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SARS-CoV-2 Vaccination Not Associated With a First Episode of Thrombotic Thrombocytopenia Purpura

May 31, 2022

June 2022

Vaccination against SARS-CoV-2 does not appear to increase the risk of de novo immune thrombotic thrombocytopenic purpura (iTTP), according to a report published in Blood.1 The large, multicenter, retrospective study also showed that SARS-CoV-2 vaccination does not trigger relapse in patients with TTP, particularly if patients are monitored regularly and do not have low ADAMTS13 enzyme activity.

A study from France that was published in parallel in Blood also showed that SARS-CoV-2 vaccination does not have a causal relationship with iTTP.2

“The French results increase the confidence in our findings,” said Shruti Chaturvedi, MBBS, MS, associate professor of medicine and a hematologist at Johns Hopkins University in Baltimore, Maryland. “The bottom line [from our study and the French study] is that the benefits of vaccination likely far outweigh the risks in most individuals.”

To understand whether SARS-CoV-2 vaccination poses a risk of TTP incidence in certain individuals or whether patients with iTTP may be at risk of exacerbation of their disease, the authors tracked 79 patients with iTTP who received a SARS-CoV-2 vaccination. They also tapped into the U.S.’s passive surveillance system for adverse events following immunization, called the Vaccine Adverse Event Reporting System (VAERS), to search for individual reports consistent with iTTP.

Among the 79 patients with iTTP, the researchers looked for relapse, defined as a platelet count of less than 150×109/L and microangiopathic hemolysis with activity of the ADAMTS13 enzyme of less than 10% occurring within four weeks of immunization. Most patients received the Pfizer vaccine (n=47), while 27 received Moderna and five received Johnson & Johnson. Relapse within four weeks of vaccination occurred in one 28-year-old female patient who had an episode six days after her first dose. She was successfully treated and received her second vaccine dose uneventfully. Three additional patients had relapses between 35 and 143 days after vaccination.

Within the VAERS database, there were 37 cases of TTP after SARS-CoV-2 vaccination, of which 16 were confirmed iTTP and the remaining were probable and possible cases. Five cases were recurrences in patients with a prior history of iTTP. Eighteen cases (48%) occurred following the second vaccine dose. The calculated incidence rate of iTTP post-full vaccination was 0.195/million. While there were some cases of iTTP within a month of vaccination, the estimated incidence was not higher than the incidence of iTTP in the U.S. The France-based study also found that the incidence of iTTP after SARS-CoV-2 vaccination was not higher than the baseline incidence in France.

The researchers also observed that the only iTTP relapses that occurred in their study cohort were among those individuals with low (less than 20%) or unknown ADAMTS13 activity levels within three months prior to vaccination.

“While TTP relapse was rare, it is patients with low ADAMTS13 activity at the time of vaccination who may be at risk of a TTP recurrence after vaccination, or after any inflammatory stimulus. Relapse risk is minimal when ADAMTS13 activity is greater than 20%,” Dr. Chaturvedi explained.

Limitations of the study included the inconsistent documentation of vaccine-associated adverse events beyond acute iTTP in the medical record. Limitations with VAERS include that it is a passive surveillance system and so iTTP after vaccination may be underreported, and some cases have limited clinical and laboratory information (including ADAMTS13).

Dr. Chaturvedi and her colleagues recommended that patients with iTTP in remission be monitored with blood counts and ADAMTS13 activity every three months. Patients with ADAMTS13 activity lower than 20% should have their complete blood count checked weekly for about four weeks after vaccination, she told ASH Clinical News. Alternatively, clinicians should also discuss the risks versus benefits of delaying vaccination to allow time for preemptive rituximab therapy, although this is likely to impair response to vaccines.

“These results provide timely and important data for practicing hematologists to have informed discussions regarding vaccination with their patients with TTP who may have concerns regarding the risk of relapse,” Dr. Chaturvedi said. Still, these study conclusions need to be validated with larger cohorts.

Any conflicts of interest declared by the authors can be found in the original articles.

References

1. Shah H, Kim AS, Sukumar S, et al. SARS-CoV-2 vaccination and immune thrombotic thrombocytopenic purpura [published online ahead of print, 2022 Mar 8]. Blood. doi: 10.1182/blood.2022015545.

2. Picod A, Rebibou J-M, Dossier A, et al. Immune-mediated thrombotic thrombocytopenic purpura following COVID-19 vaccination [published online ahead of print, 2022 Mar 10]. doi: 10.1182/blood.2021015149.

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