UK study offers insight on COVID-19 vaccine-induced immune thrombocytopenia and thrombosis

Low platelet count and intracranial hemorrhage appeared associated with increased risk for death among hospitalized patients with COVID-19 vaccine-induced immune thrombocytopenia and thrombosis, according to study results.

The findings, published in The New England Journal of Medicine, suggest the identification of prognostic markers could help guide effective management of these patients as treatment remains uncertain, researchers noted.

Low platelet count and intracranial hemorrhage appeared associated with increased risk for death among hospitalized patients with COVID-19 vaccine-induced immune thrombocytopenia and thrombosis.
Data derived from Pavord S, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2109908.
“Our core group convened on March 19 — just 2 days after the realization and acknowledgement that vaccine-induced immune thrombocytopenia and thrombosis was a completely new syndrome that appeared to be related to the Oxford-AstraZeneca COVID-19 vaccine,” Sue Pavord, MB, ChB, FRCP, FRCPath, consultant hematologist and researcher in the department of hematology at John Radcliffe Hospital in the U.K., told Healio. “The presentations observed were so serious that we realized we would have to work quickly to understand the condition and the best forms of management.”

By March 22, Pavord and colleagues had established daily meetings, inviting hematologists across the U.K. to present cases they observed or had seen prior to recognition of vaccine-induced immune thrombocytopenia and thrombosis.

Sue Pavord, MB, ChB, FRCP, FRCPath
Sue Pavord
“Because of the surge in cases during the next few weeks, our daily meetings continued throughout weekends and bank holidays,” Pavord added. “We were able to describe the key clinical features and outcomes of all known cases in the U.K., the country that was hardest hit by this condition because of the early rollout of the AstraZeneca vaccine. By learning from these cases, we were able to provide guidance on management that were, and still are, updated as new information comes to light.”

The prospective cohort study included 294 patients who presented to hospitals in the U.K. between March 22 and June 6 with suspected vaccine-induced immune thrombocytopenia and thrombosis.

Pavord and colleagues analyzed baseline characteristics and clinicopathological features of these patients and sought to determine risk factors, treatment and markers for poor prognosis.

Overall, they discovered 170 definite and 50 probable cases of vaccine-induced immune thrombocytopenia and thrombosis. All patients (median age, 48 years; range, 18-79) presented to the hospital within 5 to 48 days (median, 14 days) after receipt of the first dose of the Oxford-AstraZeneca (ChAdOx1 nCoV-19) COVID-19 vaccine.

Results showed an overall mortality rate of 22%. Researchers observed increases in the odds of death by a factor of 2.7 (95% CI, 1.4-5.2) among those with cerebral venous sinus thrombosis, 1.7 (95% CI, 1.3-2.3) for every 50% decrease in baseline platelet count, 1.2 (95% CI, 1-1.3) for every increase of 10,000 fibrinogen-equivalent units in baseline D-dimer level, and 1.7 (95% CI, 1.1-2.5) for every 50% decrease in baseline fibrinogen level.

Results of a multivariate analysis showed an independent association between baseline platelet count and the presence of intracranial hemorrhage. Patients with platelet counts below 30,000 per cubic millimeter and intracranial hemorrhage had an observed mortality rate of 73%.

Plans for additional research include determining the genetic factors that may increase risk for vaccine-induced immune thrombocytopenia and thrombosis and identifying potential therapeutic agents to treat the condition.

“Vaccine-induced immune thrombocytopenia and thrombosis is a condition with a very specific mechanism,” Pavord said. “It is vital to get the diagnosis right — not only for correct management of the patient, but also to help determine accurate incidences. Our study established the case definition criteria. [The condition] predominantly affects young people, with 85% of the study cohort aged younger than 60 years, despite the vaccine rollout starting with the older age groups. Also, patients with known medical illness or a history of thrombosis or prothrombotic disorders do not appear to be at increased risk.”

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