What is the association between the Ad26.COV2.S and AZD-1222 vaccines and thrombosis with thrombocytopenia syndrome (TTS)?

Updated: Sep 24, 2021
  • Author: David J Cennimo, MD, FAAP, FACP, FIDSA, AAHIVS; Chief Editor: John L Brusch, MD, FACP  more...
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Thrombosis with thrombocytopenia syndrome (TTS) 

Cases of thrombosis with thrombocytopenia with the Ad26.COV2.S (Janssen [Johnson & Johnson]) and AZD-1222 (ChAdOx1 nCoV-19; AstraZeneca) vaccines have been reported. The FDA temporarily paused use of Ad26.COV2.S in mid-April 2021 to allow the CDC's Advisory Committee on Immunization Practices (ACIP) to evaluate rare cases of cerebral venous sinus thrombosis. After discussing the benefits and risks of resuming vaccination, ACIP reaffirmed its interim recommendation for use of the Janssen COVID-19 vaccine in all persons aged 18 years and older under the FDA’s EUA. The EUA now includes a warning that rare clotting events may occur after vaccination, primarily among women aged 18-49 years. The risk for death and serious outcomes of COVID-19, including thrombosis, far outweigh the risk for TTS possibly associated with highly efficacious vaccines. [38]   

TTS is a rare syndrome that involves acute venous or arterial thrombosis and new-onset thrombocytopenia in patients with no known recent exposure to heparin. Although the mechanism that causes TTS is not fully understood, and appears similar to heparin-induced thrombocytopenia, a rare reaction to heparin treatment. In the United States, 12 of 15 persons with TTS that occurred after Janssen COVID-19 vaccination had CVST with thrombocytopenia. [38]   

The American Society of Hematology and the American Heart Association/American Stroke Association have published documents for clinicians to be aware of symptoms, diagnosis, and urgent treatment if TTS is suspected.  

Diagnosis includes the following 4 criteria:

  • COVID vaccine (Johnson & Johnson/AstraZeneca only to date) 4 to 30 days previously  
  • Venous or arterial thrombosis (often cerebral or abdominal) 
  • Thrombocytopenia 
  • Positive PF4 ‘HIT’ (heparin-induced thrombocytopenia) ELISA 

The following symptoms associated with TTS may emerge 4-30 days after vaccination with Ad26.COV2.S or AZD-1222:

  • Severe headache 
  • Visual changes Abdominal pain 
  • Nausea and vomiting 
  • Back pain 
  • Shortness of breath 
  • Leg pain or swelling 
  • Petechiae, easy bruising, or bleeding

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