Treatment Of Immune Thrombocytopenic Purpura Research Articles

Outcomes of rituximab as treatment for immune thrombocytopenic purpura in patients who have failed steroids or IVIG: A retrospective study in a community practice.

e23256 Background: Immune thrombocytopenic purpura (ITP) is a challenging disorder with multiple treatment options. The 2019 American Society of Hematology guidelines outline treatment recommendations for ITP which include intravenous immunoglobulin (IVIG) and steroids as first-line, with Thrombopoietin receptor agonists (TPO-RAs) and Rituximab as second-line agents. They favor TPO-RAs over Rituximab but suggest that the choice should be individualized. In this study, we explore the rate and duration of response to Rituximab as a second-line agent for ITP. We also analyze relapse rates and response to sequential TPO-RAs. Methods: A retrospective study of patients with ITP managed in a community practice from 2018 to 2022. The practice’s electronic medical records were searched for the keywords “ITP” and “Rituximab”. 87 patients fit the search terms. We included patients above age 18 treated with Rituximab for ITP after failing steroids or IVIG. We excluded duplicates, incomplete medical records, patients given Rituximab for reasons other than ITP, patients treated with medications other than steroids or IVIG prior to Rituximab, and patients given less than 4 doses of Rituximab. 60 out of 87 patients were eligible. The primary outcome was response to Rituximab defined as platelets above 30,000 per microliter of blood after 12 weeks of its initiation. Secondary outcomes include relapse rate, duration of response, and subsequent response to TPO-RAs. Secondary outcomes were determined by chart-reviewing physician documentation. Results: SAS 9.4 (SAS/STAT Inst., Carry NC) was used for all data. Categorical variables were quoted as absolute numbers and relative frequencies. A test result was considered statistically significant if p < 0.05. For categorical variables, likelihood ratio chi-square, and Fisher’s exact tests were conducted for 2*2 and r*c contingency tables to test associations. 96.7% of eligible patients responded to Rituximab (P < 0.0001), however 46.7% relapsed. 42.9% of relapses happened in less than 1 year, 14.3% in 1 year, 21.4% in 2 years, 7.1% in 3 years, 10.7% in 4 years, and 3.6% in 5 or more years (P = 0.0043). The response rate to TPO-RAs after Rituximab failure was 88%. No significant toxicity from Rituximab was noted beyond previously reported minor side effects, and there was no treatment-related death. Conclusions: The response rate to Rituximab was 96.7% (P < 0.0001) which was sustained in 53.3% of patients. Most relapsed patients responded well to TPO-RAs. These numbers are very comparable to previously reported response to Rituximab. Therefore, we believe that the strategy of using Rituximab as second-line and reserving TPO-RAs for non-responders is clinically-effective and certainly cost-effective given the fact that Rituximab is administered over four weeks as compared to the often lifetime treatment with TPO-RAs.

Red blood cell distribution width is a useful biomarker to predict bleeding and thrombosis risks in patients with immune thrombocytopenic purpura.

Bleeding and thrombosis are common complications during immune thrombocytopenic purpura (ITP) treatment. There is a strong need to predict bleeding and thrombosis risks before ITP treatment to optimize therapy and appropriately manage these complications. We performed a retrospective cohort study of 120 patients with primary ITP to identify a biomarker to predict bleeding and thrombosis. We compared blood test results at diagnosis between patients with and without bleeding or thrombosis episodes. The standard deviation of red blood cell distribution width (RDW-SD) differed significantly between those with and without bleeding and between those with and without thrombosis, leading us to identify it as a variable representative of risk. RDW-SD was significantly associated with patient age and with histories of several vascular diseases. Multivariate regression analyses showed that RDW integrated several variables associated with vascular risks. RDW-SD was significantly associated with difficulty with corticosteroid discontinuation (hazard ratio [HR], 2.22, p=0.01), incidence of bleeding (HR, 2.75, p< 0.01), incidence of thrombosis (HR, 2.67, p< 0.01) and incidence of infection (HR, 1.78, p=0.04). The RDW-SD value at the time of ITP diagnosis is a useful biomarker to predict the risks of bleeding, thrombosis, and other complications.

Immune Thrombocytopenia in Children

Immune thrombocytopenia is a hematological disorder defined by an isolated decrease in platelet numbers. We present a retrospective-descriptive study that enrolls twenty-five children (aged 0-18 years old) admitted to Brasov Children’s Hospital from the 1st of January 2020 until the 1st of September 2023 with the diagnosis of idiopathic thrombocytopenic purpura (ITP).&#x0D; We could find proof of recent viral infection in seven patients out of twenty-five; three of them also had immunological findings- positive antinuclear, positive direct Coombs test, or antiplatelet antibodies. The medical literature mentions glucocorticoids and IVIG therapy as the first line of treatment for immune thrombocytopenic purpura, while new pharmaceutical agents are still under review.

Refractory immune thrombocytopenic purpura (ITP) after accessory splenectomy: A case report and literature review.

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by a platelet count of less than 100 x 109 /L, resulting from antibody-mediated platelet destruction. Treatment for ITP typically involves steroids, and intravenous immunoglobulins (IVIG) can be added. Splenectomy is performed in cases with refractory ITP. Rituximab can suppress immunity but has limited efficacy in ITP cases. Herein, we present a rare case of a 30-year-old female who was first diagnosed with ITP and underwent a splenectomy two years later. However, seven years after surgery, she was presented with symptoms of ITP. A splenic scan showed an accessory spleen in the spleen bed, for which she underwent accessory spleen removal surgery. Her laboratory tests three days post-operation showed a rise in platelet count and hence was discharged a few days later. The patient had recurrent attacks of ITP even after the removal of the normal and accessory spleen, suggesting that accessory spleen removal may not always be an effective treatment for ITP. The patient eventually died. While splenectomy is a common treatment for ITP, it may not always be effective in all cases, and other treatments such as bone marrow transplantation may be necessary.

Treatment of patients with COVID-19-associated immune thrombocytopenia in real clinical practice

Aim. Demonstration of three clinical cases of immune thrombocytopenic purpura (ITP) that developed during the pandemic of a novel coronavirus infection (COVID-19) from the personal practice of the authors.Materials and methods. A brief review of the literature on the diagnosis and differential diagnosis of COVID-19-associated ITP is presented. Three clinical observations of this pathology are given.Results. In two situations, thrombocytopenia developed after severe COVID-19-associated pneumonia. In one case, ITP was diagnosed after a viral infection; PCR test for COVID19 was negative. A young patient without comorbidities with severe thrombocytopenia and hemorrhagic syndrome was treated with glucocorticoids and thrombopoietin receptor agonists (TPO-RAs). After achieving remission, glucocorticoids were first discontinued, and then TPO-RAs. In elderly patients with a serious comorbid pathology, glucocorticoids were prescribed for a short time, and remission was achieved with TPO-RAs.Conclusion. The choice of therapy for ITP that developed during the COVID-19 pandemic depends on the clinical situation, the presence or absence of COVID-19 infection, the patient’s somatic status, and the presence of comorbid pathology. TPO-RAs play an important role in the treatment of ITP, including those associated with COVID-19.

Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura: a case report and review of the literature

BackgroundImmune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently.Case presentationWe report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up.ConclusionsConcurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.

Safety and Efficacy of Tyrosine Kinase Inhibitors in Immune Thrombocytopenic Purpura: A Systematic Review of Clinical Trials

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.

Recent topics in the pathophysiology and treatment of immune thrombocytopenic purpura

Increased and impaired platelet productions via immunological abnormalities are the main pathophysiological mechanisms of primary immune thrombocytopenia (ITP). Recent studies have revealed that platelet removal from circulation involves not only Fc receptor-mediated phagocytosis of immunoglobulin G autoantibodies-bound platelets but also complement-dependent mechanism and platelet glycoprotein desialylation. Understanding the molecular mechanism of ITP pathophysiology has helped develop many novel molecular targeted drugs, and recent clinical trials have shown their effectiveness. In particular, fostamatinib, which is a Syk inhibitor, inhibits macrophage and B-cell activity and is already been approved in Europe for multidrug-resistant ITP. Recently, coronavirus disease-2019 (COVID-19) vaccine-associated newly-onset or ITP exacerbation has come to attention. Whether COVID-19 vaccines induce de novo ITP remains controversial. However, close attention is necessary after COVID-19 vaccination because a certain number of patients with ITP presented exacerbation after COVID-19 vaccination.

Development and Validation of Eltrombopag Determination in Human Plasma Blood by HPLC-MS Method

Introduction. "Eltrombopag" is a thrombopoietin receptor agonist (TPO-RA) that is approved for the treatment of immune thrombocytopenic purpura (ITP). According to the literature, very few analytical methods for determining eltrombopag in biological samples have been reported. To study the pharmacokinetics of new formulations of eltrombopag, a sensitive and specific method is required that allows one to accurately determine the concentration of eltrombopag in human blood plasma. Normally, HPLC methods should provide time, accuracy, and sensitivity as a result, it is necessary to develop fast or ultra-fast methods such as LC-MS/MS without any loss in sensitivity or separation efficiency.Aim. We aimed to develop and validate a method for the quantitative determination of eltrombopag levels in human plasma by using HPLC with mass spectrometric detection for performing the analytical part of pharmacokinetic studies.Materials and methods. Eltrombopag levels were determined in human plasma by HPLC with mass spectrometric detection. The samples were prepared using protein deposition.Results and discussion. The method was validated for selectivity, matrix effect, calibration curve, accuracy, precision, the limit of quantification, carry-over effect, and sample stability.Conclusion. The method for the determination of eltrombopag levels in human plasma has been developed and validated by HPLC-MS. The analytical range of eltrombopag levels in human plasma was 10–6750 ng/ml. This method could be used to determine eltrombopag levels in plasma for PK and BE studies.

A Randomized, Placebo-Controlled, Phase 1 Study in Healthy Adult Volunteers of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ALPN303, a Potent Dual BAFF/APRIL Antagonist for the Treatment of Autoimmune Cytopenias

Background B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) are tumor necrosis factor superfamily (TNFSF) members that bind transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI), B-cell maturation antigen, and/or BAFF receptor (BAFF-R) on B cells and together support B-cell development, survival, and differentiation into antibody-secreting cells (ASC). In preclinical studies, co-neutralization of BAFF and APRIL can directly suppress ASC and reduce circulating immunoglobulins. Autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) are diseases characterized by autoantibodies directed against red blood cells and platelets, respectively. Significantly higher levels of both BAFF and APRIL have been observed in the serum of patients with AIHA and ITP compared to healthy subjects, and polymorphisms in BAFF and TACI have been associated with ITP [Abdel-Hamid, et al., Am J Med, 2011; Emmerich, et al., Br J Haematol, 2007; Peng, et al., J Thromb Haemost, 2017; Yu, et al., Blood Adv, 2021]. Currently, there are no B cell targeting agents approved to treat AIHA or ITP. Rituximab, an anti-CD20 therapeutic which depletes CD20+ B cells, and thereby only indirectly reduces autoantibody production, has demonstrated some efficacy in both ITP [Neunert, et al., Blood, 2019] and AIHA [Jäger, et al., Blood Rev, 2019], though it is not approved for use in either indication. Belimumab, an anti-BAFF neutralizing antibody (Ab), has demonstrated encouraging efficacy in the treatment of ITP associated with systemic lupus erythematosus (SLE) [De Marchi, et al., Clin Exp Rheumatol, 2017] and also in combination with rituximab in patients with ITP [Mahévas, et al., Haematologica, 2021], but only had a modest impact on hematological manifestations in SLE patients [Manzi, et al., Ann Rheum Dis, 2012]. To address the shortcomings of existing B-cell-targeting agents, we have developed ALPN-303, an Fc fusion of an engineered TACI variant TNFRSF domain, which substantially improves upon the ligand affinity liabilities of wild type (WT) TACI, resulting in highly potent dual BAFF/APRIL inhibition superior to WT TACI-Fc, or to BAFF- or APRIL-specific monoclonal Abs. In preclinical studies, ALPN-303 demonstrates enhanced pharmacokinetic (PK) and immunomodulatory properties vs. WT TACI-Fc, which may translate to lower and/or less frequent doses in humans. ALPN-303 also suppresses autoantibodies and nephritis in mouse models of lupus. Taken together, these observations suggest that a potent dual BAFF/APRIL antagonist such as ALPN-303, by lowering pathogenic autoantibody levels, may be particularly beneficial in the treatment of antibody-related hematologic diseases, such as autoimmune cytopenias. Methods In this first-in-human study (NCT05034484), healthy adult volunteers have been enrolled in single ascending dose cohorts of intravenously (IV) or subcutaneously (SC) administered ALPN-303. For each IV cohort, the first 2 sentinel subjects are randomized 1:1 to receive ALPN-303 or placebo, followed by the remaining 4 subjects randomized 3:1 to receive ALPN-303 or placebo. SC cohorts are randomized 4:2 to receive a single SC dose of ALPN-303 or placebo. All subjects are followed to assess safety, PK, and pharmacodynamic (PD) effects including impacts on circulating immunoglobulins (Ig), and peripheral B-cell populations. Results ALPN-303 has been well tolerated in all cohorts evaluated to date and exhibits dose-dependent PK and expected PD effects, including dose-dependent reductions in circulating CD38+ (CD19+CD27+IgD-) ASC (Figure 1) and in serum Ig (Figure 2). To date, there have been no serious adverse events, and no events of cytokine release syndrome. Dose escalation will be complete by the time of the meeting; the presentation will include all available safety, PK, and PD data. Conclusions In this phase 1 study, ALPN-303 demonstrates acceptable preliminary safety and tolerability and exhibits dose-dependent PK and expected PD effects on circulating Ig and B-cell populations. These findings support future clinical development of ALPN-303 in patients with antibody-related diseases, including autoimmune cytopenias. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Factors Influencing the efficacy of Plasma Exchange in the Treatment of Immune Thrombocytopenic Purpura

To observe the efficacy of plasma exchange in the treatment of patients with immune thrombocytopenic purpura (ITP), and to analyze the factors influencing the efficacy of plasma exchange in the treatment of ITP. The medical records of 39 ITP patients who were treated effectively by plasma exchange in Huai'an First People's Hospital from January 2013 to January 2021 were retrospectively analyzed, and they were set as the effective group. In addition, the medical records of 39 ITP patients who were treated ineffective by plasma exchange during the same period in our hospital were collected, and they were set as the ineffective group. The general data such as sex and age of patients and laboratory indicators on admission were collected and recorded. The possible influencing factors were included, and Logistic regression analysis was used to examine the influencing factors of efficacy of plasma exchange in the treatment of ITP. The serum levels of IL-6, IL-18 and B lymphocyte activating factor (BAFF) on admission in the ineffective group were significantly higher than those in the effective group, and the proportions of Helicobacter pylori (HP) infection and splenomegaly were significantly higher than those in the effective group (P<0.05). There was no statistical significantly difference in sex, age and other data between the two groups (P>0.05). After single factor analysis, multiple regression model was established, which showed that splenomegaly, HP infection and the over expression of serum IL-6, IL-18 and BAFF on admission might be the influencing factors of ineffective treatment of ITP by plasma exchange (OR>1, P<0.05). The over expression of serum IL-6, IL-18, BAFF, splenomegaly and HP infection on admission may be the influencing factors resulting in the ineffective treatment of plasma exchange in ITP.

COVID-19-induced immune thrombocytopenic purpura; Immunopathogenesis and clinical implications.

Following the outbreak of the COVID-19 pandemic, millions of people around the world have been affected with SARS-CoV-2 infection. In addition to the typical symptoms, thrombotic events, lymphopenia, and thrombocytopenia have been reported in COVID-19 patients. Immune thrombocytopenic purpura (ITP) is one of the thrombotic events that occur in some COVID-19 patients. Hyperinflammation, cytokine storms, and immune dysregulation in some patients are the cause to the main COVID-19 complications such as ALI (acute lung injury), acute respiratory distress syndrome (ARDS), and multiple organ failure. Disruption in the differentiation of T-cells, enhanced differentiation of Th17 and Th1, cell death (pyroptosis), hyper-inflammation and dysfunction of inflammatory neutrophils and macrophages, and hyperactivity of NLRP3-inflammasome are among the important factors that may be the cause to COVID-19-induced ITP. This study aimed to give an overview of the findings on the immunopathogenesis of ITP and COVID-19-induced ITP. Further studies are required to better understand the exact immunopathogenesis and effective treatments for ITP, especially in inflammatory disorders.

Immune Thrombocytopenic Purpura as a Hemorrhagic Versus Thrombotic Disease: An Updated Insight into Pathophysiological Mechanisms.

Immune thrombocytopenic purpura (ITP) is a blood disorder characterized by a low platelet count of (less than 100 × 109/L). ITP is an organ-specific autoimmune disease in which the platelets and their precursors become targets of a dysfunctional immune system. This interaction leads to a decrease in platelet number and, subsequently, to a bleeding disorder that can become clinically significant with hemorrhages in skin, on the mucous membrane, or even intracranial hemorrhagic events. If ITP was initially considered a hemorrhagic disease, more recent studies suggest that ITP has an increased risk of thrombosis. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The autoimmune response in ITP involves both the innate and adaptive immune systems, comprising both humoral and cell-mediated immune responses. Thrombosis in ITP is related to the pathophysiology of the disease (young hyperactive platelets, platelets microparticles, rebalanced hemostasis, complement activation, endothelial activation, antiphospholipid antibodies, and inhibition of natural anticoagulants), ITP treatment, and other comorbidities that altogether contribute to the occurrence of thrombosis. Physicians need to be vigilant in the early diagnosis of thrombotic events and then institute proper treatment (antiaggregant, anticoagulant) along with ITP-targeted therapy. In this review, we provide current insights into the primary ITP physiopathology and their consequences, with special consideration on hemorrhagic and thrombotic events. The accumulated evidence has identified multiple pathophysiological mechanisms with specific genetic predispositions, particularly associated with environmental conditions.

Meta-Analysis of Jianpi Yiqi Combined with Glucocorticoid Therapy for Primary Thrombocytopenic Purpura

A systematic review of the efficacy and safety of Jianpi Yiqi combined with glucocorticoids in the treatment of immune thrombocytopenic purpura. Randomized controlled trial of Jianpi Yiqi therapy combined with glucocorticoid therapy for immune thrombocytopenic purpura was retrieved without any restrictions on blindness and language. Randomized controlled trial that met the inclusion criteria were screened, and the Revman5.3 software was used for meta-analysis. A total of 27 articles were included with 1716 cases. The results of the meta-analysis showed that in terms of the effective rate of Western medicine, the effect of Jianpi Yiqi combined with glucocorticoid therapy were significantly better than that of glucocorticoid therapy alone, with a statistically significant difference (p<0.0001). The combination of traditional Chinese and Western medicine is better than hormone therapy in improving the efficiency of traditional Chinese medicine, platelet count, syndrome score, interleukin-10 and cluster of differentiation 4/cluster of differentiation 8 levels. The effect of Jianpi Yiqi combined with glucocorticoid in the treatment of immune thrombocytopenic purpura is better than that of glucocorticoid alone, which is worthy of further study and promotion.

Practical considerations for the management ofimmune thrombocytopenic purpura.

Immune thrombocytopenic purpura (ITP) is a rare hematological disorder with an autoimmune-mediated, often dramatic reduction of platelets in peripheral blood. Thrombocytopenia results from a reduced life span of thrombocytes and an additionally decreased production in bone marrow. For decades, the first-line therapy for ITP has been corticosteroids. As significant thrombocytopenic bleedings occur, the use of additional medication may be needed. Recent updates on therapy guidelines recommend the shortest possible use of corticosteroids. Thrombopoietin-receptor agonists are often used second line. Today splenectomy, which was previously recommended after unsuccessful first-line therapy, is usually considered much later. Patients who do not respond even after multiple lines of therapy continue to pose a major challenge. New drugs for ITP treatment are now available after steroid failure and will be discussed. This review gives a short summary on actual therapy guidelines taking into account newly available therapy options. In addition, comparisons between selected published data and experience at our department are made.

Targeted therapies for immune thrombocytopenic purpura: a meta-analysis of randomized controlled trials.

Several targeted therapies have been approved in recent years for second-line treatment of immune thrombocytopenic purpura (ITP), providing an alternative to rituximab and splenectomy. The extent to which these drugs reduce bleeding risk has not been well defined. Targeted therapies recently approved for the treatment of ITP in adults were identified through a search of recently published professional guidelines. Randomized controlled trials (RCTs) supporting regulatory approval were identified through a search of drug labels on FDA@gov. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were computed for pre-specified efficacy outcomes including platelet recovery to ≥ 50,000/µL, major and minor bleeding events, and survival. ORs for all adverse events were also computed. Four targeted therapies were identified, including three thrombopoietin receptor agonists and one tyrosine kinase inhibitor. Six RCTs, comprising 752 patients, were included in the meta-analysis. More patients treated with targeted therapies for ITP as compared to placebo achieved platelet counts over ≥ 50,000/µL (OR 8.29, 95% CI 5.59-12.29). Compared to placebo, targeted therapies for ITP were associated with significantly lower odds for major bleeding (OR 0.43, 95% CI 0.21-0.91), minor bleeding (OR 0.66, 95% CI 0.45-0.97), and with numerically lower mortality rates (OR 0.24, 95% CI 0.05-1.07). The odds for adverse events were comparable between the two arms (OR 1.43 95% CI 0.76-2.67). Compared to placebo, targeted therapies for ITP increase platelet counts, decrease bleeding events, and show a trend towards lower mortality, without increased toxicity. These findings support their use as a second-line ITP treatment.

A real-world study of immune thrombocytopenia management during the COVID-19 pandemic in the UK.

SummaryThe COVID‐19 pandemic has created many challenges in the management of immune thrombocytopenic purpura (ITP). The recommendation for avoidance of steroids by WHO led to the off‐licence use, supported by NHS England, of thrombopoietin mimetics (TPO‐RA) for newly diagnosed or relapsed ITP. This is a real‐world prospective study which investigated the treatment patterns and outcomes in this setting. Twenty‐four hospitals across the UK submitted 343 cases. Corticosteroids remain the mainstay of ITP treatment, but TPO‐RAs were more effective. Incidental COVID‐19 infection was identified in a significant number of patients (9·5%), while 14 cases were thought to be secondary to COVID‐19 vaccination.

Incidence and Outcome of Severe Thrombocytopenia Associated with Zika Virus Infection - Puerto Rico, 2016

Introduction: There are many etiologies for thrombocytopenia, such as viral suppression, disseminated intravascular hemolysis, and immune thrombocytopenic purpura (ITP). Zika virus (ZIKV) recently emerged in the Americas and was first detected in Puerto Rico in late 2015. ZIKV disease is generally mild; however, it has been infrequently associated with life-threatening outcomes including severe thrombocytopenia. We sought to define incidence and outcomes of ZIKV disease patients with thrombocytopenia.Methods: We reviewed the medical records of patients with reported thrombocytopenia (platelet count ≤ 100,000 cells/µL) among patients with ZIKV disease (defined by detection of ZIKV nucleic acid by RT-PCR or anti-ZIKV IgM antibody by ELISA and the presence of symptoms) that had been reported via passive surveillance. Among patients with confirmed thrombocytopenia, we collected data on medical history, interventions, and patient outcomes. Cases of severe thrombocytopenia were defined by: a) platelet count <20,000 cells/µL; or b) platelet count <50,000 cells/µL with a clinical diagnosis of and treatment for ITP. Cases in which another likely cause of thrombocytopenia was identified (e.g., sepsis, immunosuppression) were excluded from analysis. Data were collected in REDCap®.Results: Of 37,878 patients with ZIKV disease reported during 2016, a total of 436 had reported thrombocytopenia. Among patients with medical records available for review, 48 (0.1%) had confirmed thrombocytopenia in the absence of an identified etiology. Twelve of these 48 patients (25%) had severe thrombocytopenia (Table 1), and 36 (75%) had non-severe thrombocytopenia.Median age of patients with severe and non-severe thrombocytopenia was 39.5 years (range: 2-88) and 49 years (range: 1-88 years), respectively; 7 (58%) and 19 (53%) were male. Two (17%) patients with severe and 3 (8%) with non-severe thrombocytopenia had a history of ITP. All patients reported recent illness, which most frequently included rash (73%) and/or fever (77%). Median nadir platelet count of patients with severe and non-severe thrombocytopenia was 12,500 cells/µL (range: 1,000-30,250) and 70,000 cells/µL (range: 24,000-100,000), respectively, which occurred a median of 5.7 days (range: 1.4-15.6) and 4.5 days (range: 0.4-34.1) after symptom onset. Blood smears were performed in 9 (75%) patients with severe and 18 (50%) with non-severe thrombocytopenia. No patients with severe thrombocytopenia and 1 (2.8%) patient with non-severe thrombocytopenia had fragmented red blood cells; visualization of platelets on smear was consistent with low platelet counts. Whereas 11 (30.6%) patients with non-severe thrombocytopenia had petechiae, hematuria, or gingival bleeding, all (100%) patients with severe thrombocytopenia had hemorrhagic manifestations including petechiae (66.7%), hematuria (33.3%), ecchymoses (50%), gastrointestinal bleeding (25%), or intracranial hemorrhage (8.3%). Only patients with severe thrombocytopenia were diagnosed with ITP. Only patients with severe thrombocytopenia received platelet transfusion (n = 4; 33.3%) and/or intravenous immunoglobulin (IVIG) (n = 5; 41.7%). The patients with severe thrombocytopenia that received IVIG all had an up-trending platelet count after IVIG administration. Eight (66.6%) patients with severe thrombocytopenia and 9 (25.0%) with non-severe thrombocytopenia received steroids. Among those who received platelet transfusions, the median platelet count increase following transfusion was 6,000 cells/µL; 25% had a decreased platelet count following transfusion. Outcomes among patients with severe or non-severe thrombocytopenia included hospitalization (100% vs. 53%), admission to the intensive care unit (33% vs. 0%), and death (8.3% vs. 0%).Conclusions: Thrombocytopenia appears to be an uncommon occurrence in patients with ZIKV infection. Though rare, severe thrombocytopenia associated with ZIKV disease can be fatal; treatment is necessary. Platelet transfusions alone may not be effective, whereas administration of corticosteroids and IVIG may be of benefit in some cases. Further study is needed to characterize the pathogenesis of ZIKV-associated severe thrombocytopenia and interventions associated with survival. Appropriate diagnosis of the underlying etiology of thrombocytopenia is time-sensitive and crucial to improving patient outcome. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Subcutaneous Rituximab Given to Patients for Other Indications Than CD20+ B-Cell Lymphoma: A Monocentric Study of 20 Cases

Background: Rituximab (R) is the first anti-CD20 monoclonal antibody that has demonstrated efficacy in patients with various B-cell lymphoid malignancies. Administered intravenously (IV), it has been shown to be also efficient to treat other hematologic situations such as Epstein-Barr virus (EBV) reactivation, especially after hematopoietic stem cell transplantation (HSCT), or immune thrombocytopenic purpura (ITP). Finally, survivals of younger patients with CD20-positive Philadelphia-negative acute lymphoblastic leukemia (ALL) are significantly increased when combining IV-R with chemotherapy. Recently, a subcutaneous (SC) formulation of R (SC-R) has been approved for B-cell lymphoma that provides a highly-concentrated fixed dose of rituximab with the advantages of reducing treatment times and nursing workload and potentially providing greater comfort and convenience for patients and lesser dosing errors, shorter preparation time or reduced drug wastage for pharmacy dispensers. At our knowledge, there is no published data addressing the tolerance and the efficacy of SC-R given to patients with other indications than CD20+ B cell lymphoma.Patients and Methods: We have retrospectively analyzed all cases who received at our center at least one dose of SC-R but with no lymphoma indication. Three situations were considered: EBV reactivation (post transplantation or not), ITP or ALL treatment. All patients received their first(s) dose(s) of R IV (375mg/m2/injection) and a switch to SC-R (1400mg/injection) was realized only if they didn't experience grade 3 or 4 adverse event (AE) with IV formulation. Our rules is to provide R (IV+SC) weekly, up to 4 doses for ITP (in case of platelets counts <30000/mm3 with no response to corticosteroids or immunoglobulin) and EBV reactivation (in case of 2 positive PCR > 4 log10 number of viral DNA copies), while GRAALL schedule is followed for R administration in CD20+ ALL patients. Tolerance of SC-R (mainly infusion related or late-onset neutropenia (LON)) was appreciated using National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 and any grade 3 or 4 AE related to SC-R was sufficient to stop treatment. Success of SC-R was defined by either a documentation of a negative EBV PCR or absence of ALL relapse or platelets counts reaching at least 100000/mm3.Results: Between February 2016 and June 2017, 20 patients (male n=17) with a median age of 60 years old (range: 33-76) received SC-R in our institution. Overall, 102 R including 58 SC-R were administered with a median of 3 R (range: 2-26) and 2 SC-R (range: 1-16) injection per patient, respectively. The median follow-up from the last SC-R administration was 4.4 months (range: 0.2-11.2 months).No grade 3/4 infusion related reaction were documented in this series while 4 out of 16 assessable cases presented with LON at a median of 45 days (range: 44-70) after the last SC-R injection. Neutropenia lasted a median of 6 days (range: 4-9) with the help of GCSF and was not responsible for complication.Eleven cases received SC-R for EBV reactivation (including 8 after allogeneic transplant and 3 in a context of aplastic anemia) with a median of 3 R (IV+SC, range: 1-4) and 2 SC-R (range: 1-3) injections. One patient died of concomitant invasive fungal infection and was not evaluable for efficacy. All of the ten other patients were documented with negative EBV PCR after treatment.Four patients received SC-R during ALL first line treatment with a median of 11 R (IV+SC, range: 3-26) and 6 SC-R (range: 1-16) injections. Two patients have received more than the number of R infusion scheduled (17 and 26) because of high toxicity related to the chemotherapy and it was chosen to deliver a maintenance therapy with vincristine/SC-R and prednisone. None of the four ALL patients had relapsed so far at 2, 8, 18 and 20 months from diagnosis with a median follow up of 13 months (2-20).Five patients received SC-R for ITP with a median of 3 R (IV+SC, range: 3-4) including 2 SC-R (range: 1-3) injections. Three patients obtained platelets count improvement within a median of 28 days (19-48) and none relapsed so far.Conclusion: SC-R seems to demonstrate a comparable efficacy/safety profile as IV-R when given to patients for other indications than CD20+ B-cell lymphoma. There should be no restriction to use SC-R for these patients in the future as it may improve quality of care for both patient and health providers. DisclosuresTouzeau:AbbVie: Research Funding. Le Gouill:Roche: Consultancy, Honoraria, Research Funding; janssen: Consultancy, Honoraria; servier: Consultancy, Honoraria, Research Funding; bayer: Membership on an entity's Board of Directors or advisory committees; celgene: Honoraria, Research Funding. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen, Roche: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Novartis: Consultancy, Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Consultancy, Honoraria; Takeda: Honoraria; Janssen: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Onyx Pharmaceutical: Consultancy, Honoraria.

Innovative methods of treatment of immune thrombocytopenic purpura in young people

This article is about describing innovative methods of treatment of immune thrombocytopenic purpura in young people. Moreover, a great many useful instructions are given in order to enhance immune system.