Vaccination against COVID-19 reduces infection-related mortality. Unfortunately, reports of vaccine-induced immune thrombotic thrombocytopenia (VITT) in individuals administered adenovirus-vector-based vaccines (ChAdOx1 nCoV-19 and Ad26.COV2.S) have spurred side effect concerns. To address vaccine hesitancy related to this, it is essential to determine the incidence of VITT (defined by a 50% decrease in platelet count and positive anti-PF4 immunoassay within 4-28 days after vaccination) among patients administered two doses of an mRNA-based COVID-19 vaccination. We identified a retrospective cohort of 223,345 patients in the Cleveland Clinic Enterprise administered a COVID-19 vaccine at any location in Northeast Ohio and Florida from 12/4/2020 to 6/6/2021. 97.3% of these patients received an mRNA-based vaccination. Patients with: (1) a serial complete blood count both before and after vaccination and (2) a decrease in platelet count of ≥ 50% were selected for chart review. The primary outcome was the incidence of thrombotic events, including venous thromboembolism (VTE) and arterial thrombosis, 4-28 days post vaccination. Of 74 cohort patients with acute thrombosis, 72 (97.3%) demonstrated clear etiologies, such as active malignancy. Of two patients with unprovoked thrombosis, only one had findings concerning for VITT, with a strongly positive anti-PF4 antibody assay. In this large, multi-state, retrospective cohort, of 223,345 patients (97.2% of whom received the mRNA-based mRNA-1273 or BNT162b2 vaccines), we detected a single case that was concerning for VITT in a patient who received an mRNA vaccine. The overwhelming majority of patients with a thrombotic event 4-28 days following vaccination demonstrated clear etiologies.

The COVID-19 outbreak had a strong impact on people\'s lives all over the world. Patients with hematologic diseases have been heavily affected by the pandemic, because their immune system may be compromised due to anti-cancer or immunosuppressive therapies and because diagnosis and treatment of their baseline conditions were delayed during lockdowns. Hematologic malignancies emerged very soon as risk factors for severe COVID-19 infection, increasing the mortality rate. SARS-CoV2 can also induce or exacerbate immune-mediated cytopenias, such as autoimmune hemolytic anemias, complement-mediated anemias, and immune thrombocytopenia. Active immunization with vaccines has been shown to be the best prophylaxis of severe COVID-19 in hematologic patients. However, the immune response to vaccines may be significantly impaired, especially in those receiving anti-CD20 monoclonal antibodies or immunosuppressive agents. Recently, antiviral drugs and monoclonal antibodies have become available for pre-exposure and post-exposure prevention of severe COVID-19. As adverse events after vaccines are extremely rare, the cost-benefit ratio is largely in favor of vaccination, even in patients who might be non-responders; in the hematological setting, all patients should be considered at high risk of developing complications due to SARS-CoV2 infection and should be offered all the therapies aimed to prevent them.

The novel coronavirus pandemic has taken a toll on the global healthcare systems and economy. Safety precautions, along with vaccination, are the most effective preventive measures. The global vaccination program against COVID-19 has dramatically reduced the number of deaths and cases. However, the incidence of thrombotic events and thrombocytopenia post-COVID-19 vaccination known as vaccine-induced thrombotic thrombocytopenia has raised safety concerns. This has led to an element of vaccine hesitancy. The exact mechanism for vaccine-induced thrombotic thrombocytopenia is unknown. Although the incidence of thrombosis associated with COVID-19 vaccination is low, it still requires attention, especially in older people, smokers, and people with preexisting comorbidities. This study aims to review the pathophysiology, diagnosis, and management of vaccine-induced thrombotic thrombocytopenia, to provide a concise and comprehensive update.

The recognition of the rare but serious and potentially lethal complication of vaccine induced thrombotic thrombocytopenia (VITT) raised concerns regarding the safety of COVID-19 vaccines and led to the reconsideration of vaccination strategies in many countries. Following the description of VITT among recipients of adenoviral vector ChAdOx1 vaccine, a review of similar cases after Ad26.COV2·S vaccination gave rise to the question whether this entity may constitute a potential class effect of all adenoviral vector vaccines. Most cases are females, typically younger than 60 years who present shortly (range: 5-30 days) following vaccination with thrombocytopenia and thrombotic manifestations, occasionally in multiple sites. Following initial incertitude, concrete recommendations to guide the diagnosis (clinical suspicion, initial laboratory screening, PF4-polyanion-antibody ELISA) and management of VITT (non-heparin anticoagulants, corticosteroids, intravenous immunoglobulin) have been issued. The mechanisms behind this rare syndrome are currently a subject of active research and include the following: 1) production of PF4-polyanion autoantibodies; 2) adenoviral vector entry in megacaryocytes and subsequent expression of spike protein on platelet surface; 3) direct platelet and endothelial cell binding and activation by the adenoviral vector; 4) activation of endothelial and inflammatory cells by the PF4-polyanion autoantibodies; 5) the presence of an inflammatory co-signal; and 6) the abundance of circulating soluble spike protein variants following vaccination. Apart from the analysis of potential underlying mechanisms, this review aims to synopsize the clinical and epidemiologic features of VITT, to present the current evidence-based recommendations on diagnostic and therapeutic work-up of VITT and to discuss new dilemmas and perspectives that emerged after the description of this entity.