medicines agency (ema), the regional regulatory authority for the eu. medicines and healthcare products regulatory agency (mhra), the medical authority for the united kingdom. paul ehrlich institute (pei), a german federal agency supervised by the federal ministry of health with expertise in vaccines and biomedicines. it is a who collaborating centre. syndrome identification a number of covid‑19 vaccines began to become approved and available at scale in december 2020, with vaccinations beginning to ramp up at scale from the beginning of 2021, among them the oxford–astrazeneca covid‑19 vaccine, based on an adenovirus vector and internally termed azd1222. on 11 march 2021, the ema issued a statement noting denmark had suspended azd1222 vaccinations due to a vaccinated patient dying with blood clots. while noting there had been reports of other vaccinated people having blood clots and that its safety committee is already reviewing such cases, the number of thromboembolic events in vaccinated people is no higher than in the general population. the world health organization (who) global advisory committee on vaccine safety on 19 march 2021, issued a statement relating to safety signals related to azd1222 relating to thromboembolic events and thrombocytopenia following review of available data and conclusions included that azd1222 "a positive benefit-risk profile, with tremendous potential to prevent infections and reduce deaths across the world". in its safety update of 29 march 2021, the ema indicated it had initiated investigations into the very rare cases of specific embolic and thrombotic events in combination with thrombocytopenia (low levels of blood platelets) and related bleeding including disseminated intravascular coagulation and cerebral venous sinus thrombosis (cvst), noting any link with azd1222 is not proven but could not be excluded. the ema also initiated an assessment for all covid‑19 vaccines used in the eu for immune thrombocytopenia (itp), described as low blood platelet levels that could lead to bruising and bleeding, as a possible side effect, whilst also stating that up to this point no link with any covid‑19 had been established. on 7 april 2021, the ema determined that unusual blood clots with low blood platelets should be listed as very rare side effects of azd1222, with who and uk ehra issuing generally similar statements on the same day. none of the agencies found a confirmed causal link between the vaccine and these incidents at the time, but were listing them out of an abundance of caution. a highlight of minutes of the ema's pharmacovigilance risk assessment committee (prac) concluding 9 april 2021, indicating they also were investigating four cases of unusual blood clots with low blood platelets, including one death, amongst people who had taken the janssen covid‑19 vaccine. the janssen vaccine is approved but not yet deployed in the eu, though vaccinations are in progress in the us. prac has determined that it is not clear if there is a causal association. should regulatory action prove necessary, prac have indicated the likely outcome would be an update to product information characteristics. vaccination campaign responses early reports of the events of concern seemed to indicate the presentation rate for the specific blood clots of concern might be higher for women of younger ages, uk medicines and healthcare products regulatory agency (mhra) found examples across all genders and ages, their data skewing towards these specific blood clots being more prevalent in azd1222 vaccinated persons of younger ages. the who has continued to stress the administration of vaccines is based on risk versus benefit analysis. some variables that may be factored into such analysis include risk of an individual from catching covid‑19, which relate to the infection rate in that area, and the benefits to that individual if vaccinated and exposed to covid‑19 which varies with age, versus whatever the risks of vaccination are to that individual. regional and national responses the advisory panel for the government of ontario, canada has recommended against the use of heparin for management of thrombosis after vaccination until more is known. in response to the concerns over the adverse effects relating to rare blood clotting types germany has suspended use of the azd1222 in those under 60 years of age; in contrast to a period previously having suspended use of azd1222 to over–65s due to limited data of the efficacy of the vaccine to this age group at that time. following a few days of suspended use of azd1222, the ministry of health, welfare and sport of the netherlands decided to continue administering the vaccine only to persons above the age of 60. on 8 april 2021, the australian technical advisory group on immunisation (atagi) advised the australian government that the pfizer covid‑19 vaccine is recommended over azd1222 for adults aged under 50 years. the advice is "based on the increasing risk of severe outcomes from covid‑19 in older adults (and hence a higher benefit from vaccination) and a potentially increased risk of thrombosis with thrombocytopenia following astrazeneca vaccination in those under 50 years." azd1222 is still recommended by atagi for people over 50, and those under 50 who have already had their first dose with no ill effects. in the state of victoria, there were reports of some, aged under 50, being turned away from vaccination centres, despite having confirmed appointments. it is understood a special consent process will be developed by the australian government for people under 50 who choose to receive the azd1222 vaccine. studies a study convened by a group of british hematologists on 19 march 2021, just two days after the acknowledgement of the condition, published its finding in the new england journal of medicine, establishing case definition criteria. the study included 294 participants who presented with symptoms of thrombocytopenia and thrombosis after receipt of the first dose of the oxford–astrazeneca covid‑19 vaccine, showing an independent association between baseline platelet count and the presence of intracranial hemorrhage. the study established that 85% of the participants effected by the condition were aged younger than 60 years, and that those participants with a history of thrombosis or prothrombotic disorders did not appear to be at increased risk. the study showed an overall mortality rate of 22% and set out plans for additional research to determine the genetic factors that may increase risk of the condition and identify potential therapeutic agents.