British doctors have identified two factors — very low platelet counts and brain bleeds — which they say dramatically increase the likelihood of a patient dying following the very rare but devastating side effect of vaccine-induced immune thrombocytopenia and thrombosis (VITT) after the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine.

However, they believe that the surge in the VITT side effect over the past few months is probably over now, as they revealed the terrible toll following the first few hundred confirmed cases. 

“We haven’t seen a new case for 3 or 4 weeks. It’s a tremendous relief to us all that we’re not seeing new cases now that the under-40s are getting the Pfizer vaccine,” Sue Pavord, MD, consultant haematologist from Oxford University Hospitals NHS Foundation Trust, Oxford, UK, told a press briefing yesterday.

Pavord reported on who is most at risk of dying from VITT. In a new prospective UK study, she and her colleagues found that patients with the lowest of platelet counts and intracranial hemorrhage were most likely to succumb, most always after having the first dose of the Oxford-AstraZeneca vaccine.

In the study, published yesterday in the New England Journal of Medicine (NEJM), Pavord and colleagues report on 220 confirmed cases of VITT between March and June of this year.

Overall mortality was 23%, but in patients presenting with very low platelet counts (below 30,000 per cubic millimeter) and intracranial hemorrhage following thrombosis, this figure rose to 73%.

No Predisposing Factors, but Five Diagnostic Criteria Identified

“The presentations were so serious that we had to work quickly to understand it and find a way to best manage it,” Pavord, who is also on the Expert Haematology Panel rapidly convened to investigate VITT in the UK, told the press

“In the early days, we thought people with sticky blood might be predisposed to develop VITT but the study shows it can affect anybody. There’s no predisposing factor that we can identify. Just under 50% had no previous medical diagnosis,” added co-author Beverley Hunt, MD, professor of thrombosis and haemostasis at King’s College London, who also sits on the Expert Haematology Panel.

In their paper, the team pinpoint five criteria that they say are indicative of definite VITT:

• time of presentation post-vaccination (5-30 days and not before, or ≤42 days in patients with isolated deep-vein thrombosis or pulmonary embolism)
• low platelets (<150,000 per cubic millimeter)
• documented thrombosis
• very raised D-dimers
• presence of anti-platelet factor 4 antibodies

“If all these criteria are met, it is a definite case of VITT. If one is unfulfilled…then the diagnosis is probable,” noted Pavord. A diagnosis is “possible if two are not met. If three or more are unfulfilled, or there’s an alternative diagnosis, it is unlikely to be VITT,” she said.

The Expert Haematology Panel produced guidance on diagnosing and managing VITT, which was approved as a National Institute for Health and Care Excellence (NICE) rapid guideline at the end of July.

VITT Mainly in Under 60s, Develops Around 14 Days After First Vaccine Dose

Pavord and colleagues note that, by June 6, approximately 16 million first doses of the Oxford-AstraZeneca vaccine had been administered to persons 50 years of age or older and 8 million had been administered to those younger than 50 years of age. The latter population mainly comprised healthcare and social workers and vulnerable persons.

In April, it was announced that only the over 30s would receive this vaccine in the UK, and this was later adjusted to the over 40s, in early May

They describe 170 definite and 50 probable cases of VITT identified between March and June 2021.

Most cases of VITT occurred in those under 60 years of age (median age 48, range 18 to 79 years). The incidence among those under 50 was 1:50,000 and comprised 56% of the cohort, while 85% were younger than 60 years.

All patients developed VITT after receiving the first dose of the Oxford-AstraZeneca vaccine.

“We feel as a group that this is an issue with the first dose of the vaccine. If there are any cases with the second dose, they are much rarer,” said co-author Catherine Bagot, MD, consultant haematologist at Glasgow Royal Infirmary, Glasgow, Scotland.

Cases most commonly presented at a median of 14 days (range 5 to 48 days) after vaccination with an equal split between the sexes, and no identifiable medical risk factors.

Mortality 80% in Severe Cases, Some Treated With Plasma Exchange

Hunt described one of the first patients she saw. “She was a woman around 40 years of age, with an overwhelming headache. She became very drowsy, and her consciousness deteriorated very quickly. She came to hospital and she had a very low platelet count and high level of D-Dimer and low fibrinogen. This is characteristic of the worst of the syndrome, and very sadly she died.”

Bagot also described the nature of the presentations in the study.

“Half of presentations had a cerebral blood clot. One third of these also had bleeding in the brain. The second most common site [for clots] was in the legs and lungs. Around one fifth showed blood clots in the abdomen — the liver or spleen. Another fifth had clots in the arteries that might cause stroke or heart attack.” 

“Mortality in those with clots in the head, bleeds in the head, and low platelet counts was nearly 80%. This is very significant in this young cohort,” noted co-author Marie Scully, MD, UCL Institute of Cardiovascular Science and consultant haematologist at University College London Hospital (UCLH).  

The mainstay of therapy used in the cohort was intravenous immunoglobulin (IVIG) given as soon as possible, and anticoagulants (non-heparin).

In severe cases, patients with intracranial hemorrhage and a platelet count below 30,000 per cubic millimeter were treated with plasma exchange.

“Survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics,” said Scully.

JAMA Cardiology Review Concurs

Also published this week in JAMA Cardiology was a review led by John Rizk from Arizona State University, Phoenix, Arizona and co-authors. It concurs that “VITT, while uncommon, is a clinically devastating and fatal complication after vaccination with adenoviral vector COVID-19 vaccines.”

The mechanism of development of the prothrombotic state and its association with the vaccine are still only partially known, they say, adding, “It is reasonable to avoid adenoviral vector COVID-19 vaccines in high-risk populations, especially younger female individuals, and instead consider immunization with an mRNA-based vaccine.”

“Treatment should consist of therapeutic anticoagulation mostly with non-heparin products and IVIG.”