Coronavirus (COVID-19) Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause significant morbidity and mortality worldwide, with many nations enduring multiple outbreaks of this viral illness. Besides the importance of infection control measures to prevent or decrease the transmission of SARS-CoV-2, the most crucial step to contain this global pandemic is to vaccinate individuals to prevent SARS-CoV-2 infection in communities across the world. Many vaccines have been developed at an unprecedented speed using distinctive technologies to prevent COVID-19. Vaccination triggers the immune system resulting in the production of neutralizing antibodies against SARS-CoV-2. Four vaccines, namely the BNT162b2, mRNA-1273, Ad26.COV2.S, and ChAdOx1 nCoV-19 have been approved to prevent COVID-19 in many nations worldwide, including the United States. The BNT162b2, mRNA-1273 have been approved by the U.S. FDA and the Ad26.COV2.S has received Emergency Use Authorization. One exception is the ChAdOx1 nCoV-19 vaccine, which has not yet received a EUA or approval from the U.S. Food and Drug Administration (FDA) for use in the U.S. The BNT162b2 and mRNA-1273 vaccines are both mRNA-based, while the Ad26.COV2. S and ChAdOx1 nCoV-19 vaccines incorporate replication-incompetent adenoviral vectors in them.

In late February 2021, a new clinical syndrome characterized by thrombosis at atypical sites combined with thrombocytopenia was observed in multiple patients days after vaccination with the ChAdOx1 nCoV-19 vaccine. In April 2021, similar clinical sequelae were reported in patients after vaccination with the Ad26.COV2. S vaccine. Preceding the approval of these vaccines, the clinical constellation of this new syndrome was not observed in clinical trials of the ChAdOx1 nCoV-19 vaccine, and a single case was observed in the Ad26.COV2. S vaccine trial recipient. Furthermore, the incidence of major adverse effects has remained exceptionally low following the vaccination of more than 400 million people worldwide. This novel clinical syndrome demonstrated striking similarities to heparin-induced thrombocytopenia; however, in the absence of prior heparin exposure was named vaccine-induced immune thrombotic thrombocytopenia (VITT). It is also known as vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) in some European nations and Canada. Conversely, in millions of doses of BNT162b2 or mRNA-1273 vaccines administered so far, this clinical syndrome has not been reported. Due to the concern of VITT associated with the Ad26.COV2. S vaccine, the FDA modified the EUA and recommends limiting the use of this vaccine only to individuals > 18 years of age who are otherwise ineligible to receive any other FDA-approved vaccines due to anaphylaxis to mRNA vaccines or its components or are unable/unwilling to receive any other vaccine.

Per the American Society of Hematology, vaccine-induced immune thrombotic thrombocytopenia (VITT) is defined as a clinical syndrome characterized by all of the below described abnormal laboratory and radiologic abnormalities occurring in individuals 4 to 42 days after vaccination with Ad26.COV2. S or ChAdOx1 nCoV-19 vaccines.

1. Development of thrombosis at uncommon sites includes cerebral venous sinus thrombosis (CSVT)/splanchnic venous thrombosis

2. Mild to severe thrombocytopenia. However, a normal platelet count does not exclude the possibility of this syndrome in its early stages

3. Positive antibodies against platelet factor 4(PF4) identified by enzyme-linked immunosorbent assay (ELISA) assay

4. Significantly elevated D-dimer ( > 4 times ULN)

This review article aims to describe the etiology, epidemiology, pathophysiology, clinical features, diagnosis, and management of COVID-19 vaccine-induced thrombotic immune thrombocytopenia based on the latest available published literature.