Scientists have shed light on the cause of a rare but serious vaccine side effect which results in abnormal bleeding or clots.

A team of researchers led by the University of Aberdeen set out to unravel why adenovirus-based vaccines, including some of those used in the Covid pandemic, can lead to a life-threatening complication known as Vaccine Induced Immune Thrombocytopenia and Thrombosis (VITT).

The condition is known to occur in a very small number of people who have received the Oxford-Astra Zeneca and Johnson-Johnson.

Both these vaccines use adenovirus - a harmless virus which causes the common cold - as a vector to deliver the genetic code from SARS-CoV-2 so that the body can prepare an immune response against Covid.

READ MORE: Vaccine rollout accelerated after new Covid variant detected in Scotland 

Adenovirus vectors have been commonly used for decades in vaccines, and are also used in other aspects of medicine including as vectors in gene therapy for cancers and haemophilia.

During the vaccine rollout, a small number of previously healthy people became rapidly unwell after vaccination against Covid and developed sometimes fatal blood clots or bleeding abnormalities.

Patients with VITT have unique antibodies to a protein called platelet factor 4 (PF4).

The antibodies cause activation of small cell fragments in the blood called, platelets, and trigger blood clotting.

In the case of VITT blood clots were often present in unusual sites such as the brain, gut and liver.

Working in collaboration with NHS Grampian, NHS Greater Glasgow & Clyde and NHS Lothian, the Aberdeen team, led by Professor Nicola Mutch, analysed samples from all suspected cases of VITT from hospitals across Scotland.

Emeritus Professor, Henry Watson said: “This research was triggered by the recognition of the catastrophic outcomes of VITT, in which previously healthy, frequently young individuals were becoming rapidly unwell.

"This extremely rare but often fatal reaction to the adenovirus-based Covid-19 vaccine usually occurred around seven to 30 days after vaccination.

“Given that Aberdeen held all of the Scottish samples of suspected VITT, we quickly realised this was a unique opportunity to help define the features of this complex syndrome and how it differs from other thrombotic conditions.”

READ MORE: Is the all-on-one cancer blood test a Hoy Grail - or a dead end? 

Some patients were confirmed to have VITT based on the presence of antibodies to PF4 and other clinical features, including the presence of blood clots.

Analysis of the samples from these patients found that there was overactivation of the body’s natural ‘blood clot busting system’, termed fibrinolysis.

Uncontrolled fibrinolysis results in breakdown of the main building block of a blood clot, called fibrinogen.

The researchers were also able to make comparisons between patients with a VITT diagnosis and those initially suspected but who were ultimately found to be negative for the condition.

Patients with VITT showed a very high incidence of a complication called disseminated intravascular coagulation (DIC), a severe abnormality in the blood clotting cascade which can cause organ damage and uncontrollable bleeding.

In patients with VITT there was also evidence of excessive breakdown of these blood clots and their precursor, fibrinogen, suggesting overactivation of fibrinolysis.

The results, published in the Journal of Thrombosis & Haemostasis, help to explain both the clot formation and the bleeding complications, commonly intracranial haemorrhage, seen in VITT patients.

Understanding the mechanisms by which adenovirus-based products can cause adverse reactions, like VITT, is crucial in considering future use in other medicinal products.

It may also guide therapeutic strategies to treat similar conditions to VITT in the future.

READ MORE: Hundreds of hospital wards closed due to Covid outbreaks 

Professor Nicola Mutch added: “Our work identifies a novel aspect of VITT which was previously unrecognised.

"It helps us to understand the mechanisms underlying the clinical observations, whereby the patients suffer from complications due to both blood clots and bleeding at the same time.

“The demonstration of overt disseminated intravascular coagulation and the breakdown of the clotting protein fibrinogen in VITT had not previously been recognised but this helps explain the acute symptoms and rapid course of this extremely rare complication of vaccination with adenovirus-based vaccines."

The work was funded by The University of Aberdeen Development Trust SCIO.

Liza Boffen-Yordanov, Aberdeen University's director of advancement, said: “We are grateful to the donors whose generous gifts enabled this critical research to be undertaken.

"Their philanthropic support meant our researchers were able to respond quickly to the emergence of this rare condition in response to certain vaccines.”