Thrombotic thrombocytopenia associated with COVID-19 infection or vaccination: Possible paths to platelet factor 4 autoimmunity

Goldman, Michel; Hermans, Cédric

doi:10.1371/journal.pmed.1003648

Cited by 47 publications

(50 citation statements)

References 59 publications

(71 reference statements)

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“…Гамалеи»), использующие в качестве вектора аденовирус человека. Недавно появились данные о вероятном развитии после вакцинации ChAdOx1 nCoV-19 тяжелой тромботической тромбоцитопении с необычной локализацией тромбозов, затрагивающих мозговые вены, а также вены кишечника и печени, легочной эмболии, артериального тромбоза, напоминающей иммуноопосредованную гепарин-индуцированную тромбоцитопению [170][171][172][173]. Примечательно, что патогенез этого осложнения связан с аутоиммунными нарушениями, проявляющимися синтезом антител к тромбоцитарному фактору 4.…”

Section: Discussionunclassified

Coronavirus Disease 2019 (COVID-19) and Immune-mediated Rheumatic Diseases. Recommendations of the Association of Rheumatologists of Russia

Насонов

Лила

Мазуров

et al. 2021

Naučno-praktičeskaâ revmatologiâ

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In mid-2021, the SARS-CoV-2 (Severe Acute Respiratory coronavirus 2) infection, which caused the coronavirus disease (COVID-19) pandemic, affected more than 157 million people in all regions of the world and led to more than 3.2 million deaths. It is assumed that elderly age, uncontrolled inflammation, anti-inflammatory therapy, comorbid pathology, genetic and other factors can potentially lead to an increase in “sensitivity” to viral and bacterial infections, including SARS-CoV-2. The new version of the recommendations of the Association of Rheumatologists of Russia formulates the main provisions concerning the tactics of managing patients with Immune-mediated Rheumatic Diseases during the ongoing COVID-19 pandemic.

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Section: Discussionunclassified

Coronavirus Disease 2019 (COVID-19) and Immune-mediated Rheumatic Diseases. Recommendations of the Association of Rheumatologists of Russia

Насонов

Лила

Мазуров

et al. 2021

Naučno-praktičeskaâ revmatologiâ

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show abstract

“…Generally, the activation of platelets is known to result in increased release of PF4. As adenoviruses are known to activate platelets, it would be plausible that the replication-deficient adenoviral vector could be directly responsible for the release of platelet-derived PF4, which as highly positively charged PF4 tetramers can bind to negatively charged glycosaminoglycan structures on endothelial cells [ 120 ]. This implies the release of significant amounts of vaccine particles into the bloodstream, which is what would happen in cases of inappropriate administration, with damage or injection into small blood vessels.…”

Section: The Impact Of the Adenoviral Vectormentioning

confidence: 99%

Coagulopathies after Vaccination against SARS-CoV-2 May Be Derived from a Combined Effect of SARS-CoV-2 Spike Protein and Adenovirus Vector-Triggered Signaling Pathways

Kircheis¹

2021

IJMS

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Novel coronavirus SARS-CoV-2 has resulted in a global pandemic with worldwide 6-digit infection rates and thousands of death tolls daily. Enormous efforts are undertaken to achieve high coverage of immunization to reach herd immunity in order to stop the spread of SARS-CoV-2 infection. Several SARS-CoV-2 vaccines based on mRNA, viral vectors, or inactivated SARS-CoV-2 virus have been approved and are being applied worldwide. However, the recent increased numbers of normally very rare types of thromboses associated with thrombocytopenia have been reported, particularly in the context of the adenoviral vector vaccine ChAdOx1 nCoV-19 from Astra Zeneca. The statistical prevalence of these side effects seems to correlate with this particular vaccine type, i.e., adenoviral vector-based vaccines, but the exact molecular mechanisms are still not clear. The present review summarizes current data and hypotheses for molecular and cellular mechanisms into one integrated hypothesis indicating that coagulopathies, including thromboses, thrombocytopenia, and other related side effects, are correlated to an interplay of the two components in the vaccine, i.e., the spike antigen and the adenoviral vector, with the innate and immune systems, which under certain circumstances can imitate the picture of a limited COVID-19 pathological picture.

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“…A role for the complement system and cytokines also merits consideration [ 166 – 168 ]. Theories of pathogenesis abound [ 102 , 169 , 170 ]. These events and many similar published are intriguing but do not guarantee a mechanism understood for post-vaccination thrombosis.…”

Section: Thrombotic Events and Covid-19 Vaccinationmentioning

confidence: 99%

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

Cimolai

2021

SN Compr. Clin. Med.

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Advanced SARS-CoV-2 infections not uncommonly associate with the occurrence of silent or manifest thrombotic events which may be found as focal or systemic disease. Given the potential complexity of COVID-19 illnesses, a multifactorial causation is likely, but several studies have focused on infection-induced coagulopathy. Procoagulant states are commonly found in association with the finding of antiphospholipid antibodies. The correlation of the latter with thrombosis and/or clinical severity remains controversial. Although measures of antiphospholipid antibodies most commonly include assessments for lupus anticoagulant, anticardiolipin, and anti-ß2-glycoprotein-I antibodies, lesser common antibodies have been detected, and there remains speculation that other yet undiscovered autoimmune thrombotic events may yet be found. The recent discovery of post-vaccination thromboses associated with platelet factor 4 antibody has created another level of concern. The pathogenesis of antiphospholipid antibodies and their role in COVID-19-related thrombosis deserves further attention. The multifactorial nature of thrombosis associated with both infection and vaccination should continue to be studied as new events unfold. Even if a cause-and-effect relationship is variable at best, such dedicated research is likely to generate other valuable insights that are applicable to medicine generally.

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Thrombotic thrombocytopenia associated with COVID-19 infection or vaccination: Possible paths to platelet factor 4 autoimmunity

Abstract: Michel Goldman and Cédric Hermans discuss thrombotic mechanisms in COVID-19 and rare adverse reactions to SARS-CoV-2 vaccinations.

Cited by 47 publications

References 59 publications

Coronavirus Disease 2019 (COVID-19) and Immune-mediated Rheumatic Diseases. Recommendations of the Association of Rheumatologists of Russia

Coronavirus Disease 2019 (COVID-19) and Immune-mediated Rheumatic Diseases. Recommendations of the Association of Rheumatologists of Russia

Coagulopathies after Vaccination against SARS-CoV-2 May Be Derived from a Combined Effect of SARS-CoV-2 Spike Protein and Adenovirus Vector-Triggered Signaling Pathways

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

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