Last checked at 
(Adds details of U.S. move to pause J&J vaccinations following
rare clotting reports)
By John Miller and Ludwig Burger
ZURICH, April 13 (Reuters) - U.S. regulators have
recommended pausing the use of Johnson & Johnson's
COVID-19 vaccine, as they investigate rare blood clotting in six
women.
J&J also said it was stopping the rollout of its vaccine in
Europe.
The move comes after Europe's drug regulator earlier this
month said it had found a possible link between AstraZeneca's
COVID-19 vaccine and very rare blood clots in some
adults who had received the shot.
Britain's health regulator, meanwhile, has recommended
people under the age of 30 get an alternative COVID-19 vaccine,
if possible, rather than the AstraZeneca shot.
Here's what we know so far:
WHAT HAS HAPPENED?
With both the AstraZeneca and Johnson & Johnson
(J&J)vaccines, the reports involve extremely rare clotting,
including a type of blood clot called cerebral venous sinus
thrombosis (CVST), that were seen in combination with low levels
of blood platelets, called thrombocytopenia.
A U.S. Centers for Disease Control and Prevention (CDC)
committee plans to review the cases linked to the J&J vaccine,
and the U.S. Food and Drug Administration (FDA) will review its
analysis.
The agencies, like their European counterparts, described
the clotting as extremely rare.
The European Medicines Agency (EMA) has said its vaccine
side effects monitoring system, as of April 4, had received 169
reports of cases of CVST, or clots in blood vessels exiting the
brain, and 53 cases of splanchnic vein thrombosis (SVT), or
clotting in veins in the abdomen.
That's out of 34 million AstraZeneca vaccine doses
administered in Britain and the European Economic Area over the
past three months.
The EMA's safety committee carried out a review of 62 cases
of CVST and 24 cases of SVT, of which 18 were fatal.
Most cases occurred within two weeks of the person receiving
their first dose.
German vaccination officials, who recorded 29 cases of CVST
in women aged 20 to 59 who received the AstraZeneca vaccine,
said the occurrence rate in that group was 20 times higher
within 16 days of vaccination than what would have typically
been expected.
Germany's health ministry has said 1 to 1.4 cases of CVST
would have been expected during that time.
WHO EXPERIENCED THE RARE SIDE EFFECTS?
In J&J's case, all six recipients were women between the
ages of 18 and 48, and the symptoms occurred six to 13 days
after vaccination. In total, more than 6.8 million doses of the
Johnson & Johnson vaccine have been given in the United States
through April 12.
Similarly, most of the cases reported in Europe have
occurred in women under 60, though that could be misleading,
since Germany and Britain say more women got AstraZeneca's shot
than men.
Most cases occurred within two weeks of people getting the
first AstraZeneca dose.
WHAT HAVE THE COMPANIES SAID?
J&J said it was working closely with regulators and noted no
clear causal relationship had been established between the
events and its shot.
AstraZeneca said it was "working to understand individual
cases and "possible mechanisms that could explain these
extremely rare events".
WHAT HAVE REGULATORS SAID?
The CDC is recommending pausing using J&J's single-dose
vaccine "out of an abundance of caution" to ensure that the
health care providers are aware of potential side effects and
can plan for "proper recognition and management."
Britain's Medicines and Healthcare products Regulatory
Agency, meanwhile, made its recommendation for an alternative
vaccine to AstraZeneca's to be used for people under 30 after
reviewing 79 cases of rare clotting coupled with low platelets,
with 19 fatalities - 13 women and six men. Eleven of the deaths
were of people under the age of 50 and three were under the age
of 30.
HOW DO TREATMENT RECOMMENDATIONS DIFFER?
In the United States, health officials said treatment of the
blood clots with possible ties to the J&J vaccine differs from
what might be considered standard in such situations.
"Usually, an anticoagulant drug called heparin is used to
treat blood clots," they said. "In this setting, administration
of heparin may be dangerous, and alternative treatments need to
be given."
By contrast, German doctors and scientists investigating
clotting associated with AstraZeneca shots have recommended that
doctors give high concentrations of heparin, Fc
receptor-blocking monoclonal antibody and intravenous
immunoglobulin.
HOW DID REGULATORS COME TO THEIR DECISIONS?
In its findings, the EMA said on March 18 that, on average,
just 1.35 cases of CVST might normally have been expected among
people under 50 within 14 days of receiving AstraZeneca's
vaccine, whereas by the same cut-off date 12 cases had been
recorded.
By comparison, four women out of 10,000 would get a blood
clot from taking oral contraception.
British officials drew on statistics from the University of
Cambridge's Winton Centre for Risk and Evidence Communication to
explain their recommendations that young people get an
alternative shot while older people can continue to get
AstraZeneca's.
According to the Centre, the risk of serious harm due to
vaccination falls the older people get and the number of
admissions to intensive care units falls sharply thanks to
vaccinations, boosting the AstraZeneca shot's benefit-to-risk
ratio.
The Centre concluded that only 0.4 people for every 100,000
in the 50-59 age group would suffer vaccine-linked harm, while
95.6 ICU admissions per 100,000 people would be prevented.
WHAT'S THE EU DOING NOW?
The EMA, which said the benefits of using AstraZeneca's
vaccine continue to outweigh any risks, said that unusual blood
clots with low blood platelets should be listed as very rare
side effects and countries should decide on how to proceed.
These may vary from nation to nation, the EMA said,
depending on factors like infection rates and whether there are
vaccine alternatives.
ANY THEORIES ON CAUSE OF THE CLOTS?
Among possible causes being investigated are that the
vaccine triggers an unusual antibody in rare cases. So far, risk
factors like age or gender have not been singled out.
German scientists at Greifswald University concluded in a
paper published last week in the New England Journal of Medicine
that the extremely rare cases of clotting with low platelets -
something they are calling "vaccine-induced immune thrombotic
thrombocytopenia" - are triggered by antibodies found in the
affected patients following vaccination with AstraZeneca's shot.
A separate group of Norwegian scientists have made similar
conclusions - that AstraZeneca's vaccine triggered an immune
response that may have led to clotting in a small number of
people - in their own article, also published in the New England
Journal of Medicine.
Andreas Greinacher, an Greifswald expert on drug-induced
immune responses, is, like the EMA, seeking clues about why in
rare cases people developed clots and low platelets after
getting the vaccine, while the vast majority did not.
(Reporting by Ludwig Burger in Frankfurt, Matthias Blamont in
Paris and John Miller in Zurich
Additional reporting by Kate Kelland and Alistair Smout in
London and Julie Steenhuysen in Chicago
Editing by Josephine Mason, Angus MacSwan and Susan Fenton)
