Thrombosis
Maria G. Tanzi, PharmD
In early April, the New England Journal of Medicine (NEJM) published three independent case series of 39 patients who developed a newly described syndrome characterized by thrombosis and thrombocytopenia soon after they were vaccinated with AstraZeneca’s COVID-19 vaccine (which is not available in the United States).
Around the same time, CDC and FDA recommended a pause in the use of Johnson & Johnson’s (Janssen) COVID-19 vaccine as they evaluated reports of an increased risk of thrombosis with thrombocytopenia, primarily in adult women younger than 50 years.
Though the agencies subsequently lifted the pause after a thorough safety review, it is essential for clinicians to rapidly identify and manage COVID-19 vaccine-induced immune thrombotic thrombocytopenia to reduce the potential for serious adverse outcomes.
“Clinicians should be aware that in some patients, venous or arterial thrombosis can develop at unusual sites such as the brain or abdomen, which becomes clinically apparent approximately 5 to 20 days after vaccination,” wrote one of the authors of the NEJM case series. “If such a reaction is accompanied by thrombocytopenia, it can represent an adverse effect of the preceding COVID-19 vaccination.”
Clinical presentation, diagnostic workup
The syndrome is characterized by venous or arterial thrombosis, particularly at unusual sites; mild to severe thrombocytopenia; and a positive PF4-heparin ELISA (i.e., heparin-induced thrombocytopenia [HIT]) in individuals who have received the AstraZeneca or Johnson & Johnson (Janssen) vaccine. Both vaccines use recombinant adenoviral vectors that encode for the SARS-CoV-2 spike protein immunogen. Symptoms of the syndrome vary. Patients may present with a severe headache, visual changes, change in mental status, abdominal pain, nausea and vomiting, back pain, shortness of breath, leg pain or swelling, and/or bruising or bleeding.
If vaccine-induced thrombotic thrombocytopenia is suspected, an immediate CBC with platelet count should be performed, along with imaging for thrombosis.
The HIT assay should also be performed, as almost 100% of cases reported positive assays despite the lack of exposure to heparin.
Fibrinogen (some cases have reported low levels) and D-dimers (the majority of patients had markedly elevated values) should also be evaluated.
Suggested management
The authors of the NEJM case series suggest a potential therapeutic strategy for management of suspected vaccine-induced thrombotic thrombocytopenia. Their recommendations include
- Administering high-dose IVIG 1 g/kg daily for 2 days
- Using nonheparin anticoagulation, with potential options including direct oral Xa inhibitors (apixaban, rivaroxaban), direct thrombin inhibitors (argatroban, bivalirudin), and indirect Xa inhibitors (fonda-parinux), chosen on the basis of the patient’s clinical status and organ function
- Avoiding platelet transfusions and the use of unfractionated or low-molecular-weight heparin in patients with a positive PF4 ELISA (or while awaiting test results) because of the similarities of this syndrome to HIT
Providing perspective to patients
According to CDC, a review of all the available data as of early May 2021 showed that the known and potential benefits of Johnson & Johnson’s (Janssen) COVID-19 vaccine outweigh its known and potential risks. Both FDA and CDC noted that the available data suggest that the chance of thrombotic thrombocytopenia syndrome occurring is very low. However, the agencies will continue to investigate this risk.
Clinicians should educate patients on the potential for vaccine-induced thrombotic thrombocytopenia with the use of select COVID-19 vaccines. Inform patients that the syndrome is more common in adult women younger than 50 years who have received the Johnson & Johnson (Janssen) COVID-19 vaccine, and explain that the benefits of vaccination far outweigh the risks for this potential, rare adverse event. Some patients may choose to be vaccinated with one of the mRNA COVID-19 vaccines as an alternative.