Primary Immune Thrombocytopenia in Elderly Patients: Clinical Profile, Efficacy and Safety of Treatment Protocols

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4196-4196 ◽  
Author(s):  
Maria Cristina Moragues Martinez ◽  
Kati Hurst ◽  
Maria Eva Mingot Castellano ◽  
Ana Isabel Heiniger Mazo

Abstract Introduction: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by accelerated platelet destruction and inadequate platelet production mediated by autoantibodies. As there are no specific diagnostic tests, the diagnosis of ITP remains one of exclusion. Although the incidence of ITP increases with age, there are no practice guidelines for elderly patients and few studies have been conducted. Compared with younger patients, older patients have a higher incidence of serious bleeding complications and increased related mortality. Therefore we propose to describe our experience in the management of ITP in patients over 65 years old. Methods: We conducted a retrospective study of 44 patients over 65 years old at the moment of the ITP diagnosis, treated in our center from January 1995 to March 2014. Variables analyzed were age, Charlson score, clinical manifestations and platelet count at diagnosis, type of treatment, response to treatment and adverse events. Results: The median current age is 77 years (IQR, 70-84 years), with a median age at diagnosis of 69 years (IQR, 65-75 years). The ratio of males to females was 0.91. Eighteen (40.9%) patients had a Charlson score greater than or equal to 2. The comorbilities were 27.8% diabetes with damage to target organs; 11.4% coronary disease; 9.8% solid metastatic tumor, 9.8% peripheral vascular disease, 9.8% chronic pulmonary disease; 5% congestive heart failure, 5% peptic ulcer, 5% cerebrovascular disease, 5% moderate-severe liver disease, 5% moderate-severe renal disease y 1.6% connective tissue disease, 1.6% dementia, 1.6% hemiplegia and 1.6% leukemia. The mean platelet count at diagnosis was 28x109 / L (IQR, 8-74x109 / L). Initial presentation was thrombocytopenia on a routine blood count in 43% of patients while the rest presented bleeding symptoms. Fourteen patients (31.8%) required admission on diagnosis. 18.8% showed major bleeding: 6 (13.63%) gastrointestinal haemorrhages, 1 (2.2%) hematuria and 47.7% minor bleeding: 8 (18.18%) bruising, 7 (15.9%) mucosal bleeding and 7 (15.89%) purpura and epistaxis. Regarding treatment, observation was used in 11 patients (25%), all of whom subsequently acheived spontaneous remission. Corticosteroid therapy (prednisone 0.5-1mg/kg), was the initial treatment used in 13 patients (29.5%), 15.9% received intravenous inmunoglobulins (1gr/kg x 2 days) and 18.2% combination therapy. A response was obtained in 75.6% of patients (35.6% CR, 40% R). Seven (16%) subjects received second-line treatment (1 splenectomy, 3 romiplostim, 1 eltrombopag, 1 rituximab, 1 Imurel). The patient that underwent splenectomy obtained CR. Of the 3 patients treated with romiplostim, 2 achieved CR directly, and the third required rescue therapy with eltrombopag to reach CR. The patient that received second line treatment with eltrombopag obtained R and the patient treated with Rituximab failed and needed rescue therapy with romiplostim. Finally the patient treated with azathioprine is in CR but still on treatment. At present we have an 84.1% response rate after a median follow up of 66 months (IQR, 27-100 months). During treatment we observed a single vascular event in the form of deep vein thrombosis with associated pulmonary embolism in a subject with additional thromboembolic risk factors. We found no infections, hyperglycemia or hypertensive crisis which required hospital admission or special monitoring. Five patients (11.4%) developed neoplasms (hepatocellular carcinoma, rectal neoplasm, pancreatic adenocarcinoma and Hürthle cell carcinoma), none of which were haematological. Three patients died: 2 due to neoplasm progression and 1 to acute renal failure. Conclusions: Low and intermediate doses of corticosteroids are a good first line treatment option in elderly patients. Close monitoring of the patient is advisable to ensure the early detection and treatment of adverse events and possible underlying diseases that could justify the thrombocytopenia. In our series the incidence of major bleeding in over 65s with ITP is clearly superior to that reported in younger subjects. Therefore, it is essential to optimize the intensity and duration of treatment in these patients. Disclosures No relevant conflicts of interest to declare.

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 385-386 ◽  
Author(s):  
Adam Cuker ◽  
Douglas B. Cines

Abstract Clinical scenario: An otherwise healthy 25-year-old woman returns to your office for management of chronic primary immune thrombocytopenia. She was diagnosed 6 months earlier and continues to require prednisone 15 mg daily and periodic infusions of intravenous immunoglobulin to maintain a hemostatic platelet count. You discuss second-line treatment options, including splenectomy. The patient asks if there are any means by which to predict likelihood of response to splenectomy. You have heard about the use of indium-labeled autologous platelet scanning for this purpose and wonder what the evidence shows.


Blood ◽  
2010 ◽  
Vol 115 (14) ◽  
pp. 2755-2762 ◽  
Author(s):  
Francesco Zaja ◽  
Michele Baccarani ◽  
Patrizio Mazza ◽  
Monica Bocchia ◽  
Luigi Gugliotta ◽  
...  

Abstract Previous observational studies suggest that rituximab may be useful in the treatment of primary immune thrombocytopenia (ITP). This randomized trial investigated rituximab efficacy in previously untreated adult ITP patients with a platelet count of 20 × 109/L or less. One hundred three patients were randomly assigned to receive 40 mg/d dexamethasone for 4 days with or without 375 mg/m2 rituximab weekly for 4 weeks. Patients who were refractory to dexamethasone alone received salvage therapy with dexamethasone plus rituximab. Sustained response (ie, platelet count ≥ 50 × 109/L at month 6 after treatment initiation), evaluable in 101 patients, was greater in patients treated with dexamethasone plus rituximab (n = 49) than in those treated with dexamethasone alone (n = 52; 63% vs 36%, P = .004, 95% confidence interval [95% CI], 0.079-0.455). Patients in the experimental arm showed increased incidences of grade 3 to 4 adverse events (10% vs 2%, P = .082, 95% CI, −0.010 to 0.175), but incidences of serious adverse events were similar in both arms (6% vs 2%, P = .284, 95% CI, −0.035 to 0.119). Dexamethasone plus rituximab was an effective salvage therapy in 56% of patients refractory to dexamethasone. The combination of dexamethasone and rituximab improved platelet counts compared with dexamethasone alone. Thus, combination therapy may represent an effective treatment option before splenectomy. This study is registered at http://clinicaltrials.gov as NCT00770562.


2021 ◽  
Vol 12 ◽  
pp. 204062072110483
Author(s):  
Monica Carpenedo ◽  
Erminia Baldacci ◽  
Claudia Baratè ◽  
Alessandra Borchiellini ◽  
Francesco Buccisano ◽  
...  

Introduction: In patients with primary immune thrombocytopenia (ITP), a short course of steroids is routinely given as first-line therapy. However, the response is often transient and additional therapy is usually needed. Thrombopoietin receptor agonists (TPO-RAs) are frequently used as second-line therapy, although there is little clinical guidance on the timing of their administration and on tapering/discontinuation of the drug. To provide clinical recommendations, we used the Delphi technique to obtain consensus for statements regarding administration and on tapering/discontinuation of second-line TPO-RAs among a group of Italian clinicians with expertise in management of ITP. Methods: The Delphi process was used to obtain agreement on five statements regarding initiation and on tapering/discontinuation of second-line TPO-RAs. Agreement was considered when 75% of participants approved the statement. Eleven experts participated in the voting. Results: Full consensus was reached for three of the five statements. The experts held that an early switch from corticosteroids to a TPO-RA has the dual advantage of sparing patients from corticosteroid abuse and improve long-term clinical outcomes. All felt that dose reduction of TPO-RAs can be considered in patients with a stable response and platelet count >100 × 109/L that is maintained for at least 6 months in the absence of concomitant treatments, although there was less agreement in patients with a platelet count >50 × 109/L. Near consensus was reached regarding the statement that early treatment with a TPO-RA is associated with an increase in clinically significant partial or complete response. The experts also agreed that optimization of tapering and discontinuation of TPO-RA therapy in selected patients can improve the quality of life. Conclusion: The present consensus can help to provide guidance on use of TPO-RAs in daily practice in patients with ITP. Plain language summary Second-line administration of thrombopoietin receptor agonists in immune thrombocytopenia There is little guidance on the timing of administration and tapering/discontinuation of thrombopoietin receptor agonists (TPO-RAs) in patients with primary immune thrombocytopenia (ITP). The Delphi technique was used to obtain consensus for five statements. The present consensus among Italian clinicians aims to provide guidance on second-line use of TPO-RAs for patients with ITP in daily practice.


2021 ◽  
pp. 102620
Author(s):  
Gardellini Angelo ◽  
Guidotti Francesca ◽  
Feltri Maddalena ◽  
Zancanella Michelle ◽  
Maino Elena ◽  
...  

2018 ◽  
Vol 5 (8) ◽  
pp. 2565-2571
Author(s):  
Mehrdad Payandeh ◽  
Afshin Karami ◽  
Noorodin Karami ◽  
Jafar Barati Masgareh

Immune thrombocytopenia is characterized by reduced platelet count. This condition occurs in both adults and children. The most common form of thrombocytopenia is primary ITP and autoantibodies are involved in its development. In this study, our patient was a pregnant woman with ITP who showed refractory to prednisolone and splenectomy as first and second line treatment, respectively, but the response to treatment with Romiplostim and platelet count was favorable, and delivery was reported without fetal complications.


Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3670-3676 ◽  
Author(s):  
Tadeusz Robak ◽  
Jerzy Windyga ◽  
Jacek Trelinski ◽  
Mario von Depka Prondzinski ◽  
Aristoteles Giagounidis ◽  
...  

Abstract Rozrolimupab, a recombinant mixture of 25 fully human RhD-specific monoclonal antibodies, represents a new class of recombinant human antibody mixtures. In a phase 1 or 2 dose escalation study, RhD+ patients (61 subjects) with primary immune thrombocytopenia received a single intravenous dose of rozrolimupab ranging from 75 to 300 μg/kg. The primary outcome was the occurrence of adverse events. The principal secondary outcome was the effect on platelet levels 7 days after the treatment. The most common adverse events were headache and pyrexia, mostly mild, and reported in 20% and 13% of the patients, respectively, without dose relationship. Rozrolimupab caused an expected transient reduction of hemoglobin concentration in the majority of the patients. At the dose of 300 μg/kg platelet responses, defined as platelet count ≥ 30 × 109/L and an increase in platelet count by > 20 × 109/L from baseline were observed after 72 hours and persisted for at least 7 days in 8 of 13 patients (62%). Platelet responses were observed within 24 hours in 23% of patients and lasted for a median of 14 days. Rozrolimupab was well tolerated and elicited rapid platelet responses in patients with immune thrombocytopenia and may be a useful alternative to plasma-derived products. This trial is registered at www.clinicaltrials.gov as #NCT00718692.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3149-3149
Author(s):  
Alexandra Schifferli ◽  
Axel Rüfer ◽  
Alicia Rovo ◽  
Nathan Cantoni ◽  
Andreas Holbro ◽  
...  

Abstract Introduction : To date most treatment strategies of primary immune thrombocytopenia (ITP) are symptomatic, preventing premature platelet destruction and increasing their production. New strategies should focus on targeting the immune dysregulation, rather than the platelet count. Rituximab and dexamethasone have the potential to induce tolerogenic mechanisms, however with moderate long-term results (<30%). Thrombopoietin-receptor agonists (TPO-RAs) obviously have the potential to affect the course of the disease with up to 30% treatment-free remission. Possible mechanisms could be exposure to high-dose antigen and/or the innate immune activity of platelets, especially the release of TGF-ß, which may stimulate or restore regulatory T cells (Tregs). Tregs play a fundamental role in the maintenance of immune tolerance. Previous studies have shown lower and impaired function of Tregs in the peripheral blood of ITP patients. Methods: The iROM study is a national multi-center, open label, single arm pilot study that aims to explore possible immunomodulatory effects of romiplostim administered as second line drug in young adults with ITP. Patients who failed, did not tolerate or relapsed after first-line treatment with steroids and/or intravenous immunoglobulin (IVIG) were included, irrespective of disease duration. Romiplostim was administered subcutaneously for 22 weeks and then stopped. The dose was adjusted every week depending on platelet response, following the product information (target platelet count 50-200x10 9/l). Follow-up was performed until week 52. Immunologic investigations were done at weeks 1, 6, 12, 22 and 52. Tregs (CD4 +, CD25 +, CD127 low) were investigated by flow cytometry and reported as percentage Tregs/CD3. Because of comedication at week 1 (IVIG, steroids), week 6 was defined as the initial immunological state. Confirmatory tests were performed using a paired samples Wilcoxon test at a two-sided alpha of 5%. The p-values are adjusted using the Holm method for all secondary analyses. Results: Between 2016 and 2020, 15 patients were enrolled, including two dropouts. Of the 13 patients analyzed, 9 had newly diagnosed ITP (<3 months), median age 31 years (IQR 8), and 4 chronic ITP (>12 months), median age 31.5 years (IQR 8.75), with a median platelet count at enrollment of 26x10 9/l (IQR 41) and 49.5x10 9/l (IQR 88.5), and at week 52, 168x10 9/l (IQR 88) and 96x10 9/l (IQR 23.5), respectively. All patients were on ITP treatment at enrollment (steroids and/or IVIG). In 6 out of 9 patients with newly diagnosed ITP, discontinuation of romiplostim was successful with sustained treatment-free complete remission (TFR) at 1 year, whereas all patients with chronic ITP relapsed and restarted various treatments. Interestingly, romiplostim dose titration was lower and platelet count response higher and more stable in patients achieving TFR (Fig 1). Platelet counts in patients with relapse showed a very jagged curve over the 22 weeks of treatment. Tregs increased between weeks 6 and 22 (end of treatment), so as between weeks 6 and 52 (end of study) in the whole group of patients with a median change of 0.62 (CI95 (0.14, 1.26)) (p=0.017) at end of study. Tregs variation for patients with sustained TFR versus no remission is shown in Fig 2a, and for the 9 patients with newly diagnosed ITP in Fig 2b. Conclusion : These results support the assumption that early treatment of ITP with TPO-RAs, e.g. romiplostim, could positively influence the natural course of ITP. Induction of tolerance may be more successful in the early stage of an autoimmune disorder because of autoimmune expansion and epitope spreading. We also assume that induction of tolerance may be more successful in younger patients because of potentially reduced immunosenescence. In this small trial only 3 out of 9 patients (33%) with newly diagnosed ITP relapsed after stopping treatment according to the iROM protocol. In contrast, all 4 patients with chronic ITP relapsed after stopping treatment. Our observation of a higher increase of platelets and a more stable increase of Tregs in patients with sustained TFR in comparison to those with relapse corroborate the hypothesis that the tolerogenic stimulus may be supported by the platelet mass. Limitations of the study were the small sample size, the heterogeneity of the patient population regarding ITP duration, and preceding medications overlapping the first study weeks. Figure 1 Figure 1. Disclosures Schifferli: Sobi: Honoraria; Novartis: Honoraria, Research Funding. Rovo: Novartis: Research Funding; AG Alexion: Honoraria; BMS: Honoraria; OrPhaSwiss GmbH: Honoraria; Swedish Orphan Biovitrum AG: Honoraria; Amgen: Other: Financial support for congresses and conference travel; AstraZeneca: Other; BMS: Other; Sanofi: Other; Roche: Other; AstraZeneca: Honoraria; Novartis: Honoraria; CSL Behring: Research Funding; AG Alexion: Research Funding. Kuehne: Novartis: Research Funding; UCB: Honoraria; SOBI: Honoraria; Amgen: Research Funding.


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