at a higher dose could be an efficacious therapeutic option for acute ITP patients with severe lethal bleeding.