COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management

Abstract

With over 600 million coronavirus (COVID-19) vaccine doses administered globally, adverse events are constantly monitored. Recently however, reports of thrombosis and thrombocytopenia following vaccination with the ChAdOx1 nCoV-19 vaccine have emerged. This paper aims to review the available literature and guidelines pertaining to vaccine-induced immune thrombotic thrombocytopenia (VITT) and the proposed guidelines, while offering a potential approach that unifies the available evidence. While the risk of VITT remains extremely low and the benefits outweigh the risks, experimental studies are needed to clarify the pathophysiology behind VITT and possibly decrease the risk of thrombosis and other adverse events occurring. However, treatment should not be delayed in suspected cases, and IV immunoglobulin and non-heparin anticoagulation should be initiated.

The role of anti-platelet factor 4 antibodies and platelet activation tests in patients with vaccine-induced immune thrombotic thrombocytopenia: Brief report on a comparison of the laboratory diagnosis and literature review

“…Regarding the laboratory aspects, apart from thrombocytopenia, the key diagnostic feature is the positivity of the ELISA test for VITT, which identifies antibodies to PF4 and still needs to be confirmed by a functional heparin-induced platelet activation assay (HIPA) or serotonin-release assay (SRA) [9] , [19] , [20] .…”

Non-clinical immunogenicity, biodistribution and toxicology evaluation of a chimpanzee adenovirus-based COVID-19 vaccine in rat and rhesus macaque

“…Although little is known so far, the pathophysiology of TTS is thought to be similar to that of aHIT’s. The anti-PF4 antibodies bound to the complex of PF4-polyanion (unknown or yet to be characterized) subsequently binds to FcRγIIA receptor on the platelets, resulting in platelet activation and aggregation, which leads to platelet consumption, thrombocytopenia and thrombosis (Alam 2021 ). Although evidence of the pathological antibody role of PF4 is being established, it is still necessary to clarify which component of the vaccine can form a complex with PF4, and whether genetic factors may play a role in the immune response leading to thrombocytopenia after vaccination.…”

Pathophysiology of Vaccine-Induced Prothrombotic Immune Thrombocytopenia (VIPIT) and Vaccine-Induced Thrombocytopenic Thrombosis (VITT) and Their Diagnostic Approach in Emergency

“…Scientific reports underlined that AstraZeneca or Johnson and Johnson vaccines are more frequently associated with VITT. Pathophysiological mechanisms of VIPIT refer to a specific type of blood clot associated with immunological abnormalities after vaccination [41]. These mechanisms are different from the blood's regular clotting mechanism or conditions like deep vein thrombosis, while seeming to be similar to those described for other types of vaccines, although further studies may be useful on this topic [42]; furthermore, as far as for other viral infections, immune thrombocytopenia may be a consequence of infection by SARS-CoV-2 [43] and this condition should always be first taken into account to confirm or disconfirm a diagnosis of VITT/VIPIT.…”