Heparin and platelets are discouraged as treatment for patients who develop blood clots in the brain and low platelet counts 6-15 days after receiving Johnson & Johnson’s Janssen COVID-19 vaccine, following a clinical investigation review of 12 U.S. cases conducted by the Centers for Disease Control and Prevention and institutions including Vanderbilt University Medical Center.
Typically, when people develop blood clots they are treated with the anti-coagulant heparin, used to thin the blood.
“It is a common anticoagulant that we use to thin the blood but unfortunately, in this clinical scenario, if the theories about the pathophysiology are correct then heparin would be a very dangerous medication to use,” said Allison Wheeler, MD, associate professor of Pathology, Microbiology and Immunology at VUMC. “Given the presence of low platelets, some patients may also receive platelet transfusion, which can also be dangerous in this scenario.”
The clinical investigation review for public health purposes was published in the Journal of the American Medical Association (JAMA).
The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Johnson & Johnson’s Janssen single dose COVID-19 vaccine on Feb. 27, 2021; approximately 7 million doses had been administered nationwide before the CDC and FDA recommended a pause in the use of the vaccine on April 13, 2021.
Reviewers noted that the adverse events are “rare and clinically similar to clotting events that occurred in Europe after vaccination with the Oxford/AstraZeneca COVID-19 Vaccine.”
“It’s just really important to say that this work has looked at a very small number of patients who have a very serious complication, and the most important thing that we need to do is keep learning and keep trying to understand why that complication occurred,” said Wheeler, also an associate professor of Pediatrics and director of research for Benign Hematology.
“I have recommended the vaccine to my family members as well as friends,” she said. “I think that, overwhelmingly, the benefit of receiving the COVID vaccine is above and beyond the potential risks that we understand now.”
The complication is known as cerebral venous sinus thrombosis (CVST) with thrombocytopenia following J&J/Janssen vaccination. It is part of a new syndrome called thrombosis with thrombocytopenia syndrome (TTS).
TTS, which has not been reported with the Pfizer or the Moderna mRNA vaccines, may also involve blood clots in other parts of the body outside of the brain.
The 12 U.S. patients were all white females ages 18-60 who received J&J/Janssen vaccination. Six of these patients were treated with heparin but the CDC now recommends not administering heparin when TTS is suspected.
Eleven of the 12 patients came to the hospital with a headache that began six or more days after vaccination and the other patient came to the hospital with back pain and later developed a headache. Most of these headaches were described as “severe and persistent.”
Headaches are common shortly after vaccination but usually start and resolve within two days.
Seven patients had at least one risk factor for CVST, including obesity (6), hypothyroidism (1) and combined oral contraceptives (1) but none of the patients had the most common CVST risk factors such as pregnancy, 12 weeks postpartum, prior thrombosis, or a family history of clotting disorders.
All 12 patients were hospitalized, 10 in the intensive care unit (ICU). By April 21, three patients had died, three continued ICU care, two had non-ICU hospitalization and four were discharged home.
“We found there were a lot of similarities between these patients, specifically they were all females within the same general age group and most of them had some similarities between the laboratory testing that had been done and as a part of their clinical evaluations,” Wheeler said.
“I think this surveillance can be used in many ways,” she added. “Right now, it is being used to help us understand these presentations. It’s new. It is not something that we have seen before in this clinical context and so, with every patient, there comes learning for the clinicians who are taking care of those patients and also for the group at the CDC who is looking at all of the patients together.”
Wheeler is a hematology advisor to the CDC’s Clinical Immunization Safety Assessment (CISA) group.
“The CISA network is so lucky to have the expertise of Dr. Wheeler to rapidly evaluate these adverse events,” said Kathryn Edwards, MD, scientific director of the Vanderbilt Vaccine Research Program and professor of Pediatrics in the Division of Infectious Diseases at Vanderbilt University School of Medicine.
“Her expertise from the coagulation work here at Vanderbilt laboratory has led the CDC efforts to define what is needed in these evaluations. She has been available day and night to address questions from providers dealing with these patients,” Edwards said.
Reviewers noted that healthcare providers should be alert to symptoms of TTS in patients who received J&J/Janssen vaccination, including delayed onset of severe, persistent headache or persistent abdominal pain, shortness of breath, chest pain, leg swelling and bruising.
“Most of these patients came in with symptoms of headache, although some patients came in with pain in other areas,” Wheeler said. “But predominantly headache.”
“Where we go from here is we continue learning. Right now, there is an association between the J&J/Janssen vaccine and a series of symptoms, but what we don’t have is a clear causal relationship between these two things and that is something that scientists are working on.”
This work was supported by the CDC’s CISA Project contracts 200-2012-53664 to Johns Hopkins University and 200-2012-50430 to VUMC.
