Researchers Offer Algorithm for Managing Thrombosis and Thrombocytopenia After COVID-19 Vaccination

By Amy Orciari Herman

Edited by André Sofair, MD, MPH, and William E. Chavey, MD, MS

Patients with thrombosis and thrombocytopenia in the weeks after COVID-19 vaccination should not receive platelet transfusions or heparin and rather should be treated with a nonheparin anticoagulant and intravenous immune globulin, researchers suggest in the New England Journal of Medicine. The article includes an algorithm for testing and treating such patients.

The researchers detail 22 cases of thrombosis, most often central venous sinus thrombosis, with thrombocytopenia — and 1 case of thrombocytopenia with a hemorrhagic phenotype — in U.K. patients 6 to 24 days after receiving the first dose of the AstraZeneca adenovirus-vectored COVID-19 vaccine (ChAdOx1 nCoV-19). Patients ranged in age from 21 to 77, and over half were female. Just two of the patients had known thrombosis risk factors — one had a history of deep venous thrombosis and the other was using combination oral contraceptives.

Fibrinogen levels were frequently low and D-dimer levels elevated. Enzyme-linked immunosorbent assay was positive for antibodies to platelet factor 4 (PF4) in nearly all patients, despite the lack of exposure to heparin.

Overall, one third of the patients died.

The researchers conclude that "a pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine." They add: "Although evidence does not yet suggest that the use of heparin will exacerbate this condition, pending further data, we would recommend considering anticoagulation with the use of a nonheparin anticoagulant agent, such as argatroban, danaparoid, fondaparinux, or direct oral anticoagulants. Intravenous immune globulin (IVIG) has been used successfully in the treatment of patients with 'spontaneous' autoimmune [heparin-induced thrombocytopenia], which is the closest comparison to this vaccine-induced syndrome, and IVIG would be expected to have direct antibody-mediated toxic effects."

Editorialists write, "The very low prevalence of this complication of vaccination, however severe, relative to the benefits of preventing COVID-19 (a condition with 1 to 2% mortality and potential long-term sequelae) must be emphasized." They conclude, "The questions of whether certain populations can be identified as more suitable candidates for one or another vaccine and who and how to monitor for this rare potential complication will require additional study."