ITP In Patients Research Articles

De Novo ITP Diagnosed during Pregnancy : Outcome for the Mothers and the Neonates and Prospective Comparative Study with Chronic ITP Pregnant Women

Background and Objective : Outcome, severity and transition to chronic illness of de novo ITP diagnosed during pregnancy and incidence of neonatal ITP (NITP) in this subset of patients have never been prospectively described. We conducted a prospective multicentric study in France to evaluate the outcome of patients with ITP during pregnancy (Clinical Trials.gov ID NCT02892630). One of the aims of this study was to investigate the evolution of ITP in patients with known ITP prior to pregnancy (« chronic group »). The results of this first part of the study have been recently published (Guillet et al, Blood ; 141 :11-21). Another aim was also to prospectively study the outcome of patients with ITP appeared and diagnosed during pregnancy (“ de novo group”) and to compare them with the previous group. We report the results here. Methods: De novo ITP was defined by a normal platelet count before pregnancy and a nadir < 50x10 9/L during pregnancy without any other clinical or biological abnormalities in particular no sign of pregnancy-specific causes of thrombocytopenia. We used a stringent platelet count threshold <50x10 9/L to avoid misdiagnosis with gestational thrombocytopenia. Patients were followed during pregnancy and 6 months after delivery. We compared ITP outcome in both groups (“ chronic” and “ de novo” groups) including episodes of bleeding events, severe thrombocytopenia (<30x10 9/L) and ITP treatment modification. We also studied obstetrical complications and NITP incidences in both groups. Results: 34 “ de novo” ITP women diagnosed during pregnancy were included and compared with 61 chronic ITP pregnant women. De novo ITP was diagnosed equally during the first, second and third trimester, in respectively 29.4% (10/34), 32.4% (11/34) and 38.2% (13/34). Among these 34 women, 29.4% (10/34) were primiparous. De novo ITP pregnant women experienced during follow-up, severe thrombocytopenia in 50% [35.5-91.9], bleeding events in 41.2% [26.8-59.4] including 11.8% [4.6%-28.4%] severe bleeding events with a French bleeding score > 8 and ITP therapeutic interventions in 76.5% [61.4-88.9]. Episodes of severe thrombocytopenia and bleeding events including severe bleeding event were similarly observed in “ de novo” and “ chronic” groups (data not shown). However, chronic ITP pregnant women underwent less ITP therapeutic interventions 50.8% [39.1-63.8], p=0.039. Obstetrical complications including preterm delivery, postpartum hemorrhage and cesarean delivery rates were similar in both groups (data not shown). NITP <50x10 9/L was observed in 6/31 (19.3%) neonates of women with de novo ITP and was similar to those observed in neonates of chronic ITP women 9/53 (17%). With a median follow-up of 6 months [5-7] after delivery, de novo ITP remained active for 25/34 women (73.5%). Conclusion: The severity of de novo ITP diagnosed during pregnancy and the risk of NITP are closely similar to those observed in chronic ITP pregnant women. Non-fatal severe bleeding events occur in around 10% of patients. De novo ITP remains active 6 months after delivery in a large majority of patients. Our study is still in progress to better assess the risk of chronic evolution (more than one year of duration) of de novo ITP after delivery.

P1646: PRIMARY IMMUNE THROMBOCYTOPENIA (ITP) IN PATIENTS OLDER THAN 75 YEARS: REAL WORLD DATA FROM THE ITP REGISTRY OF THE HELLENIC SOCIETY OF HEMATOLOGY

Background: ITP incidence is known to increase in adults aged >60 years and even more in men aged >75 years (Moulis G et al., Blood 2014; 124(22):3308). As population aging and life-expectancy continues to increase worldwide, ITP in the elderly is a growing concern in everyday clinical practice. There are only a few studies regarding the features of ITP in patients (pts) aged >60-65 years and data are even scarcer in pts aged ≥75 years Aims: To describe real world characteristics at diagnosis and evaluate disease outcome in a group of pts aged 60-74 years (Group-1) as compared to very old pts (≥75 years; Group-2) with primary ITP, using data from the national database (ITP registry) operated under the auspices of the Hellenic Society of Hematology Methods: The Greek ITP registry recruits pts (n=1560, to date) nationally through a network of 25 sites. In the present study we retrospectively analyzed data from pts with primary ITP aged ≥60 years, who were diagnosed from 1979 to 2021. Results: The total number of evaluable pts was 298. Group-1 consisted of 180 and Group-2 of 118 pts. The mean age at diagnosis was 68 years (60.1-74.9) in Group-1 and 81 years (75.2-97.1) in Group-2. The female to male ratio did not differ between the 2 groups. The median platelet count at diagnosis was significantly higher in Group-1 (20x109/L, interquartile range: 5-44x109/L) than in Group-2 (11x109/L, interquartile range: 5-32x109/L; P=0.0096). Comorbidity rates did not differ between Group-1 and Group-2, with the exception of hypertension and chronic kidney disease, which were less frequently reported in Group-1 (P=0.0092 and P=0.0179, respectively). Concurrently used medications as a whole and also vitamin-K antagonists were reported less frequently in Group-1 (P=0.03 and P=0.049, respectively). Bleeding manifestations at diagnosis were comparable across the two age-groups. The choice of diagnostic procedure did not differ between Goup-1 and Group-2, with the exception of anti phospholipid antibody and anti nuclear antibody testing which were performed more frequently in Group-1 (P=0.048 and P=0.0002, respectively). Similar rates of positive laboratory test results were reported in the two age-groups. Fewer pts received treatment at diagnosis in Group-1 (P=0.023). Overall response rate did not differ between the two Groups. A similar proportion of Group-1 and Group-2 patients were treated with corticosteroids, intravenous IgG or both, rituximab, anti-D, immunoglobulin or thrombopoietin receptor agonists. Splenectomy was performed in 2.8% of Group-1 pts but in none of Group-2 pts. At 1 year after diagnosis, a similar proportion of Group-1 and Group-2 pts had developed chronic ITP. Summary/Conclusion: Very elderly pts (Group-2) presented with lower platelet counts at diagnosis and required ITP treatment more frequently than elderly pts (Group-1). Furthermore, Group-2 pts suffered more often from hypertension and chronic kidney disease and used more often anticoagulant agents. On the other hand, the 2 age-groups did not differ in the frequency or the location of bleeding. Age did not seem to particularly influence the diagnostic workup or the choice of treatment, with the exception of splenectomy which was not performed in Group-2 patients. The outcome of the disease was comparable in the 2 age-groups, as suggested by the similar treatment response rates and chronic ITP frequencies. Further investigation is warranted to full characterize the very elderly pts with ITP and unravel the unmet need of this cohort in order to optimize management.

Does Autoimmunity in Family Members of Children with Immune Thrombocytopenia Help Identify Patients at Higher Risk of Chronic Immune Thrombocytopenia?

BackgroundImmune thrombocytopenia (ITP) is the most common cause of thrombocytopenia during childhood. Approximately 10-30% of pediatric patients will develop chronic ITP (cITP), which is defined as thrombocytopenia lasting over 12 months, and constitutes a significant burden for patients and their caregivers. Patients with cITP may require ongoing medications to treat symptomatic thrombocytopenia, may have asymptomatic thrombocytopenia not requiring medical interventions, or may experience complete resolution of their ITP. There are not specific patient nor disease characteristics that can help us predict how cITP may progress, and which patients are more likely to require ongoing treatments. ITP can be a manifestation of immune dysregulation in patients with other autoimmune conditions or primary immunodeficiency disorders (PIDDs). We aimed to assess the characteristics of patients with cITP including the presence of autoimmune or allergic disorders in the patients and in first-, second-, and third-degree family members. We hypothesized that patients with cITP may have a higher incidence of immune dysregulation in family members in contrast to patients with acute aITP.MethodsThe study was approved by the institutional review and ethics boards at the University of Utah. We queried the Primary Children's Hospital database for cases of “immune thrombocytopenia” from January 1 st, 2001 to January 1 st,2021. Retrospective chart review was done to confirm the diagnosis. Patient demographics, clinical presentation, and family history of patients were reviewed. Data was collected in RedCap at the University of Utah. Descriptive summaries of data were done.ResultsMedical charts from 266 ITP patients diagnosed during the study period were reviewed; 182/266 (68.5%) had acute ITP (aITP) and 84/266 (31.5%) patients had cITP, defined as platelet count <150 K/µl for >12 months. Resolution of ITP occurred in 28/84 (33.3%) patients with cITP (resolved cITP), while 56/84 (66.7%) had ongoing thrombocytopenia (unresolved cITP). Mean duration of ITP in patients with resolved cITP was 2.9 years, and 4.6 years in patients with unresolved cITP at the time of the last known platelet count. Mean age at diagnosis was 7.4 years in the cITP group and 5.1 years in the aITP group.Concurrent allergic conditions were identified in 10/84 (12%) of patients with cITP and 5/182 (2.7%) of patients with aITP. Autoimmune conditions were identified in 3 patients (3.5%) with cITP, and 4 patients (2.2%) with aITP. First-degree family members of cITP patients were more likely to be reported with an autoimmune condition than first-degree family members of aITP patients (15.5% vs. 5.5%, p=0.007 using Chi-square test); this effect was not seen amongst second- or third-degree relatives. The most common autoimmune condition reported in family members was autoimmune thyroid disease in both cohorts (2.7% in aITP and 9.5% in cITP). Common variable immunodeficiency (CVID) was reported in second degree relatives of 3/84 (3.6%) patients with cITP; no relatives of patients with aITP had a report of PIDD. Additionally, we identified 14 patients with Evans syndrome (ES), all with chronic immune thrombocytopenia and all patients had been followed for over a year at the time of the chart review. Four ES patients were previously diagnosed with 22q11.2 deletion, and one with CVID. In patients with ES, 4/14 (28.6%) and 5/14 (35.7%) had first- and second-degree family members with a reported autoimmune condition, respectively. No PIDDs were identified in first, second-, or third-degree relatives of patients with ES.ConclusionsThere is increasing evidence that patients with chronic ITP may exhibit polyautoimmunity or other signs of immune dysregulation, suggesting that ITP may be the initial manifestation of another autoimmune process or PIDD. We evaluated medical histories of patients with ITP and their family members. Patients with cITP have a history of autoimmunity in their family stronger than in patients with aITP. This association was even stronger in patients with ES. DisclosuresNo relevant conflicts of interest to declare.

Rituximab As Second Line Treatment For Adult Immune Thrombocytopenia (ITP): A Multicentre, Randomized, Double Blind, Placebo-Controlled Study – The Ritp Study (NCT00344149)

Introduction Splenectomy is recommended by ASH and other guidelines as the main 2nd line therapy for ITP in patients who fail to respond or relapse after initial treatment with steroids. However, because of the possible peri- and postoperative complications, irreversibility and unpredictable response of splenectomy, medical alternatives that lead to avoidance of splenectomy are of great interest. Despite the lack of evidence-based data, rituximab (RTX) is now commonly used to manage ITP. RTX has not been properly evaluated in randomized placebo-controlled trials to determine its role as a splenectomy-sparing agent in ITP. This study aimed to assess the efficacy of RTX against placebo in steroid- unresponsive ITP patients. Methods In this multi center (n=14) international, double blind placebo-controlled study, patients were randomly allocated to receive 4 weekly infusions of 375mg/m2 RTX or placebo. Steroids were allowed throughout the study. Main inclusion criteria were: 1- unsplenectomized patients with primary ITP with platelet count (PC) &lt;30 or 30-50 x109/L if a higher PC was required, 2- failure to achieve sustained response to 1-2 mg/kg prednisone/prednisolone given ≥ 2 weeks (w) or relapse during steroid-tapering or after discontinuation. Exclusion criteria included previous administration of 2nd line treatments for ITP. The Primary endpoint was the rate of treatment failure within 78 w; treatment failure was defined as splenectomy or meeting criteria for splenectomy after w 12 if splenectomy was not be performed because of contraindication or patient's refusal. Criteria for splenectomy were defined as either PC &lt;20 x109/L or a need of dose increment &gt; 7.5 mg/day of Prednisone/prednisolone to maintain PC ≥20 x109/L. Secondary endpoints were rate of complete response (CR) at 24 w (PC &gt;100 x109/L without administration of any platelet elevating therapy except steroids within the last 2 w) and safety. Analysis was performed on intention to treat basis. The Kaplan-Meier method and logrank test were used for efficacy outcomes; all statistical tests were 2-sided with a significance level of 5%. The study was approved by National Ethics Committees. Written informed consent was obtained from all patients. Results Characteristics, response and safety outcomes of the 109 randomized patients are shown in the table. Treatment with RTX did not reduce the rate of treatment failure at 78 w (logrank test p=0.6). However, there was a trend toward a reduction in the rate of splenectomy in the RTX-arm. Seventeen (31%) in the RTX-arm vs 6 (11%) in the placebo-arm achieved CR at 24 w (p=0.01). CR continued to occur after 24 w, figure. Although a number of patients in both arms relapsed during the follow-up, the difference in CR between the 2 arms remained significant throughout the study (p=0.02). RTX was associated with a higher rate of infections compared to placebo; one infection in each arm was evaluated as severe. Conclusions This is the first randomized placebo-controlled study aiming to assess both short and long-term efficacy and safety of RTX in steroid-unresponsive ITP patients. The study shows that treatment of steroid-unresponsive ITP with RTX did not reduce the rate of treatment failure, which was defind as a composite of splenectomy or meeting the predefined criteria for splenectomy if spenectomy was not performed. However, there was a trend toward a lower rate of splenectomy in the RTX-arm. Conversely, RTX resulted in a significnatly higher rate of CR at 24 w compared to Placebo - a difference that remained significant throughout the study. In conclusion, monotherapy with RTX in steroid unresponsive patients did not alter the rate of treatment failure but yielded a significantly higher rates of CR as compared to placebo, which seems to be the main benift of treatment with RTX . Disclosures: Ghanima: Roche: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; GSK: Honoraria. Off Label Use: Rituximab is not approved for the treatment of ITP. Michel:Roche: Honoraria, Research Funding; Amgen: Honoraria. Holme:Roche: Research Funding.

ITP in Patients With CLL: Practicing With Patrick F. Fogarty, MD

ITP in Patients With CLL: Practicing With Patrick F. Fogarty, MD

ITP in Patients Infected With Hepatitis C Virus: Practicing With Howard Liebman, MD

ITP in Patients Infected With Hepatitis C Virus: Practicing With Howard Liebman, MD

ITP in Patients with HCV

Autoantibodies are found in as many as 40% of patients who are infected with hepatitis C virus (HCV). Although it is unlikely that these autoantibodies

Hemophilia and thrombocytopenia in a patient with impaired cellular immunity

ITP in hemophiliacs may produce severe bleeding complications. We here report on an eight-year-old boy suffering from severe hemophilia A, who developed ITP and an acquired impaired immune function similar to AIDS. Steroid therapy reverted the thrombocyte count to normal, however it had to be discontinued because of a severe Cushing syndrome. The thrombocytopenia also responded to IgG-therapy and the patient is treated with a long term schedule according to Imbach. It is of interest that the impaired T-helper/T-suppressor cell ratio (0.45) improved to a value of 1.0 after initiation of this therapeutic regimen. We conclude from our observation that i.v. immunoglobulin therapy is of particular value for the treatment of ITP in patients with impaired cellular immunity.