{"id":798,"date":"2021-06-23T10:35:41","date_gmt":"2021-06-23T10:35:41","guid":{"rendered":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/?p=798"},"modified":"2021-06-23T10:35:41","modified_gmt":"2021-06-23T10:35:41","slug":"theories-behind-rare-blood-clots-related-to-covid-19-vaccines-karolina-bentkowska-2","status":"publish","type":"post","link":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/2021\/06\/23\/theories-behind-rare-blood-clots-related-to-covid-19-vaccines-karolina-bentkowska-2\/","title":{"rendered":"Theories behind rare blood clots related to\u00a0COVID-19\u00a0vaccines\u00a0– Karolina Bentkowska"},"content":{"rendered":"

\"\"<\/p>\n

AstraZeneca and Johnson\u00a0&\u00a0Johnson\u00a0are two amongst many vaccines which have been accepted\u00a0for immunisation\u00a0against SARS-CoV-2 (coronavirus)\u00a0\u2013\u00a0the\u00a0virus\u00a0causing the\u00a0COVID-19\u00a0pandemic. Despite passing\u00a0all clinical trials and being\u00a0approved for emergency use to halt the spread of coronavirus, these\u00a0vaccines have recently made headlines due to their possible link to rare\u00a0cases of blood clots, some of which were fatal.\u00a0When the correlation was first\u00a0suspected\u00a0for the AstraZeneca vaccine, many European countries\u00a0decided to\u00a0suspend its use\u00a0and wait for more information regarding its safety\u00a0(1). Similarly, in recent weeks,\u00a0the rollout of\u00a0the\u00a0Johnson\u00a0&\u00a0Johnson vaccine\u00a0was\u00a0also suspended\u00a0under the same suspicion.\u00a0After careful consideration, the European Medicines Association (EMA) have now concluded that blood clots should be listed as a very rare side effect of both\u00a0the\u00a0AstraZeneca and Johnson\u00a0&\u00a0Johnson vaccines\u00a0(2, 3).\u00a0As a result, many countries have\u00a0now\u00a0resumed vaccinations with AstraZeneca\u00a0(4)\u00a0and the same is expected for the Johnson\u00a0&\u00a0Johnson vaccine.<\/span>\u00a0<\/span><\/p>\n

What does\u00a0\u2018very\u00a0rare\u2019\u00a0really mean?<\/span><\/b>\u00a0<\/span><\/p>\n

As of\u00a07<\/span>th<\/span>\u00a0of April,\u00a0over 25\u00a0million doses of AstraZeneca vaccines\u00a0were\u00a0administered\u00a0and\u00a086\u00a0people who received it developed blood clots\u00a0(<0.0005%), 19 of which died\u00a0(5, 6). Considering Johnson\u00a0&\u00a0Johnson,\u00a0out of over 7 million\u00a0people who received it, 8 developed blood clots\u00a0(~0.0001%)\u00a0and 1 died (data from 21<\/span>st<\/span>\u00a0of April; 7).\u00a0These numbers, although\u00a0very small,\u00a0are slightly higher than seen in the\u00a0non-vaccinated population therefore\u00a0raising concerns. However, it is important to remember that the\u00a0risk of developing blood clots after receiving the vaccine\u00a0is\u00a0significantly lower than\u00a0when infected with coronavirus\u00a0(8).\u00a0<\/span>\u00a0<\/span><\/p>\n

What are\u00a0the mentioned \u2018blood clots\u2019?<\/span><\/b>\u00a0<\/span><\/p>\n

The blood clots that can be caused by one of the mentioned vaccines\u00a0are formally called cerebral venous sinus thrombosis (CVST) which\u00a0means\u00a0that\u00a0they form in large veins\u00a0in the brain. They can block\u00a0blood flow to the brain\u00a0and\u00a0hence reduce\u00a0oxygen supply\u00a0which can\u00a0lead to damage\u00a0of\u00a0the brain tissue. When this damage is severe it can affect the function of\u00a0the\u00a0central\u00a0nervous system and\u00a0can\u00a0potentially lead to death.\u00a0Fortunately, when identified early, many\u00a0blood clots can be treated preventing brain damage\u00a0and death.\u00a0To learn more about the\u00a0blood\u00a0clots and their symptoms, visit\u00a0<\/span>https:\/\/www.bbc.co.uk\/news\/health-56674796<\/span><\/a>\u00a0(6).\u00a0<\/span>\u00a0<\/span><\/p>\n

Possible causes<\/span><\/b>\u00a0<\/span><\/p>\n

Although\u00a0the\u00a0biological mechanism\u00a0linking\u00a0vaccines to blood clots is currently unknown,\u00a0scientists came up with several possible theories. It is important to note that these are not mutually exclusive and\u00a0can overlap or reinforce one another:<\/span>\u00a0<\/span><\/p>\n

    \n
  1. Antibodies Against Platelet Factor 4<\/span>\u00a0<\/span><\/li>\n<\/ol>\n

    The focus on platelets was triggered by the findings that many patients developing CVSTs had low platelet blood count.\u00a0This\u00a0might seem unintuitive\u00a0since platelets are the building blocks of blood clots.\u00a0However, this phenomenon\u00a0has\u00a0previously been\u00a0seen in some patients receiving a blood-thinning drug called heparin.\u00a0In those patients, heparin\u00a0forms\u00a0a complex with\u00a0a molecule called platelet factor 4, which is released by damaged platelets and\u00a0this complex\u00a0can\u00a0be mistaken\u00a0by the immune system for a pathogen. The\u00a0immune system will then react by attacking this complex\u00a0and can proceed onto attacking platelets themselves\u00a0which sometimes can lead to\u00a0formation of\u00a0clots. This\u00a0theory is supported by\u00a0studies finding\u00a0antibodies against\u00a0platelet factor 4 in\u00a0100% and 80% of\u00a0patients\u00a0who developed blood clots after receiving\u00a0the\u00a0AstraZeneca\u00a0or Johnson & Johnson\u00a0vaccine\u00a0respectively.\u00a0A lot remains to be confirmed and\u00a0further research should be done to determine whether these vaccines are the only ones causing this immune reaction\u00a0(9).<\/span>\u00a0<\/span><\/p>\n

      \n
    1. The Spike Protein<\/span><\/li>\n<\/ol>\n

      The\u00a0spike protein is\u00a0a protein\u00a0present on the surface of the virus and\u00a0is\u00a0used to infect cells. It\u00a0is also\u00a0involved in every currently available vaccine, highlighting it as a possible\u00a0culprit in blood clot formation. Some scientists suggested that\u00a0due to the structural similarity to\u00a0the mentioned platelet factor 4, the spike protein can\u00a0trigger the immune system to produce antibodies which might attack platelet factor 4\u00a0and\u00a0consequently\u00a0platelets. However, a study by\u00a0Greinacher\u00a0<\/span>et al.<\/span><\/i>\u00a0(10)\u00a0found that antibodies\u00a0against the platelet factor 4 do not bind to the spike protein and hence\u00a0contradict\u00a0this theory.\u00a0Other\u00a0explanations\u00a0include\u00a0the spike protein\u00a0directly\u00a0interacting\u00a0with platelets stimulating\u00a0them to produce\u00a0platelet factor 4;\u00a0or\u00a0damaging\u00a0blood vessels\u00a0and\u00a0releasing\u00a0molecules which can bind to platelet factor 4 turning\u00a0it into a target for the immune system.\u00a0Although plausible, these theories require a lot of further research\u00a0in order\u00a0to be confirmed\u00a0(9).<\/span>\u00a0<\/span><\/p>\n

        \n
      1. A problem with delivery<\/span><\/li>\n<\/ol>\n

        Both\u00a0the\u00a0AstraZeneca and Johnson & Johnson vaccines contain genetic material\u00a0for the spike protein delivered by an\u00a0adenovirus\u00a0vector.\u00a0While\u00a0adenoviruses are harmless to humans, some studies suggest that they can\u00a0stimulate\u00a0platelets to secret clotting molecules which increase the risk of clot formation. Additionally, there were some suspicions around the \u2018promoter\u2019 region used in the genetic\u00a0material of the AstraZeneca vaccine as it is derived from a gene\u00a0coding for a tissue\u00a0Plasminogen\u00a0Activator\u00a0(tPA)\u00a0which is involved in blood clotting.\u00a0However, this theory was largely disregarded as\u00a0the\u00a0genetic\u00a0fragment used does not\u00a0produce\u00a0tPA\u00a0and should not have any effect on blood clotting.\u00a0Nonetheless, these theories remain an important note in future further research\u00a0(9).<\/span>\u00a0<\/span><\/p>\n

          \n
        1. Other factors<\/span><\/li>\n<\/ol>\n

          Finally, some scientists urge not to\u00a0put all the blood clotting cases in one bag as there is no guarantee\u00a0there is\u00a0a single\u00a0common biological mechanism behind them.\u00a0There are multiple proteins and molecules involved\u00a0in blood clotting,\u00a0such as annexin A2 or fibrinogen,\u00a0which can be detected at altered\u00a0levels in\u00a0COVID-19\u00a0patients or people who received the vaccine.\u00a0This is supported by\u00a0a study involving a patient diagnosed with blood clots after receiving the AstraZeneca vaccine, who did not\u00a0have antibodies against the platelet factor 4 or its complexes\u00a0(9).\u00a0<\/span>\u00a0<\/span><\/p>\n

          While it is\u00a0important to understand the biological mechanism causing these rare blood clots,\u00a0we should remember that the risk of developing\u00a0them\u00a0is significantly lower in vaccinated people than in COVID-19 patients.\u00a0The key message remains\u00a0that vaccines are safe and\u00a0efficacious,\u00a0and they continue to save thousands of lives every day.<\/span>\u00a0<\/span><\/p>\n

          \u00a0<\/span><\/p>\n

          Further reading:<\/span><\/b>\u00a0<\/span><\/p>\n

          https:\/\/www.bbc.co.uk\/news\/health-56674796<\/span><\/a>\u00a0<\/span><\/p>\n

          https:\/\/www.theatlantic.com\/science\/archive\/2021\/04\/vaccine-related-blood-clot-mystery-must-be-solved\/618623\/?utm_source=Nature+Briefing&utm_campaign=81889634d4-briefing-dy-20210420&utm_medium=email&utm_term=0_c9dfd39373-81889634d4-46155150<\/span><\/a>\u00a0<\/span>\u00a0<\/span><\/p>\n

          All information is correct as of 24<\/span>th<\/span>\u00a0April 2021<\/span>\u00a0<\/span><\/p>\n

          References:<\/span><\/b>\u00a0<\/span><\/p>\n

            \n
          1. https:\/\/www.theguardian.com\/society\/2021\/mar\/15\/which-european-states-have-paused-astrazeneca-jabs-due-to-clotting-concerns<\/span><\/a>\u00a0<\/span><\/li>\n
          2. https:\/\/www.ema.europa.eu\/en\/news\/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood#:~:text=EMA’s%20safety%20committee%20(PRAC)%20has,COVID%2D19%20Vaccine%20AstraZeneca<\/span><\/a>\u00a0<\/span>\u00a0<\/span><\/li>\n
          3. https:\/\/www.bbc.co.uk\/news\/world-europe-56820970<\/span><\/a>\u00a0\u00a0<\/span>\u00a0<\/span><\/li>\n
          4. https:\/\/www.sciencemag.org\/news\/2021\/03\/european-countries-resume-use-astrazenecas-covid-19-vaccine-hoping-pause-has-not-dented<\/span><\/a>\u00a0<\/span>\u00a0<\/span><\/li>\n
          5. https:\/\/www.bbc.co.uk\/news\/world-europe-56820970<\/span><\/a>\u00a0\u00a0<\/span>\u00a0<\/span><\/li>\n
          6. https:\/\/www.bbc.co.uk\/news\/health-56674796<\/span><\/a>\u00a0<\/span><\/li>\n
          7. https:\/\/www.bbc.co.uk\/news\/world-europe-56820970<\/span><\/a>\u00a0<\/span><\/li>\n
          8. https:\/\/www.bbc.co.uk\/news\/health-56760163<\/span><\/a>\u00a0<\/span><\/li>\n
          9. https:\/\/www.theatlantic.com\/science\/archive\/2021\/04\/vaccine-related-blood-clot-mystery-must-be-solved\/618623\/?utm_source=Nature+Briefing&utm_campaign=81889634d4-briefing-dy-20210420&utm_medium=email&utm_term=0_c9dfd39373-81889634d4-46155150<\/span><\/a>\u00a0<\/span>\u00a0<\/span><\/li>\n
          10. https:\/\/www.researchsquare.com\/article\/rs-404769\/v1<\/span><\/a>\u00a0<\/span>\u00a0<\/span><\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

            AstraZeneca and Johnson\u00a0&\u00a0Johnson\u00a0are two amongst many vaccines which have been accepted\u00a0for immunisation\u00a0against SARS-CoV-2 (coronavirus)\u00a0\u2013\u00a0the\u00a0virus\u00a0causing the\u00a0COVID-19\u00a0pandemic. Despite passing\u00a0all clinical trials and being\u00a0approved for emergency use to halt the spread of coronavirus, these\u00a0vaccines have recently made headlines due to their possible link to rare\u00a0cases of blood clots, some of which were fatal.\u00a0When the correlation was first\u00a0suspected\u00a0for the Read more about Theories behind rare blood clots related to\u00a0COVID-19\u00a0vaccines\u00a0– Karolina Bentkowska<\/span>[…]<\/a><\/p>\n","protected":false},"author":1421,"featured_media":799,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[83],"tags":[263,144,81,285,232,283,289,284,288,14,287,286,282],"class_list":["post-798","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-interesting-research","tag-263","tag-astrazeneca","tag-biology","tag-blood-clot","tag-brain","tag-johnsonjohnson","tag-news","tag-pandemic","tag-protein","tag-science","tag-spike","tag-theory","tag-vaccine"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/wp.lancs.ac.uk\/bls-student-blog\/files\/2021\/06\/artery-4769605_1920.jpg?fit=1920%2C1080","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p9dFBD-cS","jetpack_likes_enabled":true,"jetpack-related-posts":[],"_links":{"self":[{"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/posts\/798","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/users\/1421"}],"replies":[{"embeddable":true,"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/comments?post=798"}],"version-history":[{"count":2,"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/posts\/798\/revisions"}],"predecessor-version":[{"id":801,"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/posts\/798\/revisions\/801"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/media\/799"}],"wp:attachment":[{"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/media?parent=798"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/categories?post=798"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/wp.lancs.ac.uk\/bls-student-blog\/wp-json\/wp\/v2\/tags?post=798"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}