Over a month ago, Iceland, Denmark, and Norway suspended use of the AstraZeneca COVID-19 vaccine, citing rare blood clotting adverse events. What’s the actual data surrounding these events?
Unlike the first vaccines deployed against COVID-19, AstraZeneca and Johnson & Johnson use a slightly different vaccine technology to deliver mRNA instructions to cells. Where Pfizer and Moderna use lipid nanoparticle technology to present mRNA transcripts to ribosomes, these companies utilize a more traditional method of cellular delivery–viral vectors.
AstraZeneca uses chimpanzee adenoviruses, while Johnson & Johnson uses the human version, to house the mRNA instructions which code spike proteins–the part of the virus that our body needs to recognize to generate antibodies to fight off COVID-19 infection.
Interestingly, both AstraZeneca and Johnson & Johnson have been under global scrutiny in the past few months due to occurrences of rare blood clotting events, which many news outlets have attributed to vaccinations. On March 11, 2021, a series of European countries pulled AstraZeneca from the market, citing these clotting events. Just days later, on March 14, AstraZeneca released a statement defending its vaccine, citing that after 17 million vaccinations, just 15 deep-vein thrombosis events were reported, and 22 pulmonary embolisms; no more, they claim than what would occur in a general population sample of this size, and no more than have occurred with other vaccine types in similar populations. They went on to state, “in clinical trials, even though the number of thrombotic events was small, these were lower in the vaccinated group.”
Regardless of the defense by AstraZeneca, as of March 16th, eighteen countries suspended use of the vaccine. And on April 14th, Denmark became the first country to permanently cease use of the AstraZeneca vaccine, citing specifically concerns surrounding cases of cerebral venous sinus thrombosis (CVST) in otherwise healthy individuals, possibly linked to vaccination. These cases are linked by an atypical presentation, generally not seen in other clotting disorders.
In this article, I will attempt to present the most whole picture I can gather as to the current data surrounding the AstraZeneca clotting issues. As I will show through different sources, many different organizations hold different claims regarding this topic, and as long as the data remains hazy, this controversy will persist. While no statistical correlation can link the unusual clotting events to the AstraZeneca vaccine, many of the cases in question share atypical clinical presentations that are worth close examination. It’s important to note that even if we assumed casual correlation between the vaccine and clotting events, that this side effect would still be considered extremely rare, according to the European Medicines Agency–but they also agree the condition warrants further investigation.
The unusual nature of the blood clots that are being reported is concerning. Many otherwise-healthy individuals have a clotting event, while also exhibiting very low platelet counts–two typically incongruent features. Generally, and intuitively, most patients with varying types of thromboses (blood clots) present with elevated platelet counts; these platelets contribute to the “traffic jam” which causes clots to form, and are the component of blood responsible for clotting to stop or slow bleeding.
While the statistical occurrence fails to show a definitive correlation between the AstraZeneca vaccine and the clotting events, the unique nature of the cases in question may explain why many countries continue to limit or suspend use of the AstraZeneca vaccine. Take for instance the case study of an otherwise-healthy 49 year old medical worker, published in the New England Journal of Medicine. She received the first of the two shots in the AstraZeneca series, and in the subsequent days reported typical side effects (muscle pain, fatigue, headache) which did not resolve. After five days, more severe symptoms began to manifest, with chills, fever, nausea, and abdominal pain. Ten days after her first shot, she was admitted to the hospital. Upon admission, her platelet count was found to be only 18,000 per cubic millimeter– a normal range is between 150,000 to 400,000. She also had elevated levels of C-reactive protein (CRP) which is an indicator of inflammation, and elevated gamma glutamyl transferase levels, which can signal damage to the liver.
Typically, a low platelet count prevents your blood from clotting at all– a condition called thrombocytopenia. But in this patient, a CT scan confirmed the presence of a portal-vein thrombosis (vessel responsible for blood flow into the liver from the intestine) as well as peripheral pulmonary emboli (pulmonary artery clots). After 11 days hospitalized, the patient died from a cerebral venous thrombosis–a clot which prevents blood from returning to the heart from the brain.
This case is not a one-off. One German blood clotting expert dubbed this condition–characterized by low platelet counts and large numbers of clots–vaccine-induced prothrombotic immune thrombocytopenia, now more commonly known as thrombosis with thrombocytopenia syndrome (TTS). The criteria list for this condition includes recent vaccination (Johnson & Johnson OR AstraZeneca), the presence of venous or arterial thrombosis, thrombocytopenia (low blood platelet count), and finally, a positive immunochemical test for the presence of a protein called PF4, which is implicated in a condition called heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia, or HIT, is an autoimmune condition in which the body’s immune system (specifically, the PF4 antibody) attacks platelets. Platelets are the normal components of blood which are responsible for clotting. In cases of HIT, the presence of heparin–an anticoagulant naturally produced to prevent blood clots–causes PF4 antibodies to activate platelets, causing clotting to occur when it shouldn’t. Some platelets are activated, while others are targeted by antibodies for the immune system to destroy–hence a low platelet count in these patients. Although heparin is the primary substance implicated in this type of clotting disorder, it’s not the only trigger for HIT; and many researchers speculate that in cases of TTS, the vaccine in question may serve as the activator for this damaging autoimmune response.
The New England Journal of Medicine characterizes this condition even further, analyzing 39 cases of TTS in people with no preexisting clotting conditions. It seems that a common tie between several of these cases is the presence of oral contraceptives or estrogen-replacing therapy in women under 50 years of age. This particular study found that 40% of those 39 patients died as a result of their clots, with many clots appearing in “unusual sites”, including the hepatic portal veins and the cerebral venous sinuses.
Overall, this condition is so rare, that at the time that this article was written, no statistically significant correlation is possible. Even though there is a condition with criteria including vaccination with AstraZeneca or Johnson & Johnson recognized by the medical community, the occurrence remains low enough for the statistical data to remain foggy. With a vaccine that provides 76% protection against symptomatic COVID-19 and 100% protection against severe COVID-19 cases requiring hospitalization, it is necessary for each consumer to seriously weigh the benefits of receiving a vaccine with such a low incidence of serious side effects.
It’s important also to note that one study of 184 people found that up to 31% of patients with severe or critical cases of COVID-19 experienced thrombosis events, which the study defines as “remarkably high”. I don’t feel comfortable citing a source describing the exact percentage of AstraZeneca recipients that experience TTS, due to the lack of reliable studies surrounding it and the lack of statistical relevance of the data that does exist, but it is certainly lower than this statistic.
It is my opinion that each consumer should educate themselves on the relative risk and benefits of receiving this vaccine. It is a murky set of data, with this condition being so newly reported, but I believe it is fair to state that there is a newly-defined condition, TTS, that is linked with vaccination with the AstraZeneca and Johnson & Johnson vaccines, and that it has been fairly well-defined and reported in a few different studies. It is also fair to state, however, that the occurrence seems to be very low, and that TTS could be considered an extremely rare side effect among the approximately 17 million recipients in the UK and EU alone. It is certain that COVID-19 is a dangerous disease, with a massive death toll globally, and that AstraZeneca, in the vast majority of cases, protects against it safely and effectively. In the end, it is best to research your relative risk of thrombosis events, your vaccination options, and the opinions of your national health services on different vaccines before accepting it. I believe that it is fair to say COVID-19 is a threat orders of magnitude higher than TTS, but it is certainly an interesting and novel condition that I hope to see better-defined in coming months.
Ally Answers 