Early in March, some four weeks after the first AstraZeneca vaccine was administered in Europe, little signals - like flares - started to go off all over the continent.

First in Austria, on March 7, and days later in Denmark, Norway and Iceland, European healthcare regulators began to report small numbers of blood clots and deaths among people who had received the vaccination.

Then on 15 March, Germany announced seven cases and three deaths and, like others, suspended use of the vaccine. The AstraZeneca jab was associated with a “striking accumulation of a special form of very rare cerebral vein thrombosis in connection with a deficiency of blood platelets and bleeding,” said the Paul-Ehrlich Institut, Germany’s renowned medicines regulator.

But in Britain, where the AstraZeneca rollout had started a full month earlier and 11 million doses had already been administered, there was nothing. On March 11, the UK's newly sovereign Medicines and Healthcare products Regulatory Agency (MHRA) put out a statement saying it could see no evidence of a problem.

“We continually monitor the safety of vaccines to ensure that the benefits outweigh any potential risks,” said Dr Phil Bryan, the MHRA’s Vaccines Safety Lead.

“Reports of blood clots received so far are not greater than the number that would have occurred naturally in the vaccinated population.

“The safety of the public will always come first.”

But the MHRA was, it appears, wrong. An investigation by The Telegraph has established that signals had been firing unnoticed in the UK’s Yellow Card database for at least a month, perhaps longer.

In January, a patient suffered a brain clot following their first dose of the AstraZeneca jab, The Telegraph has confirmed. Then in early February, two similar cases followed, including a death and a life-changing CVST clot in a young adult. All had low platelets and all were reported into the Yellow Card system.

On Friday, the MHRA told The Telegraph: “We are aware of thromboembolic events that occurred in January, however, our first report was received in the week commencing 8 February.... we cannot disclose information about individual cases to protect patient and reporter confidentiality.”

There remains no doubt the benefit of taking the AstraZeneca jab outweighs the risk now associated with the vaccine. This is the judgment not just of the MHRA but also the European Medicines Agency (EMA) and the World Health Organization (WHO).

The risk of developing cerebral venous sinus thrombosis (CVST) in combination with a low platelet count or thrombocytopenia after getting the vaccine is vanishingly small, and estimated to occur in just 1-in-100,000 cases, perhaps less.

This, says Sir David Spiegelhalter, Britain’s foremost expert in risk, is about the same chance of dying from a general anaesthetic, or of correctly guessing the last five digits of a stranger’s mobile phone number. With Covid itself, the risk of CVST alone is estimated to be eight to 10 times higher, according to an analysis of US data published last week.

Nonetheless, the MHRA faces serious questions as to why it did not detect the signals sooner. The issue is not that it has been left looking flatfooted or even that earlier detection would necessarily have altered its advice, but that the delay left it unable to shape international policy and confidence in what remains a vital vaccine in the fight against Covid 19 for the world.

Prof Stephan Lewandowsky, a psychologist at the University of Bristol studying the rollout of Covid-19 vaccines, told the Financial Times on Friday: “The MHRA was slow in responding to the emergence of a specific constellation of symptoms associated with the AstraZeneca vaccine and slow to communicate what they were finding — and I am not the only one who thinks so.”

So why was the MHRA slower than others to spot the early signals? The Telegraph’s investigation suggests the issue relates to the algorithms it had in place to interrogate the UK data and its limited access to early emerging data from Europe.

Observers say this should be seen in the context of the “operational and logistical challenges” the regulator faced in the run-up to the UK formally leaving the EMA on December 31, and the MHRA formally becoming a sovereign regulator for the first time on January 1.

The key to fast-moving pharmacovigilance is to efficiently sift the wheat from the chaff. When a new drug launches thousands of adverse reactions start pouring into regulatory reporting systems from both patients and clinicians.

From January 4 to March 14, a total of 532 “blood system events”, including 20 deaths, came through the UK’s Yellow Card system relating to the AstraZeneca jab, according to an analysis of published MHRA data by Dr Hamid Merchant, a pharmaceutical scientist at the University of Huddersfield. There were thousands of non-blood-related reports besides.

Of the thrombotic events recorded, four related to CVST (but no deaths were recorded), 55 were non-site specific and there were clusters of 64 and 66 cases in the lungs and deep veins respectively. There were then 267 general bleeding events and six deaths, three of which resulted from cerebral haemorrhage. Finally, there were 60 cases of thrombocytopenia, including 2 deaths.

To sift such data, regulators build algorithms that must balance “sensitivity” against leg-work. The more sensitive the algorithm, the more warning signals it will throw up to investigate - and many of those labour-intensive investigations will prove fruitless.

It is not known exactly what parameters the MHRA set but it is clear they were not as sensitive as those used by some regulators in Europe.

The MHRA says it followed a principle of applying “statistical techniques which can tell us if we are seeing disproportionately more cases than we would expect to see based on what is known about background rates of illness in the absence of vaccination”. This is reflected in the regulator’s initial statement when it said clotting reports were not above normal.

But other countries turned the sensitivity gauge up to 11. “Our policy is if it is associated with a death, or very serious adverse drug reaction, we will look into it right away,” David Benee Olsen, senior advisor at the Norwegian Medicines Agency, told The Telegraph.

“I think you have to be careful with looking at the background rate, because for example in this instance, what we were told by physicians was that this rare combination, this thrombocytopenia and CVST, they had never seen this in these kinds of patients, young patients, so it was very difficult to do a background rate versus incidence rate.”

There are also cultural differences as regards paternalism and transparency between regulators. An extreme example of the latter was demonstrated in the US last week when distribution of the Johnson and Johnson Covid vaccine was “paused” and a public hearing called to discuss the six cases of CVST and thrombocytopenia which had prompted it.

A similar approach was taken in Europe. In Norway, the first suspicious death was reported on the day it occurred, March 12 - the day after similar reports emerged from neighbouring Denmark.

On March 13, Norway identified three more cases, and all of the patients were flown to the same hospital for treatment and real-time analysis by a single team of specialists. Again, the incident was made public immediately in a bid to build trust.

When the Pfizer jab was first launched in the UK, the MHRA appeared to have resolved to adopt the same, very modern approach.

On December 9, just a day after the UK vaccine rollout started, the regulator announced three people had suffered serious allergic reactions after receiving the Pfizer jab and warned that “any person with a history of anaphylaxis to a vaccine, medicine or food” should not have it. The tell-it-like-it-is approach worked perfectly and scarcely a word was written about the issue until the advice was withdrawn a month later when more data showed it was not a risk.

Unfortunately, perhaps, the MHRA did not adopt the same approach with the problems surrounding the AstraZeneca jab - or at least it does not appear to have.

The MHRA says it got its first report of CVST with thrombocytopenia in the week of February 8, but the regulator did not tell the public about the issue until March 18 when it announced five cases. It did so just moments before the EMA opened a high profile press briefing on the issue, which by then was dominating world headlines.

Since then, the MHRA has made three further announcements regarding new cases identified in the UK. Late on Good Friday, after most people had tuned out for the bank holiday weekend, it said it had recorded a total of 30 cases, including seven deaths. Then on 7 April, again during a high profile EMA press conference, it revealed the count had grown to 79 and 19 deaths. The latest figures, quietly released on Thursday evening, show the number of UK clotting cases with thrombocytopenia to stand at 100 with 22 deaths.

It is not known how many of those 22 deaths are covered in the Yellow Card data Dr Merchant analysed between January 4 and 14 March but it seems likely that a large number of them - perhaps the great bulk - will date back to that period.

Despite requests from several newspapers including The Telegraph, the MHRA has not released the dates on which the deaths occurred or were reported into the Yellow Card system, citing the need to preserve patient confidentiality.

There is no suggestion whatever that the MHRA covered up the reporting of CVST with thrombocytopenia - it just did not spot the still unproven issue as early as others.

Another reason for the MHRA’s slower reaction, suggest observers, could be that it lost access to Eudravigilance, the vast European database into which all adverse drug reactions are reported, when the UK left the orbit EMA regulation on 31 December last year.

An EMA spokeswoman told The Telegraph: “The MHRA has access to the EudraVigilance gateway only. This allows them to submit cases (or to receive Northern Irish cases), but they cannot check the data in EudraVigilance.

“Should the MHRA need data they will have to ask for it... In addition, they can of course look at the data published on the adverse drug reaction (ADR) website.”

Dr June Raine, chief executive of the MHRA, faced “operational and logistical challenges” caused by the UK leaving the EMA in January, including loss of access to the EU's  Eudravigilance database

British haematologists described the rare clotting associated with the AstraZeneca jab, and now the Johnson & Johnson vaccine, as “a unique syndrome that we have never seen before” and said it only became apparent once the alarm had been raised in Europe.

On March 16, a group of leading UK experts had started to discuss a case seen by Dr Sue Pavord, a consultant haematologist at Oxford University Hospitals, which had the same hallmarks as the German cases being openly reported.

“I’d actually seen a mild case, and I remember he had thrombosis and his platelets were very low, and it was very rare to see that combination in our experience,” Dr Pavord told The Telegraph. The normal tests came back negative but then it was confirmed through background checks he had been given the AstraZeneca jab.

“So I was talking to colleagues and we realised that this was probably a unique syndrome. And as more data came out from the German group, we could see that there was a proposed mechanism and it all fitted.”

The following day - March 17 - Dr Pavord and her colleagues called the MHRA.