Recurrence of Thrombotic Thrombocytopenic Purpura after mRNA-1273 COVID-19 Vaccine Administered Shortly after COVID-19

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening consumptive coagulopathy requiring emergent diagnosis and timely treatment. It is characterized by microangiopathic hemolytic anemia and thrombocytopenia with the development of microthrombi caused by inherited or acquired deficiency of the von Willebrand factor-cleaving protease ADAMTS13 and resulting end-organ damage. Most of the cases are the result of acquired deficiency of ADAMTS13, for which the exact etiology is unknown but reported to be related to various autoimmune disorders, infections, and medications. Our case report features of a patient with a history of idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura, who developed a recurrence of TTP 5 days after his first dose of the mRNA Coronavirus disease 2019 (COVID-19) vaccine (mRNA-1273 vaccine) in the setting of recent COVID-19. The close temporal association between vaccine administration, recent COVID-19, and relapse of remitted TTP raises concern for an enhanced immune reaction to COVID-19 vaccine in the setting of recent COVID-19 and underlying autoimmune disease. The association is not absolute, but given the novelty of COVID-19 and the mRNA COVID-19 vaccine and the relapse timing, it leads us to pose this hypothesis. Vaccine distribution to a larger and more diverse population will allow for an increased rate of adverse event reporting. This case report exemplifies potential safety issues that may be encountered with new vaccine administration in patients with recent COVID-19 and underlying autoimmune disease. There are no specific recommendations for COVID-19 vaccine administration in such patients.

Emerging Concepts in Immune Thrombotic Thrombocytopenic Purpura

“…Globally, during the last 50 years only a few cases of TTP have been documented for influenza vaccines (Table 3) (139), even though 3100 million seasonal influenza vaccine doses have been administered in the United States of America alone since 1980 (140). A similar remark can be made of COVID vaccines, where, at the time of writing, only 2 cases of relapsing iTTP (134,135) and 8 de novo iTTP cases (136)(137)(138)141) were identified, among many millions of doses administered currently in the world. In this context, it is important not to confuse iTTP with vaccineinduced thrombotic thrombocytopenia (VITT), which has different mechanisms compared to iTTP (142,143).…”

SARS-CoV-2 vaccination and immune thrombotic thrombocytopenic purpura

“…These concerns were further compounded by reports of de novo and relapsed iTTP following mRNA vaccines. [6][7][8][9][10] Whether SARS CoV-2 vaccination is associated with iTTP recurrence has significant clinical implications; however, this has not been systematically investigated. We conducted a multicenter retrospective cohort study to evaluate the safety of SARS-CoV2 vaccination in patients with pre-existing iTTP.…”

“…While the temporal relationship of several cases occurring within a month of vaccination is concerning for an association, the estimated incidence is not higher than the incidence of iTTP in the United States (1.7 to 3.7 per million). 15,16 De novo and relapsed iTTP have been reported after various vaccines [17][18][19] , including SARS-CoV-2 vaccines [6][7][8][9][10] , where the association is supported by absence of another proximate cause and a temporal relationship with most cases occurring between 5 -15 days after vaccination. Most cases of iTTP following COVID-19 vaccination in VAERS occurred within 14 days after vaccination, which is concerning for a possible association.…”

Peptide Nanoarray Scaffold Vaccine for SARS-COV-2 and Its Variants of Concerns

“…The ongoing SARS-CoV-2 and its variants of concerns (VOCs) pandemic has demonstrated the need for vaccine technologies capable of ensuring rapid and e cient response to novel pathogens. Current vaccines for SARS-CoV-2 are extremely effective [1][2][3][4][5] , but their in ammatory nature limits the use in individuals with immune disorders [6][7][8][9][10][11][12] . Moreover, herd immunity towards novel pathogens has proven unreliable and di cult to achieve, leaving immunocompromised individuals at risk 13,14 .…”