Persistence of Anti-PF4 levels in VITT patients four months after AstraZeneca COVID-19 vaccine

In March 2020, the World Health Organization declared the rapid spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. This ongoing pandemic is popularly known as coronavirus disease 2019 (COVID-19). Several COVID-19 vaccines have received emergency use authorization (EUA) from various global regulatory bodies.

One of the approved vaccines used globally is the ChAdOx1nCoV-19 (AZD1222) by Oxford-AstraZeneca. In many countries worldwide, vaccination programs have commenced, and vulnerable groups such as older adults and front-line workers prioritize vaccination.

Study: Anti-PF4 levels of patients with VITT do not reduce 4 months following AZD1222 vaccination. Image Credit: vipman/ ShutterstockStudy: Anti-PF4 levels of patients with VITT do not reduce 4 months following AZD1222 vaccination. Image Credit: vipman/ Shutterstock

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Background

What is vaccine-induced thrombocytopenia and thrombosis?

In April 2021, researchers reported a new syndrome called vaccine-induced thrombocytopenia and thrombosis (VITT), closely resembling Heparin-Induced Thrombocytopenia (HIT). In most cases, this syndrome resulted in 4-30 days post-vaccination with AZD1222. However, in fewer instances, VITT occurred following the Johnson and Johnson vaccine (Ad26.COV2.S).

Previous studies that analyzed serum from these vaccinated individuals reported Anti-Platelet Factor 4 (PF4) IgG antibodies that activate platelets through FcγRIIa, which are an important factor behind the pathophysiology of VITT. In these patients’ activation of platelets occurred through the low-affinity FcγRIIa receptor.

One of the problems associated with mRNA vaccines is storage and transportation at a particular temperature. However, such problems are absent in adenoviral vector vaccines, available at a relatively low cost. Thus, adenoviral vector vaccines have an important role in global vaccination. Therefore, it is important to understand VITT to enable mass vaccination with adenoviral vector vaccines, such as AZD1222.

Treatments for VITT

Scientists have rapidly identified many new treatment modalities for VITT. The first line of treatment includes non-heparin anticoagulants, corticosteroids, thrombectomy, and intravenous immunoglobulin (IVIg). If a patient fails to respond to these treatments, Plasma Exchange (PEX) and the anti-CD20 monoclonal antibody rituximab could be used.

Although several treatment options are available, the mortality rate associated with VITT remains between 20-50%. Scientists have observed that VITT patients, who positively respond to the treatments, tend to do so quickly and are discharged on non-heparin anticoagulation.

There are many unknown factors associated with VITT, such as its medium to long-term prognosis and treatment. A new study published on the medRxiv* preprint server focused on clinical course, laboratory results, and anti-PF4 antibody levels of seven patients with VITT. Researchers followed up with these patients after three months following their triggering vaccination. They reported the over-time changes in the ability of the serum to activate platelets (VTT patients’ as well as those from healthy donors) in vitro.

A new study

In this study, researchers evaluated the anti-PF4/heparin antibodies using an anti-PF4/heparin enzymatic immunoassay. Further, flow cytometry was used to assess the FcγRIIa levels on patient platelets. The responsiveness of the platelets (both from patients’ and healthy donors) was analyzed, in the presence and absence of PF4, using Light Transmission Aggregometry.

All patients were discharged on direct oral anticoagulants. While two patients remained symptom-free, two had neurological deficits, and three had ongoing headaches. Two patients had to be re-treated for mild thrombocytopenia and headache, and one had to be treated with Rituximab. Except for this patient, all others had comparable anti-PF4 antibody titers.

Platelets at follow-up did not have abnormalities in the levels of FcγRIIa and responses to thrombin and collagen-related-peptide. Scientists observed that serum from the follow-up was much weaker at stimulating platelets, even in the presence of PF4. The D-dimers and fibrinogen levels were also normal, which is expected given the use of anticoagulants.

Researchers observed differences in patient serum that are not apparent, despite similar PF4 antibody titers at diagnosis and during follow-up. These differences result in lower levels of platelet activation during the follow-up period. It is crucial to understand these differentiating factors better to assess the duration of anticoagulation in these patients.

Conclusion

Researchers hypothesize that the reduction in PF4 levels in patients over time may be brought about by the ongoing use of anticoagulants or by the consumption of high-affinity PF4 antibodies. Scientists observed that serum samples could activate platelets in the presence of PF4, which is alarming as it implies that any event that causes the release of PF4 can potentially cause a relapse of thrombocytopenia. Equally, Rituximab may well be the appropriate treatment. Scientists believe that more research still needs to be conducted before recommendations about the medium or long-term treatments can be made.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • Apr 11 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Bose, Priyom. (2023, April 11). Persistence of Anti-PF4 levels in VITT patients four months after AstraZeneca COVID-19 vaccine. News-Medical. Retrieved on June 17, 2024 from https://www.news-medical.net/news/20210825/Persistence-of-Anti-PF4-levels-in-VITT-patients-four-months-after-AstraZeneca-COVID-19-vaccine.aspx.

  • MLA

    Bose, Priyom. "Persistence of Anti-PF4 levels in VITT patients four months after AstraZeneca COVID-19 vaccine". News-Medical. 17 June 2024. <https://www.news-medical.net/news/20210825/Persistence-of-Anti-PF4-levels-in-VITT-patients-four-months-after-AstraZeneca-COVID-19-vaccine.aspx>.

  • Chicago

    Bose, Priyom. "Persistence of Anti-PF4 levels in VITT patients four months after AstraZeneca COVID-19 vaccine". News-Medical. https://www.news-medical.net/news/20210825/Persistence-of-Anti-PF4-levels-in-VITT-patients-four-months-after-AstraZeneca-COVID-19-vaccine.aspx. (accessed June 17, 2024).

  • Harvard

    Bose, Priyom. 2023. Persistence of Anti-PF4 levels in VITT patients four months after AstraZeneca COVID-19 vaccine. News-Medical, viewed 17 June 2024, https://www.news-medical.net/news/20210825/Persistence-of-Anti-PF4-levels-in-VITT-patients-four-months-after-AstraZeneca-COVID-19-vaccine.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Study finds short-term side effects of COVID-19 mRNA vaccines boost long-term antibody response