EMA adds unusual blood clots to adverse drug reaction profile of AstraZeneca vaccine

The European Medicines Agency (EMA) has stated that ‘unusual blood clots’ with low blood platelets should be listed as very rare side effects of the AstraZeneca/Oxford vaccine, but added that overall benefits of the vaccine in preventing Covid-19 outweigh the risks of side effects.

This was the conclusion of EMA’s Pharmacovigilance Risk Assessment Committee (PRAC), which evaluated cases of thromboembolic events and considered all currently available evidence, including the advice from an ad hoc expert group.

The PRAC carried out a detailed review of 62 cases of cerebral venous sinus thrombosis and 24 cases of splanchnic vein thrombosis in the EU drug safety database (EudraVigilance) as of 22 March 2021, 18 of which were fatal.

Most of the cases reported had occurred in women under 60 years of age within two weeks of vaccination.

Condition similar to heparin induced thrombocytopenia

The regulator said that one plausible explanation for the combination of blood clots and low blood platelets was an “immune response”, leading to a condition similar to one seen sometimes in patients treated with heparin, which is know as heparin induced thrombocytopenia (HIT).

Sabine Straus, PRAC Chair, said: “It is of great importance that healthcare professionals and the people coming for vaccination are aware of these risks and look out for possible signs or symptoms that usually occur in the first two weeks following vaccination.”

The regulator added that people who have received the vaccine should seek medical assistance immediately if they develop symptoms of this combination of blood clots and low blood platelets.

The PRAC noted that the blood clots occurred in veins in the brain (cerebral venous sinus thrombosis, CVST) and the abdomen (splanchnic vein thrombosis) and in arteries, together with low levels of blood platelets and sometimes bleeding.

Updated advice from the MHRA

Following the announcement, the Medicines and Healthcare products Regulatory Agency (MHRA) has advised that careful consideration should be given to people who are at higher risk of specific types of blood clots because of their medical condition.

The MHRA’s scientific review concluded that the evidence of a link with the AstraZeneca vaccine and the extremely rare blood clots with lowered platelets was stronger, but more work is still needed.

It said that by 31 March, 20.2 million doses of the Covid-19 vaccine AstraZeneca had been given in the UK meaning the overall risk of these blood clots is approximately four people in a million who receive the vaccine.

Recommendations are that anyone who did not have these side effects should come forward for their second dose when invited and as data suggests a slightly higher incidence reported in the younger adult age groups, it advises that this evolving evidence should be taken into account when considering the use of the vaccine.

The MHRA is now issuing updated guidance for healthcare professionals on how to minimise risks, as well as further advice on symptoms for vaccine recipients to look out for four or more days after vaccination.

Number of blood clotting cases in UK

Up to and including 31 March 2021, the MHRA had received 79 UK reports of blood clotting cases alongside low levels of platelets following the use of the  AstraZeneca vaccine:

• 44 of the 79 cases were of CVST with thrombocytopenia
• 35 of the 79 cases were of thrombosis in other major veins with thrombocytopenia
• 79 cases occurred in 51 women and 28 men, aged from 18 to 79 years. It should be noted that more women have been vaccinated with Covid-19 Vaccine AstraZeneca than men.
• Sadly, 19 people have died out of the 79 cases – 13 females and 6 males. 11 out of the 19 people who died were under the age of 50, 3 of whom were under 30. 14 of these 19 cases were of CVST with thrombocytopenia and 5 were of thrombosis with thrombocytopenia.
• All 79 cases occurred after a first dose of the vaccine.

This risk, based on reports up to and including 31 March, is slightly higher than the risk calculated from the reports published up to and including 24 March. However, likelihood of these blood clots occurring is still extremely rare.

As a precaution, administration of the AstraZeneca vaccine in people of any age who are at higher risk of blood clots because of their medical condition should be considered only if benefits from the protection from Covid-19 infection outweighs potential risks.

It added that anyone who experienced cerebral or other major blood clots occurring with low levels of platelets after their first vaccine dose of the AstraZeneca vaccine should not have their second dose. Anyone who did not have these side effects should come forward for their second dose when invited.

Dr June Raine, MHRA Chief Executive, said: “Over 37 million doses of vaccines against Covid-19 have now been administered in the UK, saving thousands of lives through the biggest vaccination programme that has ever taken place in the UK.

“No effective medicine or vaccine is without risk. We continually monitor safety during widespread use of any vaccine. This is to ensure vaccines are performing as expected, to identify any new side effects that may arise, and to ensure the benefits continue to outweigh the risks.

“The public’s safety is always at the forefront of our minds and we take every report of a suspected side effect very seriously indeed. We thoroughly analyse each and every report as we receive it and although the number of reports of CVST and other thromboembolic events has increased over the last week, so has the overall number of vaccinations administered, therefore these blood clots remain extremely rare and unlikely to occur.”

Patients should seek medical assistance immediately if they have the following symptoms:

• shortness of breath
• chest pain
• swelling in your leg
• persistent abdominal (belly) pain
• neurological symptoms, including severe and persistent headaches or blurred vision
• tiny blood spots under the skin beyond the site of injection