The overall incidence is extremely low
The overall incidence is extremely low. main reported entities are secondary immune thrombocytopenia, immune thrombotic DL-AP3 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 HNPCC2 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. Keywords: COVID-19, vaccines, ITP, VITT, TTP, AIHA and Evans syndrome, antiphospholipid syndrome, catastrophic antiphospholipid syndrome 1. Introduction The exceptional scenario conditioned by the sudden outbreak of SARS-CoV-2 infection all over the world prompted the search for vaccines that are efficient and easy to manufacture at huge scale. Extensive research led to the production of more than 20 compounds that successfully passed phase III trials and, thus, were deemed to be safe. Nevertheless, the extended use in the real-world of drugs that have DL-AP3 successfully passed the test of clinical trials often involves the emergence of adverse events (AEs). Although these are infrequent and will not tip the balance towards product withdrawal, they can be serious and their occurrence has to be envisaged. Indeed, this phenomenon occurred when COVID-19 vaccines started being administered throughout the world. Statements documenting AEs started being reported. Although regular updates repeatedly demonstrate that the majority of these episodes are mild and transient, serious AEs (SAEs) are occasionally described that, albeit rarely, may be fatal. These SAEs are particularly of an autoimmune nature. This is not unexpected, since humoral immune response to vaccination involves the production of antibodies against foreign antigens that, occasionally, could mimic self-ones. Structures often affected by autoimmune disorders include platelets, RBCs and blood vessels. Thus, it is not surprising that hematologic autoimmune disorders are associated with SARS-CoV-2 vaccines, either the mRNA or adenoviral vector-based ones. When a hematologic autoimmune disorder develops following vaccination, a prompt and accurate diagnosis is essential to initiate the appropriate treatment and avoid bleeding or thromboembolic complications that may sometimes be life-threatening. The main autoimmune disorders of a hematologic nature that have been linked to SARS-CoV-2 vaccination are addressed herein. Commonly used therapies and outcomes are revised. Where suggested, potentially involved mechanisms linking vaccines and autoimmune pathology are described. Finally, guidelines to follow in order to promptly recognize and manage these complications are provided. 2. Methods In order to select the eligible studies whose results would be considered a comprehensive update about the AEs of hematologic autoimmune nature reported in the context of COVID-19 infection, the authors searched the PubMed registry and the regular updates of the European Database of Suspected Adverse Drug Reaction (EudraVigilance), United Kingdom Medicines & Healthcare Products Released Regulatory Agency (MHRA), Health-Infobase Government of Canada, and the Vaccine Adverse Events Reporting System (VAERS). The search criteria consisted of considering all reports regarding phase III clinical trials and the real-world use of vaccines, stating that any hematologic AE had occurred. The latest search date included was 9 May 2022. Although some reports were limited to enumerating AEs, the scarcity of available literature prompted us to consider all statements addressing the occurrence of hematologic AEs, even if the information was incomplete. The chosen keywords or word combinations to track the information of interest were COVID-19, vaccines, ITP, VITT, TTP, AIHA, Antiphospholipid and Evans syndrome, autoimmune disorder, thrombocytopenia, and anemia. 3. Commercially Available COVID-19 Vaccines More than 100 vaccines have been developed against SARS-CoV-2, 26 of which have been evaluated in phase III clinical trials according to the World Health Organization (WHO) [1]. These can be stratified into up to five different categories according to how they generate immunity. The classically DL-AP3 used methods based on whole inactivated or live attenuated virus, although effective, have always raised concerns. Incomplete viral inactivation may not be discarded, and every batch needs to be checked [2]. The development of antibody disease enhancement (ADE) DL-AP3 syndrome due to non-neutralizing antibodies may be a risk which, in the COVID-19 scenario, can increase lung pathology [3]. Furthermore, there was a need for quickly available, massively produced vaccines. Nucleic acid-based vaccines.