Recommendations for the Clinical Approach to Immune Thrombocytopenia: Spanish ITP Working Group (GEPTI)

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Primary immune thrombocytopenia (ITP) is a complex autoimmune disease whose hallmark is a deregulation of cellular and humoral immunity leading to increased destruction and reduced production of platelets. The heterogeneity of presentation and clinical course hampers personalized approaches for diagnosis and management. In 2021, the Spanish ITP Group (GEPTI) of the Spanish Society of Hematology and Hemotherapy (SEHH) updated a consensus document that had been launched in 2011. The updated guidelines have been the reference for the diagnosis and management of primary ITP in Spain ever since. Nevertheless, the emergence of new tools and strategies makes it advisable to review them again. For this reason, we have updated the main recommendations appropriately. Our aim is to provide a practical tool to facilitate the integral management of all aspects of primary ITP management.Peer reviewe

COVID-19 vaccines and autoimmune hematologic disorders

Worldwide vaccination against SARS-CoV-2 has allowed the detection of hematologic autoimmune complications. Adverse events (AEs) of this nature had been previously observed in association with other vaccines. The underlying mechanisms are not totally understood, although mimicry between viral and self-antigens plays a relevant role. It is important to remark that, although the incidence of these AEs is extremely low, their evolution may lead to life-threatening scenarios if treatment is not readily initiated. Hematologic autoimmune AEs have been associated with both mRNA and adenoviral vector-based SARS-CoV-2 vaccines. The main reported entities are secondary immune thrombocytopenia, immune thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and a newly described disorder, so-called vaccine-induced immune thrombotic thrombocytopenia (VITT). The hallmark of VITT is the presence of anti-platelet factor 4 autoantibodies able to trigger platelet activation. Patients with VITT present with thrombocytopenia and may develop thrombosis in unusual locations such as cerebral beds. The management of hematologic autoimmune AEs does not differ significantly from that of these disorders in a non-vaccine context, thus addressing autoantibody production and bleeding/thromboembolic risk. This means that clinicians must be aware of their distinctive signs in order to diagnose them and initiate treatment as soon as possible

COVID-19 vaccines and autoimmune hematologic disorders

Worldwide vaccination against SARS-CoV-2 has allowed the detection of hematologic autoimmune complications. Adverse events (AEs) of this nature had been previously observed in association with other vaccines. The underlying mechanisms are not totally understood, although mimicry between viral and self-antigens plays a relevant role. It is important to remark that, although the incidence of these AEs is extremely low, their evolution may lead to life-threatening scenarios if treatment is not readily initiated. Hematologic autoimmune AEs have been associated with both mRNA and adenoviral vector-based SARS-CoV-2 vaccines. The main reported entities are secondary immune thrombocytopenia, immune thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and a newly described disorder, so-called vaccine-induced immune thrombotic thrombocytopenia (VITT). The hallmark of VITT is the presence of anti-platelet factor 4 autoantibodies able to trigger platelet activation. Patients with VITT present with thrombocytopenia and may develop thrombosis in unusual locations such as cerebral beds. The management of hematologic autoimmune AEs does not differ significantly from that of these disorders in a non-vaccine context, thus addressing autoantibody production and bleeding/thromboembolic risk. This means that clinicians must be aware of their distinctive signs in order to diagnose them and initiate treatment as soon as possible

COVID-19 Vaccines and Autoimmune Hematologic Disorders

Worldwide vaccination against SARS-CoV-2 has allowed the detection of hematologic autoimmune complications. Adverse events (AEs) of this nature had been previously observed in association with other vaccines. The underlying mechanisms are not totally understood, although mimicry between viral and self-antigens plays a relevant role. It is important to remark that, although the incidence of these AEs is extremely low, their evolution may lead to life-threatening scenarios if treatment is not readily initiated. Hematologic autoimmune AEs have been associated with both mRNA and adenoviral vector-based SARS-CoV-2 vaccines. The main reported entities are secondary immune thrombocytopenia, immune thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and a newly described disorder, so-called vaccine-induced immune thrombotic thrombocytopenia (VITT). The hallmark of VITT is the presence of anti-platelet factor 4 autoantibodies able to trigger platelet activation. Patients with VITT present with thrombocytopenia and may develop thrombosis in unusual locations such as cerebral beds. The management of hematologic autoimmune AEs does not differ significantly from that of these disorders in a non-vaccine context, thus addressing autoantibody production and bleeding/thromboembolic risk. This means that clinicians must be aware of their distinctive signs in order to diagnose them and initiate treatment as soon as possible.Peer reviewe

Novel therapies to address unmet needs in ITP

Primary immune thrombocytopenia (ITP) is an autoimmune disorder that causes low platelet counts and subsequent bleeding risk. Although current corticosteroid-based ITP therapies are able to improve platelet counts, up to 70% of subjects with an ITP diagnosis do not achieve a sustained clinical response in the absence of treatment, thus requiring a second-line therapy option as well as additional care to prevent bleeding. Less than 40% of patients treated with thrombopoietin analogs, 60% of those treated with splenectomy, and 20% or fewer of those treated with rituximab or fostamatinib reach sustained remission in the absence of treatment. Therefore, optimizing therapeutic options for ITP management is mandatory. The pathophysiology of ITP is complex and involves several mechanisms that are apparently unrelated. These include the clearance of autoantibody-coated platelets by splenic macrophages or by the complement system, hepatic desialylated platelet destruction, and the inhibition of platelet production from megakaryocytes. The number of pathways involved may challenge treatment, but, at the same time, offer the possibility of unveiling a variety of new targets as the knowledge of the involved mechanisms progresses. The aim of this work, after revising the limitations of the current treatments, is to perform a thorough review of the mechanisms of action, pharmacokinetics/pharmacodynamics, efficacy, safety, and development stage of the novel ITP therapies under investigation. Hopefully, several of the options included herein may allow us to personalize ITP management according to the needs of each patient in the near future