Cause Of Secondary Immune Thrombocytopenia Research Articles

Good Prognosis of Adult Immune Thrombocytopenia in a Provincial Hospital

Background: Immune thrombocytopenia (ITP) is an autoimmune disease resulting from platelet destruction and impaired platelet production. Some patients experience relapses or refractoriness after corticosteroid treatment, necessitating second-line treatments. The majority of adult ITP cases become chronic or relapsing. The aim of this study was to assess the clinical course and identify factors related to sustained responses to treatment in patients with ITP. Methods: This observational retrospective cohort study was conducted from January 2013 to December 2022 at Trang Hospital, Trang Province, Thailand. Results: A total of 125 newly diagnosed ITP patients were enrolled, with an average follow-up duration of 48.49 ± 41.49 (mean ± SD) months. The average age was 42.34 ± 18.44 years, the average platelet count was 11.66 ± 14.39 x 10 9 /L, and the average platelet recovery time after treatment was 43.14 ± 101.32 days. The mean response duration after the first-line treatment was 25.99 ± 29.39 months. The characteristics of the patients were as follows: age below 60 years (78.4%), female sex (75.2%), pregnancy (1.6%), primary ITP (67.2%), secondary ITP (32.8%), bleeding symptoms (54.4%), platelet count <10 x 10 9 /L (64%), platelet count 10-30 x 10 9 /L (28.8%), platelet count 30-50 x 10 9 /L (5.6%), platelet count >50 x 10 9 /L (1.6%), splenectomy (4%), observation only (2.4%), loss to follow-up (10.4%), and death (4%). The most common cause of secondary ITP was systemic lupus erythematosus (63%). The first-line treatment consisted of dexamethasone (70.4%), prednisolone (23.2%), and/or intravenous immunoglobulin (4%). The clinical courses were as follows: recovery within 3 months in 68.8%, persistence in 13.6%, and chronic ITP in 17.6%. The sustained responses to corticosteroid treatment at 6 months included complete response (CR) (58.4%) and response (R) (9.6%), as shown in Table 1. Second-line treatments were required in 22.4% of cases, including colchicine (60.7%), azathioprine (35.7%), cyclophosphamide (25%), dapsone (17.8%), vincristine (10.7%), mycophenolate mofetil (7.1%), cyclosporine (3.5%), and/or eltrombopag (3.5%). The sustained responses to second-line treatments at 6 months were CR in 12% and R in 8.8%. Female sex ( P-value 0.007) and primary ITP ( P-value 0.046) were significantly associated with the sustained response (CR+R) to corticosteroids at 6 months. Secondary ITP ( P-value 0.036) was also associated with the sustained response (CR+R) to second-line treatments at 6 months (Table 2). Conclusions: This study reveals a favorable prognosis for ITP, with a majority of patients showing sustained response (CR+R), which differs from findings in studies conducted at referral centers. Female patients and those with primary ITP are more likely to respond. Further confirmation is needed through a large prospective cohort study in community hospitals.

Very severe immune thrombocytopenia following SARS-CoV-2 vaccination requiring splenectomy: a case report

BackgroundSome conventional vaccines have been recognized as a cause of secondary immune thrombocytopenia (ITP). According to recent publications, mRNA vaccines are probably associated with an increased risk of ITP.Case presentationOur patient developed severe ITP one week after the second dose of COVID-19 mRNA vaccine. Medical management was not effective, requiring splenectomy to obtain sustained remission.ConclusionConsidering the temporality and immunological hypothesis, we consider the vaccine to be the trigger of this ITP. To our knowledge, our case is, to date, the most severe case of ITP reported following SARS-CoV-2 vaccination and could help for the therapeutic management of similar patients.

International survey on Helicobacter pylori testing in patients with immune thrombocytopenia: Communication of the platelet immunology scientific and standardization committee

Unlabelled Box AbstractBackgroundInvestigations for patients suspected of immune thrombocytopenia (ITP) lack standardization. A controversial issue is whether such patients should be tested for Helicobacter pylori, a known cause of secondary ITP. ObjectivesThis Scientific and Standardization Committee Communication reports the results of an international survey to describe patterns of practice with respect to screening and treatment of H pylori among patients with ITP. Patients/MethodsA 17‐item scenario‐based questionnaire was delivered to hematologists in countries across the world. The questionnaire was pilot tested before use. We used snowball sampling and a contact list of physicians from the Platelet Disorders Support Association to identify survey respondents. Data were analyzed descriptively. ResultsA total of 186 respondents from 39 countries completed the survey. Response rate from the snowball sample was 53.6%. Twenty‐nine percent (n = 55) of respondents always tested ITP patients for H pylori, and 53% (n = 98) sometimes tested. Of the 37 respondents from Asia and the Middle East, 51.4% (n = 19) always tested for H pylori for the stated reasons of high local prevalence and perceived benefit of treatment on platelet count levels. Respondents were more likely to test patients who were from Asia (145/177, 80%) and who had concomitant gastrointestinal symptoms (133/183, 72%). For eradication therapy, 71 of 118 (60.2%) respondents used the combination of a proton pump inhibitor, clarithromycin, and amoxicillin for 14 days. ConclusionsThis international survey showed that testing for H pylori was most common in Asia and in patients from Asia. Testing and treating practices varied across geographic regions.

Treatment Patterns Among Patients with Immune Thrombocytopenia (ITP) in the United States: An Electronic Medical Record (EMR)-Based Analysis

Introduction ITP is an autoimmune disorder characterized by platelet destruction and impaired production. Some patients with ITP are refractory or unresponsive to existing therapies, indicating significant unmet medical needs. An assessment of current real-world treatment patterns among patients with ITP should enhance understanding of the ITP disease population and current unmet need. Here we present real-world data describing the ITP population in the United States in terms of demographic and clinical characteristics and use of available ITP therapies. Methods This was a longitudinal, retrospective, observational cohort study utilizing data from the Optum® Clinformatics® claims database. Patients with newly diagnosed ITP were included; defined as patients with ≥1 inpatient claim or ≥2 outpatient claims within 90 days of ITP-related diagnosis codes (International Classification of Diseases [ICD], Ninth and Tenth Revision; ICD-9: 287.3x; ICD-10: D69.3x or D69.4x) between October 1, 2015 and March 31, 2020. The index date was the date these criteria were met. Patients were excluded if they had <12 months continuous coverage or any record of thrombopoietin receptor agonist (TPO-RA) use before the index date. All patients were required to have ≥1 prescription during follow-up. Primary ITP was defined as patients who met the inclusion criteria and also had no ICD codes for secondary ITP, and no causes of secondary ITP in an identified time period prior to the index date. Here we describe clinical characteristics and medication use among newly diagnosed patients with primary ITP and the proportion of patients who went on to develop persistent (90 days to <12 months) or chronic (≥12 months) ITP. Results There were 19,376 newly diagnosed patients who met inclusion criteria; 15,798 (82%) had primary ITP and 3,578 (18%) had secondary ITP. Among patients with primary ITP, median (min-max) duration of follow-up was 16 (0-55) months and 61% had ≥12 months of follow-up (median duration: 26 months). At baseline, mean (standard deviation [SD]) age was 67 (16) years and 53% of patients were male. Mean (SD) Charlson Comorbidity Index (CCI) was 0.94 (1.41) and 11% of patients fell into a CCI category ≥3. The most common comorbid conditions were hypertension (60%), cardiovascular disease (37%), diabetes (29%), and anemia (27%). The most commonly used concomitant medications were lipid-lowering medications (44%), pain medications (24%), corticosteroids (23%), and anticoagulants (11%). During follow-up, use of these medications increased (lipid-lowering medications [46%], pain medications [38%], corticosteroids [39%], and anticoagulants [15%]). The most commonly used ITP medications during follow-up were corticosteroids (33%), rituximab (3.3%), TPO-RA (2.8%), immunosuppressants (2.6%), intravenous immunoglobulin (2.5%), and immunomodulators (2.4%). There were 1935 (12%) deaths during follow-up, and 87 (0.6%) patients underwent a splenectomy. Of the patients with ≥12 months of follow-up (n=9610), 16% and 32% developed persistent ITP and chronic ITP, respectively. Among the patients with persistent/chronic ITP and ≥12 months of follow-up, 242 (5.3%) received TPO-RA during follow-up. Of these, 93% concomitantly received ≥1 additional ITP treatment-related medication (TRM), 73% of the patients who received TPO-RA and ≥1 other TRM received ≥2 additional ITP TRMs, and 68% of patients who received TPO-RA and ≥2 other TRMs received ≥3 additional ITP TRMs. Of the 242 patients with ≥12 months of follow-up and persistent/chronic ITP who received TPO-RA, 55 (23%) either received an additional TPO-RA therapy or received another newly initiated ITP-related medication ≥30 days after starting TPO-RA. Almost half of the patients with primary ITP developed persistent/chronic disease. However, only a small percentage of these patients in the Optum® Clinformatics® claims database with no history of TPO-RA use received TPO-RA during follow-up. The majority of patients treated with TPO-RA received ≥1 other ITP TRM during follow-up and nearly 1 in 4 persistent/chronic patients receiving TPO-RA required ≥1 additional TPO-RA or switched to another ITP medication. Conclusion Even with the availability of many ITP drug therapies, there is still a considerable current unmet need for effective treatments among patients with primary ITP. The authors acknowledge Rajeshwari Punekar for contributions to study design. Disclosures Wilson: Sanofi: Current Employment, Current equity holder in publicly-traded company. Daak:Sanofi: Current Employment. Su:Sanofi: Current Employment.

Les purpuras thrombopéniques immunologiques secondaires de l’adulte

Secondary forms of immune thrombocytopenia (ITP) represent approximately 20% of all ITP cases in adulthood and this rate increases with age. Since some causes may influence both the prognosis and outcome but also the management of ITP, a minimal workup must be performed at ITP diagnosis to look for an associated or underlying cause. Among adults, B-cell lymphomas and mainly chronic lymphocytic leukemia, systemic auto-immune diseases such as systemic lupus or primary immunodeficiencies mainly represented by common variable immunodeficiency are the most frequent causes of secondary ITP. Whereas first-line therapy used for secondary ITP is usually similar to the one commonly used in primary ITP and relies mostly on corticosteroids±intravenous immunoglobulin according to the severity of bleeding, second and third-line treatments must take into account the type and degree of activity of the underlying disease.

Toll-Like Receptor 9 (TLR9) Gene C/T (rs352140) Polymorphisms in Adult Primary Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count and increased bleeding risk. The initial event(s) leading to antiplatelet autoimmunity remains unclear. Toll-like receptors (TLRs) are the most well-characterized pattern recognition receptors and are a transmembrane protein coded by the Toll genes family. In addition to their protective role in immunity, it is also becoming clear that TLRs exhibit homeostatic roles. Toll-like receptors play potential roles in the development of disease and its maintenance. The objective of this study is to evaluate the distribution of TLR9 gene C/T (rs352140) polymorphisms and its possible association with clinicopathological finding in Egyptian adult primary ITP. This study was carried out at Internal Medicine Department, Menoufia University Hospital, Egypt, from August 2018 to January 2020. Eighty adults (≥ 18 years) were enrolled in the study; 40 patients with primary ITP and 40 healthy individuals as controls. Identification of the TLR9 C/T (rs352140) polymorphic variant was performed by polymerase chain reaction–restriction fragment length polymorphism. In our study, we excluded any other causes of secondary ITP. Distribution of the TLR9 C/T genotypes did not exhibit significant deviation between patients and controls. There was no significant difference between studied groups as regards allele (C and T) frequency. There was no significant difference regarding TLR9 gene C/T (rs352140) polymorphisms between Egyptian adult with primary ITP and controls. TLR9 gene C/T (rs352140) polymorphisms have no relation to any of the clinicohematological variables in primary ITP in Egyptians.

Helicobacter pylori infection presenting as a hypereosinophilic syndrome and secondary immune thrombocytopenia

Eosinophilia is seen in patients with parasitic infections, various inflammatory and allergic diseases, as well as hematologic malignancies and autoimmune conditions. The bacterial infections as a cause of hypereosinophilia (HE) are rare. In the following article, we report a case of HE with rare etiology. Sixty-six-year-old male, presented with symptomatic thrombocytopenia and pain abdomen of 6 months duration. The evaluation revealed HE on the peripheral blood smear, and bone marrow studies, without atypical cells. During workup for complications, eosinophilic duodenitis was present with a positive rapid urease test, without the involvement of other systems. Etiological workup was negative for other secondary causes of hypereosinophilic syndrome (HES) and immune thrombocytopenia (ITP). The patient responded to anti-Helicobacter pylori treatment, with clinical and hematological improvement. Hence, the final diagnosis of H. pylori-associated HES and secondary ITP was made. The clinicians should bear in mind that H. pylori is an established cause of secondary ITP. However, it has never been reported to cause HES. Anti H. pylori treatment can reverse all the changes without the need for corticosteroids and other therapies. Hence, in an Indian setting, it should always be considered.

Early sofosbuvir-ledipasvir treatment for acute HCV infection induced severe immune thrombocytopenia \u2013 a case report

BackgroundHepatitis C virus (HCV) infection is a recognised cause of secondary immune thrombocytopenia (ITP). While its incidence has been largely described during chronic HCV infection, only one case of ITP secondary to acute HCV infection has been reported at this time.Case presentationWe report herein the case of severe ITP secondary to an acute HCV genotype 1a reinfection in a human immunodeficiency virus (HIV)-negative man having sex with men who had been cured several years before of a previous acute genotype 4d HCV infection. After an unsuccessful standard therapy with two courses of intravenous immunoglobulin (at 1 g/kg daily for 2 days) associated with methylprednisolone 1 mg/kg daily, antiviral treatment with sofosbuvir-ledipasvir rapidly achieved virological response and normalised the platelet count.ConclusionsAs a direct effect of HCV on megakaryocytes could be the predominant cause of ITP during acute infection, early antiviral treatment may be beneficial in this case.

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.

Incidence of immune thrombocytopenia in Taiwan: a nationwide population-based study.

The incidence of immune thrombocytopenia (ITP) is not well known in Asians. The aims of this study were to survey incidences and clinical features of ITP in Taiwan. This study identified 4855 incident ITP cases from the population-based National Health Insurance Research Database from mid-2006 to mid-2013, and compared incidences, patient characteristics, and clinical manifestations of ITP by age. Respective ITP incidence rates among those aged <15, 15 to 59, and ≥60 years were 4.0, 2.0, and 5.4 per 100,000 person-years. A male predominance was noted in children, and a female predominance was found in adults. The most common causes of secondary ITP were systemic lupus erythematosus (21.8%), viral hepatitis C (16.9%), and viral hepatitis B (13.4%). The rate of secondary ITP in children was less than one fifth that in adults (4.2% vs. 23.8%). Rates of central nervous system (1.1%) and gastrointestinal tract bleeding (3.3%) were rare, with variations by age. The rate of splenectomies in children (0.4%) was only one tenth that in adults (4.1%). The disease in 25% of children and 30% of adults became persistent or chronic. A decreasing trend in the ITP incidence was found (annual percentage change, -4.9%), and it was confined to those aged >15 years. Incidence estimates of ITP in Taiwan were close to those of Western countries, with age-specific variations in sex ratio, comorbidity, splenectomy, secondary causes, and incidence trends. The results suggest no racial variations in ITP incidences, but a geographical difference in causes of secondary ITP.

Épidémiologie et pharmacoépidémiologie du purpura thrombopénique immunologique

During the last decade, the development of large clinical and population-based cohorts led to new findings in the epidemiology and the pharmacoepidemiology of immune thrombocytopenia (ITP). The incidence is estimated to 3–4 for 105 inhabitants/year, with a slight female predominance and peaks in children and patients after 60 years. The incidence rate is 9 for 105 inhabitants/year in males after 75 years. Variations across ethnic groups are discussed. In France, there is a North-South gradient and a peak of incidence during winter suggesting the role of viruses in ITP pathophysiology. Myelodysplastic syndromes are an emergent cause of secondary ITP. The incidence of intracranial bleeding is about 1% by year and the risk increases with aging. Exposure to splenectomy decreases while rituximab and thrombopoietin receptor agonists (TPO-RA) are the most used second-line drugs for persistent ITP. Mortality is slightly increased in primary ITP as compared with the general population. ITP patients have an increased risk of infection, thrombosis and hemorrhage. Aging, lung diseases, splenectomy, corticosteroids and rituximab are risk factors for infection while influenza and pneumococcal vaccines are associated with a 50% decrease of infection risk. Aging, cardiovascular risk factors, lupus anticoagulant and splenectomy are risk factors for thrombosis. The risk of thrombosis associated with corticosteroids and TPO-RAs must be further investigated.