Diagnosis Of Primary Immune Thrombocytopenia Research Articles

Can Machine Learning Assist in Diagnosis of Primary Immune Thrombocytopenia? A Feasibility Study.

Primary Immune Thrombocytopenia (ITP) is a rare autoimmune disease characterised by the immune-mediated destruction of peripheral blood platelets in patients leading to low platelet counts and bleeding. The diagnosis and effective management of ITP are challenging because there is no established test to confirm the disease and no biomarker with which one can predict the response to treatment and outcome. In this work, we conduct a feasibility study to check if machine learning can be applied effectively for the diagnosis of ITP using routine blood tests and demographic data in a non-acute outpatient setting. Various ML models, including Logistic Regression, Support Vector Machine, k-Nearest Neighbor, Decision Tree and Random Forest, were applied to data from the UK Adult ITP Registry and a general haematology clinic. Two different approaches were investigated: a demographic-unaware and a demographic-aware one. We conduct extensive experiments to evaluate the predictive performance of these models and approaches, as well as their bias. The results revealed that Decision Tree and Random Forest models were both superior and fair, achieving nearly perfect predictive and fairness scores, with platelet count identified as the most significant variable. Models not provided with demographic information performed better in terms of predictive accuracy but showed lower fairness scores, illustrating a trade-off between predictive performance and fairness.

Clinical significance of antinuclear antibodies in primary immune thrombocytopenia.

There are discrepancies across guidelines about whether the dosage of antinuclear antibodies (ANAs) is of use at the diagnosis of primary immune thrombocytopenia (ITP). This review describes the current knowledge about ANA prevalence in patients with primary ITP, and their potential usefulness as biomarkers for ITP evolution, response to treatments and increased risk of subsequent development of systemic lupus and thrombosis.

Pediatrik İmmün Trombositopeni (İTP) Vakalarının ve Kronik İTP için Risk Faktörlerinin Değerlendirilmesi - Tek Merkez Deneyimi

Aim: Immune thrombocytopenia (ITP) is the most common acquired bleeding disorder in childhood. The study aimed to assess the demographic and clinical characteristics, and treatment responses and to evaluate their effects on chronicity in pediatric ITP cases.
 Material and Methods: Primary ITP patients aged 1 month to 18 years, who were diagnosed and followed up in the Pediatrics Clinic of Tokat Gaziosmanpaşa University Hospital between January 2010 and December 2018, were retrospectively analyzed.
 Results: Thirty-eight patients with a diagnosis of primary ITP were included in the study. The mean age of the patients was 94.3±53.4 (14-199) months. The female/male ratio was 1. Twenty (57.1%) patients had acute ITP, and 15 (42.9%) patients had chronic ITP. There was no significant difference between the acute ITP group and the chronic ITP group in demographic, clinical features, laboratory findings, and treatment responses. In the first 12 months, the number of admissions with a platelet count of

The Effect of Platelet and Mean Platelet Volume Levels on Standard-dose Methylprednisolone Treatment Response in Primary Immune Thrombocytopenia.

Standard-dose methyl-prednisolone (methyl-Pd) is generally preferred as the first-line treatment in immune thrombocytopenia (ITP) unless there is an urgent indication to increase the platelet value. A significant proportion of patients (around 40%) does not benefit from this treatment. This study investigated whether pretreatment platelet level and other hemogram indices in patients with ITP patients can be used to predict early response to standard-dose methyl-Pd treatment. Patients who received first-line standard-dose methyl- Pd therapy with the diagnosis of primary ITP were included. Patients were categorized as complete responder (CR), responder (R), and non-responder (NR) according to the response status obtained within the first 14 days of treatment. The hemogram indices of the CR, R, and NR groups measured at the start of the treatment were compared retrospectively. One hundred forty four patients with ITP were included in the study. The number of patients with NR, R, and CR were 47 (33%), 40 (28%), and 57 (39%), respectively. The mean platelet level of the NR group was lower than responders (R and CR groups) (p=0.002 and p=0.049, respectively). The mean platelet volume (MPV) levels of the NR group were statistically lower than that of the CR group (p=0.018). If MPV ≥10 fL and platelet >12,000/mm³, the probability of an early response with methyl-Pd is higher [sensitivity =98.1% (95% confidence interval (CI) =89.7-99.9%), specificity =45% (95% CI =23.1-68.5%), positive predictive value =82.3% (95% CI =75.7-87.4%), negative predictive value =90% (95% CI =54.9-98.5%)]. Patients with ITP with low platelet and MPV levels were less responsive to standard-dose methyl-Pd treatment. It may be more appropriate to apply more effective treatments to these patients other than standard-dose methyl-Pd alone.

Primary immune thrombocytopenia and cytomegalovirus infection About a case

Primary Immune Thrombocytopenia (ITP) is an acquired coagulation disease characterized by a decrease in platelets below 100 x 109/L in the absence of other causes of thrombocytopenia and that may be preceded by viral processes or vaccination. A 16-year-old male adolescent who presented a febrile syndrome was diagnosed as part of the studies as an infection by cytomegalovirus, later he began to present purpuric hemorrhagic manifestations on the skin and mucous membranes, for which a medulogram was performed and the diagnosis of Primary ITP was made. Conclusions: an adolescent who developed a TIP after cytomegalovirus infection, requiring treatment with steroids and valganciclovir for its management.

Diagnostic Value of Peripheral Blood Lymphocytes for Primary Immune Thrombocytopenia.

The purpose of this study was to investigate the absolute value of peripheral blood lymphocytes in patients with primary immune thrombocytopenia and the diagnostic effect on patients with primary immune thrombocytopenia. From January 2020 to June 2021, 76 patients with primary immune thrombocytopenia and 80 healthy check-ups admitted to our hospital were selected as study subjects and divided into a control group (80 patients, healthy check-ups) and an observation group (76 patients, primary immune thrombocytopenia), according to the health status of the organism. Early morning fasting venous blood was collected from both groups, and the absolute value of peripheral blood lymphocytes was measured and compared using a fully automated hematology analyzer to investigate the diagnostic value of absolute peripheral blood lymphocytes in primary immune thrombocytopenia. The CD3+, CD3+CD4+, CD4+/CD8+, and CD16+CD56+ assay values in the observation group were lower than those in the control group, and the CD3+CD8+, CD19+, and ALC assay values were higher than those in the control group (P < 0.05). The CD3+CD8+ detection values of newly diagnosed patients were similar to those of relapsed refractory patients (P > 0.05); CD3+, CD3+CD4+, CD4+/CD8+, and CD16+CD56+ detection values of newly diagnosed patients were lower than those of relapsed refractory patients, and CD19+ and ALC detection values were higher than those of relapsed refractory patients; CD3+, CD3+CD4+, CD4+, CD4+/CD8+, and CD16+CD56+ detection values of mild patients were lower than those of relapsed refractory patients; CD3+, CD3+CD4+, CD4+/CD8+, and CD16+CD56+ detection values were higher in mild patients than in severe patients, and CD3+CD8+, CD19+, and ALC detection values were lower than in severe patients (P < 0.05). The absolute lymphocyte values were of high diagnostic value in primary immune thrombocytopenia, with a sensitivity and specificity of 93.42% and 90.00%. The application of absolute peripheral blood lymphocyte value in the clinical diagnosis of primary immune thrombocytopenia can achieve a better detection and diagnosis effect, which has a positive impact on the early diagnosis rate and can help patients to obtain more timely, effective and targeted treatment, and is worthy of promotion.

Immune thrombocytopenia

An inherited condition with isolated thrombocytopenia, immune thrombocytopenia (ITP) is still unknown in terms of the cause. A primary or secondary ITP diagnosis is determined by whether or not an underlying treatable cause exists. Diagnosis of primary ITP is based on the exclusion and hence does not have a gold standard test to validate it. Before classifying a patient as primary ITP, recent medication use, infections, lymphoproliferative illnesses, and connective tissue disorders should be checked out. An in-depth look at the most recent developments in ITP diagnostics and treatment is provided in this study. Our research was supported by GOOGLE Scholar, PUBMED, and ClinicalTrial.gov databases. Idiopathic thrombocytopenic purpura was also included in the search, as was "immune-mediated thrombocytopenia," "idiopathic thrombocytopenic purpura," and "isolated thrombocytopenia." It was found that more research is needed to better understand the underlying mechanisms of ITP. For example, corticosteroids have both short- and long-term side effects when used in the first place. In light of this, future research may need a rethinking of ITP treatment recommendations and the use of viable alternative drugs.

Primary immune thrombocytopenia: a 'diagnosis of exclusion'?

Current diagnosis of primary immune thrombocytopenia (ITP) is presumptive, centered on excluding other causes of thrombocytopenia. The diagnosis of ITP is challenging because of the wide range of potential inherited and acquired causes of thrombocytopenia. The treatment of ITP is empiric with steroids, high-dose immunoglobulin, immunosuppressants and thrombopoietin agonists with potential side effects. We searched Medline and Cochrane databases, reviewed the study data and analyzed the individual diagnostic tests for their evidence-based role in the diagnosis of ITP. We then analyzed the strength of the scientific evidence for each diagnostic test in the diagnosis of ITP and identified gaps in the diagnostic accuracy. The diagnostic challenges in ITP include: insufficient evidence for the individual test for diagnosis of ITP, no standardized protocol/guideline for diagnosis, hurdles in accessing the available resources and failure to correlate the clinical data while reviewing the blood smear. We did not identify a diagnostic test that clinicians can use to confirm the diagnosis of ITP. In the absence of a diagnostic test of proven value in ITP, the clinician is best served by a comprehensive history and physical examination, complete blood count and review of the peripheral blood smear in evaluating thrombocytopenia.

P1647: CONTRIBUTION OF NEXT GENERATION FLOW (NGF) CYTOMETRY IN PRIMARY IMMUNE THROMBOCYTOPENIA (ITP): UTILITY FOR THE DIFFERENTIAL DIAGNOSIS WITH MYELODYSPLASTIC SYNDROMES

Background: Primary immune thrombocytopenia (ITP) is an immune-mediated acquired disorder characterized by impaired production and increased destruction of platelets with an elevated risk of bleeding. At present, diagnosis of primary ITP still remains one of exclusion with a need to discard other causes of isolated thrombocytopenia, in the absence of robust and accurate clinical and laboratory diagnostic criteria. For the diagnosis of ITP, a bone marrow (BM) study may be useful to differentiate between ITP and other diseases, such as myelodysplastic syndromes (MDS). Next generation flow (NGF) has emerged as a potential useful tool in these settings. Aims: In FCR-PTI-2017-01 study we prospectively evaluated the potential utility of NGF analysis of BM for more accurate diagnosis of ITP vs MDS. Methods: Multicenter, prospective, Spanish study to investigate morphological and/or immunophenotypic profiles among BM cell compartments from patients ≥ 18 years with newly diagnosed ITP or MDS. A multiparameter characterization of multiple compartments of BM cells was performed using the 8-color panel designed and validated by the EuroFlow Consortium for the diagnosis and characterization of MDS and acute myeloid leukaemia. NGF BM blinded results were then compared with the BM cytomorphological diagnosis. Results: 62 patients, median age 71 years, 59% male, were included. Main comorbidities were neoplasms (19%), diabetes (17%), chronic respiratory disease (12%) and cardiac insufficiency (10%). Median platelet count at diagnosis was 45 x 109/µL (range: 4-98 x 109/µL) and 20.6% of patients had bleeding at diagnosis. By cytomorphology, expert hematologists were able to conclude an ITP or MDS diagnosis in only 31 cases of the 53 samples that could be analyzed (58.5%) [ITP (n=18), MDS (n=10) or inconclusive, i.e. unclassifiable, (n= 25)]. 62 BM samples evaluated by NGF were allocated in 4 immunophenotypic groups attending to: maturation blockades, abnormal antigen expression and cross lineage markers. We observed normal phenotype cases (n=10), isolated (unilineage) alterations (n=24), mild multilineage (>1) alterations (n=20) and severe multilineage (MDS-like) phenotypes (n=8). Cytomorphology diagnosed our cases as ITP, MDS or unclassifiable with a median number of alterations observed by BM NGF of 4 (IQR, 3-6), 2 (IQR, 1-6) and 4 (IQR, 3-5) respectively. For ITP cytomorphology group, NGF demonstrated numerous BM alterations being monocytic alterations (n=17, 94%) the most frequent finding observed. MDS presumed cases were also associated with monocytic alterations (n=5, 50%) with a frequent decrease in neutrophil precursors (n=4, 40%). On the contrary, when cytomorphology was not capable to establish a diagnosis, NGF showed a mixture of alterations with no clear predominance of none of them (Table 1). Image:Summary/Conclusion: Limitations of BM cytomorphology when facing an isolated thrombocytopenia were demonstrated here. However, normal or unilineage BM NGF alterations may lead us to an ITP diagnosis while mild or severe multilineage BM phenotypes may correlate good with MDS.

The Treatment of Newly Diagnosed Primary Immune Thrombocytopenia by Recombinant Human Thrombopoietin Combined with Glucocorticoid

To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) combined with glucocorticoid in treatment of newly diagnosed adult primary immune thrombocytopenia (ITP). Eleven male and 23 female patients with the diagnosis of primary ITP in our hospital from November 2018 to October 2019 were enrolled and randomly divided into test group (17 cases) and control group (17 cases), the median age was 52 years old (range: 20-76 years old). The patients in test group were treated with rhTPO 300 IU/(kg·d) combined with glucocorticoid , while the patients in control group were treated with rhTPO (15 000 IU/d) combined with glucocorticoid. Platelet count, platelet increase, as well as the overall response rate were compared. At the same time, the drug tolerance and any adverse drug reactions were observed. The platelet counts and platelet increase of the patients in the test group were significantly higher than those in control group (P<0.05). There was no significant difference in platelet counts and platelet increase between the patients in the test group and control group at day 3, 7 after treatment. There was no significant difference in overall response rates and complete response rates at day 7, 14 between the two groups either. In test group, there were 13 cases received platelet transfusion, while 12 cases in control group. The muscle aches occurred in one patient, and mild aminotransferase increased in another patient in test group which was self-recovery without treatment. RhTPO 300 U/(kg·d) combined with glucocorticoid could rapidly increase the platelet count with a low incidence of tolerable adverse events compared with conventional dose rhTPO with glucocorticoid.

The Value of Combined Detection of Megakaryocyte and Platelet Parameters for the Diagnosis of Primary Immune Thrombocytopenia

Objective:To investigate the application value of bone marrow megakaryocyte count, the proportion of megakaryocytes at each stage, and the platelet parameter in the clinical diagnosis of primary immune thrombocytopenia (ITP). Methods: The megakaryocyte and platelet parameter level in 62 ITP and 40 control group patients were compared and analyzed. Linear correlation analysis, Pearson correlation analysis, and ROC curves were performed for the correlation between megakaryocytes and platelet parameters. Results: Compared to the control group, the total number of megakaryocytes, the promegakaryocytes the granular megakaryocytes (GMeg), and naked megakaryocytes (NMeg), MPV, and P-LCR% in the ITP group increased. All differences were statistically significant (P<0.05). While the proportion of platelet-producing megakaryocytes (PMeg), PLT, and PCT decreased in the ITP group. These differences were statistically significant (P < 0.05). PLT was strongly positively correlated with PCT (r = 0.921, p<0.01). PCT was weakly positively with MPV (r = 0.309, p<0.05). MPV was positively correlated with P-LCR (r = 0.856, p<0.01). PDW was weakly positively correlated with P-LCR (r = 0.296, p<0.05) and Meg (r = 0.301, p<0.05), and negatively correlated with PMeg (r = -0.336, p<0.05). ROC curve analysis showed that PLT, PCT MPV and P-LCR% gave a high sensitivity（100.0%，81.0%，74.6%，90.5%，respectively.) and specificity (100.0%, 92.5%, 80.0%, 77.5%, respectively.) in diagnosis of ITP. Conclusion: The combined analysis of bone marrow megakaryocyte count, the proportion of megakaryocyte classification at each stage, and platelet parameters have an important reference value for auxiliary diagnosis of ITP.

Contribution of Next Generation Flow (NGF) Cytometry in Primary Immune Thrombocytopenia (ITP): Utility for the Differential Diagnosis with Myelodysplastic Syndromes

Background: Primary immune thrombocytopenia (ITP) is an immune-mediated acquired disorder characterized by impaired production and increased destruction of platelets with an elevated risk of bleeding. At present, diagnosis of primary ITP still remains one of exclusion with a need to discard other causes of isolated thrombocytopenia, in the absence of robust and accurate clinical and laboratory diagnostic criteria. For the diagnosis of ITP, a bone marrow (BM) study may be useful to differentiate between ITP and other diseases, such as myelodysplastic syndromes (MDS). Next generation flow (NGF) has emerged as a potential useful tool in these settings.Aim: In this study (FCR-PTI-2017-01) we prospectively evaluated the potential utility of NGF analysis of BM and peripheral blood (PB) for more accurate diagnosis of ITP vs MDS.Methods: 62 patients presenting with isolated thrombocytopenia and classified as ITP (n=20), MDS (n= 11) or inconclusive, i.e. unclassifiable, (n= 25) by BM cytomorphology, were studied. PB (n=47) and BM (n=62) analysis by NGF was blindly performed in parallel for the ITP, MDS and unclassifiable patient groups using the EuroFlow 8-colour AML/MDS classification antibody panel followed by automated analysis against pre-existing flow cytometry databases of normal healthy donor PB and BM immunophenotypic profiles. NGF BM and PB results were then compared with the BM cytomorphological diagnosis. In parallel, epidemiological data from patients were recorded in an electronic case report form (eCRF) and analyzed afterwards.Results: By cytomorphology, expert hematologists were able to conclude an ITP or MDS diagnosis in only 31 cases (55.3%). 62 BM and 48 PB samples with isolated thrombocytopenia were evaluated by NGF. Our 62 patients were allocated in 4 immunophenotypic groups attending to different BM variables observed: maturation blockades, abnormal antigen expression and cross lineage markers. Thus, we observed normal phenotype cases (n=10), isolated (unilineage) alterations (n=24), mild multilineage (>1) alterations (n=20) and severe multilineage (MDS-like) phenotypes (n=8). Cytomorphology diagnosed our cases as ITP, MDS or unclassifiable with a median number of alterations observed by BM NGF of 4 (IQR, 3-6), 2 (IQR, 1-6) and 4 (IQR, 3-5) respectively. For ITP cytomorphology group, NGF demonstrated numerous BM alterations being monocytic alterations (n=17, 94%) the most frequent finding observed. MDS presumed cases were also associated with monocytic alterations (50%) with a frequent decrease in neutrophil precursors (40%). On the contrary, when cytomorphology was not capable to establish a diagnosis, NGF showed a mixture of alterations with no clear predominance of none of them (table 1). Similarly to our work with BM NGF, we looked into a potential correlation of cytomorphology with PB NGF phenotypes. Thus, we observed a median number of alterations of 4 (IQR, 3-5), 4 (IQR, 2-4) and 4 (IQR, 3-5) in ITP, MDS and inconclusive cytomorphology groups. Increased platelet size and upregulated CD41, CD61 and CD63 glycoprotein (GP) expression were the most characteristic findings of ITP cohort. MDS subtype depicted an increased platelet size and overexpression of CD41. Downregulation of GP was restricted to patients with MDS-like phenotypes. (table 2). Nearly statistical significant differences at significance level of 90% were observed between cytomorphology and BM NGF results (p=0.179) (table 3), between platelet score and BM NGF findings (p=0.118) and also, among morphology, BM NGF and platelet score (p=0.179). Nevertheless, cytomorphology and PB NGF showed no statistical differences between them (p=0.206) (table 4).Conclusions: Limitations of BM cytomorphology when facing an isolated thrombocytopenia were demonstrated here. However, normal or unilineage BM NGF alterations may lead us to an ITP diagnosis while mild or severe multilineage BM phenotypes may correlate good with MDS. PB platelet GP expression allowed us to classify our patients in six groups (Gonzalez-Lopez/Matarraz platelet score) which may help ITP diagnosis when this score is low. Comparison of BM cytomorphology, BM NGF and PB NGF techniques at diagnosis showed statistically nearly comparable results (p=0.179), with a bigger amount of patients needed to confirm this trend. All these NGF findings may lead us to better address ITP at diagnosis. [Display omitted] DisclosuresGonzalez-Lopez: Novartis: Other: Advisoryboard and speakers honoraria, Research Funding; Amgen: Other: Advisory board and speakers honoraria, Research Funding; Sobi: Other: Advisory board honoraria; Grifols: Other: Advisory board honoraria.

New developments in the diagnosis of primary immune thrombocytopenia

Immune thrombocytopenia is an acquired autoimmune disorder, which can affect both adults and children, characterized by lower than normal platelet counts (below 100 × 109/l). Thrombocytopenia may result in an increased risk of bleeding and puts patients at risk for serious complications. In the last decade, the multifactorial pathogenesis of ITP has become apparent, leading to greater understanding that different immune-mediated mechanisms could be involved in each patient, explaining the variable clinical presentation and response to therapies. The management of ITP patients has changed considerably in these past 10 years, but diagnosis of the disease has changed little, and remains clinical and possible only with the exclusion of other causes of thrombocytopenia. Although the search for such a test continues, to date, there is no reliable biomarker or gold-standard diagnostic test, which contributes to the high rate of misdiagnosis of the disease. This review presents the current limitations in the identification of the molecular disease underlying this disorder.

Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed.

Risk and Prognostic Factors for Intracranial Hemorrhage in Elderly Patients with Immune Thrombocytopenia

Introduction: Immune thrombocytopenia (ITP) is a hematological disease associated with thrombocytopenia and bleeding diathesis. Intracranial hemorrhage (ICH) is the most devastating complication in ITP patients. Prophylaxis for ICH is indispensable due to its high mortality. However, the morbidity of ICH is quite low, which makes general prophylaxis unrealistic. A previous study demonstrated risk stratification of ICH in ITP patients before 60 years of age(Platelets, 2020). However, few studies have analyzed the risk factors and outcomes in ICH in elderly ITP patients. Thus, ascertaining the characteristics of ICH in elderly ITP patients is in urgent need to make effective assessments and provide personalized prophylaxis. Here, a retrospective study of a series of ITP patients who developed ICH ≥ 60 years of age was conducted to explore potential risk and prognostic factors, which may contributes to identifying the feasible personalized prophylaxis for ICH in elderly ITP patients. Patients and methods: A total of 44 patients incorporated in the study were over 60 years of age with a diagnosis of primary ITP before the onset of ICH. All measures were chronologically performed before the onset of ICH. Univariate and multivariate analyses were conducted using conditional logistic regression model. Each variables with a p-value &amp;lt; 0.10 in the univariate analysis and well-reported factors were included in the multivariate analysis. A stepwise approach was used to exclude variables with a p-value &amp;gt; 0.10. Results: Platelet counts at ITP diagnosis were significantly lower among patients who developed ICH afterwards (P=0.004). Platelet counts were dichotomized and coded into binary variables. The cut off value was 25,000/μL according to the ROC curve and Youden index. Estimation by the Kaplan-Meier method indicated that the morbidity of ICH was higher among patients with a baseline platelet count less than 25,000/μL (P=0.001). Bleeding severity was also included in the analysis. The control group had a significantly higher probability of no bleeding(P=0.008), while the case group was more likely to suffer life-threatening bleeding(P=0.006). The anatomic sites of bleeding manifestations were then examined. There existed significant difference between cases and controls with respect to skin bleeding (P=0.002), oral cavity bleeding (P &amp;lt; 0.001), gastrointestinal bleeding (P=0.022) and hematuria (P &amp;lt; 0.001). Univariate analysis also revealed that patients with a complication of diabetes mellitus (P=0.007) exhibited a significantly lower incidence of ICH, and fewer patients over 75 years of age developed ICH(P=0.021). Patients who had suffered head trauma before the end point of follow-up had a significantly higher probability of developing ICH (P=0.016). Moreover, patients with a duration of ITP no more than 7 days showed potential relevance (P=0.016). Multivariate analysis was conducted using a conditional logistic regression model. A stepwise approach identified a platelet count ≤ 25,000/μL at ITP diagnosis(OR=3.389, 95% CI 1.290-8.907, P=0.013), head trauma (OR=9.753, 95% CI 1.029-92.414, P=0.047), ITP duration less than 7 days (OR=6.741, 95% CI 1.348-33.712, P=0.020) and life-threatening bleeding(OR=13.077, 95% CI 1.104-154.865, P=0.041) as independent risk factors for ICH in elderly ITP patients. A simple predictive model was established according to the results above. Patients were segregated into a low-risk (Score=0), an intermediate-risk (Score=1-3) and high-risk (Score≥4) groups. Significant differences (P &amp;lt; 0.001) were observed in the frequencies of ICH between the 3 risk groups (Table 1). Kaplan-Meier estimations of ICH incidence were markedly different among the risk groups (Figure 1). As for prognostic factors, skin bleeding (OR=17.400, 95% CI 1.926-157.190, P=0.011) was identified as an independent poor prognostic factor. No significance was found with respect to age, platelet count or ITP duration. Conclusion: Our study revealed that platelet count ≤ 25,000/μL at ITP diagnosis, head trauma, ITP duration &amp;lt; 7 days and life-threatening bleeding are all independent risk factors for ICH in elderly ITP patients. A simple predictive model was established using these factors, and skin bleeding was a poor prognostic factor for ICH in elderly ITP patients. Disclosures No relevant conflicts of interest to declare.

Analysis of Children with Secondary ITP an Observational Study of Children of the Parc-ITP Registry of the Intercontinental Cooperative ITP Study Group (ICIS)

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder of variable origin that results in bleeding and decreased platelet count. Primary ITP in children is a diagnosis of exclusion, but following practice guidelines only medical history, clinical examination, complete blood count and blood smear analysis are mandatory for diagnosis. Secondary ITP can be difficult to be diagnosed at initial presentation and is frequently identified during the course of the disease. Little is known about children with secondary ITP after a diagnosis of primary ITP. We are describing such patients within a 2 year observation period.Methods and Materials: Data for this study were extracted from the Pediatric and Adult Registry on Chronic ITP (PARC-ITP), an international multi-center registry designed to collect data prospectively in children and adults with newly diagnosed primary ITP. Children aged 3 months to 16 years with a corrected diagnosis of secondary ITP within 24 months after having been diagnosed with primary ITP were included in this analysis. We excluded 37 patients with an undefined diagnosis of secondary ITP, i.e. all patients without a clear statement of the cause of secondary ITP. A correction of diagnosis was reported at 6, 12 or 24 months of follow-up (FU) investigations. Clinical and laboratory data were analyzed with descriptive statistics.Results: A total of 3581 evaluable children with the initial diagnosis of primary ITP were recorded in the PARC-ITP database between 2004 and 2017. Secondary ITP was reported in 99 patients within 24 months FU, 60 were females (60%) with a mean age of 7.13 years (SD 5.2). Diagnosis of secondary ITP was reported with the first FU dataset (6 months after initial diagnosis) in 66 patients. Infectious and autoimmune diseases were the main causes for secondary ITP reported in 43 and 38 patients, respectively. Mean age of patients with infectious diseases was 4.3 years (SD 4.2) and 10 years (SD 4.5) for those with an autoimmune disorder. Other underlying causes were malignancy (n=6), aplastic anemia (n=7), immunodeficiency (n=4) and drugs (n=1). Mean platelet count at initial diagnosis was 22x109/L (SD 24), and 62 patients had a platelet count of < 20x109/l. Patients with malignancy and aplastic anemia had a higher initial platelet count (37 and 38x109/l respectively), than patients with infection or autoimmune diseases (22 and 18x109/l respectively). At the time point of reported secondary ITP the median platelet count was 171x109/L (SD 124) with 59 patients exhibiting platelet counts > 100x109/L. Patients with autoimmune diseases had a higher rate of persisting ITP (61%), than patients with infectious diseases (19%). Overall initial bleeding frequency (n=82) and bleeding location were similar to children with primary ITP. Wet bleeding defined as mucosal bleeding was initially reported in 36% of patients with no differences in the various subgroups. One patient exhibited an intracranial haemorrhage during the course of secondary ITP. A watch and wait strategy was initially applied in 34 patients (34%).Discussion: The diagnosis of primary ITP appears to be accurate for most of the children reported to the PARC-ITP Registry, however, a minority of them experiences a correction of the diagnosis from primary into secondary ITP. Some differences were found for age, sex and initial platelet count in the subgroups of secondary ITP depending on etiology. The characteristics of patients with secondary ITP due to an infection are very similar to primary ITP, reflecting probably similar pathophysiological mechanisms of the immune system. Bleeding symptoms were very similar in all groups.Conclusion: Little is known about patients with initial primary ITP and revision of the diagnosis. This is the first analysis of children with a critical appraisal of the diagnosis “primary ITP”. DisclosuresKuehne:Amgen: Consultancy, Research Funding; UCB: Consultancy.

Effect of Pregnancy in Women with a History of Primary Immune Thrombocytopenia Considered As Cured

Immune thrombocytopenia (ITP) is an autoimmune disease that occurs in young women. Pregnancy is a well-known risk factor for developing newly diagnosed ITP as well as for inducing disease flares in patients with current ITP. However, the impact of pregnancy in women with an old history of ITP, considered as cured, has not been assessed. The aim of this study was to describe the course of ITP in pregnant women with an ITP in complete remission (platelets count >100x109/L and absence of bleeding symptoms) for at least 5 years without any ITP treatment.We retrospectively selected all pregnant women with delivery at Toulouse University Hospital, South of France, between 2010 and 2015 with a hospital discharge code of ITP (international classification of diseases; version 10 code D69.3). This code has a sensitivity of 81.2% and a positive predictive value of 89.8% in this database. All medical charts were reviewed to confirm the diagnosis of ITP. We included adult women (≥18 years) with a diagnosis of primary ITP according to French guidelines (platelet count <150 x 109 /L and exclusion of other causes of thrombocytopenia, especially other causes of thrombocytopenia during pregnancy) in complete remission for at least 5 years.We identified 50 pregnancies in 39 ITP patients during the study period. Eleven pregnancies occurred in 10 patients in long-term complete remission of ITP at the time of pregnancy onset. Baseline characteristics were: median age at ITP diagnosis: 21 years (range: 4-29); median age at pregnancy onset:32 years (range: 26-34; history of ITP during a previous pregnancy: 1; history of bleeding: 4 (36.4%); previous treatment for ITP: 8 (72.7%), corticosteroids-CS (5), CS and intravenously immunoglobulin-IVIg (3), splenectomy (4), dapsone (1); last median platelet count before pregnancy: 170x109/L (range: 118-363).Platelets count decreased below 100x109/L in 3 pregnancies (27.2%) from the first trimester for one patient, from the second trimester for one other and from the third trimester for the last one, with a nadir of 3, 39 and 87 (x109/L) respectively. One of them experienced a severe bleeding (grade 3 according to the International Working Group bleeding classification). All thrombocytopenic patients required treatment during pregnancy: CS+IVIg for 2 (one for bleeding and one to allow epidural analgesia) and IVIg for the other (to allow epidural analgesia). For these 3 women, the median platelet count at delivery was 128 (range: 38-159) and consequently only 2 of them could have epidural analgesia. No bleeding during delivery was observed. Transient thrombocytopenia occurred in 2 newborns.Primary ITP considered as cured may relapse during pregnancy and may induce severe bleeding requiring specific treatment. A tight monitoring should be proposed to all pregnant women with a history of primary ITP, even after several years of complete remission. DisclosuresRécher:Celgene, Sunesis, Amgen, Novartis, Chugai: Membership on an entity’s Board of Directors or advisory committees, Research Funding.

The Results of the Russian Registry of Primary Immune Thrombocytopenia (ITP) in Adults

Study objectivesThe aim of the study was to evaluate disease characteristics and treatment practices of ITP in Russia.Materials and methodsThe ITP Registry was a multicenter, prospective, observational cohort study. The observation period for each patient in the Registry was not less than 12 months. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient. Exclusion criteria: secondary thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics was used. Patients were registered since June 2011 till June 2014.ResultsFive hundred and seven adult 394female (77.7%)/113 male(22.3%) pts from 26 hematology centers in various regions of the Russian Federation were included. Observation period ranged from 1.4 to 29.8 months with an average of 18.6 ± 6.2 mo. Median age was 50.2 years (range 18.6-89.1).Median disease duration was 1.83 years (range 0-56.07). History of ITP of lasting < 1 year was reported in 186 (36.7%) pts, 1-5 years - in 142 (28%), 5-10 years - in 56 (11%), over 10 years - in 87 (17.2%), and was considered as unknown - in 36 (7.1%).Newly diagnosed ITP was reported in 19.5% of adult pts; persistent - in 16.6% and chronic ITP - in 63.9% of pts, respectively. Median platelets count was 14,0 x 109/L (range 0.0- 119.0 x 109/L). Hemorrhagic manifestations in the history of ITP were reported in 92.5% of pts: skin hemorrhages - in 89.5% of pts, oral bleeding - in 50.3% , epistaxis - in 37.3% , gastrointestinal bleeding - in 7.7%, intracranial bleeding - in 0.4%, hematuria - in 4.5%, and other hemorrhages - in 20.9% of pts. Severe ITP at the time of enrollment was observed in 158 (31.2%) pts (104 pts (20.5%) had a clinically significant bleeding at the disease onset, and 54 (10.7%) pts developed new clinically significant hemorrhages during the treatment. Refractory ITP at the time of enrollment was reported in 100 (19.7%) pts (resistance to the first, second and subsequent lines of therapy in 62 (12.2%) pts); 38 (7.5%) pts did not respond to splenectomy. At the time of enrollment, 250 (49.3%) pts received medical treatment for ITP.Severe ITP after enrollment was observed in 124 (24.8%) adult pts. Throughout the study, various hemorrhagic manifestations of ITP were reported in 48.0% of pts, severe hemorrhagic syndrome was reported in 10.0% of pts;Before enrollment, splenectomy was reported in 94 pts (18.5%); complete response (CR) was maintained in 34 (36.2%) pts, partial response - in 20 (21.3%), and no response - in 7 (7.4%). Thirty-two (34.0%) pts had lost the response after initial success. During the study, splenectomy was performed in 44 (10.8%) pts, of those - in 7 pts (15.9%) with newly diagnosed ITP; in 6 pts (13.6%) - with persistent ITP, and in 31 pts (70.5%) - with chronic ITP. The duration of the disease at the time of splenectomy varied from 0 to 21 yrs; with a median of 1.03 year. CR to splenectomy was observed in 31 (70.5%) pts, partial response - in 10 (22.7%), and no response in 1 (2.3%), while 2 (4.5%) pts lost response.Since the response to splenectomy might change during the observation in the study, the best response was registered.Table 1Distribution of the best response to splenectomy variable (before study entry and in the course of the study).Number of Pts (n)%Best response to splenectomyMissing data10.7%Complete response6547.1%A response3021.7%No response85.8%Loss of response3424.6%Total138100%Two hundred and forty-three (47.9%) pts received their first-line treatment during the study; glucocorticosteroids (GCS) - 222 (91.3%) pts, immunoglobulins (IVIG) - 2 pts (0.8%), other drugs - 26 (10.7 %) pts. A second-line therapy was administered to 133 pts (26.23%), of which 27 (20.3%) received GCS, IVIG - 23 (17.3%), alfa-interferons - 6 (4.5%), immunosuppressants - 8 (6%), rituximab - 18 (13.53%), romiplostim - 39 (29.3%), eltrombopag - 37 (27.8%), other drugs - 2 (1.5%) pts.ConclusionFor the first time in Russia, information regarding the clinical presentation and the "real life" management practice of adults with primary ITP was obtained in a large cohort of pts in a prospective study. The Registry showed a variability of ITP clinical course. One fifth of pts were refractory to therapy. The main therapy options for the ≥ 2nd line in a cohort of adult pts were splenectomy and TPO receptor agonists. However, large proportion of pts still received GCSs in the 2nd and even 3rd line of therapy. DisclosuresNo relevant conflicts of interest to declare.

Results of the Russian Registry of Primary Immune Thrombocytopenia in Pediatric Patients

Study objectivesWe aim to evaluate disease characteristics and treatment practices of pediatric pts. with Immune thrombocytopenia (ITP) in Russia.Materials and methodsThe ITP Registry was a multicenter, prospective, observational cohort study. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient/guardians. Exclusion criteria: secondary or congenital thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics were used. Patients were registered since June 2011 till June 2014.ResultsNinety-three pediatric pts, 46 male (49.5%) and 47 female (50.5%) with a median age 8.4 yrs (range 0.5-17.8) from 5 centers in various regions of Russia were included. The mean observation period reached 17.1 ± 6.5 mo (range1.4 to 28.6 months). Seventy (75.3%) pts had acute and 24.7% pts had insidious disease onset. The presence of trigger factors for ITP development was found in more than half of the cases (in 61.3% of patients), they are listed in Table 1.Table 1TriggersN%No triggers3638.7%Infection4649.5%Vaccination88.6%Other33.2%Total93100%Median disease duration at enrollment was 1.07 years (range 0 to 16.7 yrs). ITP duration shorter than 5 years at the enrollment was reported in 89.2% pts, up to 1 year - in 43 (46.2%), 1- 5 years - in 40 (43%), 5-10 years - in 8 (8.6%), >10 years - in 2 (2.2%) pts. Newly diagnosed ITP was reported in 35 (37.6 %) pts, persistent ITP - in 12 (12.9 %), chronic ITP - in 46 (49.5 %) pts.Median platelets count was 12,0 x 109/L (range 0.0 - 72.0 109/L).Ninety-two (98%) pts experienced hemorrhagic manifestations during the course of ITP: skin hemorrhages - in 98.9%, oral bleeding - in 15.1%, epistaxis - in 36.6%, gastrointestinal bleeding - in 1.1%, intracranial bleeding - in 1.1%, hematuria - in 1.1%, and other hemorrhages - in 9.7% of pts.Relationship between hemorrhagic syndrome and platelet count at the enrollment is provided in table 2.Table 2Relationship between hemorrhagic syndrome and platelet count (at enrollment)Hemorrhage highest grade according to WHOPlatelet count (visit 1)Total pts / %< 30,00030,000 -50,000>50,00003 5.5%3 5.5%49 89.1%55 100%111 40.7%5 18.5%11 40.7%27 100%25 62.5%0 0%3 37.5%8 100%32 66.7%1 33.3%0 0%3 100%Total21 22,6%9 9.7%63 67.7%93 100%Severe course of ITP after enrollment was observed in 12 (13%) pts (of whose 6 (6.5%) had clinically significant hemorrhage at the disease onset and 6 (6.5%) had new clinically significant hemorrhages during follow-up period.Refractory ITP at enrollment was reported in 9 (9.7%) pts and was associated with the resistance to the first-, second- and subsequent lines of therapy. At enrollment 42 (45.2%) pts received specific treatment for ITP. Before enrollment, splenectomy was reported in only 1 (1.1%) 14-years old patient who had a complete response. During the study, splenectomy was performed in 6 (6.6%) pts with chronic ITP; the duration of the disease at the time of splenectomy varied from 2 to 10 years, with average duration of 4.69 years (median - 4.5 years). Complete response to splenectomy was observed in 3 (50%) pts, a partial response - in 2 (33.3%), no response - in 1 (16.7%) patient. Loss of response to splenectomy was not reported. During the study, severe ITP was reported in 8 (8.7%) pts, 41 (44.6%) pt had various hemorrhagic manifestations of ITP at least at 1 visit, grade IV hemorrhagic syndrome was not reported.Thirty-eight (41%) pts received 1-st line treatment: glucocorticosteroids (GCS) - 23 (60.5%) pts, IVIG - 5 (13.2%), alfa-interferons -16 pts (42.1%). Twenty-three pts (24.7%) received second-line therapy: GCS - 1 (4.3%), IVIG -1 (4.3%), immunosupression - 1 (4.3%), rituximab - 2 (8.7%), romiplostim - 11 (47.8%), eltrombopag - 14 (60.9%).ConclusionFor the first time new information on the features of the disease and patterns of management of pediatric pts with primary ITP in Russia was obtained in a prospective study. Interestingly, the preferred therapy for the 2nd or subsequent lines are TPO receptor agonists used outside the approved indications in research institutions, based on published clinical trial data. Splenectomy rate before and during the study was only 7.5% (7 pts) with chronic ITP; in 1 child (14.3%) splenectomy was ineffective. Low acceptance of splenectomy suggests TPO-mimetics as potential second-line therapy. In total, good disease control is achievable in the majority of pediatric pts with ITP. DisclosuresOff Label Use: use of TPO-mimetics in children.

Clinical significance of IPF% or RP% measurement in distinguishing primary immune thrombocytopenia from aplastic thrombocytopenic disorders.

The diagnosis of primary immune thrombocytopenia (ITP) is based on differential diagnosis. Although the measurement of percentages of reticulated platelets (RP%) by flow cytometry is useful as a supportive diagnostic test, this method is nonetheless a time-consuming, laboratory-based assay. To identify alternative assays that are useful in daily practice, we compared three methods in parallel, IPF% measured by XE-2100 [IPF% (XE), Sysmex Corp.], IPF% measured by new XN-1000 [IPF% (XN)], and RP%. We examined 47 patients with primary ITP, 28 patients with aplastic thrombocytopenia (18 aplastic anemia and 10 chemotherapy-induced thrombocytopenia) and 80 healthy controls. In a selected experiment, we examined 16 patients with paroxysmal nocturnal hemoglobinuria (PNH) to examine the effect of hemolysis. As compared with IPF% (XE), IPF% (XN) showed better within-run reproducibility. The sensitivity and specificity for the diagnosis of ITP were 83.0 and 75.0% for IPF% (XE), 85.1 and 89.3% for IPF% (XN), and 93.6 and 89.3% for RP%, respectively. Examination of PNH patients revealed that hemolysis and/or red blood cell fragments interfered with IPF% (XE) values, but not with IFP% (XN) values. Our results suggest that IPF% measured by XN-1000 may be of comparable value with RP% as a supportive diagnostic test for ITP.