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Some Success Reining in VITT's Deadliness Across the Pond

— Mortality better than initial reports but nevertheless high

MedpageToday
A close up of blue gloved hands drawing the Oxford-AstraZeneca vaccine from a vial with a syringe while a woman waits.

Mortality was high in the U.K's early experience with vaccine-induced immune thrombocytopenia and thrombosis (VITT), though some hope this can be turned around with new clinical practices and increased recognition of the condition.

From March to June 2021, there was an overall case-fatality rate of 23% observed for the first 220 cases of VITT associated with the Oxford-AstraZeneca adenoviral vector COVID-19 vaccine, according to Sue Pavord, MBChB, of Oxford University Hospitals NHS Foundation Trust in England, and colleagues.

In the cohort study, mortality was especially high in severe cases -- reaching 73% of people with both platelet counts below 30,000 per cubic millimeter and intracranial hemorrhage, they reported in the .

Vaccination with the Oxford-AstraZeneca vaccine started in the U.K. in early January. By March, several European groups were reporting VITT, a rare but severe thrombotic syndrome that is blamed on the production of anti-PF4 antibodies (similar to heparin-induced thrombocytopenia) after exposure to vaccine components.

Those initial reports suggested mortality rates of 50% when the syndrome was still new. Yet the literature has changed rapidly since then.

"Now we know how to diagnose and treat these patients, which is very important given the continued use of these vaccines worldwide," commented Ishac Nazy, PhD, of McMaster University in Hamilton, Ontario.

Out of the 220 patients in the report from Pavord's group, the 17 with the most severe disease underwent catheter-based plasma exchange to remove anti-PF4 antibodies. "Survival after plasma exchange was 90%, considerably better than would be predicted given the baseline characteristics," the investigators noted.

Otherwise, the most common therapies for VITT were anticoagulation and IV immune globulin. Heparin, administered at some point for 23% of patients, did not appear to be harmful, though the study was too small to rule this out.

Rajiv Pruthi, MBBS, of Mayo Clinic in Rochester, Minnesota, urged the U.S. to "remain vigilant" even if the Oxford-AstraZeneca COVID vaccine is not authorized for use by the FDA. "Clinicians who are seeing patients with low platelets, headaches, blood clots coming in, regardless of the vaccine they got, should consider [VITT]," he said.

As such, Pruthi said in an interview that he would avoid heparin in this situation and opt for a non-heparin anticoagulant (e.g., bivalirudin), as was done for 68% of the patients in the U.K. study.

For this study, hematologists around the U.K. presented cases to an expert panel, which determined that out of 294 patients evaluated, 170 had definite VITT and another 50 probable VITT.

These VITT patients had presented to U.K. hospitals from March 22 to June 6 at a median 14 days after receiving their first dose of the Oxford-AstraZeneca vaccine.

Median age was 48, and 85% of people were under age 60. Women constituted 55% of the cohort. Patients were generally healthy, with no identifiable medical risk factors, Pavord's group reported.

Half of patients had clots in the cerebral veins (commonly complicated by secondary intracranial hemorrhage), and more than a third had them in the deep veins of the legs and the pulmonary arteries (commonly complicated by deep vein thrombosis and pulmonary embolism).

Pavord and colleagues estimated the incidence of VITT to be at least 1:100,000 among adults, ages 50 or older, and at least 1:50,000 for younger people. However, their study's design left room for potential case-ascertainment bias, the investigators acknowledged.

The estimates of VITT's incidence in this report seem "rather high" but need to be weighed against the risks of SARS-CoV-2 infection, Pruthi said. "What if you get COVID? The incidence of blood clots then is much, much higher -- 23% or even higher depending on the study you look at. Those blood clots can be devastating as well."

Balancing the risks of one versus the other, vaccination against SARS-CoV-2 is still advisable in aggregate, Pruthi said. He was not involved with the report from Pavord and colleagues.

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    Nicole Lou is a reporter for ֱ, where she covers cardiology news and other developments in medicine.

Disclosures

The study was supported by the Oxford University Hospitals NHS Foundation Trust.

Pavord, Nazy, and Pruthi had no disclosures.

Primary Source

New England Journal of Medicine

Source Reference: Pavord S, et al "Clinical features of vaccine-induced immune thrombocytopenia and thrombosis" New Engl J Med 2021; DOI: 10.1056/NEJMoa2109908.