05 May COVID-19: CDC Characterizes Case Reports of Clotting Disorder with Janssen/J&J Vaccine
MedicalResearch.com Interview with:
Isaac See, MD
Centers for Disease Control and Prevention COVID-19 Response Team
MedicalResearch.com: What is the background for this study?
Response: On February 27, 2021 the U.S. Food and Drug Administration (FDA) granted emergency use authorization for the Janssen/Johnson & Johnson (J&J) COVID-19 Vaccine in people 18 years of age or older in the United States. The Janssen/J&J COVID-19 Vaccine uses a replication-deficient (i.e., cannot cause infections) human adenovirus vector. In mid-March, the European Medicines Agency announced that they had conducted a preliminary investigation of cases of blood clots and low counts of blood cells called platelets in patients who had recently received the Oxford/AstraZeneca COVID-19 Vaccine, which uses a replication-deficient chimpanzee adenovirus vector. This syndrome of blood clots and low platelet counts has been called thrombosis with thrombocytopenia syndrome, or TTS. The European investigation showed that over 70% of their cases specifically involved blood clots in particular veins inside the brain, a condition caused cerebral venous sinus thrombosis (CVST), in addition to low platelet counts (thrombocytopenia is the medical term for low platelet counts).
CVST is already a rare condition, and CVST with thrombocytopenia is even rarer. By April 12, 2021, approximately 7 million doses of the Janssen/J&J COVID-19 Vaccine had been given in the United States, and six cases of CVST and thrombocytopenia after receipt of the Janssen/J&J COVID-19 Vaccine had been reported to the U.S. Vaccine Adverse Event Reporting System (VAERS), which is the U.S. national vaccine safety monitoring system. The next day (April 13, 2021) CDC and FDA recommended a pause in use of the vaccine recommended to allow for further investigation of these events. On April 23, 2021 data about the first 12 cases reported after authorization of the Janssen/J&J COVID-19 Vaccine were presented at an emergency meeting of the Advisory Committee on Immunization Practices (ACIP) to decide what to recommend regarding the Janssen COVID-19 vaccine. The ACIP concluded that the benefits of resuming Janssen COVID-19 vaccination among persons aged 18 years or older outweighed the risks and reaffirmed its interim recommendation under the FDA’s Emergency Use Authorization. The FDA’s Emergency Use Authorization includes a new warning for rare clotting events among women aged 18 to 49 years. Our report provides clinical details about these first reported 12 U.S. cases of CVST and thrombocytopenia following receipt of the Janssen COVID-19 Vaccine.
MedicalResearch.com: What are the main findings?
Response: The main findings are that all of these 12 cases of CVST and thrombocytopenia in people who had received the Janssen COVID-19 Vaccine happened in white females under the age of 60 years; 11 of the 12 were under 50 years old. Eleven of them initially presented to medical attention with headaches. Seven of the patients had a condition that would usually be considered a risk factor for CVST, but only one had a risk factor that is commonly seen in patients with CVST (oral contraceptive use); for example none of the patients were pregnant or within 12 weeks post-partum, had a prior history of a blood clot, or a personal or family history of a clotting disorder. Symptoms started between 6–15 days after vaccination, and 3 of the patients had died at our last follow-up.
Many of the U.S. cases of CVST and thrombocytopenia after Janssen COVID-19 vaccination also had blood clots in other parts of the body, which is also not typically seen with CVST otherwise.
One additional finding was that 11 of the patients received a test that is usually used to screen for another condition called heparin-induced thrombocytopenia (HIT), which can cause low platelets and blood clots usually in patients who have received the blood thinner heparin within 90 days or less. This test looks for a particular antibody and is sometimes called the heparin-platelet factor 4 (PF4) enzyme-linked immunosorbent assay (ELISA); however none of our patients were known to have recently received heparin.
The female predominance, lack of typical CVST factors, degree of low platelet counts, positive results of antibody tests for HIT (heparin-PF4 ELISA) without known previous exposure to heparin, and presence of clots elsewhere in the body were characteristics shared between the U.S. and European cases of CVST and thrombocytopenia after Janssen and Oxford/AstraZeneca COVID-19 vaccination, respectively. In short, the U.S. and European cases of CVST and thrombocytopenia appear to be clinically similar.
MedicalResearch.com: What should readers take away from your report?
Response: There are a number of takeways for both providers and patients.
First, the identification of the initial CVST reports that led to a temporary pause in J&J/Janssen vaccine, and the rapid investigation and response to these findings to inform U.S. vaccine recommendations demonstrate that the U.S. vaccine safety monitoring system is working as intended. That is a reassuring thing.
Second, patients and healthcare providers should be aware of symptoms of TTS (CVST as well as other blood clots) in patients who received the J&J/Janssen COVID-19 Vaccine. These symptoms include delayed onset of severe, persistent headache or persistent abdominal pain, as well as shortness of breath, chest pain, leg swelling, or easy bruising or petechiae. It’s important to note that while headaches are common, timing of headaches associated with CVST after J&J/Janssen vaccination differs from that of headaches that most commonly occur after vaccination. For example, headaches after J&J/Janssen vaccination usually start within 2 days of vaccination and resolve within 2 days. All patients in our report had headaches that began 6 or more days after vaccination. The majority of these headaches were severe and persistent. Healthcare providers should assess a COVID-19 vaccination history in patients presenting with these symptoms; and in patients with potential TTS symptoms who received the J&J/Janssen COVID-19 Vaccine, obtain platelet counts and evaluate for CVST and other blood clots as symptoms suggest.
Third, CDC and the American Society of Hematology have provided recommendations for providers treating patients with TTS, including avoiding administration of heparin, ordering the heparin-PF4 ELISA that is used to screen for the HIT antibody, and strong recommendations to use a non-heparin anticoagulant and consult a hematology.
Fourth, patients need to be aware of the increased risk of TTS after J&J/Janssen COVID-19 Vaccine, especially women younger than 50 years of age. Finally, providers who see patients with TTS should report the TTS event to the VAERS system (vaers.hhs.gov).
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: There is a lot of attention right now, rightly so, to better defining how and why this condition occurs. The leading hypothesis is that somehow a reaction is being triggered in the body that leads to generation of antibodies that activate platelets and form blood clots. It hasn’t been proven yet that this reaction is caused by the vaccine, but different organizations have said that it seems plausible and having a definitive answer to that question would be valuable. We also don’t yet understand why specific patients develop this and others don’t; that also would be helpful for counseling patients if it were known.
MedicalResearch.com: Is there anything else you would like to add?
Response: I want to thank my colleagues the CDC and FDA who have been working on this, and the academic investigators who collaborate with us from the Clinical Immunization Safety Assessment (CISA) Project and lent their clinical expertise during this investigation. I also want to show appreciation for the providers who took care of these patients and also reported the CVST events to VAERS.
I have no disclosures.
See I, Su JR, Lale A, et al. US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021. JAMA. Published online April 30, 2021. doi:10.1001/jama.2021.7517
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