The devastating blood-clotting disorder at the center of concerns about the Johnson & Johnson COVID-19 vaccine is so rare that doctors are scrambling to figure it out, with a few clues from similar illnesses that are not vaccine-related.

Many of these clots have occurred in veins that drain blood from the brain, and they have formed in combination with depleted platelets, cells that help blood clot. This paradoxical combo requires different treatment than most clots.

A similar problem has been seen with the AstraZeneca vaccine, which, like the Johnson & Johnson product, uses adenoviruses to deliver genetic instructions that prime the immune system to recognize the virus that causes COVID-19. AstraZeneca’s vaccine is not approved for use in the United States.

» READ MORE: J&J can resume use of COVID-19 vaccine, with warning about rare clotting disorder, federal advisors say

On Friday, a U.S. Centers for Disease Control and Prevention official told a vaccine advisory committee that the agency has confirmed 15 cases of the clotting/low-platelet disorder among 7.98 million people who received the Johnson & Johnson vaccine.

Normally, when people have strokes, a clot is found to have blocked an artery in the brain, said Charles Abrams, a hematologist and chief scientific officer in the Hospital of the University of Pennsylvania’s Department of Medicine. Arteries transport newly oxygenated blood from the heart to the rest of the body.

But many of the clots linked to the J&J vaccine are known as cerebral venous sinus thrombosis (CVST). That means they form in cerebral sinuses and veins. Sinuses are channels with a different structure than veins, but both allow oxygen-depleted blood and other fluids to leave the brain. They are outside the brain, but inside the skull, said Abrams, who did not talk at the Advisory Committee on Immunization Practices (ACIP) meeting Friday. When sinuses or veins are blocked, pressure can build up in the brain, causing vessels there to burst and bleed. While the clots do not always result in such a stroke — damage caused by depletion of oxygen to brain tissue — they can lead to strokes if not treated quickly.

In several cases, the J&J vaccine also triggered clots in veins and arteries in parts of the body besides the brain.

CVST occurs in one of 5,000 to 25,000 people who have COVID-19, Abrams said.

In the general population, 10 to 15 of every million people get it per year, said Michael Streiff, a Johns Hopkins University hematologist who testified before ACIP Friday. It is twice as common in women. Risk factors include birth control pills, clotting disorders, pregnancy, cancer, infections, and surgery.

In 30 years of practice, Abrams has seen about a dozen such clots.

The kind of clot that vaccine recipients had is even more unusual, because those patients also had thrombocytopenia, or low platelets.

“I think what that means is that there’s a process, probably an immune-mediated process … and it’s causing both the clot in the head and the low platelet count,” Abrams said. Some people have had a similar reaction to the blood thinner heparin.

Streiff said that vaccine recipients with clots and low platelets, like those with heparin-induced thrombocytopenia, have “uniformly” tested positive for antibodies to platelet factor 4, a protein in platelets. He said that what’s happening with vaccines looks most like autoimmune thrombocytopenia, which sometimes can occur after surgery. While the causes are unclear, the antibodies lead to “profound platelet activation” which ultimately triggers a “coagulation cascade” that goes well beyond platelet dysfunction.

Most people with CVST survive without lasting neurological damage, Abrams said. They are usually given drugs that reduce clotting. For those who also have low platelets, doctors often give immunoglobulin, which boosts the immune system and can increase the platelet count. Typically, doctors do not attempt to mechanically remove clots because of the risks that adds, he said.

He said, though, that the combination of the venous clots with low platelets is so rare that “none of us have enough real experience with it.”

Streiff said heparin can paradoxically make clotting worse in these patients. Platelet transfusions can also “feed the fire.” He said it is important to give patients intravenous immunoglobulin and blood thinners other than heparin as soon as possible.

He hopes that publicity will alert patients to seek attention faster and make doctors more aware of this complication.

Venous clots often go unrecognized for several days, Abrams said. The most common symptom is a bad headache, the kind that makes you say, “I’ve never had a headache like this before.” Low platelet count is also associated with easy bruising and bleeding.

People with a severe headache after vaccination should be tested for platelet count and clotting ability, he said. If doctors suspect venous clotting, they should be aware that CT scans miss about a third of cerebral venous sinus clots, Abrams said. MRIs usually pick up these clots.