The cases under consideration specifically involve embolic (obstruction in a blood vessel) and thrombotic (blood clots) events frequently associated with low levels of blood platelets. More recently, the capillary leak syndrome has been also detected, in which clots that prevent blood from leaving the brain (cerebral venous sinus thrombosis – CVST) and in the abdomen (splanchnic vein thrombosis) have been observed in the Vaxzevria recipients, mostly in women and between 0 to 16 days after the procedure. According to the occurred episodes, the first reactions may happen in the first days after the inoculation and may last for several days. This is then followed by a non-reaction period and, subsequently (6 – 12 days after vaccination), by rapid deterioration [3]. The full clinical picture may be, as of yet, incomplete. Based on individual cases, it is hypothesized that the heparin-induced thrombocytopenia-like syndrome (HITT-like syndrome) may be responsible for the effect. The syndrome (HITT) is a result of an emergence of antibodies generated against medically administered heparin. This has been named “vaccine-induced immune prothrombotic thrombocytopenia” (VIPIT) for clarity, as there is no apparent relation to previous heparin usage [4].

 In order to further investigate the potential link between the vaccine and blood clots, statistical analysis has been performed. The EMA safety committee has employed EudraVigilance (monitoring and analysis system for suspected adverse reactions to medical products in EU [5]) and AstraZeneca’s global safety database. Additionally, they have re-evaluated pre-clinical and clinical data and looked at specific incidences. The results from the vaccine developer did not show any concerning signals. The adverse events were self-limited. However, a higher frequency of platelet decrease has been observed after the second dose, although a similar trend has been found in the control group. Among multiple analyses, post-marketing data has shown 288 – 293 occurrences (cut-off dates March/April 2021, the values depend on the source) of embolic and thrombotic events after the vaccination of close to 20 million people. Among these, 39 – 45 were fatal. Moreover, EMA took into consideration the British Medicines & Healthcare Products Regulatory Agency (MHRA) analysis of the country’s data. The suspected events rate was in line with expected background trends. In other words, an increase of such adverse events should be observed after the vaccine introduction if the vaccine is a culprit. It was not possible to establish a causal relationship with the vaccine by MHRA nor by EMA [3].

 Despite the relatively narrow clinical picture of the discussed incidences, a causative relation between the vaccine and the fatal outcomes has not been established. No potential risk to the recipient has been identified either. However, the heterogeneity of the data and potential under-reporting could have influenced the results [6]. The exact reason for such effects is currently unknown, but it is speculated that the adenoviral vector used in the vaccine may be responsible [3]. This is also supported by the fact that similar safety signals have been reported for the Johnson & Johnson vaccine in the USA [7]. Also of note is the fact that the two vaccines use different adenoviral vectors and thus the similarity may be rather meager. It is important to mention that these types of effects are observed in a much higher number among COVID-19 patients – incidence of 39 (in the infected group) and for comparison 4.1 (in the vaccinated with mRNA vaccines group) or 5 (in the vaccinated with AstraZeneca’s vaccine group) per million people [8]. The viral infection itself may provide some clues about the potential mechanism in the near future.

 In summary, PRAC concluded that – despite the lack of a strong association between the vaccine and the reactions – a connection cannot be excluded. PRAC then advised that the Summary of Product Characteristics and Package leaflet should be updated to include the clinical picture and the warnings that healthcare professionals should be aware of. It is also highly recommended to seek medical attention if the inoculation results in such symptoms as chest or abdominal pain, shortness of breath, leg swelling, headache, blurred vision, or skin bruising [9].