Vaccine-induced immune thrombotic thrombocytopenia (VITT), a potentially fatal syndrome characterized by aggressive thrombosis, has recently been linked to two adenovirus vector coronavirus disease 2019 (COVID-19) vaccines. In a paper published in Seminars in Hematology, Menaka Pai, MD, of McMaster University in Ontario, Canada, described the epidemiology of VITT and discussed the vaccines implicated in the development of the condition.
The two COVID-19 vaccines associated with VITT are ChAdOx1 nCoV-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson/Janssen). No cases of VITT have been reported after the mRNA-based BNT162b2 (Pfizer-BioNTech) vaccine or the protein-based NVX-CoV2373 (Novavax) vaccine.
One case of thrombosis and thrombocytopenia was published with reference to the second dose of mRNA-1273 (Moderna). Additionally, the U.S. Vaccine Adverse Event Reporting System (VAERS) has a documented case of thrombosis with thrombocytopenia syndrome following the second dose of mRNA-1273.
Despite these reports, however, little investigation has been completed to confirm whether these cases after the mRNA-1273 vaccine were true cases of VITT. Dr. Pai cited investigators who suggested that these cases may represent background cases of spontaneous heparin-induced thrombocytopenia syndrome that are unrelated to prior vaccination.
In terms of incidence, published estimates for VITT risk are between 1/26,500 first administered doses of ChAdOx1 nCoV-19 in Norway to 1/127,300 first doses of the vaccine in Australia. Additional U.K. data suggest that the risk of VITT is estimated at 1/518,181 second administered doses of ChAdOx1 nCoV-19. A December 2021 report from the U.S. calculated the incidence of VITT at 1/263,000 administered doses of the Ad26.COV2.S vaccine.
Although risk factors for VITT have been postulated, true risk factors for the condition remain unclear. Female sex and younger age were initially identified as risk factors for VITT, which caused several regions to restrict use of adenoviral vector vaccines in these groups. Dr. Pai noted that these observations were likely “artefactual,” since health care professionals in many countries were prioritized in the initial rollout of ChAdOx1 nCoV-19, and the demographics of these professionals tend to skew toward younger women.
Available data show an association between VITT risk and younger age. For instance, data from the U.K. show a VITT risk of 1/100,000 for people older than age 50 after the first dose of ChAdOx1 nCoV-19. In contrast, the risk of VITT after the first dose of ChAdOx1 nCoV-19 rises to 1/50,000 for individuals younger than age 50. In addition, a U.K. VITT case series of 220 patients showed that 85% of affected individuals were younger than age 60.
While no large studies have compared individuals with VITT with the general population in terms of comorbidities, Dr. Pai described a case series that showed only a small percentage of patients had a history of previous venous thrombosis or a known prothrombotic disorder, while 41% of patients had no previous medical history.
“It is clear from these observations that an underlying history of thrombosis or medical comorbidity is not required to explain occurrence of VITT or associated thrombosis,” she wrote. “This supports the concept that VITT represents an independent, strongly prothrombotic hypercoagulability state.”
In addition, Dr. Pai noted that there appears to be no association between the formation of antibodies against the novel coronavirus and the formation of anti-PF4 antibodies. Studies also suggest that VITT antibodies do not cross-react with the spike protein on the severe acute respiratory syndrome coronavirus 2, suggesting that the intended generated immune response from the vaccine against the spike protein does not likely trigger VITT.
Dr. Pai concluded that although VITT is a rare adverse event related to vaccines, the morbidity and mortality associated with the condition “make it a serious entity that merits pharmacovigilance, and concerted efforts to raise health care professional and public awareness.”
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Pai M. Epidemiology of VITT [published online 2022 Feb 8]. Semin Hematol. doi: 10.1053/j.seminhematol.2022.02.002.
