Public Health Watch: Pinpointing Threat of Vaccine-Induced Immune Thrombotic Thrombocytopenia

Concern over potentially serious adverse events have been among the many factors behind a downturn in vaccination rates in many parts of the world, including the United States.

In Europe, the driving force behind much of this vaccine hesitancy has been links between the ChAdOx1 nCov-19 (the AstraZeneca/Oxford vaccine) and the Ad26.COV2.S (Janssen/Johnson & Johnson) vaccines and the development of cerebral venous thrombosis (CVT), particularly in younger adults. Unfortunately, a study published July 2nd by JAMA Network Open appears to only confirm these links, while acknowledging that these are rare events.

“This study shows that prior to the COVID-19 pandemic severe thrombocytopenia and heparin-induced thrombocytopenia (HIT) were very rare in patients with cerebral venous thrombosis [and] this is important, because it indicates that the cases of CVT with thrombocyotopenia that we are now seeing in rare occasions after vaccination with the AstraZeneca and J&J COVID vaccines are unlikely to be ‘normal cases,’” study co-author Jonathan Coutinho, MD, PhD, a neurologist at Amsterdam University Medical Centers in The Netherlands, told Contagion. “While our study does not provide direct evidence for a relationship between the vaccines and these CVT cases, it does make it much more likely.”

Of course, several countries in Europe at times briefly halted distribution of both vaccines in the spring, before later restricting them for use, at least for a time, in older adults. Now, though, there seems to be a general recognition that the risks posed by COVID-19, particularly as the Delta variant continues to spread, are more serious than those associated with vaccine-related adverse events.

However, as Coutinho and his colleagues demonstrate, that does not mean that these adverse events are not significant.

For this study, the researchers analyzed data on 865 patients (median age, 40 years) 73 of whom had mild (n=52; 100-149 ×103/μL), moderate (n=17; 50-99 ×103/μL), or severe (n=4; <50 ×103/μL) thrombocytopenia prior to the COVID-19 pandemic, and many of these cases could be explained by comorbidities, such as cancer or infection, or by their use of alcohol and certain medications. HIT with platelet factor 4/heparin antibodies was diagnosed in 1 participant. Among the participants in the convenience sample, 93 had cerebral venous sinus thrombosis (CVST), of which 8 (9%) had thrombocytopenia and none had platelet factor 4/heparin antibodies.

Meanwhile, earlier studies suggest that the incidence of vaccine-induced immune thrombotic thrombocytopenia (VITT) with the Oxford/AstraZeneca shot may be 1 in 26,000 recipients, and 1 in 533,000 recipients with the J&J shot. To date, there have been no cases of vaccine-induced immune thrombotic thrombocytopenia linked with either of the 2-dose shots from Pfizer/BioNTech and Moderna.

“There are a lot of questions regarding VITT that remain unanswered,” Coutinho said. “[Researchers] have provided important insights into the pathophysiology of VITT, but we still know very little about the clinical manifestations of the disease. Also, we have limited data on the prognosis. The mortality appeared to be high in first reports, but these were only small case series. The absolute risk of VITT after vaccination, especially within subgroups is also poorly known. Finally, now that we have treatment recommendations for VITT, it would be important to study if prognosis has improved.”

As with many issues concerning the COVID-19 pandemic, these and other questions remain unanswered.