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 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 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.

Primary Immune Thrombocytopenia (ITP) Guidelines for Bone Marrow Aspirate Reduce the Diagnostic Rate of Myelodysplastic Syndromes

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4974-4974
Author(s):  
Iolanda Vincelli ◽  
Esther Natalie Oliva ◽  
Francesca Ronco ◽  
Patrizia Cufari ◽  
Bianca Oliva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Thrombocytopenia ◽  
Bone Marrow Aspirate ◽  
Conflicts Of Interest ◽  
Autoimmune Disorder ◽  
Case Review ◽  
Initial Screening ◽  
Immune Mediated ◽  
Primary Immune Thrombocytopenia ◽  
Systemic Symptoms

Abstract Abstract 4974 Introduction: Primary immune thrombocytopenia (ITP) is an acquired immune-mediated disorder characterized by isolated thrombocytopenia, defined as a peripheral blood PLT count <100 Gi/L, and the absence of any obvious initiating and/or underlying cause of the thrombocytopenia (Rodeghiero et al, Blood, 2009). Guidelines consider bone marrow (BM) aspirate informative in patients with thrombocytopenia > 60 years of age, those with systemic symptoms or abnormal signs or in some cases where splenectomy is considered (Provan et al, Blood, 2009). Methods: We performed a retrospective chart analysis between January 2008 and June 2010 of all patients referred to our clinic for isolated thrombocytopenia but with a PLT count 100– 149 Gi/L. According to recent guidelines, these patients are not to be considered thrombocytopenic and do not require further investigation. The aim of the study was to evaluate the validity of omitting BM analysis in these cases. Results: Twenty-three cases (13 males/10 females) of mean age 58 ± SD 19 years were evaluated at our clinic for a PLT count below normal lab range values. At the time of evaluation none had bleeding symptoms. PLT counts ranged from 101 to 149 Gi/L, mean 123 Gi/L. Four patients had an enlarged spleen. After initial screening, 2 patients had a complex autoimmune disorder and 1 case had HCV hepatitis. The remaining 20 patients had a bone marrow (BM) aspirate performed: a diagnosis of myelodysplastic syndrome (MDS, WHO classification refractory thrombocytopenia) was obtained in 13 cases (65%) and BM biopsy was performed in 12, completed by cytogenetics in 9 cases (7 normal, 1 del20q, 1 –Y). Patients diagnosed with MDS were significantly older (66 ± SD 13 vs 47 ± SD 21 years, p = 0.017), but 4 cases (31%) were < 60 years of age (44, 49, 51 and 55 years of age, respectively). Conclusions: The most recent guidelines, which lower the PLT threshold to 100 Gi/L from 150 Gi/L for the investigation of causes of thrombocytopenia, reduce the diagnostic rate of MDS. In our retrospective review, 65% of patients would not have had an early diagnosis of MDS. Furthermore, BM aspirate should be considered irrespective of age, since one third of the patients in our case review had MDS with PLT > 100 Gi/L as a single cytopenia and age under 60. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effects of COVID-19 Infection during Pregnancy and Neonatal Prognosis: What Is the Evidence?

2020 ◽  
Vol 17 (11) ◽  
pp. 4176 ◽  
Author(s):  
Álvaro Francisco Lopes de Sousa ◽  
Herica Emilia Félix de Carvalho ◽  
Layze Braz de Oliveira ◽  
Guilherme Schneider ◽  
Emerson Lucas Silva Camargo ◽  
...  
Keyword(s):  
Literature Review ◽  
Pregnant Women ◽  
Cardiac Rhythm ◽  
Current Evidence ◽  
Acid Base ◽  
Potential Risks ◽  
Low Levels ◽  
Clinical Conditions ◽  
First Contact ◽  
Rule Out

Background: This study’s aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. Methods: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, “What are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?” Results: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. Conclusions: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.

scholarly journals Pathogenesis-oriented approaches for the management of corticosteroid-resistant or relapsedprimary immune thrombocytopenia

Open Medicine ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. 97-100
Author(s):  
Xin-guang Liu ◽  
Ming Hou
Keyword(s):  
Immune Thrombocytopenia ◽  
Therapeutic Strategy ◽  
Autoimmune Disorder ◽  
Initial Response ◽  
Treatment Modalities ◽  
Sustained Remission ◽  
Specific Patient ◽  
Immune Mediated ◽  
Primary Immune Thrombocytopenia ◽  
Optimal Therapeutic Strategy

AbstractPrimary immune thrombocytopenia (ITP) is a complex autoimmune disorder in which the patient’s immune system reacts with platelet autoantigens resulting in immune-mediated platelet destruction and/or suppression of platelet production. Corticosteroids can induce sustained remission rates in 50% to 75% of patients with active ITP. For these patients who are unresponsive to glucocorticoids, or relapsed after an initial response, multiple second-line treatment modalities can be chosen. However, how to make an optimal therapeutic strategy for a specific patient still remains a major challenge. As the pathogenetic heterogeneity of the ITP is increasingly identified, pathogenesis-oriented approach might offer an opportunity to improve the outcome of corticosteroid-resistant or relapsed ITP.

scholarly journals Interleukin 27 inhibits cytotoxic T-lymphocyte-mediated platelet destruction in primary immune thrombocytopenia

Blood ◽  
2014 ◽  
Vol 124 (22) ◽  
pp. 3316-3319 ◽  
Author(s):  
Hai Zhou ◽  
Ji-hua Qiu ◽  
Tong Wang ◽  
Ying-yi Yu ◽  
Xue-na Liu ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Immune Thrombocytopenia ◽  
Cytotoxic T Lymphocyte ◽  
Granzyme B ◽  
Platelet Destruction ◽  
Interleukin 27 ◽  
Key Points ◽  
Primary Immune Thrombocytopenia

Key Points IL-27 inhibits CTL cytotoxicity toward autologous platelets via decreasing granzyme B expression in 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.

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