Vaccine-induced Thrombotic Thrombocytopenia (VITT) and COVID-19 Vaccines: What Cardiovascular Clinicians Need to Know

Current Key Question on COVID-19 and Cardiovascular Disease

Organized in an FAQ format for easy navigation, this guidance is summarized from more extensive documents and approved by the ACC Science and Quality Committee. This FAQ is intended to be topical, not comprehensive.

COVID-19 Vaccine; Conceptual Image

Category: COVID Vaccination
Patient Type: COVID-19 Vaccinated
Prevalence: Extremely rare
Principal Guidance: In extremely rare cases, the Johnson & Johnson/Jansen and Astra Zeneca COVID-19 vaccinations may cause vaccine-induced thrombotic thrombocytopenia (VITT), a condition characterized by simultaneous acute thrombosis and thrombocytopenia. The condition is similar to heparin-induced thrombocytopenia. Specific risk factors for VITT have yet to be determined given the extremely low case count, though presentation seems to appear between 5-28 days post vaccination. Patients should be reassured that the benefits of vaccination against COVID-19 far outweigh any potential risk. Diagnostic, therapeutic, and patient communication recommendations are included below.
Authors: Geoffrey D. Barnes, MD, MSc, FACC; Adam Cuker, MD, MS; Gregory Piazza, MD, MS, FACC; Deborah Siegal, MD, MSc
SQC Approval Date: April 21, 2021

What is VITT and how common is it?

Vaccine-induced thrombotic thrombocytopenia (VITT) also has been referred to as vaccine-induced prothrombotic immune thrombocytopenia (VIPIT). This condition is similar to heparin-induced thrombocytopenia (HIT) but is associated with prior administration of the Johnson & Johnson/Janssen or AstraZeneca COVID-19 vaccines without prior exposure to heparin. To date (April 21, 2021), this condition has not been reported in patients who have received the Moderna or Pfizer COVID-19 vaccines.

VITT is characterized by the presence of two conditions concurrently: thrombosis (often in unusual sites like the cerebral sinus veins or splanchnic veins) AND thrombocytopenia. Early mechanistic evaluations have identified antibodies to the platelet factor 4 (PF4)-heparin complex, similar to HIT antibodies. Detection of the PF4 antibodies can be done using a HIT ELISA test, but not reliably with other HIT laboratory tests.

The incidence of VITT is not certain, but it appears to be extremely rare. The Centers for Disease Control and Prevention (CDC) announced 6 cases among more than 6 million people vaccinated with Johnson & Johnson COVID-19 vaccine. Ongoing investigations will help to better describe the incidence of VITT and inform the CDC's future decision on vaccine administration based on overall benefits and risk. The risk of death and serious outcomes of COVID-19 (including thrombosis) far outweigh the small risk of VITT.

Who is at risk for VITT?

Early data suggest that VITT occurs only following a COVID-19 vaccination with Johnson & Johnson or AstraZeneca vaccine. Note that AstraZeneca vaccine is NOT available in the United States. Furthermore, the small number of reported events occurred between 5-28 days following the vaccine. They have not been reported to occur immediately (within 1-2 days) or longer-term (beyond 3-4 weeks) after vaccination. It will be important to re-evaluate the "at risk" window as more is learned about VITT.

Demographic and clinical risk factors for the development of VITT are uncertain. Most patients who developed VITT were younger (age <60 years). While all of the cases following Johnson & Johnson vaccine in the United States occurred in women, both men and women have been diagnosed with VITT following AstraZeneca vaccine in other parts of the world.

Specific clinical risk factors for VITT have not been identified. There is no evidence that patients with a history of thrombosis, thrombophilia, or HIT are at increased risk for VITT.

What should I do if I suspect a case of VITT?

The first thing to do for a suspected case of VITT is to verify COVID-19 vaccine details – which vaccine and when was it administered? Only patients who have received Johnson & Johnson or AstraZeneca vaccine 5-28 days previous to symptoms onset are at risk based on current information.

Next, imaging appropriate to their symptoms (e.g., CT or MR venogram of the head for suspected cerebral sinus vein thrombosis) and an urgent complete blood count (including platelet count) are appropriate. If either test is normal (no thrombosis or thrombocytopenia), then VITT can be excluded. If BOTH tests are abnormal (acute thrombosis and thrombocytopenia), hospitalization for further evaluation and treatment guided by a hematologist or other thrombosis expert is appropriate.

What should I tell my patients who call with questions about VITT and COVID-19 vaccines?

First, provide reassurance that these events are extremely rare. In the rare event that VITT occurs, hospitals and doctors have the tools to diagnose and treat this condition.

Second, remind them that VITT has only been seen with the Johnson & Johnson and AstraZeneca COVID-19 vaccines. Note that AstraZeneca's vaccine is not available in the United States and the Johnson & Johnson vaccine program has been placed on hold. Furthermore, VITT has not been reported in patients who received the Moderna or Pfizer vaccines. Overall, the available COVID-19 vaccines are very safe and highly effective at preventing COVID-19 infection. All patients should be encouraged to get their first available COVID-19 vaccine given the ongoing pandemic and known risks of COVID-19 infection. Finally, the apparent risk of VITT with a COVID-19 vaccine is greatly outweighed by the risk of complications from COVID-19 infection (including hospitalization, thrombosis and death).

Third, if a patient did receive the Johnson & Johnson vaccine, the presumed window of risk is narrow – between 5 and 28 days after vaccination. Based on our initial understanding of this condition, patients outside that window can be further reassured.

Finally, use of any medication to prevent VITT (e.g., aspirin) is not recommended. These events are extremely rare and there is no evidence that any medication would prevent them from occurring.

Where can I get more information?

Published References

  1. Greinacher A, et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med 2021;April 9:[Epub ahead of print]. DOI: 10.1056/NEJMoa2104840
  2. Schultz NH, et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med 2021;April 9:[Epub ahead of print]. DOI: 10.1056/NEJMoa2104882
  3. Muir KL, et al. Thrombotic thrombocytopenia after Ad26.COV2.S vaccination. N Engl J Med 2021;April 14:[Epub ahead of print]. DOI: 10.1056/NEJMc2105869
  4. Tacquet M, et al. Cerebral venous thrombosis: a retrospective cohort study of 513,284 confirmed COVID-19 cases and a comparison with 489,871 people receiving a COVID-19 mRNA vaccine. Preprint available here.
  5. Cines DB, Bussell JB. SAR-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. N Engl J Med 2021;April 16:[Epub ahead of print]. DOI: 10.1056/NEJMe2106315

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