Secondary Immune Thrombocytopenia Research Articles

Clinical Epidemiology, Treatment Outcome and Mortality Rate of Newly Diagnosed Immune Thrombocytopenia in Adult Multicentre Study in Malaysia.

BackgroundImmune thrombocytopenia (ITP) is well characterized in Western, European and other Asia-Pacific countries. Nevertheless, the clinical epidemiology, treatment pattern and disease outcome of ITP in Malaysia are still limited and not well known.ObjectiveThis study aimed to describe the clinical epidemiology, treatment outcome and mortality of ITP patients in haematology tertiary multicentre in Malaysia.MethodsClinical and laboratory data of newly diagnosed adults with ITP by a platelet count <100 × 109/L from January 2010 to December 2020 were identified and analyzed.ResultsOut of 500 incident ITP, 71.8% were females with a striking age preponderance of both genders among those aged 18–29 years. The median age was 36 years. The median platelet count was 17.5 × 109/L, 23.0% had a secondary ITP, 34.6% had a Charlson’s score ≥1, 53.0% had bleeding symptoms including 2.2% intracranial bleedings (ICB). Helicobacter pylori screening was performed in <5% of cases. Persistency and chronicity rates were 13.6% and 41.8%, respectively. Most (80.6%) were treated at diagnosis onset and 31.2% needed second-line treatment. Throughout the course of ITP, 11.0% of patients died; 3.0% and 8.0% with bleeding and non-bleeding related ITP.ConclusionThis study confirms the epidemiology of ITP is comparable with worldwide studies. Our incidence is high in the female, Malay ethnicity, primary ITP and events of cutaneous bleeding at ITP onset with 18–29 years predominance age group for both genders. The frequency of persistent and chronic ITP is inconsistent with published literature. Corticosteroids and immunotherapies are the most prescribed first-line and second-line pharmacological treatments. Thrombopoietin receptor agonist medications (TPO-RAs) usage is restricted and splenectomy is uncommon. Our mortality rate is similar but ITP related bleeding death is fourth-fold lower than previous studies. Mortality risks of our ITP patients include age ≥60 years, male, severe bleeding at presentation, CCI≥1 and secondary ITP.

Investigation of the correlation between immune thrombocytopenia and T cell activity-regulated gene polymorphism using functional study

Thrombocytopenia is a condition where the platelet count is under 100 × 109/L, which is caused by various disorders. However, the mechanism of thrombocytopenia is still unclear. Hence, we tried to investigate the correlation between immune thrombocytopenia (ITP) and single nucleotide polymorphisms (SNPs) of genes related to T cell activation. There were 32 ITP patients and 30 healthy controls enrolled in this study. PCR and sequencing were used to find out the significant SNPs, which we focused on the promoter region of CTLA4 and CD28. In this study, the ITP cases were divided into primary ITP group, secondary ITP group, and the combination of the two to the follow-up analysis. Moreover, dual-luciferase reporter assay was used to evaluate the transcription activity of the significant SNP. We found the − 1765_rs11571315 of CTLA4 gene was associated with primary ITP (p = 0.006), secondary ITP (p = 0.008), and the combination of the two (p = 0.003). Moreover, the −318_rs5742909 also had statistical significance in secondary ITP group that was only caused by autoimmune disease (p = 0.019). In functional study, the rs5742909 would decrease 19% of the transcription activity when it carried a T-allele at this position (p = 0.040). It was noted that CTLA4 gene polymorphism was related to ITP but not CD28. According to our results, we surmised that CTLA4 is involved in the pathogenesis of ITP, and the secondary ITP result from the lower CTLA4 expression that leads to T cell over-activation.

Preliminary evaluation of a flow cytometric assay with microsphere controls for the detection of platelet-bound antibodies in canine immune thrombocytopenia.

Canine immune thrombocytopenia (ITP) ranges from a mild to severe bleeding disorder, and platelet counts do not reliably predict clinical disease course. The detection of platelet autoantibodies may further define the disease phenotype, but variability in assay configurations and a lack of well-characterized controls limit the diagnostic utility of anti-platelet antibody assays. We aimed to develop control reagents to facilitate the characterization of canine platelet surface-associated immunoglobulin (PSAIg) in flow cytometric assays. Silica microspheres were coated with canine IgG and IgM to assess the reactivity of goat and rabbit origin anti-canine immunoglobulin reagents. They were also used as positive controls in the PSAIg assay. Preliminary assay evaluation and determination of sample stability used PRP isolated from seven healthy dogs and 26 dogs newly diagnosed with thrombocytopenia. Blood sample stability was established for up to a 48-hour storage time. The conjugated positive control microspheres demonstrated stable fluorescent labeling over a 2-year observation period. Rabbit and goat origin anti-dog IgM fluorescent antibody labels reacted nonspecifically with canine IgG. Rabbit origin anti-dog IgG antibody demonstrated greater class specificity for canine IgG than a goat origin antibody. Thrombocytopenic dogs had a broad range of membrane-bound immunoglobulin. Median PSAIgG for dogs with primary or secondary ITP (18.4%, 34.1%, respectively) were significantly higher than controls (3.8%, P<.05). The described assay reagents and procedures provide positive controls and allow consistent thresholding to define a positive test result, suitable for any flow cytometer. A rabbit anti-dog IgG fluorescent label demonstrated specificity for canine IgG and was useful for the detection of PSAIgG in thrombocytopenic dogs.

Secondary Chronic Immune Thrombocytopenia in Diffuse Large B-cell Lymphoma: A Rare Case Report

Objective: To present a case of rare secondary chronic immune thrombocytopenia in diffuse large B-cell lymphoma. Methods: A case of secondary ITP associated with diffuse large B-cell lymphoma (DLBCL) in a 58-year-old woman suffering from hemorrhagic tendencies that was refractory to conventional treatments of ITP was reported. This case is a rarity because there are not many cases of secondary chronic ITP due to DLBCL have been reported to date. Results: A 58-year-old woman was diagnosed with ITP around 11 months before she was admitted to the Emergency Room with bleeding. Previous treatment with steroid and azathioprine was only temporarily effective. During the course of treatment, splenomegaly and lymphadenopathy were identified, but lymph node biopsy was delayed by the thrombocytopenia. The drug was then replaced to the eltrombopag, which showed good response. However, the patient had to undergo splenectomy because of the mechanical effect of splenomegaly, with the biopsy result showed DLBCL. Immune thrombocytopenia then went into a complete remission after splenectomy. Conclusion: In cases of ITP that are refractory to conventional treatments, a thorough search for secondary ITP might be helpful, even if no underlying disorder is detected at the initial presentation.

Factors associated with secondary immune thrombocytopenia in patients with primary Sjögren's syndrome: a retrospective study of 639 cases.

To investigate the clinical characteristics and relevant factors of secondary immune thrombocytopenia (ITP) in patients with primary Sjögren's syndrome (pSS). Patients with pSS being treated between 2013 and 2020 in China-Japan Friendship Hospital were retrospectively analysed. Clinical characteristics were compared between pSS patients with and without secondary ITP. Logistic regression analysis was performed to identify factors associated with secondary ITP in patients with pSS. 639 patients with pSS were included in this study, among which 566 (88.6%) were women. The prevalence of secondary ITP in patients with pSS were 12.4%. Among pSS patients with secondary ITP, 55.7% had mucocutaneous bleeding and 8.9% experienced visceral bleeding. Lymphopenia (OR=3.154, 95% CI 1.185-8.395, p=0.021), anaemia (OR=2.416, 95% CI 1.250-4.668, p=0.009), low C4 (OR=2.904, 95% CI 1.563-5.394, p=0.001), and positive anti-RNP (OR=2.777, 95% CI 1.070-7.202, p=0.036) were significantly related to secondary ITP, while interstitial lung disease (ILD, OR=0.429, 95% CI 0.203-0.907, p=0.027), ANA ≥1:320 (OR=0.469, 95% CI 0.221-0.996, p=0.049) and positive anti-SSB (OR=0.288, 95% CI 0.126-0.685, p=0.003) were negatively associated with secondary ITP in patients with pSS. Over 10% of patients with pSS had secondary ITP, among whom visceral bleeding was comparatively rare. Lymphopenia and anaemia were positively related to secondary ITP, while ILD was negatively associated with secondary ITP. Low C4 and positive anti-RNP seem to be two potential risk factors for secondary ITP in patients with pSS, while ANA ≥1:320 and positive anti-SSB may be two potential protective factors.

A Review on Secondary Immune Thrombocytopenia in Malaysia.

Immune thrombocytopenia (ITP) is an acquired autoimmune disease that occurs in adults and children. In Malaysia, the clinical practice guideline (CPG) for the management of ITP was issued in 2006, which focused almost exclusively on primary ITP (pITP), and only a few secondary ITP (sITP) forms were addressed. All published (twenty-three) sITP articles among children and adults in Malaysia, identified on the academic databases were retrieved. The articles were published between 1981 and 2019, at a rate of 0.62 publications per year. The publications were considered low and mainly focused on rare presentation and followed-up of secondary diseases. This review revealed that sITP in Malaysia is commonly associated with autoimmune diseases (Evan’s syndrome, SLE and WAS), malignancy (Kaposi’s sarcoma and breast cancer) and infection (dengue haemorrhagic fever, Helicobacter pylori and hepatitis C virus). The relationship between ITP and autoimmune diseases, malignancy and infections raise the question concerning the mechanism involved in these associations. Further studies should be conducted to bridge the current knowledge gap, and the further information is required to update the existing CPG of management of ITP in Malaysia.

Immune thrombocytopenia in the elderly: immunosenescent and clinical diversity.

Immune thrombocytopenia in the elderly: immunosenescent and clinical diversity.

Daratumumab As a Treatment for Adult Immune Thrombocytopenia: A Phase II Study with Safety Run-in (the DART Study)

Daratumumab As a Treatment for Adult Immune Thrombocytopenia: A Phase II Study with Safety Run-in (the DART Study)

Association between Megakaryocyte Abnormalities on Bone Marrow Smear and Response to Thrombopoietin Receptor Agonists in Adult Patients with Primary Immune Thrombocytopenia

Introduction: Immune thrombocytopenia (ITP) is an autoimmune disease due to peripheral destruction but also impaired central production of platelets. Autoimmune reaction directed against megakaryocytes (MKs) has been described, and may explain morphological abnormalities of MKs observed in some patients with primary ITP. Thrombopoietin receptor agonists (TPO-RAs) are indicated as second-line treatments for ITP, but no predictive factors of response used in clinical routine practice has been demonstrated. The utility of systematic bone marrow smears (BMS) at ITP diagnosis is discussed. Howerer, it is usually recommended before second-line treatments. Two studies have suggested an association between MK abnormalities and response to corticosteroids in primary ITP, but none have investigated this association for TPO-RAs. This study aimed to investigate the association between MK abnormalities and response to TPO-RAs in adult patients with primary ITP.Methods: The source of population was the CARMEN registry. The CARMEN (Cytopénies Auto-immunes: Registre Midi-PyréneEN) registry is aimed at the prospective follow-up of all incident ITP adults in the French Midi-Pyrénées region (South-West of France, 3 million inhabitants) since June 2013. Each investigator follows all adult patients (aged ≥18 years) with incident ITP in routine visit or hospital stay. ITP was defined by international definition (platelet count <100 x 10 9/L and exclusion of other causes of thrombocytopenia). The study population consisted in all patients included in the CARMEN registry between June 2013 and March 2018 with primary ITP, treated by TPO-RA and with a BMS before initiating TPO-RA. We excluded the patients with a number of MKs <10 MK on the BMS. Morphological abnormalities were established based on literature and defined by consensus among 3 expert cytologists (AR, JBR and VDM). All MKs present on each smear were analyzed. MKs were categorized by the presence of dysplasia (monolobed MK and/or separated nuclei and/or microMKs), and according to their stage of maturation (basophilic, granular and thrombocytogenic). All patients' medical charts were reviewed by two experts in ITP (OW and GM) to determine the response to TPO-RAs. Response was defined by a platelet count between 30 and 100 G/L with at least a doubling of basal platelet count according to the international definition. In case of subsequent exposure to both TPORAs in a single patient, response was defined by response to at least one TPO-RA in the main analysis. We performed a subgroup analysis by TPORAs.Results: During the study period, 451 patients with incident ITP were included in CARMEN-registry. Among them, 105 had been treated by TPO-RAs, including 65 with BMS before the exposure to TPORA. We then excluded 20 patients with secondary ITP and 7 with less than 10 MKs on the BMS. We finally included 38 patients in the analysis. Median age at diagnosis was 71 years (interquartile range - IQR: 31 - 94) and 34.2% were women. Thirty-three patients were treated with eltrombopag, 17 with romiplostim including 13 who were exposed to both TPORAs. Thirty-four (89.4%) achieved response. The median number of MKs analyzed per patient was 137 (IQR: 50 - 265). All results are presented in Table 1. In the main analysis, there was no significant difference in the median percentage of dysplastic MKs in responders (4.0%, 95% confidence interval - CI: 2.3 - 6.4) and non-responders (4.5%, 95% CI: 0.7 - 7.1). There was a trend for a higher proportion of granular MKs (4.5%, 95% CI: 3 - 6) and basophilic MKs (30.1%, 95% CI: 21.9 - 39.1) in non-responders comparing to responders (granular: 2.0%, 95% CI: 0 - 4.1; basophilic: 21.3%, 95% CI: 11.4 - 40.7). Results were similar in the subgroup of patients treated with eltrombopag (data not shown; the low number of patients treated with romiplostim precluded any analysis).Conclusion: In this study, neither MK abnormalities nor the pattern of MK maturation stages were significantly associated with response to TPO-RAs. These results do not support a systematic bone marrow smear in patients with primary ITP to look for morphological predictive factors of response to TPO-RA. [Display omitted] DisclosuresComont: AstraZeneca: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees; Argenx: Membership on an entity's Board of Directors or advisory committees.

Rationale and Design of a Phase 3b Multicenter, Randomized, Double-Blind Placebo-Controlled, Parallel-Group Trial with an Open-Label Extension Phase to Evaluate the Efficacy and Safety of Avatrombopag for the Treatment of Pediatric Patients with Immune Thrombocytopenia

Background: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts (PCs) caused by a combination of both impaired platelet production and increased peripheral platelet destruction. ITP in children often resolves on its own, but it may become chronic and symptomatic in a proportion of children affected. After failure of first-line therapies (e.g. corticosteroids or immunoglobulin), treatment options for children include immunosuppressants, such as rituximab, and thrombopoietin receptor agonists (TPO-RAs). Avatrombopag (AVA) is an orally administered small molecule TPO-RA. It binds the human c-Mpl at a different site than endogenous TPO, stimulating signal transduction mimicking the biological effects of endogenous TPO in a non-competitive manner. In a phase 3 trial (NCT01438840) in adults with ITP, the primary efficacy endpoint of cumulative number of weeks with PC ≥50×10 9/L during 6 months of treatment in the absence of rescue therapy, was statistically significant favoring AVA over placebo. The most common treatment-emergent adverse events (AEs) in the phase 2 and 3 trials in adults (n=128) were headache, fatigue, and contusion. AVA has no significant hepatotoxicity, is administered with food, and has no restrictions on meal composition. AVA is approved by FDA and EMA for treatment of primary chronic ITP in adult patients with an insufficient response to a previous treatment. For pediatric patients with ITP, there is an unmet need for new treatment options, given the difficult administration requirements and variable, transient response, frequent relapse, and associated toxicities of available treatments.Study Design and Methods: Described here is the rationale and design of a phase 3b multicenter, randomized, double-blind placebo-controlled, parallel-group trial with an open-label extension phase (NCT04516967), evaluating the efficacy and safety of AVA for the treatment of pediatric patients with ITP for ≥6 months with an insufficient response to a previous treatment.Main inclusion criteria (Core phase) include: Age ≥1 and <18 years; informed consent; primary ITP for ≥6 months duration and an insufficient response to previous treatment; an average of 2 PCs <30×10 9/L, with no single count >35×10 9/L. Main exclusion criteria: secondary ITP; inherited thrombocytopenia; history of arterial or venous thrombosis, myelodysplastic syndrome; or congenital heart abnormalities or arrhythmias.Subjects will be randomized to blinded therapy of AVA or placebo (3:1 ratio) for 12 weeks, stratified by age cohort and baseline PC (Figure). AVA or placebo will be administered as an oral tablet (20 mg, age cohort 1 and 2) or as an age-appropriate pediatric formulation (10 mg, age cohort 3). Subjects who complete the Core Phase and are eligible may continue to the open label extension phase (2 years).The primary endpoint is durable platelet response, defined by the proportion of subjects achieving ≥6 out of 8 weekly PCs ≥50×10 9/L during the last 8 weeks of the 12 week treatment period in the Core Phase, in the absence of rescue medication.Secondary endpoints include proportion of subjects with ≥2 consecutive PCs ≥50×10 9/L during the Core Phase (12 weeks) in the absence of rescue medication; percentage of weeks with PC ≥50×10 9/L, and between ≥50×10 9/L and ≤150×10 9/L, during Core Phase (12 weeks) in the absence of rescue therapy; proportion of subjects with PC ≥50×10 9/L at day 8, proportion of subjects who require rescue medications during Core Phase; incidence and severity of bleeding symptoms; safety and PK/PD parameters.Statistics: The primary endpoint will be tested using the Cochran-Mantel-Haenszel 2-sided test at α=0.05, adjusting for age cohort and baseline PC (≤15×10 9/L vs >15×10 9/L), or the Fisher's exact test, when data is sparse. In addition, the numbers and percentages of responders in each treatment group, the associated 95% confidence intervals (CI), and the 95% CI for the difference between AVA and placebo will be estimated.Study Status: This global study is currently enrolling patients and aims to include at least 72 patients in total, at approximately 62 sites. [Display omitted] DisclosuresGrace: Principia: Membership on an entity's Board of Directors or advisory committees; Dova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Research Funding; Novartis: Research Funding. Xue: Dova Pharmaceuticals, a Sobi company: Current Employment. Jamieson: Sobi, Inc.: Current Employment. OffLabel Disclosure:Avatrombopag is an orally administered thrombopoietin receptor agonist (TPO-RA) that mimics the biologic effects of TPO in stimulating the development and maturation of megakaryocytes, resulting in increased platelet count. It is approved by the European Medicines Agency (EMA) and the US Food & Drug Administration (FDA) for the treatment of thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure, and for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Adolescents and Young Adults with Immune Thrombocytopenia (ITP): A Project of the Carmen-France and Parc-ITP Registry

Introduction The prognosis of ITP is age-related. In 80% of cases, children have a self-limiting course, whereas adults recover less frequently or relapse and overall ITP has a chronic course in ~70% of the cases. The risk of chronicity increases above the age of 10 years in pediatric cohorts, but data describing adolescents and young adults (AYAS) are lacking. Based on the assumption that adults are at greater risk of bleeding, treatment protocols and practice guidelines usually advise medical intervention. This is surely the right strategy for elderly patients or those with co-morbidities with indisputable higher bleeding risks. We assume that defining ITP in only two age categories might be an inaccurate oversimplification. AYAS have other needs, such as body appearance, mental health, social and financial issues. In addition, limitation of activity, side effects of steroids and risk of chronic disease are major reasons to adapt medical care. Even if AYAS have a similar risk of chronicity like adults, they may have greater potential to restore immune tolerance -in analogy to children- but with the help of an appropriate immunomodulatory therapy. The analysis of clinical data is the first step to design new strategies.Methods Data were extracted from the PARC-ITP and the CARMEN-France registry, open since 2004 and 2013, respectively. PARC is an international multi-center registry collecting data prospectively of children and adults with newly diagnosed ITP. The CARMEN-France registry enrolls all incident ITP in adults 18 years from the French Midi-Pyrénées region, and since 2016 increasingly in other French centers. Demographics, diagnostic methods, clinical data, management are continuously documented in CARMEN and at defined timepoints in PARC (initial, at 6,12 months follow-up (FU), and then yearly). Patients 12-25 years old with initial platelet counts <100x10 9/l were included. Patients with secondary or misdiagnosed ITP (n=57), and pregnant women were excluded (n=10). Sustained remission was defined as a platelet count 100x10 9/l at 12 months (measured at 11-18 months) and without treatment for at least 6 months. For patients with borderline values (100-149 x10 9/l), later FUs were analyzed to determine the persistency of remission, and, if necessary, reassign patient's remission state. Only bleeding location, but not grade was analyzed in common. Data were analyzed with descriptive statistics.Results A total of 656 AYAS (61% female) with the initial diagnosis of primary ITP were recorded in the combined database until 2021. FU information was available for 547 (83%) and 470 (72%) patients at 6 and 12 months, respectively. Initial median platelet count was 12 x10 9/l (IQR 5). In 109 patients the diagnosis was incidental (17%), 538 patients suffered of bleeding symptoms (82%) (Table 1). At 6 months 49% of patients had platelets <100 x10 9/l. At 12 months 50% fulfilled the criteria of chronic disease, with a median platelet count of 57x10 9/l (IQR 32). Asymptomatic chronic ITP was reported in 40% (no bleeding between 6-12 months).Platelet-enhancing drugs were reported in 66%, 45% and 30% at diagnosis, until 6 months and between 6-12 months, resp. Corticosteroids were preferred at all time-points, second-line treatments were various and given to 29% of patients with treatment beside 6 months (Table1).There were no differences in initial diagnostic procedures, comorbidity, bleeding symptoms, median platelet counts, percentage of severe thrombocytopenia (<20 x10 9/l) and need of treatment and drug choice between women and men (besides gynecological bleeding). There were small differences in the subgroup of adolescents (12-18 years, 59% female) compared to young adults (18-25 years, 70% female), the later had more moderate thrombocytopenia at diagnosis, less bleeding at all FUs, but similar or even more treatments (Table 2).Conclusion This is the first prospective project describing AYAS with a diagnosis of primary ITP. Analysis exhibited a clinical pattern among children and adults, with a risk of chronicity of 50%, and prolonged need of treatment (6-12 months) in 30% of cases. At diagnosis 17% had no bleeding signs, compared to 9% of children and 31% of adults in previous analysis of the PARC. There were no gender differences. Surprisingly, young adults experienced a greater number of non-bleeding phenotype than adolescents at all FUs, with comparable need of treatment between 6-12 months FU. [Display omitted] DisclosuresSchifferli: Novartis: Honoraria, Research Funding; Sobi: Honoraria. Moulis: Argenx: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Godeau: Novartis: Consultancy; Grifols: Consultancy; Sobi: Consultancy; Amgen: Consultancy. Michel: Rigel: Honoraria; Argenx: Honoraria; UCB: Honoraria; Alexion: Honoraria; Amgen: Consultancy; Novartis: Consultancy. Grainger: Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Kuehne: Amgen: Research Funding; SOBI: Honoraria; UCB: Honoraria; Novartis: Research Funding.

Splenectomy for Primary Immune Thrombocytopenia Revisited at the Era of Thrombopoietin Receptor Agonists: New Insights for an Old Treatment

▪IntroductionAlthough splenectomy is still considered as the most effective curative treatment for primary immune thrombocytopenia (ITP), its use has significantly declined in the last decade, especially since the emergence of thrombopoietin receptor agonist (TPO-RAs) and anti-CD20 monoclonal antibodies 1-3. The main objective of our study was to evaluate if splenectomy was still as effective in the modern era, particularly for patients who failed to respond to TPO-RAs and rituximab. One of the secondary objectives was to assess, among patients who did not respond to or relapse after splenectomy, the pattern of response to subsequent intervention with treatments used before splenectomy and particularly TPO-RAs.MethodsThis multicentre retrospective observational study involved adults who underwent surgical splenectomy for primary ITP in France from 2011 (authorization of TPO-RAs in France) to 2020. To be included in the study, patients had to fulfil the following criteria : age ³18 years, primary ITP diagnosis defined according to the usual international criteria 2. Patients with abnormal spleen histology (other than reactional lymphoid hyperplasia, white-pulp hypoplasia or red pulp hyperplasia) or yet definite secondary ITP were excluded. Response was defined according to international criteria 4. Sustained response was defined as the absence of ITP relapse at last visit. We performed univariable and multivariable logistic regression procedures to calculates the odds ratio associated with a sustained response.ResultsIn total,185 patients, 98 (53 %) women, with median age at splenectomy of 43.3 [interquartile range 27.6-64.3] years, were included in 18 French university and general hospitals from the French reference center network. Most of the patients were splenectomised at the chronic phase of ITP (n=150, 81.1%) and only two patients had undergone surgery within 3 months after ITP onset. Of note, 100 (54.1%) and 135 (73.0%) patients received TPO-RAs and/or rituximab prior to the splenectomy, respectively. The median time of follow-up after splenectomy was 39.2 months [16.5-63.0]. Overall, 144 (77.8%) of patients had an initial response and 23 patients (12.4%) relapsed during follow-up leading to an overall rate of sustained response of 65.4%, similar to the one observed in the pre-TPO-RA's era 1. Characteristics of patients according to the period during which occurred the splenectomy is available in Table 1.Among the 14 patients who failed to respond to both eltrombopag and romiplostim prior to splenectomy a sustained response after splenectomy was observed in 7 (50%). Among the 13 patients who had failed after both TPO-RAs and rituximab, we observed a sustained response in 6 (46%).In the multivariate analysis, an older age (60-75 years: OR 0,39 [0,17-0,86], p=0.02; >75 years: OR 0,28 [0,10-0,75], p=0.013) and a history of more than 4 treatment lines for ITP before splenectomy (OR 0.25 [0.08-0.66], p=0.010) were significantly associated with a lack of sustained response after splenectomy.TPO-RAs were used for 57/64 (89.1%) patients who failed to respond to splenectomy. Among them, 21 were treated with one TPO-RA (i.e. eltrombopag or romiplostim) which was previously used before splenectomy without any efficacy and a response was observed in 13 (62%) of them.ConclusionsIn conclusion, splenectomy seems to be still a relevant option for treating adult primary ITP not responding to TPO-RAs and rituximab. Patients who fail to respond or relapse after splenectomy should be re-challenged with TPO-RAs.1. Kojouri, K., Vesely, S. K., Terrell, D. R. & George, J. N. Splenectomy for adult patients with idiopathic thrombocytopenic purpura: a systematic review to assess long-term2. Provan, D. et al. Updated international consensus report on the investigation and management of primary immune thrombocytopenia. Blood Adv.3.Neunert, C. et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 3, 3829-3866 (2019).4. Rodeghiero, F. et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113, 2386-2393 (2009). [Display omitted] DisclosuresTerriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ebbo: Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Other: Attendance Grant; Sobi: Other: Attendance Grant. Viallard: Novartis: Consultancy; Amgen: Consultancy; Grifols: Consultancy; LFB: Consultancy. Jeandel: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Support for congress; Sobi: Membership on an entity's Board of Directors or advisory committees; Amgen: Other: Support for congress; GSK: Other: Support for congress; Pharming: Other: support for congress. Michel: Amgen: Consultancy; Novartis: Consultancy; Rigel: Honoraria; UCB: Honoraria; Alexion: Honoraria; Argenx: Honoraria. Godeau: Grifols: Consultancy; Sobi: Consultancy; Amgen: Consultancy; Novartis: Consultancy. Comont: Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding.

Immature Platelet Fraction Does Not Correlate with Treatment Response in Immune Thrombocytopenia

Background: As the treatment options for immune thrombocytopenia (ITP) continue to expand, the choice of which treatment to give to an individual patient has become increasingly complex. Therefore, a laboratory marker to help guide treatment selection would be clinically useful. The immature platelet fraction (IPF), measured clinically by automated Sysmex hematologic analyzers, correlates with bone marrow thrombopoietic activity and may correlate with disease activity in patients with ITP.Objective: To investigate the relationship between pre-treatment immature platelet fraction (IPF) and treatment response among pediatric patients with ITP.Methods: This is an observational cohort study of 148 patients with ITP who received ITP-directed treatment as monotherapy at 3 tertiary academic children's hospitals. Eligibility included a clinical diagnosis of ITP, ITP-directed surgical or pharmacologic treatment given as monotherapy, and available pre-treatment IPF values. The Sysmex XN-series measures IPF by adopted fluorescence flow cytometry using a semiconductor dioxide laser to measure platelets stained with oxazine fluorescent dyes. Demographic and clinical characteristics, laboratory studies, and treatments were collected. Response to treatment was defined as a platelet count ≥30 x 10 9/L and at least 2-fold increase from the baseline platelet count within 3 weeks of first dose of IVIG, Rh(D) immune globulin, or corticosteroid or within 3 months of all other therapies. For second-line treatments, platelet counts within 1 month after a rescue therapy were excluded. Regression analysis was utilized to estimate association between variables; estimated coefficients and p values are reported.Results: The cohort included 148 patients, 52% (n=77) of whom were female. Median age of diagnosis was 8 years (IQR: 3-13). Twenty percent (n=29) of treated patients had secondary ITP including 9 (6%) with Evans syndrome. Median platelet count at time of diagnosis was 5 x 10 9/L, and median IPF at diagnosis was 16.7% (IQR: 7.7-25.8). Median pre-treatment platelet count was 17 x 10 9/L with a median pre-treatment IPF of 16.6% (IQR: 10.0-25.7). There was a significant association between pre-treatment platelet count and pre-treatment IPF (coefficient -0.176, p = 0.003). Increased variation in IPF was seen at lower platelet counts compared to higher platelet counts (p=0.014, Figure 1a).IPF at diagnosis and pre-treatment IPF were not correlated with platelet response to treatment overall (p=0.28 for pre-treatment IPF, p=0.31 for IPF at diagnosis). IPF prior to treatment did not correlate with platelet response to individual medications: IVIG (coefficient 0.001, p=0.78, n=64), corticosteroids (coefficient 0.007, p=0.28, n=43), Rituximab (coefficient -0.01, p=0.52, n=10), and thrombopoietin receptor agonists (coefficient 0.0006, p=0.93, n=26, Figure 1b). Similarly, IPF at diagnosis of ITP did not correlate with platelet response to individual medications.Conclusions: Pre-treatment platelet count and IPF are inversely correlated in children with ITP, although there is significant variability in IPF at low platelet counts. The IPF at ITP diagnosis and prior to treatment does not correlate with platelet response to the most common ITP-directed treatments in children. A normal or elevated IPF should not impact decision-making about initiation of any specific ITP-directed treatments, including thrombopoietin receptor agonists or immunosuppressive therapy, in children with ITP. [Display omitted] DisclosuresLambert: Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy; Sysmex: Research Funding; Astra Zeneca: Research Funding; Dova: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; PDSA: Research Funding; Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; ClinGen, ISTH, ASH, GW University: Honoraria; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenx: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Shionogi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Despotovic: Apellis: Consultancy; UpToDate: Patents & Royalties: Royalties; Novartis: Consultancy, Research Funding; Agios: Consultancy. Kirk: Biomarin: Honoraria. Grace: Agios: Research Funding; Novartis: Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Principia: Membership on an entity's Board of Directors or advisory committees.

Secondary immune thrombocytopenia after Streptococcus infection

Immune thrombocytopenia is typically characterized by a decrease in platelet (PLT) count and bleeding diathesis symptoms or increased bleeding risk. In the report, we describe a case of a 19-year-old female patient who suffered from secondary immune thrombocytopenia in the course of streptococcal pharyngitis. After diagnosis, the patient received pharmacotherapy for thrombocytopenia according to Polish standards (intravenous dexamethasone sodium phosphate) which improved the platelet level. However, the change from dexamethasone intravenous to oral prednisone resulted in PLT level decrease. Hematological improvement was observed only after changing prednisone to methylprednisolone.

Secondary immune thrombocytopenia with elevated serum ferritin in a patient with anti-MDA5 antibody-positive dermatomyositis

Secondary immune thrombocytopenia with elevated serum ferritin in a patient with anti-MDA5 antibody-positive dermatomyositis

Hematologic Autoimmune Manifestation Secondary to Coronavirus Disease 19 Infection – A Single-Center Experience

Introduction: Since December 2019, multiple human cases of novel coronavirus infection were reported, representing with upper respiratory symptoms (influenza-like presentation). The virus was named the Severe acute respiratory system coronavirus 2 (SARS-COV-2). Studies have reported cases of patients with COVID-19 infection, including development of several autoimmune events that suggests that infection with SARS CoV-2 may be associated with initiation of autoimmune hematological autoimmune disorders.&#x0D; Aim: Review the hematological autoimmune phenomenon after infection with SARS-COV-2 in order to assist into the pathogenic mechanisms, clinical manifestations and treatment of this group of patients. &#x0D; Materials and methods: This is a retrospective study that includes 21 patients with autoimmune diseases like secondary immune thrombocytopenia (ITP), autoimmune hemolytic anemia( AIHA) and thrombotic thrombocytopenic purpura (TTP) that have emerged after COVID-19 infection. The patients were diagnosed and treated at the University Clinic of Hematology for a period of time from January 2020 to April 2021.&#x0D; Results: The most common hematologic autoimmune disorder was ITP in 13 cases (62%) followed by AIHA in 5 cases (24%) and TTP in 3 individuals (14%). The mean time of onset of the hematologic auto-immune presentations was 18,4 ± 10,3 days. The therapy of this conditions in patients with COVID-19 infection requires an individualized approach to achieve a precise balance between the risk of severe bleeding and of thromboembolic events. &#x0D; Conclusion: Causal relationship between COVID-19 infection and these autoimmune events still requires further studies. We should all have in mind the risk of development of hematologic autoimmune disorders in infected patients.

Eltrombopag treatment of patients with secondary immune thrombocytopenia: retrospective EHR analysis

Immune thrombocytopenia (ITP) may occur in isolation (primary) or in association with a predisposing condition (secondary ITP [sITP]). Eltrombopag is a well-studied treatment for primary ITP, but evidence is scarce for sITP. We evaluated real-world use of eltrombopag for sITP using electronic health records. Eligible patients had diagnoses of ITP and a qualifying predisposing condition, and eltrombopag treatment. We described patient characteristics, treatment patterns, platelet counts, and thrombotic and bleeding events. We identified 242 eligible patients; the most common predisposing conditions were hepatitis C and systemic lupus erythematosus. Average duration of eltrombopag treatment was 6.1 months. Most (81.4%) patients achieved a platelet count ≥ 30,000/µL at a mean of 0.70 months, 70.2% reached ≥ 50,000/µL at a mean of 0.95 months, and 47.1% achieved a complete response of > 100,000/µL at a mean of 1.43 months after eltrombopag initiation. At eltrombopag discontinuation, 105 patients (43%) experienced a treatment-free period for a mean 3.3 months. Bleeding events occurred with similar frequency before and during eltrombopag treatment whereas thrombotic events were less frequent during eltrombopag treatment. Our results suggest similar rates of platelet response with eltrombopag in patients with sITP as compared with primary ITP. In addition, a treatment-free period is possible for a substantial minority of patients.

Heritable platelet disorders: an enigma even guidelines can't unravel.

Heritable platelet disorders: an enigma even guidelines can't unravel.

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.

Response to rituximab in children and adults with immune thrombocytopenia (ITP)

BackgroundRituximab is a monoclonal anti‐CD20 antibody used as a second‐line treatment for immune thrombocytopenia (ITP). As additional treatments for ITP emerge, identifying the most appropriate patients and optimal timing for rituximab are important but challenging without established predictors of response to therapy. ObjectivesThe purpose of this study was to describe demographic, clinical, and laboratory characteristics of pediatric and adult patients with ITP to identify differences in evaluation before rituximab administration and correlates of platelet response. MethodsThis is a retrospective cohort study describing the characteristics of patients with ITP treated with rituximab from 2010 to 2020 at two academic tertiary care centers. ResultsA total of 64 patients met criteria for inclusion. Complete rituximab response (56%) was not significantly different between children (58%, n = 24) and adults (55%, n = 40). Response rate was similar in those with primary versus secondary ITP (53% vs 62%). Among patients treated with rituximab, Evans Syndrome was more common in children than adults (42% vs 18%). Immunologic labs assessed before rituximab varied by age and were more commonly evaluated in children (lymphocyte subsets 88% vs 22%). Immunologic markers, including antinuclear antibody, direct antiglobulin testing, immunoglobulin levels, and lymphocyte subsets, did not predict response to rituximab in pediatric or adult patients with ITP. ConclusionsPre‐rituximab immunologic evaluation varied significantly between adults and children, which could represent institution‐specific practice patterns or a more general practice difference. If the latter, underlying immunodeficiency in adults with ITP may be underrecognized. Standardized guidance for pre‐rituximab immunologic evaluation is needed.