scholarly journals Emerging Therapies in Immune Thrombocytopenia

2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sylvain Audia ◽  
Bernard Bonnotte
Keyword(s):  
Tyrosine Kinase ◽  
Immune Thrombocytopenia ◽  
Plasma Cells ◽  
Autoimmune Disorder ◽  
Intravenous Immunoglobulins ◽  
Therapeutic Interventions ◽  
Autoimmune Response ◽  
Platelet Destruction ◽  
Classical Complement Pathway ◽  
Splenic Macrophages

Immune thrombocytopenia (ITP) is a rare autoimmune disorder caused by peripheral platelet destruction and inappropriate bone marrow production. The management of ITP is based on the utilization of steroids, intravenous immunoglobulins, rituximab, thrombopoietin receptor agonists (TPO-RAs), immunosuppressants and splenectomy. Recent advances in the understanding of its pathogenesis have opened new fields of therapeutic interventions. The phagocytosis of platelets by splenic macrophages could be inhibited by spleen tyrosine kinase (Syk) or Bruton tyrosine kinase (BTK) inhibitors. The clearance of antiplatelet antibodies could be accelerated by blocking the neonatal Fc receptor (FcRn), while new strategies targeting B cells and/or plasma cells could improve the reduction of pathogenic autoantibodies. The inhibition of the classical complement pathway that participates in platelet destruction also represents a new target. Platelet desialylation has emerged as a new mechanism of platelet destruction in ITP, and the inhibition of neuraminidase could dampen this phenomenon. T cells that support the autoimmune B cell response also represent an interesting target. Beyond the inhibition of the autoimmune response, new TPO-RAs that stimulate platelet production have been developed. The upcoming challenges will be the determination of predictive factors of response to treatments at a patient scale to optimize their management.

scholarly journals Antiplatelet Antibodies Do Not Predict the Response to Intravenous Immunoglobulins during Immune Thrombocytopenia

2020 ◽  
Vol 9 (6) ◽  
pp. 1998 ◽  
Author(s):  
Thomas Rogier ◽  
Maxime Samson ◽  
Guillaume Mourey ◽  
Nicolas Falvo ◽  
Nadine Magy-Bertrand ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Poor Response ◽  
Intravenous Immunoglobulins ◽  
Dependent Manner ◽  
Platelet Destruction ◽  
Independent Manner ◽  
Antiplatelet Antibodies ◽  
Splenic Macrophages ◽  
Dependent Mechanism

Immune thrombocytopenia (ITP) is a rare autoimmune disease due to autoantibodies targeting platelet glycoproteins (GP). The mechanism of platelet destruction could differ depending on the specificity of antiplatelet antibodies: anti-GPIIb/IIIa antibodies lead to phagocytosis by splenic macrophages, in a Fcγ receptor (FcγR)-dependent manner while anti-GPIb/IX antibodies induce platelet desialylation leading to their destruction by hepatocytes after binding to the Ashwell–Morell receptor, in a FcγR-independent manner. Considering the FcγR-dependent mechanism of action of intravenous immunoglobulins (IVIg), we assumed that the response to IVIg could be less efficient in the presence of anti-GPIb/IX antibodies. We conducted a multicentric, retrospective study including all adult ITP patients treated with IVIg who had antiplatelet antibodies detected between January 2013 and October 2017. Among the 609 identified, 69 patients were included: 17 had anti-GPIb/IX antibodies and 33 had anti-GPIIb/IIIa antibodies. The response to IVIg was not different between the patients with or without anti-GPIb/IX (88.2% vs. 73.1%). The response to IVIg was better in the case of newly diagnosed ITP (odds ratio (OR) = 5.4 (1.2–24.7)) and in presence of anti-GPIIb/IIIa (OR = 4.82 (1.08–21.5)), while secondary ITP had a poor response (OR = 0.1 (0.02–0.64)). In clinical practice, the determination of antiplatelet antibodies is therefore of little value to predict the response to IVIg.

Immune Thrombocytopenia Associated to Low-Dose Alemtuzumab Therapy in Chronic Lymphocytic Leukemia: A Single Retrospective Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4598-4598
Author(s):  
Gianluigi Reda ◽  
Francesco Maura ◽  
Giuseppe Gritti ◽  
Daniele Vincenti ◽  
Mariarita Sciumé ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Disease Progression ◽  
Cumulative Dose ◽  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Autoimmune Disorder ◽  
Intravenous Immunoglobulins ◽  
Lymphocytic Leukemia ◽  
Platelet Counts

Abstract Abstract 4598 Immune thrombocytopenia (ITP) is a common autoimmune complication in chronic lymphocytic leukemia (CLL), occurring in up to 5% of patients. The occurrence of alemtuzumab-associated ITP have been rarely reported in CLL and it has never been reported so far as a significant event complicating alemtuzumab treatment in clinical trials. Recently, a new distinctive form of secondary ITP occurring in 6 out of 215 patients with relapsing-remitting multiple sclerosis treated with alemtuzumab in a randomized, controlled phase II trial has been reported (Cuker et al, Blood 2011). We investigated the incidence of ITP in a cohort of 64 consecutive patients treated with low-dose alemtuzumab for relapsed/refractory CLL from 2003 to 2010. Subcutaneous alemtuzumab was administered at the dose of 10 mg three times a week, up to 18 weeks. ITP was documented in 12/64 patients: in 3 patients (4.7%) ITP developed before alemtuzumab treatment and no relapses of the autoimmune disorder were observed during the treatment; in 9 patients (14.8%, with an incidence of 5.7 events/100 patient-year) ITP developed after alemtuzumab treatment. Median time to ITP from initial alemtuzumab exposure was 12 months (range 1–42 months). Concomitant hemolytic anemia (Evans syndrome) was observed in one patient. At ITP onset, median platelet counts were 11×109/L (range 3–70) and anti-platelet antibodies (Capture P® Method, ImmucorGamma, Norcross GA, USA) were found in 7 of the 8 patients tested. No patients showed severe or life-threatening bleeding. Three of nine patients who developed ITP after alemtuzumab therapy, experienced CLL progression requiring chemo-immunotherapy after 3, 4 and 13 months from ITP onset, respectively. One patient achieved a partial remission of CLL with ITP resolution, while the other two died of disease progression. In the remaining six cases, ITP was not associated with disease progression and was treated with corticosteroids and/or intravenous immunoglobulins. Five patients achieved normal platelet counts, while one patient did not respond. Low-dose alemtuzumab (theoretical cumulative dose 540 mg, equal to half of the classic cumulative dose and one-third of the individual dose) is an effective, safe and well tolerated treatment for CLL, as reported by several recent studies (Cortelezzi et al, Leukemia 2009; Brit J Haematol 2011). In our cohort of CLL patients treated with alemtuzumab, the incidence of ITP was 14.8% that is almost three times higher than previously reported in CLL. These data may indicate a role of T-lymphocyte dysregulation induced by alemtuzumab in the pathogenesis of ITP. Our data also suggested the importance of monitoring platelet counts during follow-up in patients treated with low-dose alemtuzumab for both haematological and non-haematological diseases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Idiopathic thrombocytopenic purpura (ITP) – new era for an old disease

2019 ◽  
Vol 57 (4) ◽  
pp. 273-283 ◽  
Author(s):  
Minodora Onisâi ◽  
Ana-Maria Vlădăreanu ◽  
Andreea Spînu ◽  
Mihaela Găman ◽  
Horia Bumbea
Keyword(s):  
Laboratory Data ◽  
Autoimmune Disorder ◽  
Intravenous Immunoglobulins ◽  
Prolonged Treatment ◽  
Platelet Destruction ◽  
New Era ◽  
Long Term Effect ◽  
Life Threatening ◽  
Potential Risks ◽  
Challenging Situation

Abstract Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via antiplatelet antibodies which may also affect marrow megakaryocytes. Patients may present in critical situations, with cutaneous and/or mucous bleeding and possibly life-threatening organ hemorrhages (cerebral, digestive, etc.) Therefore, rapid diagnosis and therapeutic intervention are mandatory. Corticotherapy represents the first treatment option, but as in any autoimmune disorder, there is a high risk of relapse. Second line therapy options include: intravenous immunoglobulins, thrombopoietin receptor agonists, rituximab or immunosuppression, but their benefit is usually temporary. Moreover, the disease generally affects young people who need repeated and prolonged treatment and hospitalization and therefore, it is preferred to choose a long term effect therapy. Splenectomy – removal of the site of platelet destruction – represents an effective and stable treatment, with 70–80% response rate and low complications incidence. A challenging situation is the association of ITP with pregnancy, which further increases the risk due to the immunodeficiency of pregnancy, major dangers of bleeding, vital risks for mother and fetus, potential risks of medication, necessity of prompt intervention in the setting of specific obstetrical situations – delivery, pregnancy loss, obstetrical complications, etc. We present an updated review of the current clinical and laboratory data, as well as a detailed analysis of the available therapeutic options with their benefits and risks, and also particular associations (pregnancy, relapsed and refractory disease, emergency treatment).

Zastosowanie eltrombopagu w leczeniu przewlekłej małopłytkowości immunologicznej u dziecka – doświadczenia własne

2018 ◽  
Vol 22 (3) ◽  
Author(s):  
Anna Adamowicz-Salach ◽  
Michał Matysiak
Keyword(s):  
Immune Thrombocytopenia ◽  
Autoimmune Disorder ◽  
Intravenous Immunoglobulins ◽  
Severe Form ◽  
Small Subset ◽  
Severe Thrombocytopenia ◽  
Permanent Improvement ◽  
Acute Form ◽  
Clinically Significant ◽  
Immune Thrombocytopenia Purpura

Immune thrombocytopenia purpura (ITP) is a rare autoimmune disorder but it is one of the most common bleeding disorder in childhood. Most children with this disease have acute form of ITP with self-limiting thrombocytopenia. A small subset of children with ITP has clinically significant disease with severe thrombocytopenia. We presented the case of a boy with a severe form of chronic immune thrombocytopenia who was treated for the first time six years before presented. At first autoimmunohemolytic anaemia was recognized. Next in therapeutic procedure, multi-drug treatment, including intravenous corticosteroids, intravenous immunoglobulins, and cyclosporine were used to achieve permanent improvement. Due to a chronic ITP and significant decrease platelets counts and severe symptoms of nose bleeding and anaemia, eltrombopag, thrombopoiesis stimulating factor, was used. After 16 weeks of treatment, as a result of triple therapy consisting of eltrombopag, prednisone and azathioprine, the platelets counts were normalized and the symptoms of bleeding resolved.

scholarly journals Is dapsone still relevant in immune thrombocytopenia in resource limited settings?

2019 ◽  
Vol 12 (12) ◽  
pp. e232217
Author(s):  
Preeti Dalal ◽  
Manisha Gulia ◽  
Monica Gupta ◽  
Anita Tahlan
Keyword(s):  
Side Effects ◽  
Immune Thrombocytopenia ◽  
Autoimmune Disorder ◽  
Intravenous Immunoglobulins ◽  
Autoantibody Production ◽  
Standard Drug ◽  
Low Socioeconomic ◽  
Resource Limited ◽  
Steroid Dependent ◽  
The Cost

Immune thrombocytopenia is an autoimmune disorder characterised by autoantibody production against platelets, increased platelet destruction and impaired thrombopoiesis. Steroids are the first-line agents whenever treatment is indicated; however, some patients may not respond and the responders may as well relapse while the dose is being tapered. Side effects of steroids prohibits their long-term use and patients often have to be switched to other agents. Standard drug management with intravenous immunoglobulins and thrombopoietin receptor analogues is difficult to administer in patients from low socioeconomic regions of the world making the management even more challenging. Hence, after reviewing the literature and considering the cost in comparison to all the second-line agents available, we tried dapsone in a steroid-dependent patient of immune thrombocytopenic purpura who had developed major steroid-related side effects. Patient showed good response to dapsone and has been in remission for around one and a half years.

scholarly journals Primary Immune Thrombocytopenia: Novel Insights into Pathophysiology and Disease Management

2021 ◽  
Vol 10 (4) ◽  
pp. 789
Author(s):  
Anurag Singh ◽  
Günalp Uzun ◽  
Tamam Bakchoul
Keyword(s):  
Blood Circulation ◽  
Immune Thrombocytopenia ◽  
Autoimmune Disorder ◽  
Current Evidence ◽  
Platelet Destruction ◽  
Comprehensive Overview ◽  
Primary Immune Thrombocytopenia ◽  
Recent Developments ◽  
Low Levels ◽  
Clinical Conditions

Immune thrombocytopenia (ITP) is an autoimmune disorder defined by a significantly reduced number of platelets in blood circulation. Due to low levels of platelets, ITP is associated with frequent bruising and bleeding. Current evidence suggests that low platelet counts in ITP are the result of multiple factors, including impaired thrombopoiesis and variations in immune response leading to platelet destruction during pathological conditions. Patient outcomes as well as clinic presentation of the disease have largely been shown to be case-specific, hinting towards ITP rather being a group of clinical conditions sharing common symptoms. The most frequent characteristics include dysfunction in primary haemostasis and loss of immune tolerance towards platelet as well as megakaryocyte antigens. This heterogeneity in patient population and characteristics make it challenging for the clinicians to choose appropriate therapeutic regimen. Therefore, it is vital to understand the pathomechanisms behind the disease and to consider various factors including patient age, platelet count levels, co-morbidities and patient preferences before initiating therapy. This review summarizes recent developments in the pathophysiology of ITP and provides a comprehensive overview of current therapeutic strategies as well as potential future drugs for the management of ITP.

scholarly journals Pathogenesis in immune thrombocytopenia: new insights

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 306-312 ◽  
Author(s):  
Jill Johnsen
Keyword(s):  
Immune Thrombocytopenia ◽  
Molecular Mimicry ◽  
Autoimmune Disorder ◽  
Immune Dysregulation ◽  
Common Elements ◽  
Platelet Destruction ◽  
Immunomodulatory Agents ◽  
Loss Of Tolerance ◽  
Immune Related Genes

Abstract Idiopathic (immune) thrombocytopenic purpura (ITP) is a common autoimmune disorder resulting in isolated thrombocytopenia. ITP can present either alone (primary) or in the setting of other conditions (secondary) such as infections or altered immune states. ITP is associated with a loss of tolerance to platelet antigens and a phenotype of accelerated platelet destruction and impaired platelet production. Although the etiology of ITP remains unknown, complex dysregulation of the immune system is observed in ITP patients. Antiplatelet antibodies mediate accelerated clearance from the circulation in large part via the reticuloendothelial (monocytic phagocytic) system. In addition, cellular immunity is perturbed and T-cell and cytokine profiles are significantly shifted toward a type 1 and Th17 proinflammatory immune response. Further clues into immune dysregulation in ITP may be gleaned from studies of secondary ITP. Some infections can induce antiplatelet Abs by molecular mimicry, and there may be common elements involved in breaking tolerance with other autoimmune disorders. There is also evidence for a genetic predisposition to both ITP and responsiveness to therapy, which may in part lie within immune-related genes. Lastly, treatment with immunomodulatory agents remains the mainstay of ITP therapies.

scholarly journals B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

2021 ◽  
Vol 14 (1) ◽  
pp. 37
Author(s):  
Jan Traub ◽  
Leila Husseini ◽  
Martin S. Weber
Keyword(s):  
B Cells ◽  
Neuromyelitis Optica ◽  
Plasma Cells ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Complement Factor ◽  
Major Subset ◽  
Spectrum Disorders

The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

scholarly journals B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells

2012 ◽  
Vol 123 (1) ◽  
pp. 432-442 ◽  
Author(s):  
Matthieu Mahévas ◽  
Pauline Patin ◽  
François Huetz ◽  
Marc Descatoire ◽  
Nicolas Cagnard ◽  
...  
Keyword(s):  
B Cell ◽  
Immune Thrombocytopenia ◽  
Plasma Cells ◽  
Cell Depletion ◽  
B Cell Depletion

scholarly journals Pathophysiology, Diagnosis and Treatment of Immune Thrombocytopenia

2017 ◽  
Vol 5 (1) ◽  
pp. 32-36
Author(s):  
Mihnea-Alexandru Găman ◽  
Amelia Maria Găman
Keyword(s):  
Peripheral Blood ◽  
Immune Thrombocytopenia ◽  
Blood Count ◽  
Complete Blood Count ◽  
Anabolic Steroids ◽  
Peripheral Blood Smear ◽  
Intravenous Immunoglobulins ◽  
First Line Therapy ◽  
Anti Cd20 ◽  
Immunosupressive Therapy

Immune thrombocytopenia (ITP) is an acquired disorder characterized by isolated thrombocytopenia with a peripheral blood count < 100.000/ mm3 in the absence of any obvious initiating or underlying causes, by antibody mediated destruction of platelets and suppression of megakaryocyte and platelet production on the basis of immune deregulation. ITP is idiopathic (primary) in 80% of cases and secondary to several associated disorders in 20% of cases. A diagnosis of exclusion, based on patient history, physical examination, complete blood count and examination of the peripheral blood smear, is used for ITP. The treatment of ITP is indicated in adult patients with platelet counts below 20.000-30.000/ mm3, with bleedings or risk for bleeding. First line therapy is represented by corticosteroids, intravenous immunoglobulins and intravenous anti-RhD. Second-line treatment is represented by: splenectomy, inhibition of the monocytic phagocytic system therapy, immunosupressive therapy, anabolic steroids, anti-CD20 therapy, and thrombopoietin receptor agonists.

Sign in / Sign up

Export Citation Format

Share Document