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Pathologic Antibodies to PF4 After ChAdOx1 nCoV-19 Vaccine
Quick Takes
- VITT is a rare condition of thrombocytopenia and thrombosis following COVID-19 vaccine (to date only AstraZeneca and Johnson & Johnson).
- VITT presents similar to heparin-induced thrombocytopenia but without prior heparin exposure.
- Management includes IV Ig, glucocorticoids, and nonheparin anticoagulation under the direction of a thrombosis expert.
Study Questions:
What adverse events have occurred after receipt of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination?
Methods:
The authors report on findings in 23 patients who present with thrombosis and thrombocytopenia occurring 6-24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).
Results:
Twenty-two patients presented with acute thrombocytopenia and thrombosis in the absence of previous prothrombotic medical conditions. The thrombotic events were predominantly cerebral venous thrombosis. One additional patient presented with isolated thrombocytopenia and hemorrhage. All patients had low or normal fibrinogen levels with elevated D-dimer at the time of presentation. There was no identified thrombophilia or causative precipitants identified. Testing for antibodies to platelet factor 4 (PF4) was positive in 21 patients, negative in one patient, and equivocal in one patient.
Conclusions:
The authors concluded a pathogenic PF4-dependent syndrome that is unrelated to heparin therapy can occur after administration of the ChAdOx1 nCoV-19 vaccine (AstraZeneca). The authors also note that vaccination against SARS-CoV-2 remains critical for control of the coronavirus disease 2019 (COVID-19) pandemic.
Perspective:
This is the second paper to describe a new clinical syndrome, vaccine-induced thrombotic thrombocytopenia (VITT). This syndrome has many similarities to heparin-induced thrombocytopenia (HIT), including both thrombosis and thrombocytopenia related to PF4 antibodies. However, while HIT occurs after exposure to heparin, patients with VITT typically have not had prior heparin exposure; instead they seem to develop PF4 antibodies in response to COVID-19 vaccination. To date, this has been most widely described following the AstraZeneca vaccine, but recently has been described following the Johnson & Johnson vaccine.
Overall, this condition is quite rare following vaccination. And vaccination is critical to control the COVID-19 pandemic, which has a significant risk of complications (including thrombosis for hospitalized patients).
Key features for clinicians to be aware of include development of VITT between 5-28 days following vaccination, presence of acute thrombosis (including unusual sites), and thrombocytopenia. Testing should include D-dimer, fibrinogen, and ELISA-based PF4 (HIT) antibody testing. The authors of this paper suggest avoiding platelet transfusion, initiation of intravenous immunoglobulin (IV Ig) and glucocorticoids, and use of nonheparin anticoagulation for patients with highly suspected or confirmed VITT. Management under the direction of a thrombosis expert, such as a hematologist or vascular medicine specialists, is highly recommended.
Clinical Topics: Anticoagulation Management, COVID-19 Hub, Prevention, Vascular Medicine
Keywords: Antibodies, Anticoagulants, Coronavirus, COVID-19, Fibrinogen, Glucocorticoids, Hemorrhage, Heparin, Immunoglobulins, Intravenous, Platelet Factor 4, Platelet Transfusion, Primary Prevention, SARS-CoV-2, Thrombocytopenia, Thrombophilia, Thrombosis, Venous Thrombosis, Vaccination, Vaccines, Vaccines, DNA, Vascular Diseases
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