Acute Immune Thrombocytopenic Purpura Research Articles

Is Childhood Immune Thrombocytopenia Associated With Acquired Toxoplasmosis? An Unusual Case of Infection That Led to Acute ITP in a Greek Male Toddler and Implications for Guidelines.

Childhood immune thrombocytopenic purpura (ITP) is a heterogeneous immune-mediated process triggered by infections, vaccines, allergies and parasites. Currently, there is little evidence in the literature beyond case reports of an association with Toxoplasma gondii (T. gondii). The authors describe the unusual case of an earlier healthy 2.5-year-old Greek boy who developed acute ITP with a life-threatening platelet count a few days after a T. gondii infection. Evidence for the infection onset was found incidentally 3 months after the initial admission to the hospital and only after any other plausible cause of thrombocytopenia was excluded, according to diagnosis guidelines. The boy underwent 3 intravenous immunoglobulin treatments within a trimester, a period during which his alarming platelets count levels led to housebound activities. A quite slow recovery was only ignited after the third treatment, which was administered in conjunction with a mild antibiotic medication for the T. gondii infection. Full recovery was obtained 9 months after the initial admission, although the boy's potential scored high in clinical prediction models for developing transient ITP. There is a need for more research on ITPs with no obvious cause to investigate a causal association with toxoplasmosis. Currently, testing for diseases of greater rarity and of higher diagnostic cost than T. gondii is included in the ITP guidelines. Hence, routinely testing for toxoplasmosis when considering potential childhood ITP triggers and infection treatment complementary to treating the ITP might be the key to accelerating the healing process and improving the quality of life of otherwise confined children.

Immune thrombotic thrombocytopenic purpura: Spotlight on long-term outcomes and survivorship.

Advances in diagnosis and treatment have dramatically improved survival of acute immune thrombotic thrombocytopenic purpura (iTTP) and iTTP has evolved from an acute fatal condition to a chronic relapsing disorder. In addition to the risk of iTTP relapse, iTTP survivors are at risk of multiple adverse health outcomes including higher than expected rates of all-cause mortality, increased rates of stroke and other cardiovascular disease, and higher rates of morbidities such as obesity, hypertension, and autoimmune disorders. iTTP survivors also report neurocognitive impairment, depression, and reduced quality of life. Women with iTTP are at risk for recurrent iTTP, preeclampsia, and other maternal and fetal complications in subsequent pregnancies. ADAMTS13 activity during clinical remission has emerged as an important targetable risk factor for iTTP relapse and other outcomes including stroke and all-cause mortality. This review summarizes current literature regarding the epidemiology and potential mechanisms for adverse long-term sequelae of iTTP, outlines current best practices in iTTP survivorship care, and highlights a research agenda to improve long-term iTTP outcomes.

Assessment of plasmablast cells in immune thrombocytopenic purpura in children

Primary immune thrombocytopenic purpura (ITP) is an autoimmune disorder with platelet destruction due to B- and T-cell dysregulation and antiplatelet autoantibodies production. Flow cytometry can be used to further characterize the B- and T-cell compartments involved in platelet destruction. This case-control study was to enumerate plasmablast cells in pediatric ITP patients and to correlate their levels with disease course. This study included 30 ITP patients and 10 controls. Identification and enumeration of Plasmablast were done by multicolor flow cytometry using specific antibody panels (CD19, CD27 & CD38) and sequential gating using FACSCanto flow cytometer and FlowJo software. We found that lymphocytes subpopulation in ITP patients and controls revealed increase in frequency of CD19 (B lymphocytes) in acute, persistent, and chronic ITP patients in comparison with controls (p < 0.001, 0.023, 0.001) respectively. Plasmablast cells could play a role in the pathogenesis of ITP and might guide therapy in ITP patients in the future.

Mortality in Acute Immune-Mediated Thrombotic Thrombocytopenic Purpura (iTTP) Is Unpredictable: Poor Statistical Performance of Mortality Prediction Models

Background:Mortality due to acute immune thrombotic thrombocytopenic purpura (iTTP) is estimated at 10% with current standard treatment with plasma exchange (PLEX) and corticosteroids. Caplacizumab was recently shown to reduce mortality in acute iTTP, but may not be cost-effective in treating all patients. Predicting the risk of iTTP-related mortality has been of interest as it may help individualize treatment by considering more intensive treatment approaches that could further reduce mortality, as well as improving cost-effectiveness by restricting caplacizumab use to high-risk patients. The French Thrombotic Microangiopathy (TMA) Reference Score was developed as predictive model for acute iTTP mortality and was validated in the French TMA registry. External validation of the score on a large United States population has not been performed. The USTMA iTTP registry contains outcome data on 771 patients diagnosed with iTTP from 15 high-volume TTP referral centers. The aim of this study was to validate or improve upon the French TMA Reference Score using the USTMA iTTP registry.Methods:We included participants with initial presenting iTTP episode (n=419) from the USTMA iTTP registry (n=771) between 1985 and 2019. We analyzed thirty different baseline patient demographics, laboratory findings and treatment variables at time of initial presentation. We excluded ADAMTS13 inhibitor/antibody levels due to inconsistency in reporting of assays. We defined acute iTTP mortality as death within 30 days of last PLEX.Validation of French score:Risk scores of 0 - 4 were assigned according to the French TMA Reference score based on age, lactate dehydrogenase (LDH) level, and presence of neurologic symptoms. After the analysis demonstrated low area under the receiver operating characteristic curve (AUC) in our population, we then utilized our registry to develop a novel mortality prediction model.Development of the USTMA TTP Mortality Index:Patient characteristics at presentation were compared between first episode survivors vs. non-survivors, and those with p values < 0.1 were entered as candidate predictors to develop a logistic regression model. Missing values were imputed using multiple imputation using chained equations (MICE), and 15 augmented datasets were generated. For each of the imputed datasets a model was selected using the Lasso method, and then the coefficients from the 15 models were averaged to form a final prediction model. Odds ratios (ORs), 95% confidence intervals (CIs) and p-values were reported from the final model. AUC was evaluated on the pre-imputed data (n=348), as well as using 5 fold cross validation on the imputed data sets.Results:Validation of the French TMA Reference Score:We found that the French TMA Reference Score performed poorly to predict death from acute iTTP in our cohort: AUC 0.63 (95% CI: 0.50-0.77) (Figure 1a), compared to the AUC of 0.77 reported in the French population. Using a cut-off of ≥ 3, the sensitivity was 0.35, specificity was 0.84, and positive predictive value was 0.1.Development of the USTMA TTP Mortality Index:There were 24 deaths (5.7%) in our cohort. We identified six variables to be included in the predictive model below. A nomogram for the model was developed and is depicted in Figure 2. •Age: OR = 1.12 (0.99,1.58)•Male sex: OR = 1.16 (0.93,3.04)•Stupor or coma on presentation: OR: 2.08 (0.90,8.87)•Hemoglobin level (g/dL): OR = 1.23 (1.00,1.43)•LDH level (U/L): OR = 1.08 (0.91,1.32)•Creatinine level mg/dL: OR = 1.10 (1.00,1.81)Performance of the USTMA TTP Mortality Index model:The model has an AUC of 0.78 (95% CI 0.67-0.90) on the pre-imputation cohort of 348 patients who had complete data on the model variables (Figure 1b), and a 5 fold cross-validated AUC of 0.69 (95% CI: 0.58 ~ 0.78) (Figure 1c).Conclusion:Both the French TMA Reference score and the USTMA TTP Mortality Index demonstrated poor performance in predicting iTTP mortality in our study. The low mortality rate observed in this database is consistent with recent randomized trials, but is lower than historically reported, and may contribute to poor accuracy of prediction models. We therefore conclude that mortality due to acute iTTP may be unpredictable with available models. Attempts to tailor caplacizumab specifically to patients with higher risk for acute iTTP-related death, based on available models, may not succeed in reducing mortality or improving cost-effectiveness. [Display omitted] DisclosuresMazepa: Answering TTP Foundation: Research Funding; Sanofi Aventis: Other. Lim: Dova Pharmaceuticals: Honoraria; Hema Biologics: Honoraria; Sanofi Genzyme: Honoraria.

Vzácné trombotické komplikace vyvolané vakcinací proti SARS-CoV-2

Shortly after the worldwide initiation of vaccination against SARS-CoV-2, concerns emerged about a possible link between vaccination, severe thrombocytopenia, and the development of atypical venous thrombosis. Concerns were primarily about AstraZeneca (ChAdOx1 nCov-19), later Johnson & Johnson (Ad26.COV2.S), but cases of acute immune thrombocytopenic purpura (ITP) and bleeding without thrombosis and also atypical venous thrombosis after exposure to the messenger RNA-based vaccines produced by Pfizer-BioNTech and Moderna have been reported. Examination of the circumstances of these complications revealed that this is a similar mechanism to heparin-induced thrombocytopenia (HIT), a prothrombotic thrombocytopenic hypercoagulable disorder with venous and arterial thrombosis. HIT is caused by platelet-activating IgG antibodies directed against an antigen that is a macromolecular complex consisting of platelet factor 4 (PF4) and heparin. Naming this new entity vaccine-induced immune thrombotic thrombocytopenia (VITT) was suggested to avoid confusion with HIT. Patients had high levels of antibodies to the immune complex formed by PF 4 and the polyanionic component of the vaccine (double-stranded DNA). In patients with thrombosis at any vascular site after vaccination, accompanied by absolute or relative thrombocytopenia and systemic manifestations, HIT Ig ELISA assay to detect antibodies against PF4 and platelet-activating functional tests may be used for VITT recognition and differentiation from venous thromboembolic disease. Immune globulin impedes antibody-mediated platelet clearance and down-regulate platelet activation by immune complexes, as in HIT. It is prudent to choose from among the nonheparin antithrombotic agents - direct oral F.Xa inhibitors, direct thrombin inhibitors and indirect F.Xa inhibitors for the treatment of thrombosis.

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.

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.

Role of platelet endothelial aggregation receptor 1 polymorphisms in idiopathic thrombocytopenic purpura: Is there an association?

Background: Genetic risk factors are implicated in the etiology and pathogenesis of immune thrombocytopenic purpura (ITP). Platelet endothelial aggregation receptor 1 (PEAR1) plays an important role in regulating megakaryopoiesis and thrombopoiesis. rs12041331 and rs12566888 single-nucleotide polymorphisms of PEAR1 are associated with megakaryocyte differentiation and platelet function. Materials and Methods: To conduct this study, 68 peripheral blood samples of patients with ITP (56 acute and 12 chronic) were collected. The amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was used to detection of rs12041331 and rs12566888 PEAR1 polymorphisms. Results: Statistically significant differences were not seen between rs12041331 and rs12566888 genotypes in acute and chronic groups (P = 0.778, P = 0.844). The frequency of rs12041331 AG/AA genotypes and the rs12566888 GT genotype was more in acute ITP patients; on the other hand, the rs12566888 TT genotype was more in the chronic group. The highest platelet counts and platelet distribution width (PDW) were related to the rs12041331 AG allele. GT and TT of rs12566888 had more PDW and platelet count, respectively. Mean platelet volume values between alleles of both the polymorphisms were constant and did not differ much. In general, no statistically significant differences were observed between genotypes of polymorphisms and platelet parameters. Conclusions: There was no association between rs12041331 and rs12566888 with platelet parameters in ITP patients and the severity of this disease. Further investigation with a larger size is recommended.

Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which autoantibodies react with platelet surface antigens and results in mild to severe thrombocytopenia due to decreased platelet count or inhibition of platelet production. Given the relatively high prevalence of ITP among children and the lack of standard diagnostic testing for the diagnosis of chronic disease, this study evaluated the predictive value of risk factors for chronic ITP in hospitalized patients.&#x0D; METHODS: This prospective cohort study was performed on 65 children with ITP who referred to Ali Asghar and Rasool Akram Hospitals in Tehran, Iran, during the years 2017 and 2018. Relationships between different risk factors, including age of diagnosis, gender, white cell count, primary platelet count, mean platelet volume (MPV), history and type of the previous patient infection, FCG gene mutation, and type of FCG mutation with a chronic disease incidence were investigated using multiple logistic regression model.&#x0D; RESULTS: Of 65 patients, 31 (47.69%) were male and 34 (52.31%) were female included in the study. Twenty-eight patients (43.08%) had acute ITP and 37 (56.92%) had chronic ITP. Frequency of FCG gene mutation in patients with chronic and acute type ITP was 16.36% and 7.27%, respectively (p = 0.51). No association was found between the history of the previous infection and its type with the chronic incidence of ITP. The multiple logistic regression model showed that three factors, including the absolute number of lymphocytes, age of diagnosis, and primary white blood cells (WBC) count were directly linked to chronic ITP. Furthermore, three factors of platelet, sex, and MPV were indirectly related to chronic ITP. In addition, the absolute number of lymphocytes, age of diagnosis and primary WBC count were significantly associated with chronic ITP. The receiver operating characteristic analysis showed that the cutoff rate of these factors was 0.31. Further analysis of these risk factors in comparison with the gold standard demonstrated that the diagnostic sensitivity and specificity of these risk factors for chronic ITP were 73.08% and their specificity was 88.57%, indicating the high importance and predictive power of these risk factors.&#x0D; CONCLUSIONS: According to the results of this study, for the first time in Iran, six risk factors, including the absolute number of lymphocytes, age at diagnosis, sex, MPV level, platelet level at time of diagnosis, and primary WBC count were considered as the most important risk factors affecting the incidence of chronic ITP. Of course, more comprehensive studies can definitely lead to more comprehensive models.

Relationship of primary immune thrombocytopenic purpura and atopia among children: a case control study

Atopic dermatitis (AD) is a chronic disease affecting 10–30% of children and 2–10% of adults worldwide. It is manifested by the pruritus eczema lesions on the skin. Immune thrombocytopenic purpura (ITP) is the most common cause of acute onset of thrombocytopenia in childhood. The aim of this study was association of primary immune thrombocytopenic purpura and atopia among children. This case control study was performed on patients with acute and chronic ITP who were confirmed by a hematologist. The control group was also selected from the siblings of the patients who were healthy and almost matched by age and sex with the patient group. Data were entered into a questionnaire under the SPSS-20 program, and demographic data were analyzed descriptively. In the present study, 120 patients were enrolled, 60 of whom were in the patient group and 60 in the control group. Mean age was 95 and 98 months for patients and control. This study showed a significant association of ITP with allergic rhinitis (P = 0.02), atopic dermatitis (P = 0.004), itching (P = 0.042), and dry skin (P = 0.015). However, no significant relationship was found between ITP and asthma (P-value = 0.18). This study does not reveal the causality between atopy and ITP but clearly shows the association between atopy and ITP disease, so the prevalence of atopy in ITP patients is higher than the normal population. According to the results of this study, it is necessary to investigate the cause of atopy and ITP and to find other immunological and possibly genetic commonalities.

Efficacy and Safety of Anti-D for Acute Immune Thrombocytopenic Purpura in Children in El-Nasr Hospital - Case Report

Efficacy and Safety of Anti-D for Acute Immune Thrombocytopenic Purpura in Children in El-Nasr Hospital - Case Report

Rotational thromboelastometry parameters as predicting factors for bleeding in immune thrombocytopenic purpura

Objective/BackgroundPatients with immune thrombocytopenic purpura (ITP) often present with a severe reduction in platelet counts and suffer from an increased risk of bleeding. However, platelet counts do not accurately predict bleeding risk in these patients. MethodsWe thereby conducted a case series prospective study to compare the ability to predict hemorrhage in ITP patients between platelet counts and various rotational thromboelastometry (ROTEM) parameters. ResultsThe inclusion criteria for patients diagnosed with acute, persistent, and chronic ITP were platelet counts of <30 × 109/L and no clinically significant bleeding (grade ≥ 2 according to the WHO Bleeding Scale) at the beginning of the study. After 24 hours of follow-up, of the 45 enrolled patients, 14 (31.1%) experienced clinically significant bleeding. The mean platelet counts of patients with and without clinically significant bleeding were not statistically different (p = .09). However, the mean EXTEM maximum clot firmness (MCF), EXTEM A10, EXTEM area under the curve (AUC), and platelet maximum clot elasticity (MCE) values of the two groups were statistically different (p < .05). There was also a significant difference in IPF values between these two groups (p < .05.) ConclusionResults obtained from this preliminary study demonstrate that ROTEM parameters might be useful in predicting factors for hemorrhage in ITP patients. Future studies with a larger sample size is warranted to confirm our findings, which will allow prompt and effective bleeding management in ITP patients.

Humoral and Complement Systems in Children With Acute Immune Thrombocytopenic Purpura

Humoral and Complement Systems in Children With Acute Immune Thrombocytopenic Purpura

Deaths and complications associated with the management of acute immune thrombotic thrombocytopenic purpura.

The introduction of therapeutic plasma exchange (TPE) dramatically decreased mortality in patients with immune thrombotic thrombocytopenic purpura (iTTP). However, there are few modern descriptions of residual causes of death from iTTP and complications associated with TPE. This was a retrospective study in a multi-institutional cohort of 109 patients with iTTP between 2004 and 2017. Complications of TPE were analyzed in a subset of this cohort (74 patients representing 101 treatment courses). Death occurred in 8 of 109 patients (7.3%) and in 8 of 219 captured episodes of acute iTTP (mortality rate per episode: 3.7%). Neither the number of TPE treatments nor length of hospitalization predicted mortality. The majority of deaths (5/8) were associated with delay in the diagnosis of iTTP or initiation of TPE or presentation to the hospital in a moribund state. A subset of patients (N = 74) was analyzed for TPE-related complications. Most patients (56/74; 76%) had at least one minor or major complication of TPE. Seven of 101 (6.9%) discrete treatment courses were associated with one or more severe complications, including anaphylaxis and line-associated infections and thrombosis. Overall, the most frequent adverse events were mild allergic (urticarial) transfusion reactions, which affected 34 of 101 (34%) treatment courses. One patient died from a TPE-related complication, line-associated bacteremia. Early identification of patients with iTTP and the rapid initiation of TPE are paramount in preventing mortality. While TPE was associated with a high rate of adverse events, the vast majority were treatable and TPE-related mortality is low.

Outcome of Immune Thrombocytopenic Purpura In a Tertiary Care Centre

Background : The study aimed to demonstrate the pattern of clinical presentations and outcome of Immune Thrombocytopenic Purpura (ITP) in Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka.&#x0D; Materials and methods: A retrospective study was conducted by record reviewing and analyzing the data of 103 patients of acute ITP, ageing between 1-16 years, at the Department of Paediatric Haematology and Oncology, Bangabandhu Sheikh Mujib Medical University (BSMMU) Dhaka from June 2017 to December 2019. We reviewed the data regarding age, sex, clinical presentations, history of preceding viral infections, vaccination history, laboratory values, different treatment options used and response to the treatment concerning complete response, partial response and poor responders. Statistical analysis performed by using IBM SPSS statistics version 20.&#x0D; Results: We retrospectively reviewed a total of 103 patients. The median age, at the time of presentation, was 5±3.4 years while the mean age was 4.5±2.9 years. The male to female ratio was 1.28:1. Mean platelet count on presentation was 7 x 109/L (Range: 0-24). Twenty three (22.3%) patients had the history of preceding febrile illness. Bruises, petechiae, epistaxis and hematemesis remained the common presentations. Six (5.8%) patients showed spontaneous recovery while 97 (94%) patients received treatment for ITP. Overall, 71 (68.9%) showed a response after treatment. Sixty-two patients (59.22%) showed loss of response and received treatment again. Among these patients, thirty-four patients (33%) developed chronic disease.&#x0D; Conclusion: Majority of patients presenting to our tertiary care centre had severe acute ITP on presentation.After management and follow-up, almost one third of the patients develop chronic disease hence the incidence of developing chronic disease remained high as compared to the other centers.&#x0D; JCMCTA 2019 ; 30 (2) : 81-85

Diagnostic Value of MPV, PDW, PAIg and Their Combination for Megakaryocyte Dysmaturity in Children with Acute Immune Thrombocytopenic Purpura

To investigate the changes of mean platelet volume (MPV), platelet distribution width (PDW) and platelet associated antibodies (PAIg) in children with acute immune thrombocytopenic purpura (aITP), and to explore the diagnostic value of MPV, PDW, PAIg and their combination for megakaryocyte dysmaturity in aITP children. Plt count, MPV and PDW of 36 aITP children were measured by using Sysmex XN automatic blood cell analyzer, and 33 children with acquired thrombocytopenic purpura (ATP) without megakaryocyte dysmaturity. The expression of PAIg was detected by flow cytometry, and the number and classification of megakaryocytes in the bone marrow were performed by marrow cytology. The diagnostic significances of MPV, PDW, PAIg and their combination as well as the sensitivity and specificity for megakaryocytes dysmaturity in aITP were assessed through calculating the area under ROC curve (AUC), after determining the influence of each parameters on the megakaryocyte dysmaturity by Logistic regression. MPV, PDW and PAIg of aITP children were significantly higher than those of the ATP children (P＜0.05), while the Plt count and number of thromocytogenic megakaryocytes per area (1.5 cm×3 cm) were less than those of the controls (P＜0.05). Count of RBC and WBC, percentages of neutrophil granulocytes and lymphocydes in aITP were similar to those in the controls（P＞0.05）. The results of Logistic regression showed that Plt count, MPV, PDW and PAIg were the factors influencing megakaryocyte dysmaturity in aITP children, and the regression model has a high statistical significance (χ2=65.491，P=0.001) and r square (R2=0.713). The AUC of the combined detection of Plt count, MPV, PDW and PAIg was 0.863, which was much higher than that of Plt count, MPV, PDW, PAIg individually or in pairs. The sensitivity and specificity of the combined detection were 79.167% and 89.697%, which were higher than those of Plt count, MPV, PDW, PAIg individually or in pairs. The diagnostic significance of MPV and PDW for megakaryocyte dysmaturity in aITP are insufficient, but the diagnostic efficacy can be improved by combined examination with PAIg.

Platelets level response after three days therapy in children with acute Immune Thrombocytopenic Purpura (ITP): a 10 years’ experience at the tertiary hospital

Background: Immune thrombocytopenic purpura (ITP) is the most common cause of thrombocytopenia in children that characterized by isolated thrombocytopenia that vary in bleeding manifestations. The onset of disease is sudden and a self-limiting condition that requires treatment when clinically significant bleed occurs. A treatment goal is to increase platelet level above safety level and reduce the risk of severe bleeding. This study aims to evaluate the platelets level increment after three days treatment among children with acute ITP.Methods: An analytic retrospective cross-sectional study was conducted in Haematology-Oncology Paediatric Division Sanglah General Hospital, Bali, Indonesia from October 2008 to October 2018 in ITP patients. Diagnosis of ITP was evaluated based on the clinical manifestation and laboratory finding. Oral corticosteroid medication with dosage 2 mg/kg/day or 4 mg/kg/day with or without platelets transfusion were enrolled in this study from medical records. Data were analyzed using SPSS version 20 for Windows.Results: There were 93 children met the inclusion criteria and included in this study. A median platelets level at admission was 6.81(1-86.8) x 109/L. Majority symptoms of children with ITP in our tertiary care centre presented with mild to moderate clinical bleeding symptoms. Only 5.6% children with platelets level below 10x109/L had intracranial bleeding. Median platelets level was 31(2.47-382) x 109/l and there was a significant platelets level increment after three days of therapy (P&lt;0.05).Conclusion: The platelets level increment significantly in children with acute ITP after three days of therapy.

The retrospective evaluation of patients diagnosed with acute immune thrombocytopenic purpura and comparison of treatments of high-dose methylprednisolone and intravenous immunoglobulin

Amac: Cocukluk caginda en sik gorulen edinsel trombositopeni nedenlerinden birisi immun trombositopenik purpuradir. Immun trombositopenik purpura (ITP), otoantikorla kapli trombositlerin retikuloendotelyal sistemde doku makrofajlari araciligiyla yikilarak dolasimdaki trombosit sayisinin azalmasi ve bu otoantikorlarin trombosit uretimini inhibe etmesi ile seyreden otoimmun bir hastaliktir. Bu calismada akut immun trombositopenik purpura tanisi almis hastalarin dosyalari retrospektif olarak incelendi. Hastalarin basvuru sirasindaki klinik ozellikleri ve tedavi seciminin etkinlikleri belirlenmeye calisildi. Gerec ve Yontemler: Hastanemiz Cocuk Hematoloji Kliniginde, Ocak 2010 - Agustos 2014 tarihleri arasinda akut immun trombositopenik purpura tanisi alan hastalar calismaya dâhil edildi. Hasta dosyalari retrospektif olarak incelendi. Yuksek doz metilprednizolon ve intravenoz immunglobulin (IVIG) tedavileri alan hastalarin tedaviye yanitlari karsilastirildi. Bulgular: Calismamiza alinan hastalarin 91’i (%56,9) erkek idi. Hastalarin %48,13’unde basvurudan 1-4 hafta oncesinde gecirilmis enfeksiyon oykusu mevcuttu. Hastalarin ortalama trombosit sayisi 12081±11912 /mm3 idi. Yuz bes (%65,6) hastaya yuksek doz metilprednizolon, 55 (%34,4) hastaya IVIG tedavileri verilmisti ve tedavinin 10. gununde, tedaviye yanit acisindan istatistiksel olarak yuksek doz metilprednizolon ile intravenoz immunglobulin arasinda anlamli fark saptanmadi (p=0,732). Alti ayin sonunda yuksek doz metilprednizolon verilen hastalar ile intravenoz immunglobulin verilen hastalar arasinda kroniklesme acisindan anlamli iliski saptanmadi (p=0,468). Basvuru aninda bakilan kanama zamani 7 dakikanin uzerinde olan %15 hastanin kroniklesme gelisme orani daha yuksek saptandi (p=0,031). Sonuc: Immun trombositopenik purpura cocukluk caginda sik gorulen bir hastalik olup hastalarin %20-30’u kroniklesmektedir. Yuksek doz metilprednizolon ile intravenoz immunglobulin tedavilerinin kroniklesme uzerine etkisi acisindan aralarinda fark saptanmamistir.

Predictive Value of Risk Factors for Chronic Idiopathic Thrombocytopenic Purpura in Patients with Acute Type of Disease

Background: Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which autoantibodies react with platelet surface antigens and results in mild to severe thrombocytopenia due to decreased platelet count or inhibition of platelet production. Given the relatively high prevalence of ITP among children and the lack of standard diagnostic testing for the diagnosis of chronic disease, this study evaluated the predictive value of risk factors for chronic ITP in hospitalized patients. Methods: This prospective cohort study was performed on 65 children with ITP who referred to Ali Asghar and Rasool Akram hospitals in Tehran, Iran during the years 2017 and 2018. Relationships between different risk factors including age of diagnosis, gender, white cell count, primary platelet count, Mean platelet volume (MPV) , history and type of previous patient infection, FCG gene mutation, and type of FCG mutation with chronic disease incidence were investigated using multiple logistic regression model. Results: Of 65 patients, 31 (47.69%) were male and 34 (52.31%) were included in the study. 28 patients (43.08%) had acute ITP and 37 (56.92%) had chronic ITP. Frequency of FCG gene mutation in patients with chronic and acute type ITP was 16.36% and 7.27%, respectively (p = 0.51). No association was found between the history of previous infection and its type with the chronic incidence of ITP. Multiple Logistic regression model showed that 3 factors including absolute number of lymphocytes, age of diagnosis and primary WBC count were directly linked to chronic ITP. Furthermore, 3 factors of platelet, sex and MPV were indirectly related to chronic ITP. In addition, absolute number of lymphocytes, age of diagnosis and primary WBC count were significantly associated with chronic ITP. The ROC analysis showed that the cut off rate of these factors was 0.31. Further analysis of these risk factors in comparison with the gold standard demonstrated that the diagnostic sensitivity and specificity of these risk factors for chronic ITP were 73.08% and their specificity was 88.57%, indicating the high importance and predictive power of these risk factors. Conclusion: According to the results of the current study, evaluation of 6 major risk factors including absolute lymphocyte count, age at diagnosis, sex, MPV level, platelet level at diagnosis and primary WBC count for the identification of chronic ITP is recommended before IVIG treatment. Of course, more comprehensive studies can definitely lead to more comprehensive models. Funding Statement: The authors stated: Not applicable. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The children participated in the study with the full parental consent, ensuring that all children's information was kept confidential. The project was initially approved by the Ethics Committee of Iran University of Medical Sciences with code IR.IUMS.FDM.REC. 1396.29265

CHARACTERISTIC OF TIM-3 EXPRESSION IN T CELL SUBSETS IN PATIENTS WITH IMMUNE THROMBOCYTOPENIC PURPURA

T cell dysregulation is a common event involved in immune thrombocytopenic purpura (ITP). Recent findings indicated that aberrant expression of immune checkpoints may be related to autoimmune disease pathogenesis as well as in ITP. However, the distribution of Tim-3 and its co-expression with exhausted phenotype in T cell subsets remain unclear. In this study, the frequency of T-cell immunoglobulin mucin 3 (TIM-3) expression and co-expression with CD244 and CD57 in CD3+, CD4+ and CD8+ T cells were evaluated in peripheral blood (PB) from 16 cases with ITP and 21 healthy individuals (HI). Overall, the frequency of Tim-3+CD3+, CD4+ and CD8+T cells in ITP is similar to HI. However, Tim-3+CD244+CD8+ and Tim-3+CD57+CD8+T cells were increased in ITP in compared with HI group. While the percentage of CD244+ and CD57+CD3+, CD4+ or CD8+T cells was similar between ITP and HI groups. Moreover, the Tim-3+CD244+CD3+ and Tim-3+CD244+CD8+ T cells in newly diagnosed ITP group were higher than that in relapsed ITP group, similar trends showed in Tim-3+CD57+CD3+T cells. Obviously, relative higher Tim-3+T cells in most T cell subsets were detected in a case with acute ITP with viral infection. The distribution of Tim-3+ T cells in different subsets was also compared between PB and bone marrow (BM). High trends of Tim-3+T cells was detected in BM group. In conclusion, we firstly characterized T cell immune disorder with higher level of Tim-3+exhausted+CD8+T cells in ITP, the effect and mechanism of such alteration in ITP is needed further investigation.