J&J Covid-19 Vaccine Pause Spotlights Science of Rare Clotting Disorder -- 3rd Update

By Daniela Hernandez and Brianna Abbott

Scientists are racing to gain a better understanding of a rare blood-clotting disorder that affected six recipients of Johnson & Johnson's Covid-19 vaccine and led health authorities on Tuesday to recommend a pause in its use.

"It is quite a rare disease, and an unusual manifestation of abnormal blood clotting in the body, but it is very serious," Thomas Oxley, an interventional neurologist and stroke expert at Mount Sinai Health System in New York City, said of the clotting disorder.

The six people in the U.S. known to have been affected by the disorder after vaccination are among almost seven million Americans to have received the vaccine.

The reports echo similar ones involving rare clotting disorders seen in Europe among recipients of the Covid-19 vaccine manufactured by AstraZeneca PLC.

Doctors aren't certain what causes the clots to form. One hypothesis, based on preliminary data from a small number of patients in Europe, is that the AstraZeneca vaccine can cause the body to mount an immune reaction that triggers clot formation, according to Jean Connors, a hematologist at Brigham and Women's Hospital. Doctors said something similar likely explains the clotting problem seen rarely in recipients of the J&J vaccine.

In two studies published in April in the New England Journal of Medicine, German and Norwegian researchers detailed this rare immune response, which seems to target a protein on the surface of platelets, blood components that aid in the formation of clots. Patients examined by the researchers developed a severe clotting condition.

The J&J vaccine recipients who experienced the rare clotting condition were diagnosed with cerebral venous sinus thrombosis, or CVST, which involves the formation of clots within large blood vessels in the brain. That was accompanied by a drop in platelet levels.

The immune reaction can translate into unchecked clot formation, Dr. Connors said.

The brain-vessel clots can increase pressure within the skull, leading to hemorrhaging and stroke, doctors said.

Doctors don't have enough data yet to know whether clots associated with the J&J shots form preferentially in blood vessels in the brain.

The six affected recipients of the J&J vaccine, all women between the ages of 18 and 48 years, developed symptoms six to 13 days after vaccination. Peter Marks, director of the Center for Biologics Evaluation and Research at the Food and Drug Administration, said Tuesday during a webinar that a man who participated in the clinical trial of the J&J vaccine experienced similar clotting.

"This event was initially thought to be related to the study product by the investigator and prompted a study pause," according to an FDA briefing document on the J&J clinical trial. The investigators' final assessment was that the complication was unrelated to the vaccine.

Oral contraceptives can increase the risk of certain blood clots, but Dr. Marks said most of the women who developed clots after vaccination weren't taking the drugs. There is no clear association between oral birth control and the clots seen in the women, he said. The agency is continuing to evaluate various risk factors.

"This is a very, very rare event," Dr. Marks said, adding that the agency recommended the pause in part to educate medical providers about spotting and treating the potential complication.

People who develop severe headache, abdominal or leg pain, or shortness of breath within three weeks after vaccination should immediately contact their healthcare providers, according to federal officials. Headaches within 24 hours of getting vaccinated are normal, doctors said. The risk of clotting among people who got the J&J shot more than a month ago is very low, said Anne Schuchat, the principal deputy director at the Centers for Disease Control and Prevention.

Doctors have documented a similar disorder after treatment with the blood thinner heparin. Dr. Connors and other blood specialists cautioned against using that drug to treat vaccine-associated clots because it could aggravate the condition.

The AstraZeneca vaccine and Johnson & Johnson's both use so-called viral vector technology, in which genetic instructions for a key component of the novel coronavirus are placed within a harmless virus and then injected into the body to trigger immunity to the pathogen.

"The beauty is that you use natural systems, which are optimized by millions of years of evolution, to deliver what you want to have your body respond to," said Vincent Munster, chief of the virus ecology section at the National Institute of Allergy and Infectious Diseases, which helped with development of the AstraZeneca vaccine.

These vaccines offer several advantages over shots using older technology. They seem to activate not just the antibodies that neutralize a virus but also the memory and T-cells that keep the immune defense alert for the long-term.

The vaccines developed by Moderna Inc. and by Pfizer Inc. with BioNTech SE use a different technology, known as mRNA. Health authorities haven't seen any cases of clotting with low platelet counts associated with those vaccines, the CDC's Dr. Schuchat said.

In the case of the J&J vaccine, clots also might be forming in other parts of the body but only ones in the blood vessels in the brain have been detected so far, in part because the vaccine has had a limited rollout in the U.S.

In Europe, there has been a wider range of abnormal clots among the 34 million people who received the AstraZeneca shot.

"We don't know if we had given a lot more doses of the J&J vaccine if we would have seen other [types of] clots," said Gary Raskob, a blood-clotting expert at the University of Oklahoma.

Doctors said they would keep monitoring patients to determine the exact mechanism behind the clotting. They said the risk of experiencing a dangerous side effect from vaccination is very low and is outweighed by the potential short- and long-term risks of catching Covid-19.

The pause in the J&J rollout in the U.S. comes at a precarious time in the pandemic, with more infectious and potentially more deadly variants taking hold around the world and creating renewed urgency to boost vaccination rates globally. Some countries might be at greater risk than others.

"The majority of vaccines administered [in the U.S.] have been mRNA-based -- Moderna and Pfizer," said Abraar Karan, a global health physician at Brigham and Women's Hospital. "I don't expect that, right now, this will have an exceptionally outsize role in slowing down the vaccine rollout."

--Joseph Walker and Bojan Pancevski contributed to this article.

Write to Daniela Hernandez at [e-mail] and Brianna Abbott at [e-mail]

(END) Dow Jones Newswires

04-13-21 2009ET