Expert opinion on antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia
Expert opinion on antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia
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On July 7, 2021 at 17:00 Taipei time, the international journal Nature published a new study on the COVID-19 vaccines and their possible mechanism of thrombosis. Heparin, a commonly used antithrombotic drug, was previously known to cause platelet drop and thrombosis (Heparin-Induced Thrombocytopenia, HIT). This study analysed five patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT), who were on average 44 years old and had received a single dose of the AstraZeneca vaccine. The study found that antibodies and heparin in the sera of these patients both bound to similar sites of platelet factor 4 (PF4). The antibodies from the VITT patients bound PF4 more strongly than those from the 10 HIT patients. It is hypothesised that the combination of PF4 and the antibodies of VITT patients may activate platelets through specific receptors and initiate clotting mechanism, similar to the mechanism caused by heparin. The Emerging Technology Media Centre invited an expert to comment on the findings of this study.
On July 7, 2021 at 17:00 Taipei time, the international journal Nature published a new study on the COVID-19 vaccines and their possible mechanism of thrombosis. Heparin, a commonly used antithrombotic drug, was previously known to cause platelet drop and thrombosis (Heparin-Induced Thrombocytopenia, HIT). This study analysed five patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT), who were on average 44 years old and had received a single dose of the AstraZeneca vaccine. The study found that antibodies and heparin in the sera of these patients both bound to similar sites of platelet factor 4 (PF4). The antibodies from the VITT patients bound PF4 more strongly than those from the 10 HIT patients. It is hypothesised that the combination of PF4 and the antibodies of VITT patients may activate platelets through specific receptors and initiate clotting mechanism, similar to the mechanism caused by heparin. The Emerging Technology Media Centre invited an expert to comment on the findings of this study.
Publication
What our experts say
Context and background
Resources
Resources
1. Huynh, A. et al. (2021)“Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia.”Nature.
Resources
1. Huynh, A. et al. (2021)“Antibody epitopes in vaccine-induced immune thrombotic thrombocytopenia.”Nature.
Expert Comments:
Nan-Chang Chiu
This study reaffirms that AstraZeneca vaccine-induced thrombosis is similar to HIT and is different in causes from other thrombosis. Previous studies have found that a high proportion of these patients who developed HIT after AstraZeneca vaccination were found to have rare anti-PF4 antibodies. [1-3] This study goes further and identifies that the anti-PF4 antibodies and heparin in these patients bind to the platelets at the same sites. The anti-PF4 antibodies generated after vaccination in these individuals with particular anatomies bind to platelets, resulting in clotting, decreased platelets and vascular embolism. Although there may be other factors that contribute to thrombosis, several recent studies indicate that anti-PF4 antibodies should be the most important factor.
The two important conclusions are:
(1) These antibodies do not occur in everybody but only in people with particular anatomies. The chances are low, as recent statistics suggest that the most worrying incidence of venous sinus thrombosis in the brain is about 3 to 5 per million, [4-5] so there is no cause for concern.
(2) Unlike this response mechanism, people at risk of thrombosis from other causes can still receive the AstraZeneca vaccine without an increased incidence of thrombosis. For people who are taking medication to prevent thrombosis, they should not stop taking medication when receiving the AstraZeneca vaccine as this could increase the risk of thrombosis.
If doctors know the causes of the disease, they can provide the appropriate treatment and therefore reduce the risk of death for the patient. In fact, when doctors know the causes and provide the correct treatment to patients, the mortality rate of such patients has been reduced by almost half.
- Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. Published online April 9, 2021. doi:10.1056/NEJMoa2104840PubMedGoogle Scholar
- Schultz NH, Sørvoll IH, Michelsen AE, et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med. Published online April 9, 2021. doi:10.1056/NEJMoa2104882PubMedGoogle Scholar
- Scully M, Singh D, Lown R, et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCov-19 vaccination. N Engl J Med. Published online April 16, 2021. doi:10.1056/NEJMoa2105385PubMedGoogle Scholar
- Public Health England. Blood clotting following COVID-19 vaccination - Information for health professionals. Published 7 April 2021. Public Health England gateway number: 2021217.
- Bikdeli B, Chatterjee S, Arora S, et al. Cerebral Venous Sinus Thrombosis in the US Population, After Adenovirus-Based SARS-CoV-2 Vaccination, and After COVID-19. J Am Coll Cardiol 2021;Jun 8:[Epub ahead of print].
