An Update on Pediatric Immune Thrombocytopenia (ITP): Differentiating Primary ITP, IPD, and PID

Blood ◽  
2021 ◽  
Author(s):  
Rachael F. Grace ◽  
Michele P Lambert
Keyword(s):  
Immune Thrombocytopenia ◽  
Clinical History ◽  
Immune Dysregulation ◽  
Diagnostic Evaluation ◽  
Primary Immune Deficiency ◽  
Immune Disorders ◽  
Platelet Destruction ◽  
Hypothetical Patient ◽  
Immune Mediated ◽  
Clinical Scenarios

Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia in children and is caused by both immune-mediated decreased platelet production and increased platelet destruction. In the absence of a diagnostic test, ITP must be differentiated from other thrombocytopenic disorders, including inherited platelet disorders (IPD). In addition, a diagnosis of secondary ITP due to a primary immune deficiency (PID) with immune dysregulation may not be apparent at diagnosis but can alter management and should be considered in an expanding number of clinical scenarios. The diagnostic evaluation of children with thrombocytopenia will vary based on the clinical history and laboratory features. Access to genotyping has broadened the ability to specify the etiology of thrombocytopenia, while increasing access to immunophenotyping, functional immunologic and platelet assays, and biochemical markers has allowed for more in-depth evaluation of patients. With this greater availability of testing, diagnostic algorithms in patients with thrombocytopenia have become complex. In this article, we highlight the diagnostic evaluation of thrombocytopenia in children with a focus on ITP, including consideration of underlying genetic and immune disorders, and utilize hypothetical patient cases to describe disease manifestations and strategies for treatment of pediatric ITP.

scholarly journals Diagnosis and Management of Immune Thrombocytopenia in the Era of Thrombopoietin Mimetics

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 384-390 ◽  
Author(s):  
Howard A. Liebman ◽  
Vinod Pullarkat
Keyword(s):  
Immune Thrombocytopenia ◽  
Randomized Trials ◽  
Current Data ◽  
Disease Course ◽  
Efficacy And Safety ◽  
Platelet Destruction ◽  
Immune Mediated ◽  
Thrombopoietin Receptor ◽  
Diagnostic Work ◽  
Work Up

Abstract The recognition of that patients with Immune Thrombocytopenia (ITP) have functional thrombopoietin deficiency and decreased platelet production due to immune-mediated megakaryocytic injury has challenged the traditional view of this disease as predominantly a disorder of antibody-mediated platelet destruction. The therapy of chronic refractory ITP has been transformed by the approval of the thrombopoietin minetics, romiplostim and eltrombopag, which have shown remarkable efficacy in randomized trials. The use of these agents earlier in the disease course after failure of corticosteroid therapy remains controversial. In this article, we review the current data on the efficacy and safety of thrombopoietin receptor agonists and discuss other therapies as well as diagnostic work up of ITP.

scholarly journals Persistent thrombocytopenia in Dengue Fever is rare but not uncommon - can be treated with steroid successfully

2021 ◽  
Vol 32 (1) ◽  
pp. 62-64
Author(s):  
Md Daharul Islam ◽  
Khaleda Akter ◽  
Ranajit Sen Chowdhury ◽  
Mohammad Abdus Sattar Sarkar ◽  
Aminur Rahman
Keyword(s):  
Platelet Count ◽  
Dengue Fever ◽  
Immune Thrombocytopenia ◽  
Haemorrhagic Fever ◽  
Platelet Destruction ◽  
Immune Mediated ◽  
Immune Injury ◽  
Underlying Mechanisms ◽  
Common Manifestation ◽  
Persistent Thrombocytopenia

Fever, skin rash, thrombocytopenia and bleeding are common manifestation of dengue fever (DF). Thrombocytopenia usually gets better and platelet count normalizes by day 10 of fever. Chronic thrombocytopenia is not a feature of dengue fever. Proposed mechanisms behind thrombocytopenia are many. Direct platelet destruction by dengue virus, immune-mediated platelet destruction and evenmegakaryocytic immune injury are proposed as underlying mechanisms. We are reporting a case of a 43 year old female who presented in dengue season in 2019 with fever and bleeding and wasdiagnosed as a case of dengue haemorrhagic fever. She had persistent thrombocytopenia which neededto be treated on the lines of immune thrombocytopenia and responded to steroids. Other causes of thrombocytopenia were ruled out. Bangladesh J Medicine January 2021; 32(1) : 62-64

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 Dimethyl fumarate inhibits antibody-induced platelet destruction in immune thrombocytopenia mouse

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Huan Tong ◽  
Yangyang Ding ◽  
Xiang Gui ◽  
Zengtian Sun ◽  
Guozhang Wang ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Mononuclear Cells ◽  
Dimethyl Fumarate ◽  
Treg Cells ◽  
Antiplatelet Antibody ◽  
Platelet Destruction ◽  
Immune Mediated ◽  
Ifn Γ

Abstract Background Immune thrombocytopenia (ITP) is an autoimmune disease characterized as a low platelet count resulting from immune-mediated platelet destruction. Dimethyl fumarate (DMF) is widely applied for the treatment of several autoimmune diseases with immunosuppressive effect. However, whether it ameliorates ITP is unclear. This study aims to evaluate whether DMF has a preventive effect on ITP in mice. Methods DMF (30, 60 or 90 mg/kg body weight) was intraperitoneally injected into mice followed by injection of rat anti-mouse integrin GPIIb/CD41antibody to induce ITP. Peripheral blood was isolated to measure platelet count and spleen mononuclear cells were extracted to measure Th1 and Treg cells along with detecting the levels of IFN-γ, and TGFβ-1 in plasma and CD68 expression in spleen by immuohistochemical staining. Additionally, macrophage cell line RAW264.7 was cultured and treated with DMF followed by analysis of cell apoptosis and cycle, and the expression of FcγRI, FcγRIIb and FcγRIV mRNA. Results DMF significantly inhibited antiplatelet antibody-induced platelet destruction, decreased Th1 cells and the expression of T-bet and IFN-γ, upregulated Treg cells and the expression of Foxp3 and TGF-β1 as well as reduced CD68 expression in the spleen of ITP mouse. DMF-treated RAW264.7 cells showed S-phase arrest, increased apoptosis and downregulated expression of FcγRI and FcγRIV. Meanwhile, in vitro treatment of DMF also decreased the expression of cyclin D1 and E2, reduced Bcl-2 level and increased Bax expression and caspase-3 activation. Conclusions In conclusion, DMF prevents antibody-mediated platelet destruction in ITP mice possibly through promoting apoptosis, indicating that it might be used as a new approach for the treatment of ITP.

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 Case Report: Oxaliplatin-Induced Immune-Mediated Thrombocytopenia

2018 ◽  
Vol 11 (3) ◽  
pp. 880-882 ◽  
Author(s):  
Elizabeth Pan ◽  
Eric Hsieh ◽  
Caroline Piatek
Keyword(s):  
Case Report ◽  
Cancer Therapy ◽  
Cancer Patients ◽  
Immune Thrombocytopenia ◽  
Drug Induced ◽  
Gastrointestinal Malignancies ◽  
Common Cause ◽  
Immune Mediated ◽  
Chemotherapy Agents ◽  
Platinum Derivative

Thrombocytopenia is a frequent complication of cancer may be due to a variety of causes including malignancy itself, acute disease processes, or cancer therapy. Systemic cancer therapy is the most common cause of thrombocytopenia in cancer patients observed nearly two-thirds of patients with solid tumors. Thrombocytopenia with traditional chemotherapy agents is most frequently the result of megakaryocyte cytotoxicity. Oxaliplatin is a platinum derivative commonly used in gastrointestinal malignancies and is associated with drug-induced immune thrombocytopenia.

scholarly journals Analysis of Interleukin-17 Levels in Patients with Thrombocytopenia

Biomedika ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 68-73
Author(s):  
Lidwina Septie Christyawardani ◽  
Mansyur Arief ◽  
Uleng Bahrun
Keyword(s):  
Blood Circulation ◽  
Immune Thrombocytopenia ◽  
Research Unit ◽  
Comparative Test ◽  
P Value ◽  
Interleukin 17 ◽  
Platelet Production ◽  
Immune Mediated ◽  
Significant Difference ◽  
Primary Immune Thrombocytopenia

Thrombocytopenia or platelet deficiency is a condition, in which platelet level in the blood circulation is below normal, which is less than 150,000 cells/µl. Thrombocytopenia is classified into some conditions, including decreased platelet production, increased need for platelets, and other thrombocytopenia. The need for increased platelets can be subdivided into primary immune thrombocytopenia, secondary immune thrombocytopenia, non-primary ITP, and thrombocytopenia that are not immune-mediated. Several cytokines play a role in the process of thrombocytopenia, one of which is Interleukin-17 (IL-17) that will be further discussed in this study. A previous study reported that IL-17 production increased in ITP and cITP patients. The objective of this study was to analyze the IL-17 levels and figure out the differences in IL-17 levels in the serums of patients with primary ITP and secondary ITP. The samples were taken from Wahidin Sudirohusodo Hospital and the specimens were examined in the Research Unit Laboratory of the Faculty of Medicine, Universitas Hasanuddin/Hospital of Universitas Hasanuddin. The comparative test resulted in p-value = 0.005, where p <α = 0.05; and therefore, there was a significant difference between IL 17 levels in ITP and non-primary ITP.

scholarly journals Immune Thrombocytopenia

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 377-384 ◽  
Author(s):  
Adam Cuker ◽  
Douglas B. Cines
Keyword(s):  
Immune Thrombocytopenia ◽  
Therapeutic Decision ◽  
Platelet Destruction ◽  
Aggressive Therapy ◽  
Pulse Dose ◽  
Thrombopoietin Receptor ◽  
History Of ◽  
Associated Conditions ◽  
Therapeutic Decision Making

Abstract Immune thrombocytopenia (ITP) comprises a heterogeneous group of disorders characterized by autoimmune-mediated platelet destruction and impairment of thrombopoiesis. ITP may occur in the absence of an evident predisposing etiology (primary ITP) or secondary to a growing list of associated conditions (secondary ITP), and must be differentiated from other causes of thrombocytopenia. This review focuses on primary ITP in adults. The traditional goal of therapy in this population is to achieve a hemostatic platelet count of 30 × 109/L or above for most patients while minimizing treatment-related morbidity. This approach has been called into question by the recent advent of well-tolerated and effective agents for the management of ITP, including pulse-dose dexamethasone, rituximab, and the thrombopoietin receptor agonists. Recent studies suggest the potential for aggressive therapy at the time of diagnosis to alter the natural history of ITP and point to the importance of quality-of-life considerations in therapeutic decision making.

scholarly journals Immune-mediated Neuropathies Our Experience over 3 Years

2018 ◽  
Vol 09 (01) ◽  
pp. 030-035 ◽  
Author(s):  
Sadanandavalli Retnaswami Chandra ◽  
Venkata Raviteja Karru ◽  
M. A. Mukheem Mudabbir ◽  
Subashree Ramakrishnan ◽  
Anitha Mahadevan
Keyword(s):  
Clinical Laboratory ◽  
Clinical Course ◽  
Immune Dysregulation ◽  
Response To Treatment ◽  
Dominant Type ◽  
The Past ◽  
Immune Mediated ◽  
Sensory Motor ◽  
Chronic Neuropathy

ABSTRACT Introduction: Immune-mediated peripheral neuropathy is the term applied to a spectrum of peripheral nerve disorders where immune dysregulation plays a role. Therefore, they are treatable. We analyzed the cases seen in the past 3 years by us and evaluated the clinical, laboratory, and outcome parameters in these patients. Patients and Methods: Consecutive patients seen by the authors and diagnosed as immune-mediated neuropathy were analyzed for etiology, pathology, and outcome assessed. Results: A total of sixty patients, 31 acute and 29 chronic neuropathies, were identified. Their subtypes treatment and outcome assessed. Males were significantly more in both acute and chronic cases. Miller Fisher 4, AMAN 1, paraplegic type 1, motor dominant type 19, Sensory-motor 1, MADSAM 3, Bifacial 2. Nonsystemic vasculitis was seen in 16 out of 29 chronic neuropathy and HIV, POEMS, and diabetes mellitus one each. Discussion: There is a spectrum of immune-mediated neuropathy which varies in clinical course, response to treatment, etc., Small percentage of uncommon cases are seen. In this group, mortality was nil and morbidity was minimal. Conclusion: Immune-mediated neuropathies are treatable and hence should be diagnosed early for good quality outcome.

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