Presentation Details
Impact of mRNA COVID-19 Vaccination on D-Dimer Levels and Anti-PF4 Seroconversion in Healthy Adults: A systematic review

Evan Y Maroun M.S., Megan Centrella, Grace Hansen, Trevor Forsberg, Tariq Rahaman M.L.I.S., Hoang Nguyen M.D.Ph.D..

Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, FL, USA

Abstract


Introduction: Vaccination complications have recently increased due to the novel world-wide administration of COVID-19 vaccinations since 2020. Considering the United States has paused Johnson & Johnson vaccine’s administration, this paper aimed to analyze the coagulative effects of mRNA vaccinations (Pfizer-BioNTech and Moderna). Numerous research studies have explored the association of AstraZeneca and Johnson & Johnson vaccines with thromboembolic and coagulative events post-administration, however, few have studied the complications, or lack thereof, after receiving mRNA vaccines1,2. Objective: Two outcomes of interest explored were D-dimer levels as well as positive serology of anti-platelet factor 4 (anti-PF4) antibodies after healthy participants received COVID-19 mRNA vaccination as compared to prior the administration of vaccination. Methods: A search conducted across multiple databases, shown in the PRISMA diagram, included keywords relating COVID-19 vaccination with measured D-dimer levels or anti-PF4. After extraction, abstracts were de-duplicated and blindly screened according to pre-defined inclusion/exclusion criteria using Rayyan platform. D-dimer levels were compared with established normal value of less than 0.5 mg/L, while positive serology for anti-PF4 post-vaccination percentage increases were analyzed. Initial database searches yielded 2007 articles which were de-duplicated to 1240. Further abstract screening and full-text analysis narrowed the search to 6 papers which included healthy participants with no predisposing autoimmune diseases or underlying complications, no COVID-19 infection within the past 3 months, as well as collected blood samples prior to COVID-19 vaccination. Results: Among 471 subjects analyzed for positive anti-PF4 serology, 10 (2.12%) tested positive post-vaccination. These antibodies remained stable post-vaccination with no adverse complications reported in all studies analyzed. Chi-square test revealed a statistically insignificant chi-square of 1.88 with p-value > 0.05. Out of 278 participants tested for D-dimer levels, there was an 8.00% total increase between mean D-dimer levels of pre-vaccination (0.25 mg/L [95% CI 0.238-0.265]) and post-vaccination (0.27 mg/L [95% CI 0.254-0.289]). A paired sample t-test was conducted to analyze means of difference between before and after vaccination, yielding a p-value > 0.05 with an effect size of 0.12. These tests show no significance of association in both frequency of anti-PF4 seroconversion and d-dimer elevation post-vaccination with mRNA COVID-19 vaccine. There was no significance associated with either one or two doses administered to participants, as well as absence of thromboembolic events within the time periods followed (up to 57 days, median follow-up of 15 days). Conclusions: The results of this systematic review are two-fold. First, there is no large population analyzed for D-dimer levels or anti-PF4 seroconversion post-vaccination, excluding recently infected COVID-19 participants or any underlying condition that may exponentiate these levels. Second, based on the study data included in this review, mRNA vaccines were not found to be associated with significant increases in D-dimer levels relative to 0.5 mg/L. Moreover, there is a minor anti-PF4 seroconversion rate post-vaccination, which remaining stable even after another dose, which resulted in no further complications during the follow-up period. These results support the continued administration of both Pfizer-BioNTech and Moderna vaccines to the public for COVID-19 infection preventative measures.

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