Amarin Corp Plc (AMRN)

[north40000]

The other mystery, for which you posit Vascepa as a potential solution, remains a mystery, at least to me. Here's why--it is a fascinating story:

https://www.washingtonpost.com/health/2021/04/19/johnson-and-johnson-vaccine-blood-clots/

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During the next decades, recognition grew that rare reactions to heparin were real and that they were probably triggered by the immune system. A 1977 study detailing the cases of eight patients, six of whom were women, was considered key in establishing heparin-induced thrombocytopenia — known as HIT — as a recognized condition. A vascular surgeon in Milwaukee coined the term “white clot syndrome.”

Scientists would continue to learn more about HIT, discovering that a protein found inside platelets that also coated the surface of arteries and veins, called platelet factor 4, could bind strongly to heparin, forming a two-part complex.

In some people, when heparin and the protein bonded, the body’s disease-fighting system went on alert, triggering antibodies against platelet factor 4. That could wreak havoc. The antibodies could activate platelets, but with seemingly contradictory consequences: Some platelets would clot, while others would vanish. The antibodies could damage the cells lining blood vessels, helping trigger clots in more ways than one.
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Because those antibodies could be detected in laboratory tests, physicians had an indispensable tool to diagnose the condition. The first iteration of a test was created by Warkentin’s mentor, John Kelton, in 1984.

It has taken years to work out the science of what is going on in HIT, and it remains an ongoing project. Scientists painstakingly developed mouse models that allowed them to study the condition and made a lab-generated monoclonal antibody that mimicked the one in the body. Warkentin and colleagues discovered a mysterious form of the condition that could occur, even in the absence of heparin.

“It’s funny, because you work in these areas and everyone in your family thinks it’s so esoteric and then something like this happens,” said Mortimer Poncz, division chief of pediatric hematology at Children’s Hospital of Philadelphia. “On the other hand, every time there is an unusual clot, someone is testing it for HIT these days. So it is simply exciting that turned out to be useful.”

An unusual type of clot
When something bad happens to a person after receiving a vaccine, the first question most scientists consider is whether it is related to the shot or simply a coincidence.

In the case of the brain blood clots identified in people in Europe who recently received the AstraZeneca vaccine, early inquiries focused on whether it was happening more frequently than the typical rate of such clots in the general population.

The brain blood clots, called cerebral venous sinus thrombosis, are rare — with about two to 14 cases expected in a population of 1 million people each year. The clots in recently vaccinated people were clearly more common than would be normal, occurring in a matter of weeks after healthy, young people received shots.

So far, 222 clots in the brain or abdomen have been identified out of 34 million people vaccinated in Europe — in far less than a year. But what stood out to physicians was that the ensemble of symptoms surrounding these clots was so atypical there wasn’t even an easy way to look up the rate of how often they would normally occur.

“People get blood clots. Those things happen,” said Steven Coutre, a hematologist at Stanford University Medical Center. “It’s one thing to have a blood clot; it’s another to have disseminated blood clots in an otherwise healthy woman who dies from it. That gets your attention.”

On a Friday in early March, Sabine Eichinger, a physician in Austria involved in the care of the first patient, a 49-year-old health-care worker, told Andreas Greinacher, an expert in Germany on HIT, about the unusual case. She agreed to send him a sample, and by the following Tuesday, Greinacher was talking with Warkentin about the parallels between the cases and the rare immune reaction to heparin, about which they had co-authored a medical textbook.

By the next day, Greinacher and colleagues had determined that a diagnostic test for the same antibodies implicated in HIT could be useful. Their paper was published in the New England Journal of Medicine alongside a report from Norwegian specialists, and proposed a new name for the syndrome: vaccine-induced immune thrombotic thrombocytopenia, or VITT. They suggested a possible treatment course, including intravenous immunoglobulin and other anticoagulants.

In the heparin-triggered condition, the culprit was the combination of heparin and platelet factor 4. In the vaccine cases, it appeared that something in the vaccine — what, exactly, is still under intense investigation — bound to platelet factor 4 and triggered a similar response.

“Just as an occasional patient zings off one of these huge responses after being given heparin and gets in trouble, the occasional person given these vaccines loses the regulatory control that keeps this immune response and zings off one of these high-titer antibody responses,” said Richard Aster, a senior investigator emeritus at Versiti, a nonprofit focused on blood health and research.

In five of the six U.S. patients who developed clots after receiving the Johnson & Johnson vaccine, physicians performed tests and found those same HIT antibodies. A 25-year-old man who received the vaccine in the clinical trial of the vaccine and suffered a brain clot also had HIT antibodies. The existence of those tests — and the ability to treat the condition — is a tribute to the years of experience studying HIT.

Paul A. Offit, a vaccine expert at Children’s Hospital of Philadelphia who developed a rotavirus vaccine, said the swift revelations about the mechanism of the blood clots in people receiving coronavirus vaccines stand in marked contrast to the experience trying to understand rare events associated with other vaccines. A vaccine for rotavirus, RotaShield, was pulled off the market in 1999 because it was found to carry a rare risk of intussusception, a condition that can cause intestinal blockage and may be deadly.

“It’s amazing, having lived through the intussusception experience,” Offit said. “That was 20-plus years ago, and we still don’t know the reason.”

But even as the science behind the clots is untangled, the parallel public health question of what to do with an effective vaccine with a rare risk remains.

Many have pointed out that the risk remains lower than the risk of clots from birth control or from a serious case of covid-19. But the clots are serious and can be devastating to individuals, and some groups appear to be at higher risk for the rare reaction. The Nebraska patient was initially treated with heparin, but was switched to a regimen recommended for patients with the rare vaccine reactions, according to a case study in the New England Journal of Medicine. She was critically ill as of Wednesday, when the report was published.

A panel of expert advisers to the Centers for Disease Control and Prevention is scheduled to debate the matter again Friday. European countries have, for the most part, restarted use of the AstraZeneca vaccine, often restricting it to older people for whom the benefits clearly outweigh the risks.

“We’ll never have perfect data, and there will always be uncertainty,” Grace Lee, a professor of pediatrics at Stanford University School of Medicine, said as the CDC committee debated how to move forward Wednesday. “But it’s really for me about getting better risk estimates … if we can, to minimize exposure to those who may be at highest risk for this particular adverse event.”

Lena H. Sun contributed to this report.

Updated April 16, 2021