Persistent ITP Research Articles

Platelet dropping, bleeding and new treatment requirements in ITP patients after inactivated COVID-19 vaccination

Significant decreases in platelet counts and ITP relapses have been documented in ITP patients receiving COVID-19 mRNA vaccines; however, the effect of the inactivated COVID-19 vaccine on ITP patients remains unclear. The present study aimed to investigate the impact of inactivated COVID-19 vaccines on ITP patients, with a focus on platelet dropping events, bleeding events/scores, and the requirement of a new round of treatment. A total of 118 ITP patients, with 97 chronic ITP and 21 persistent ITP, who received inactivated COVID-19 immunization were investigated retrospectively. Following vaccination (within 1 month), ITP patients reported platelet dropping (31.36 %), new bleeding events (22.88 %), increases in bleeding scores (23.73 %), and new treatment requirements (22.03 %). Among them, persistent ITP patients with disease duration of 3–12 months had higher ratios of the above adverse events (71.43 %, 57.14 %, 61.90 % and 71.43 %, respectively) than chronic ITP patients with duration > 1 year (22.68 %, 15.46 %, 15.46 % and 11.34 %, respectively); patients’ disease duration was negatively correlated with platelet dropping events and new treatment requirements. Furthermore, logistic regression analysis also supported the above findings, revealing that persistent ITP patients had 9.40–9.70, 7.24–10.08, and 27.17–28.51 times incidence of having platelet dropping events, new bleeding events, and new treatment requirements after vaccination, respectively, when compared to chronic ITP patients. In conclusion, the present study demonstrates that after receiving inactivated COVID-19 vaccines, ITP patients may experience platelet dropping, which may lead to new bleeding events and the requirement of a new round of treatment for ITP recurrence. As a result, platelet level monitoring is crucial for ITP patients during the vaccination, especially those with persistent ITP.

Rilzabrutinib for Persistent ITP: New Kid on the Block?

Rilzabrutinib for Persistent ITP: New Kid on the Block?

Clinical features and treatment effect of HIV-associated immune thrombocytopenia—single center Ten-Years data summary

Thrombocytopenia represents one of the most prevalent hematologic complications observed in patients infected with the human immunodeficiency virus (HIV). In this study, we sought to analyze the clinical characteristics and treatment outcomes of patients with coexisting HIV and thrombocytopenia. Specifically, we retrospectively examined the medical records of 45 patients diagnosed with HIV/AIDS and thrombocytopenia at the Yunnan Infectious Diseases Specialist Hospital between January 2010 and December 2020, all of whom received highly active antiretroviral therapy (HAART) with/without glucocorticoids. The median follow-up period was 79 days, ranging between 14 and 368 days, the total platelet count was higher after receiving treatment than before (Z = −5.662, P < .001). Among the cohort, 27 patients (60.0%) responded to treatment, with 12 patients (44.44%) experiencing relapse during the follow-up period. The response rate (80.00%) of newly diagnosed ITP were significantly higher than of persistent ITP (28.57%) and chronic ITP (38.46%) ( \\x 2 = 9.560, P = .008) and the relapse rate of the newly diagnosed ITP (30.00%) was significantly lower than the persistent ITP and chronic ITP (100.00%, 80.00%) ( \\x 2 = 6.750, P = .034). Notably, we found that the number of CD4+ T cells, duration of HIV infection, selection of HAART and type of glucocorticoids administered displayed no statistically significant effect on platelet count, treatment response, or relapse rate. However, we observed a significant decrease in platelet count in hepatitis C virus-positive individuals coinfected with HIV compared to those with HIV alone (Z = −2.855, P = .003). Our findings suggest that patients diagnosed with HIV and thrombocytopenia exhibit a low response rate to treatment and have an increased likelihood of relapse.

P1632: PROSPECTIVE OBSERVATIONAL STUDY IN PATIENTS WITH IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP) TREATED WITH TPO-R AGONISTS (TPO-RA): ELTROMBOPAG (EPAG) AND ROMIPLOSTIM (ROMI) - THE PEPITE STUDY

Background: Initially, the marketing authorization (MA) of EPAG and ROMI was to adult patients (p.) with ITP ≥12 months (m.) and refractory to other treatments (t.), splenectomized or contraindicated to splenectomy. The MA was extended for EPAG in 2019 to p. aged ≥1 year with ITP ≥6 m., refractory to other t. (corticoids (CS), IgIV). In 2017, French national guidelines suggested the use of TPO-RA as an option of t. in 2nd line (L). Aims: The PEPITE study, still ongoing, aims to assess the modalities of use, effectiveness and safety of TPO-RAs in real-life. Methods: Prospective, observational, multicenter study including adult p. who initiated TPO-RA with persistent (pITP) or chronic (cITP) ITP. Inclusions occurred between 12/21/2018 and 07/17/2020. Here’s the interim analysis, cut-off date: 03/22/2021. Characteristics at baseline were presented in 114 p. (analyzed pop). Efficacy analysis of TPO-RA was assessed in p. with a platelet count (PLAT) <100 G/L at TPO-RA initiation (efficacy pop 113 p.). Responses were defined as: response (R) = PLAT ≥30 G/L, complete response (CR) = PLAT ≥100 G/L and non-response (NR) = PLAT <30 G/L. Results: 123 p. included through 40 centers by 25 hematologists and 15 internists, and 77 p. were still on TPO-RA at 6 m. At baseline, mean age 62.7 ± 20.1 years, 55% men, 29% with at least 1 cardiovascular risk factor. At diagnosis: median PLAT = 26 G/L [0 to 134 G/L], 31% of p. with bleedings. 97% of p. received at least one L of t. before TPO-RA: CS 96%, IVIG 56%, rituximab 47%, dapsone 18%, hydroxychloroquine 11%, danazol 6% and 7% of p. were splenectomized. Median number L of t. = 2 and 8% of p. had more than 4 L. Median time between diagnosis and TPO-RA initiation was 2.6 years [0.3 to 49.3 years], 33% of p. with pITP (n=21 with ITP 3 -<6 months, n=16 with ITP 6 - <12 months) and 67% with cITP. At TPO-RA initiation: 9% of p. were on CS and 48% p. had PLAT <30 G/L (median PLAT = 30 G/L), 95 p. (83%) received EPAG and 19 p. (17%) ROMI. For the 77 p. still on TPO-RA at 6 m., R rate = 97% and CR = 60%. Within 6 m., 10 p. had permanently (perm.) discontinued TPO-RA, main causes were therapeutic effect deemed sufficient (TEDS) for 6 p. and NR for 2 p. For the 27 p. still treated with TPO-RA at 18 m., R rate = 93% and CR = 48%. Within 18 m., 12 p. had perm. stopped TPO-RA, including 7 p. for TEDS and 1 p. NR. P. initiated TPO-RA with ITP 3 -<6 months (N = 21), 9 (43%) p. were still on TPO-RA at 6 months, 5 (56%) in CR. Over the entire follow-up, 24p. (21%) perm. discontinued TPO-RA, main causes were TEDS for 9 p., adverse event (AE) for 5 p. and absence of R for 4 p. Of the 105 p. treated with EPAG at least once, 62 (59%) experienced at least one AE, and 26 SAE occurred in 17 p. The most common AEs were respectively 6% for headache and 3% for SARS-CoV-2 infections, diarrhea, asthenia, insomnia, arthralgia and alopecia. Of the 40 p. treated with ROMI at least once, 19 (48%) experienced at least one AE and 17 SAEs occurred in 10 p. The most common AEs: SARS-CoV-2 infections (5%) and arthralgias (5%). No deaths related to TPO-RA was reported. Summary/Conclusion: Preliminary data from the PEPITE study show that TPO-RA are prescribed in early ITP, including 33% with pITP (18% with ITP 3-<6 m.) and are used in 7% of cases after splenectomy. At 6 m. R on t. was 97% and CR on t. was 60%. Within 6 m., 6 p. had perm. stopped TPO-RA due to TEDS. The real-life effectiveness and safety data for EPAG and ROMI are consistent with data reported in extension studies, with the specificity of occurrence of SARS-CoV-2. The final analysis is scheduled after 24 m. follow-up

The Use of Clinical Scores in the Management of Immune Thrombocytopenic Purpura in Children.

While the majority of children with recently diagnosed ITP have a benign, self-limiting condition, most often with a spontaneously recovery, 40% of children with ITP progress toward persistent ITP and 10–20% goes toward chronicity. Several clinical scores have been developed with the aim to perform a better monitoring outcome or to differentiate transient vs. persistent ITP (e.g., Donato score). Our paper aims to describe and to compare the most important scores used in the management of ITP in children: bleeding severity scores and chronicity prediction scores. These scores include a combination of different already known risk factors: age, gender, presence of a previous infections or vaccination, bleeding grade, type of onset, platelet count at diagnosis. The real utility of these scores has been a matter of debate and no consensus has been reached so far as to their necessity to be implemented as compulsory tool in the care of children with ITP.

Generic romiplostim for Indian children with persistent and chronic ITP

Generic romiplostim for Indian children with persistent and chronic ITP

Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice

AbstractImmune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.

Eltrombopag (EPAG) Treatment Improved Platelet Counts in Patients with Persistent or Chronic Immune Thrombocytopenia during a 2-Year, Phase IV, Open-Label Study

Background: ITP, characterized by isolated platelet reduction, is classified as persistent within 3- et al. Acta Haematol 2017;137:66-72) was performed. Aims: To evaluate the effects of EPAG on platelet counts, and long-term safety, during 2 yrs9 treatment, in persistent or cITP pts. Methods : Adults ≥18 yrs old diagnosed with persistent ITP (3- Results: At BL, 37/162 (23%; mean ± SD age 44 ± 16 yrs; 57% female) and 124 (77%; mean ± SD age 43 ± 16 yrs; 66% female) pts had persistent or cITP, respectively. One pt (1%) had ITP diagnosis duration 9 /L and 100% had no prior TPO-RA exposure; of those with cITP, 27% were splenectomized, 60% had platelet 9 /L and 90% had no prior TPO-RA exposure. 13 persistent ITP pts (35%) and 31 cITP pts (25%) withdrew early from the study, most commonly because of AEs (n=8, 22% and n=13, 10%, respectively) and lack of efficacy (n=4, 11% and n=7, 6%). Median exposure duration was 2.0 yrs (range 31 days to 2.1 yrs) and 2.0 yrs (range 21 days to 2.2 yrs); mean daily dose was 48.8 (range 11-75) mg/day and 48.8 (range 5-75) mg/day. Median platelet counts in all pts increased to ≥50×10 9 /L within 1 wk in both groups (Figure). Overall, 31 (84%) persistent ITP and 109 (88%) cITP pts achieved a platelet count ≥50×10 9 /L without rescue therapy; 19 (51%) and 62 (50%) maintained platelet counts continuously ≥50×10 9 /L for ≥28 wks. In pts with BL platelets 9 /L who achieved platelet counts ≥50×10 9 /L (on treatment, no rescue therapy; n=25 persistent ITP, n=99 cITP), median (95% CI) time to platelets ≥50×10 9 /L was 4.0 (1.3-14.4) wks in persistent ITP and 2.1 (1.4-2.1) wks in cITP pts. Sixteen (43%) persistent and 50 (40%) cITP pts received rescue therapy, most frequently a new ITP medication (n=9 [24%] and n=34 [27%], respectively). Compared with BL, 17/18 persistent ITP pts (94%) remained MF-0 at 2 yrs, 1 (6%) had a 1-grade increase; in cITP pts, 62/75 (83%) remained MF-0, 8 (11%) had a 1-grade increase, 2 had a 1-grade decrease and 1 (1%) remained MF-1. No pts had symptoms or abnormalities typical of MF. AEs were reported in 32 (86%) persistent ITP pts and in 108 (87%) cITP pts (Table). Serious AEs occurred in 12 (32%) persistent ITP pts, most frequently (≥5%) nausea (n=2, 5%) and fatigue (n=2, 5%), and in 29 (23%) cITP pts, most frequently (≥2%) gastrointestinal hemorrhage, gingival bleeding, tooth abscess, cerebral hemorrhage, lethargy, thrombocytopenia and menorrhagia (all n=2, 2%). No pt with persistent ITP died while on treatment (+ 1 day), and 3 (2%) cITP pts died (cerebral hemorrhage, n=2 [platelets 9 /L, not considered drug-related] and acute respiratory distress syndrome, n=1). Summary/conclusions: The effects of EPAG on platelet counts in persistent ITP pts were consistent with that seen in the cITP population, with sustained platelet increases. Overall AE rates were similar in both subgroups and AEs reported were consistent with the known EPAG safety profile or underlying disease. While there appeared to be an increase (>10% difference) in some AEs (vertigo, dyspepsia, arthralgia) in persistent ITP pts, this could be attributed to the limited pt number in this subgroup. These results are encouraging; outcomes following EPAG treatment in persistent ITP are consistent with reports in cITP. Disclosures Wong: Novartis: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; GlaxoSmithKline: Research Funding; Johnson & Johnson: Research Funding; Merck Sharp & Dohme: Research Funding; Pfizer: Research Funding; Roche: Research Funding; Biogen-Idec: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Research Funding. Brynes: Novartis: Research Funding. Arikan: Novartis: Employment. Maier: Novartis: Employment. Shamsi: Fresenius Germany: Research Funding; Novartis Pharma Pakistan: Consultancy; Roche Diagnostic Pakistan: Consultancy.

Retrospective Study for Immune Thrombocytopenia Outcome in Children in Benha

Immune thrombocytopenia (ITP, formerly idiopathic thrombocytopenic purpura) is an acquired disease characterized by immune-mediated destruction of normal platelets and suppression of platelet production that is associated with variable bleeding symptoms. This review study is intended to dissect subtleties of safe thrombocytopenia (ITP) cases, assessment of treatment modalities and result among kids in Benha. Also, to decide the prognostic variables as rules for new cases at diagnosis. Techniques: One hundred and 50 instances of youngsters who were analyzed ITP and followed up in pediatric hematology department in Benha University Hospitals were incorporated. All the patients were exposed to Full history taking, Through clinical assessment, Laboratory examinations: Complete blood picture, Bone marrow sample (for indicated cases only) were done to affirm the diagnosis of ITP. Results : Of 150 patients, 79(52.7%) were guys, and 71(47.3%) were females, 59.5% of cases had intense ITP, 11% had persistent ITP, and 29.5% had ongoing ITP, we merged the first two groups. there was a critical contrast in platelet count between acute+persistent and ongoing ITP, the median platelet count was 12.4 x103 (range 2-54)in acute+persistent cases. We found that middle platelet count at finding was fundamentally lower for patients who showed acute+persistent ITP with middle platelet tally of 21.5 x103 (range 2-49) (p < 0.001), We found young age had favorable outcome (p < 0.001).

Efficacy and Safety of a Combination of Thrombopoietin Receptor Agonist with an Immunosuppressant Therapy for the Management of Multirefractory Adult ITP: Results from a Retrospective, Multicenter, Observational Study

Introduction Multirefractory adult ITP, defined as no response to splenectomy, rituximab, and thrombopoietin receptor agonists (TPO-Ra), is associated with high morbidity and mortality. In a previous study, we have shown that combining an immunosuppressant therapy with one TPO-Ra could be a promising therapeutic strategy for managing patients with multirefractory ITP. Objective The aim of this study was to assess the efficacy and safety of such combination in multirefractory ITP on a larger series of patients. Patients and methods We conducted a retrospective, multicenter, observational study in France. Adult patients treated by a combination of a TPO-Ra with an immunosuppressant therapy (i.e., mycophenolate mofetil, azathioprine, ciclosporin, everolimus, or cyclophosphamide) for chronic (&amp;gt; 12 months) or persistent (&amp;gt; 3 months) multirefractory ITP, were included through the national reference center for adult immune cytopenia (CERECAI) network. Multirefractory ITP was defined as disease not responding to rituximab, to splenectomy (or contraindication to splenectomy), and to the 2 TPO-Ras licensed in France (romiplostim and eltrombopag) administered at the maximal approved dose. Clinical and biological data were retrospectively collected using a standardized form. Complete response (CR) was defined by a platelet count &amp;gt;100 x109/L and response (R) by a platelet count between 30-100 x109/L with at least a 2-fold increase from baseline, according to the international recommendations. Results Thirty-one patients (65% female, median age 57 years [range 23 - 82]) were included. Five (16%) of them had secondary ITP (Evans syndrome (n=2), systemic lupus (n=1) with antiphospholipid syndrome (APS), primary APS (n=1), and Waldenstrom macroglobulinemia (n=1). Four patients had a monoclonal gammopathy of undetermined significance, and 11 (35%) had antinuclear antibodies (titer &amp;gt;1/160) without definite clinical autoimmune disease. All patients had previously received corticosteroids and 16/31 (52%) were corticosteroid-refractory. Previous treatments lines also included intravenous immunoglobulin (28/31, 90%) and at least one immunosuppressant therapy (16/31, 52%). Splenectomy was performed in 25 patients (81%), and not performed in the remaining 6 patients because of advanced age and comorbidities (n=3), underlying APS (n=2), or patient refusal (n=1). At the time of treatment combination initiation, median ITP duration was 57 months [3 - 393], with 28/31 (90%) chronic ITP and 3/31 (10%) persistent ITP. Bleeding symptoms were present in 23 patients (74%) and the median platelet count was 10 x109/L [range 1 - 35]. The combination regiment included eltrombopag (n=18) or romiplostim (n=13), associated with either mycophenolate mofetil (n=15), azathioprine (n=12), cyclophosphamide (n=2), ciclosporine (n=1), or everolimus (n=1). Median duration of combination therapy was 12 months [range 1 - 103]. Nineteen patients (61%) had no therapeutic intervention other than the combined treatment, while 10 patients were also given corticosteroids (either short course of high dose steroids [n=5], or on a long-term at low dose [n=5]), and/or hydroxychloroquine (n=5). Overall, 81% of patients (25/31) achieved at least a R, including 19/31 (61%) CR. Among responders, the median time to response was 30 days [range 7 - 270], and the median duration of the response was 12 months [4 - 55]. Response rates were similar in patients who did not receive concomitant corticosteroids (59% CR, 12% R), and in patients that were previously exposed to immunosuppressant therapy given alone (63% CR, 25% R). Regarding safety, 13/31 (42%) patients experienced at least one adverse event potentially related to treatment, including 7 severe adverse events. Three patients without APS but who were splenectomized had a thromboembolic event, including 3 deep vein thrombosis/pulmonary embolism, and 1 cerebral venous thrombosis; Three patients had an infection (one cholecystitis, one herpes zoster, and one dental abscess). After a median follow-up of 18 months [6-103], one patient died (from a previously diagnosed adenocarcinoma). Conclusion In summary, these data show that most of the patients managed for multirefractory ITP may benefit from the combination of TPOra with an immunosuppressant therapy by achieving a durable response. The safety profile of this combination in this population seems acceptable. Disclosures Moulis: Novartis SAS: Membership on an entity's Board of Directors or advisory committees, Other: meeting attendance grant, Research Funding; Amgen: Other: meeting attendance grant; Grifols: Research Funding. Michel:Bioverativ: Consultancy; Rigel: Consultancy; Alexion Pharmaceuticals: Consultancy. Godeau:LFB: Honoraria; Amgen: Research Funding; Amgen: Honoraria; Novartis: Honoraria. Mahevas:GSK: Research Funding. OffLabel Disclosure: Some immunosuppressant drugs were given off-label for adult ITP.

Silent bleeding in children and adolescents with immune thrombocytopenia: relation to laboratory parameters and health related quality of life.

Occult hemorrhage can occur in any internal organ in ITP patients. Four sites of occult hemorrhage require attention including microscopic hematuria, fecal occult blood loss, retinal hemorrhage, and silent intracranial hemorrhage. The aim of this study was to investigate the frequency of subclinical bleeding in children with ITP and its relation to clinical and laboratory disease parameters including bleeding score and health related quality of life. This cross-sectional study included 40 ITP patients recruited from the Pediatric Hematology/Oncology unit, Children's Hospital, Ain Shams University, Cairo, Egypt. Inclusion criteria were patients with ITP (acute, persistent or chronic) having platelet count of 20,000/cmm or less at diagnosis/relapse, patients with overt bleeding and patients with secondary ITP were excluded. Occult blood in stools and urine analysis, fundus examination, and non-contrast brain MRI for microbleeds were done. Out of the forty included patients, 24 had chronic, 11 had acute and 5 had persistent ITP. Eleven patients had occult bleeds. Two patients had occult blood in stools, five had microscopic hematuria, one had retinal bleeds and three patients had brain microbleeds. Their mean age was 10.23 ± 4.18years and their mean initial bleeding score was 2.55 ± 0.82. Nine patients with occult bleeding were chronic, one persistent and one acute ITP patients. There were no significant differences between patients with occult bleeding and those without as regards the initial bleeding score, platelet counts and hemoglobin level, as well as the mean platelet counts and mean hemoglobin level over the disease duration (p > 0.5). The scoring of the parent's life, Child and parents' quality of life was low in 3 out of 11 patients with occult bleeding. There was no significant difference between patients with occult bleeding and those without as regards the ITP child and parents' quality of life items (p = 0.850 and 0.511 respectively). Our results suggest that subclinical bleeding is a potential risk in children with ITP, more commonly chronic ITP patients. We could not demonstrate a significant relation of occult bleeding to the laboratory findings, bleeding score, and the ITP health quality of life; nevertheless, the significance of the routine assessment of occult bleeding in ITP and the identification of high-risk patients require additional studies.

PF694 TREATMENT‐FREE REMISSION AFTER TPO RECEPTOR AGONISTS IN ADULT ITP PATIENTS IN BELGIUM

Background:Since 2009 treatment of chronic ITP patients with thrombopoietin receptor agonists (TPO‐RA) (romiplostim‐eltrombopag) has been reimbursed in Belgium. Despite the initial assumption that this would be a life‐long therapy, practical experience has shown that a significant number of patients do stop treatment. Reasons of TPO‐RA discontinuation can be no efficacy, adverse events, ITP or non‐ITP related death or spontaneous remission. Spontaneous remission (SR) or treatment free‐remission (TFR) is defined as a treatment‐free period of 3 6 months (mo) with platelets 3 50000/ml and no need of ITP rescue medication.Aims:We performed a survey to know how many patients were treated with TPO‐RA (trial, reimbursed, medical need) and how many of these had stopped this treatment. More details were gathered of patients who discontinued treatment.Methods:The survey was sent by mail to all hematologists who were member of the Belgian Hematological Society.Results:20 Belgian centers participated in our survey and sent data. 42 patients fulfilled the definition of TFR, while 3 of these patients had several episodes of TFR. The baseline characteristics of the patients obtaining TFR were as follows: 26 patients were male and 16 were female; diagnosis of primary ITP was made in 34 patients; the 8 patients with secondary ITP had an underlying lymphoma (n = 5), an Evans syndrome (n = 2) or a previous transplant (n = 1); mean age at ITP diagnosis was 50.5 years (y) (range 1–87y); median platelet count at ITP diagnosis was 5000/ml; median time between ITP diagnosis and the start of TPO‐RA was 5 y (range 1 mo‐24y); at start of TPO‐RA 5 patients fulfilled the definition of acute, 8 of persistent and 28 of chronic ITP; 54% (22/41) were splenectomized; 55% (22/40) needed 3 3 ITP treatments before the start of the TPO‐RA (corticosteroids, intravenous immunoglobulins, rituximab, cyclophosphamide, cyclosporin, fansidar…); median platelet count at start of TPO‐RA was 11000/ml; median time on TPO‐RA was 8 mo (range 0–74 mo); median platelet count was 267000/ml at discontinuation of TPO‐RA and 177000/ml 6 mo later. 178 patients (provided by 15 centers) were treated with TPO‐RA. Of these 100 patients discontinued treatment. 21% of the total cohort discontinued TPO‐RA because of TFR and 37% of the discontinuations was due to TFR.Summary/Conclusion:Our survey confirmed that SR or TFR on TPO‐RA is seen in about 20% of ITP patients treated in daily clinical practice in Belgium. TFR is seen not only in acute or persistent ITP but also in chronic ITP. TFR is seen in patients independent of splenectomy and independent of the number of treatments given before. In the future the incidence of TFR is thought to be even higher when the use of a forced tapering schedule will become common practice.

Excessive expressions of T cell activation markers in pediatric immune thrombocytopenia

BackgroundImmune thrombocytopenia (ITP) is an immune-mediated bleeding disorder in children. Activated T cells have been shown to play important roles in ITP. The aims of this study were to evaluate whether these T cell activation markers could be used as indicators to differentiate ITP patients from controls, and to assess whether they could be used as predictors of IVIG response in ITP patients. MethodsA cohort of 92 hospitalized ITP patients, 49 unrelated healthy children, and 48 thrombocytosis patients were enrolled in this retrospective study between February 2013 and September 2018. Expression of CD25, HLA-DR, and CD69 on the surfaces of CD4+ and CD8+ T cells were detected by flow cytometry. All statistical analyses were performed using SPSS 20.0 software. ResultsCompared to the healthy controls, ITP patients had higher percentages of CD4 + CD25+ T cells, CD4 + HLA-DR+ T cells, CD8 + HLA-DR+ T cells, and CD8 + CD69+ T cells. Compared to the thrombocytosis patients, ITP patients had higher percentages of CD4 + HLA-DR+ T cells and CD8 + HLA-DR+ T cells, and lower CD4 + CD69+ T cells and CD8 + CD69+ T cells. Platelet count at admission had a negative correlation with CD4 + CD25+ T cells in ITP. CD4 + CD69+ T cells were decreased in chronic compared to the newly diagnosed and persistent ITP patients. Activated T cell markers had no predictive value for IVIG response in ITP patients. ConclusionsT cell activation markers were excessively expressed in pediatric ITP, and those markers had no predictive value for IVIG response in ITP patients.

Assessment of IL-17F rs763780 gene polymorphism in immune thrombocytopenia

Interleukin-17F rs763780 (7488A/G) gene polymorphism obviously affecting the expression and activity of IL17F and may affect primary immune thrombocytopenia (PIT) susceptibility and its clinical features in Egyptian children and adults. 105 ITP patients divided into (63 pediatric and 42 adult patient) and 112 age and sex matched healthy controls were enrolled in this case control study. All patients were subjected to history taking; clinical examination, CBC, bone marrow aspiration and genotyping of IL17F rs763780 polymorphism by (PCR-RFLP) technique. Our results revealed significant decrease in the mutant heterozygous genotype AG and also in IL-17F mutant allele G frequency in ITP patient group and associated with increased risk for ITP compared with the control group (P = 0.04 and P = 0.005 respectively). Furthermore, the mutant allele G frequency was significantly decreased in childhood onset than adult onset ITP (OR = 0.31, P = 0.02) and also was significantly lower in chronic ITP when compared with newly diagnosed and persistent ITP (P = 0.005). Patients with the AA genotype showed severe thrombocytopenic state at diagnosis than those with the AG genotype (P = 0.04). We concluded from our results that interleukin-17F rs763780 (7488A/G) polymorphism is strongly correlated with susceptibility and severity of ITP.

A Systematic Literature Review to Assess Long-Term Outcomes Associated with Splenectomy in Patients with Chronic Immune Thrombocytopenia

Introduction: Chronic immune thrombocytopenia (cITP) is an autoimmune disorder defined by low platelet count (<100 x 109/L) lasting ≥12 months in the absence of other causes of thrombocytopenia. Splenectomy is an option for patients with cITP who fail to respond to oral corticosteroids and/or intravenous immunoglobulin or relapse after treatment is discontinued. A systematic literature review (SLR) conducted in 2004 (Kojouri et al) identified articles describing outcomes associated with splenectomy in patients with cITP. The objective of this study was to update this SLR with a focus on contemporary data on long-term outcomes (≥12 months of follow-up).Methods: MEDLINE, Embase, Cochrane CENTRAL and recent congresses were searched in June 2018. Results were screened against predefined criteria by two independent researchers. Included studies assessed patients with cITP (N≥15) who underwent splenectomy; studies of patients with secondary ITP, newly diagnosed ITP, and/or persistent ITP were excluded unless separate outcomes were reported for cITP subgroups. Outcomes of interest were clinical efficacy (response and relapse rates), safety (rates of complications), mortality, and health-related quality of life (HRQoL). Prospective or retrospective clinical studies or real-world study types were included. English-language studies published during or after 2000 were included, with no geographic restrictions.Results: The literature search identified 3140 records for title-abstract screening. Of these, 159 full-text studies were evaluated and 108 were included in the analysis. Most studies (93) were retrospective. Fifteen prospective studies (9 interventional, 6 observational) but no randomized controlled trials were identified. Nine studies were comparative (all retrospective): splenectomy vs rituximab (3), splenectomy vs rituximab vs romiplostim (1), and splenectomy vs non-splenectomy (5).Reports of the long-term efficacy of splenectomy varied widely, with multiple definitions of response and remission across the heterogeneous study types. Among 40 studies, the mean complete response (CR) rate within 12 months of surgery was 77% (median: 81%; range: 26-97%). Relapse rates varied widely, ranging from 0-94% among 47 studies with ≥12 months of follow up. Five of 7 studies reporting remission rates at multiple time points at ≥1 year noted a decrease in clinical remission over time. Mortality generally increased with length of follow up: in studies with ≤1 month of follow-up (28 studies) the mean mortality rate was 1% (range: 0-5%), while in studies with 1-5 years of follow-up (20 studies) and ≥5 years of follow-up (15 studies), the mean mortality rate was 2% (range: 0-17%) and 11% (range: 0-30%), respectively. Four studies reported that long-term response rates were higher with splenectomy than rituximab; all other efficacy comparisons were inconclusive.Although 11 of 15 prospective studies and 61 of 93 retrospective studies reported some safety information, there were very limited data on the long-term safety of splenectomy. Commonly reported complications were bleeding (mean: 14%; median: 12% range: 0-50%; 22 studies), infections (mean: 8%; median: 4% range: 0-33%; 38 studies), venous thromboembolism (VTE) (mean: 5%; median: 3% range: 0-21%; 27 studies) and sepsis/septic shock (mean: 2%; median: 0%; range: 0-11%; 18 studies). Rates of postoperative complications (≤30 days) ranged from 3-50% (mean: 13%; 31 studies), and 2 studies suggested that older age may be associated with higher rates of postoperative complications. HRQoL data were rarely reported (3 studies).Rates of remission, relapse, and infections for studies reporting at least 1 of these outcomes at 1 or more discrete time points are shown in Figure 1.Conclusions: Although more than 100 studies reported long-term outcomes for patients with cITP treated with splenectomy, available evidence on the durability of response and long term safety are limited. In general, most measures of efficacy declined over time, while complications (infections, bleeding, VTE) and mortality increased over time. The extent to which the outcomes for splenectomy differ from currently available treatments is unclear. Additional data are needed to understand the long-term benefits and risks of splenectomy in patients with cITP. DisclosuresNellesen:Analysis Group, Inc.: Employment; Novartis Pharmaceuticals Corporation: Consultancy. Said:Novartis: Employment. Shak:Analysis Group, Inc.: Employment; Novartis Pharmaceuticals Corporation: Consultancy. Patton:Novartis Pharmaceuticals Corporation: Consultancy; Analysis Group, Inc.: Employment. Lucas:Novartis Pharmaceuticals Corporation: Consultancy; Analysis Group, Inc.: Employment. Graves:Novartis: Employment. Nezami:Novartis Pharmaceuticals: Employment. Cuker:Kedrion: Membership on an entity's Board of Directors or advisory committees; Spark Therapeutics: Research Funding; Synergy: Consultancy; Genzyme: Consultancy.

Thrombopoietin and its receptor expression in pediatric patients with chronic immune thrombocytopenia

ABSTRACTObjectives: Chronic immune thrombocytopenia (cITP) is common in children. However, the pathogenesis has not been fully elucidated. This study aimed to determine whether thrombopoietin (TPO) and its receptor c-mannosylation of the TPO receptor (c-Mpl) have an impact on childhood cITP.Methods: Sixty-four patients with newly diagnosed ITP (nITP), 64 patients with persistent ITP, 80 patients with cITP, and 64 healthy children (control) were enrolled in this study. Plasma TPO was measured with an ELISA, and c-Mpl was determined by flow cytometry.Results: Plasma TPO levels showed differences among the four groups (p = 0.001). TPO levels in the cITP group were significantly decreased compared to those in the nITP group (p < 0.05). The mean fluorescence intensity (MFI) of c-Mpl was significantly different among the four groups (p = 0.0275). c-Mpl MFI was lower in the cITP group than in the nITP group(p < 0.05). Quantitative real-time PCR analysis showed that TPO mRNA expression was higher in the control group than in the ITP groups (p < 0.0001). The c-Mpl mRNA levels also showed significant differences among the four groups (p = 0.023). The control group, compared with the other groups, had lower levels of c-Mpl mRNA.Conclusions: The expression of TPO and c-Mpl was significantly decreased in the cITP group compared to the nITP group, suggesting that TPO and its receptor may play important roles in childhood cITP pathogenesis.

Inherited and Acquired Thrombophilia As a Modifier of Clinical Course of Chronic Idiopathic Thrombocytopenia - a Prospective Study

Background: Patients with idiopathic thrombocytopenia exhibit striking heterogeneity in bleeding manifestations even at similar platelet counts. Proposed mechanisms are generation of platelet microparticles, complement activation, NO depletion, and impact of various treatment modalities. In the present study, we studied the prevalence of thrombophilic markers in persistent and chronic ITP patients and that whether the presence of such markers modifies the clinical course of these patients.Methods: Patients diagnosed as persistent or chronic ITP (of any age group) were eligible. All patients were evaluated at baseline and at regular follow-up visits using newly available Bleeding Assessment Tool (ITP-BAT, version 1.0) proposed by International Working Group on ITP. For analyses, severity of bleeding was defined as no bleeding (bleeding score zero at all domains I.e. skin, mucosa and organ), mild bleeding (skin and mucosal bleeding score 0-2, organ bleeding score 0-1) and severe bleeding (skin and mucosa bleeding score >2, and organ bleeding score >1). Baseline thrombophilia profile was obtained for all patients, that included clot-based assays for protein C (PC), protein S (PS), ProCGlobal, FVIII levels (F8), and lupus anticoagulant assay (LA). We then compared the patients expressing atleast one thrombophilia marker (TM+) and those without (TM-), for the number of times patients in each group presented with a bleeding episode. We derived the parameter bleeding episodes per visit to estimate severity of bleeding in each group [mild bleeding episode/visit (MBE/visit) and severe bleeding/visit (SBE/visit)].Statistical analysis was done using odds ratio calculation and correlation regression analysis.Results: Of the total 88 patients enrolled, 21 were males (23.4%), and remaining 67 (76.5%) were females. Out the total, 57 patients (64.7%) tested positive for at least one thrombophilic marker, and remaining 31 patients (35.2%) were negative for all markers. Raised factor VIII was found in 36 patients (40.9%), low protein S in 29 patients (32.9%), low protein C in 14 patients (15.9%), abnormal Pro® C global in 22 patients (25%), and lupus anticoagulant positive in 9 patients (10.2%). Thirty three (37.5%) patients expressed thrombophilic markers in various combinations. Evaluation for impact of thrombophilia marker on bleeding is as shown in Table 1.Summary: Sixty-five percent of patients had thrombophilia marker positive in various combinations. Those with thrombophilia had lower bleeding tendency compared to those with none. Patients with low protein C and S, abnormal ProcGlobal and lupus positivity had significantly lower bleeding tendencies, while FVIII abundance did not impact the bleeding scores.Conclusion: We conclude that a part of the heterogeneity in the clinical presentation of persistent and chronic ITP can be explained by the presence or absence of thrombophilia, and that work-up of patients with ITP should include thrombophilia evaluation, the results of which may have a role in therapeutic decision making. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Clinical Characteristics and Quality of Life of Children with ITP Starting Second Line Treatments: Data from the ITP Consortium of North America ICON1 Study

Background: Children with ITP who are prescribedsecond line treatments vary in terms of their clinical phenotype, prior treatments, and health related quality of life (HRQoL). Objective: To describe the clinical characteristics and HRQoL of North American pediatric patients with ITP initiating second line treatments. Methods: A longitudinal observational cohort of 118 children with ITP starting second line treatments was enrolled from 2013-2015 at 21 ICON centers. Enrollment requirements included age 1-17y and starting a second line treatment (not IVIG, steroids or anti-D) as monotherapy. Baseline demographic and clinical characteristics were recorded, including response to prior treatments, worst bleeding scores, and baseline platelet counts. Fisher9s exact test was used to compare treatment with phase of ITP, age cohort, and gender. HRQoL was measured by patient/caregiver report using the Kids ITP Tool (KIT) where 0 is worst and 100 is best, while physicians assessed the perceived effect of ITP on patient HRQoL using a 5-point scale. Spearman correlations were used to test for association between bleeding, HRQoL, and duration of ITP. ANOVA was used to compare the mean KIT scores of the treatment groups. Results: The clinical characteristics of the cohort are shown in the Table. Median age at enrollment was 11.4 y and 15% had newly diagnosed ITP, 31% had persistent ITP, and 54% had chronic ITP. The median number of prior treatments was 3 (range: 1-9). The prior response rate (platelet >30 x 10 9 /µL and no bleeding) to prednisone was 59% and IVIG 66%. Fifty-five (47%) patients had received at least one prior second line treatment. At enrollment, physicians reported that ITP had impacted the patients9 HRQoL severely in 15%, significantly in 44%, moderately in 38%, and almost not at all in 3%. The mean score of the child KIT report was 71.4 (SD 17.2), the parent proxy KIT was 64.7 (SD 16.4), and the parent impact KIT was 36.1 (SD 19.2). The physician9s assessment of the patient9s HRQoL significantly correlated with the child report (p Treatments selected for second line treatment included: rituximab (n=42), romiplostim (n=31), eltrombopag (n=20), oral immunosuppressants (n=16), splenectomy (n=4), and dapsone (n=3). The selected treatment was not significantly different by age, gender, baseline child KIT score, or duration of ITP. Baseline parent proxy KIT scores varied significantly between selected treatments (p=0.03) and were significantly lower in children starting on eltrombopag in comparison to romiplostim (56.4 (SD 15.1) vs. 70.3 (SD 15.1), respectively; p=0.03). Conclusions : Children with ITP starting on new second line treatments often have received multiple prior treatments and nearly half start these treatments prior to being diagnosed with chronic ITP, including 15% who were in the newly diagnosed phase. Physician assessment of patient HRQoL correlates well with child and parent proxy report of HRQoL. The number of prior treatments and worst bleeding score did not correlate with HRQoL. Longer duration of ITP was associated with a better HRQoL, suggesting that the level of concern related to ITP may lessen over time. Baseline KIT scores were significantly different in children starting on specific treatments. Future analysis will compare the change from baseline in HRQoL in children treated with second line therapies. Disclosures Grace: Agios Pharmaceuticals: Other: Scientific Advisor, Research Funding. Neufeld: Novartis: Consultancy. Bussel: Eisai: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Symphogen: Membership on an entity9s Board of Directors or advisory committees; Shionogi: Membership on an entity9s Board of Directors or advisory committees; Protalex: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Physicians Education Resource: Speakers Bureau; Prophylix Pharma: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Rigel Pharmaceuticals: Membership on an entity9s Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Cangene: Research Funding; GSK: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Research Funding; Ligand: Membership on an entity9s Board of Directors or advisory committees, Research Funding; UpToDate: Patents & Royalties; Genzyme: Research Funding; BiologicTx: Research Funding; Momenta Pharmaceuticals: Membership on an entity9s Board of Directors or advisory committees; Sysmex: Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Research Funding. Haley: Baxalta: Membership on an entity9s Board of Directors or advisory committees; CSL Behring: Honoraria. Thompson: Baxalta (now part of Shire): Research Funding; Novartis: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; bluebird bio: Consultancy, Research Funding; Baxalta (now part of Shire): Research Funding; ApoPharma: Consultancy, Membership on an entity9s Board of Directors or advisory committees; Amgen: Research Funding; bluebird bio: Consultancy, Research Funding; Amgen: Research Funding; Mast: Research Funding; Mast: Research Funding; Celgene: Research Funding; Celgene: Research Funding; Eli Lily: Research Funding; Eli Lily: Research Funding.

Efficacy and Safety of Eltrombopag in Persistent and Newly Diagnosed ITP

Background: Eltrombopag is a thrombopoietin receptor agonist approved for primary chronic ITP patients. Due to the non-existence of clinical trials using eltrombopag in persistent and newly diagnosed ITP, there are no clear data about its usefulness in this setting.Aims: To evaluate efficacy and safety of eltrombopag in persistent, newly diagnosed and chronic ITP in routine clinical practice in Spain.Methods: Two hundred and twenty adult ITP patients from thirty Spanish centers who had been treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. This study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee.Results:Here we report efficacy and safety results of primary ITP Spanish Eltrombopag Registry cohort. According to the standard definition, patients were allocated to newly diagnosed (n=30), persistent (n=30) and chronic (n=160) ITP groups. Each group is described separately in Table I.There are no statistical significant differences regarding response and duration of response among ITP groups. There is a trend towards a greater efficacy in newly diagnosed ITP with 93.3% of responses (platelet count ≥30 x109/L and at least two-fold increase the baseline count and absence of bleeding) and 86.7% of complete responses (CR; platelet count >100 x 109/L). Persistent ITP achieved 83.3% of responses and 80.0% of CR. Similarly 79.4% of responses with 73.1 of CR were observed in chronic ITP. Response rates were similar in all groups regardless all other studied parameters.Another trend towards a longer response duration in persistent ITP was found, with a median of 424 (IQR, 288-664) days. Response durations were similar in chronic ITP (median, 370 days; IQR, 174-624) and in newly diagnosed ITP (median, 378 days; IQR, 154-485).In newly diagnosed ITP, eight adverse events (AEs) with only three grade 3-4 AEs were observed. We reported three deaths; Two of them were due to upper respiratory tract infections in previously diagnosed pulmonary patients. A cerebral hemorrhage was the only death directly related to thrombocytopenia.In persistent ITP, four grade 1-2 AEs and two grade 3-4 AEs (one stroke, one cerebral bleeding) were reported. The only observed death was secondary to the mentioned cerebral hemorrhage.Twenty-one grade 1-2 AEs, ten grade 3-4 AEs and eight deaths (only two caused by bleeding) occurred in chronic ITP.Conclusion:Use of eltrombopag for treating persistent and newly diagnosed ITP is effective and safe. However, more studies are needed to confirm usefulness of TPO-RAs in this setting.Table 1Patient characteristicsVariableNewly-Diagnosed ITP (n = 30)Persistent ITP(n=30)Chronic ITP (n=160)Age, years, median [Q1;Q3]66[46;79]66[47;76]61[47;75]Men/Women n12/1815/1547/113Charlson comorbidity Index > 1, n (%)7(25.9)5(17.2)25(16.7)Months with ITP, median [Q1;Q3]1[1;2]6[4;10]79[30;193]Past ITP treatments, median [Q1;Q3] Rituximab, n (%) Splenectomy, n (%) Romiplostim, n (%)2[1;3] 3(10.7) 2(7.1) 3(10.7)2[1;3] 5(17.2) 4(13.8) 4(13.8)3[2;4] 43(28.3) 47(30.7) 37(24.3)Platelet count at start of eltrombopag treatment, (x109/L), median [Q1;Q3]Bleeding at start of eltrombopag treatment , n (%)Concomitant treatment, n (%) Corticoids Immunoglobulins Corticoids and Immunoglobulins15[7;29] 13(43.3) 10(33.3) 6(60) 0 2(20)14[6;26] 10(33.3) 9(30) 7(77.8) 0 2(22.2)22 [9;38] 50 (31.3) 46 (28.8) 27 (57.4) 10 (21.3) 8 (17) DisclosuresOff Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for persistent and newly diagnosed ITP patients..

Effects of Anti-Glycoprotein Antibodies on Response of Immune Thrombocytopenia Patients to Thrombopoietin Receptor Agonists and on Megakaryocytes Viability

BackgroundImmune Thrombocytopenia (ITP) is a bleeding disorder due to a combination of increased platelet destruction and reduced production, often secondary to anti-platelet/megakaryocyte antibodies.The presence of antibodies to glycoproteins (GP) IIb/IIIa (integrin αIIbβ3) and GPIb/IX, detected in majority of ITP patients, may correspond to different responses to treatment, i.e., anti-GPIb is associated with more severe disease, and less responsive to intravenous immunoglobulins and steroids.Thrombopoietin Receptor Agonists (TPO-RA) increase platelet production by stimulation of megakaryopoesis. Predictors of response to TPO-RA and influence of antibody profile on response are currently unknown. In our previous study we investigated Absolute Immature Platelet Fraction (A-IPF) prior to TPO-RA treatment and did not find a correlation between A-IPF, anti-GP antibodies, and platelet counts.The aims of this study were to further investigate:1. The role of anti-GP antibodies in response to TPO-RA;2. Effect of patients' antibodies on megakaryocyte (MK) viability, maturation, apoptosis and formation of proplatelets (in vitro);3. The influence of patients' clinical characteristics on response to TPO-RA.Materials and Methods91 patients with persistent or chronic ITP, were treated at Weill Medical College of Cornell University until January 2015 with TPO-RAs: 52 patients received eltrombopag, 22 romiplostim and 17 avatrombopag. Serum samples of 84 patients were analyzed for the presence of anti-GP by MAIPA assay as previously described.Patients with baseline platelet counts less than <30x109/L were defined as responders to TPO-RA if the average of their six median monthly platelet counts was ≥50x109/L and doubled from average baseline counts (prior to TPO-RA). Patients with baseline platelet counts 30-50x109/L were responders if the average platelet count was ≥75x109/L.MKs were derived from human umbilical cord blood stem cells as previously described. Cells were grown using SFEM medium, adding on day 0 of culture 50 ng/ml recombinant TPO and aliquots of serum of ITP patients or healthy controls. The percentages of immature (CD41+/CD42-), mature (CD41+/CD42+), viable and apoptotic MKs were analyzed by flow cytometry on day 12. Apoptosis was analyzed by measuring Mitochondrial Outer Membane Potential (MOMP) and Phosphatidyl Serine (PS) externalization. MKs were considered apoptotic if they had positive staining for PS externalization, viable if positive for MOMP, and dead if positive for 7-Aminoactinomycin D (7AAD).Proplatelet formation by MKs was analyzed by microscopy.Statistical analysis using unpaired T-test and Pearson correlation test were performed.ResultsNinety-one patients were included, 40 male (44%) and 51 female (56%), with a median age of 37.4 years (range 2-87). Median duration of ITP before TPO-RA treatment was 8 years (range 0.3-45).The 18/91 (19.8%) non-responders to TPO-RA were not different from the 73/91 responders in age, gender, number of prior treatments, duration of ITP, and past splenectomy. The presence of either or both anti-GP antibodies was correlated with average lower platelet counts on TPO-RA: 82.3 x109/L versus 123x109/L in patients without detected antibodies ("neither") (p=0.003). However, the response to TPO-RA was not influenced by the type of antibody: in patients with anti-GPIb the average platelet count was 76.1x109/L, and with anti-GPIIb/IIIa 80.7x109/L (Figure 1). In culture, excess dead MKs were found in anti-GPIb group and antiGPIb&antiGPIIb/IIIa group compared to "neither" group (p=0.0013 and p=0.027 respectively) and comparing antiGPIb&antiGPIIb/IIIa to control (p=0.0025). We did not observe changes in the degree of MK apoptisis or in MK maturation in the presence of serum antibodies. In cultures treated with serum of patients having anti-GPIb, less proplatelets were detected comparing to control (p=0.044) or to "neither" (p=0.0039).We conclude that patients with anti-GP antibodies respond less to TPO-RA, however there is no difference in response to TPO-RA between patients having anti-GPIb and anti-GPIIb/IIIa, unlike responses to other treatment modalities (e.g., steroids or immunoglobulins). TPO-RA could be a preferable treatment option in ITP patients having anti-GPIb. [Display omitted] DisclosuresOff Label Use: Eltrombopag, romiplostim and avatrombopag are a thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in adults with chronic ITP. In some preliminary studies these medicines found as safe and effective treatment option in children and adolescents. Bussel:amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; Novartis: Consultancy, Research Funding; Genzyme: Consultancy; BiologicTx: Research Funding; Ligand: Consultancy, Research Funding; Eisai: Consultancy, Research Funding; Shionogi: Consultancy, Research Funding; momenta: Consultancy; Protalex: Consultancy; Symphogen: Consultancy.