NEJM with a well performed and convincing study associating the (extremely) rare clotting syndrome seen with the AZ vaccine with development of platelet factor 4 antibodies and a HIT-like syndrome. https://www.nejm.org/doi/full/10.1056/NEJMoa2105385?query=TOC

HIT is heparin-induced thrombocytopenia, a syndrome we see not-infrequently in the hospital setting as exposure to heparin products, like lovenox and unfractionated heparin, is routine.

Rarely with use of the medications patients develop a paradoxical syndrome of clotting, combined with drops in their platelet counts. It is easy to treat, but dangerous if unrecognized. And critically, you have to use *nonheparrin based anticoagulants* to treat it.

Other anticoagulants, like those that replicate how leeches block clotting, are available. And once the heparin is gone the PF4 antibodies no longer create the clotting risk because the heparin molecule has to be present to bind it to be pathogenic.

There are a few takeaways here that I get.

One is, this is rare, far rarer than the HIT associated with the anti DVT prophylaxis we give like water in the hospital.

Two, this is imminently treatable, we have lots of experience with HIT, if recognized.

Three, so far, my understanding is this is associated with the two vaccines using adenoviral vectors, and I think it merits exploring if this is a rare effect from the vector itself - we’ve never used these at scale before.

Four, this would not stop me from getting the AZ vaccine, just as it wouldn’t stop me from receiving heparin or lovenox if I were hospitalized. It’s rare, treatable, and appears to be self-limited.

Five with administration of the vaccine we should warn patients to be alert to excessive bruising or petichiae - little red spots in patches from capillary bursts in the skin. These should merit lab workup to check for drops in platelets and the development of pf4 antibodies.

Finally this seems different from reports of theombocytopenia with the other vaccines reported, with this being in primarily healthy people and those reports in patients with previous thrombocytopenia or autoimmunse disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014568/

These cases are more complex and the association harder to attribute causality. But it is possible, given ITP is sometimes a post viral syndrome, including in COVID, that antibody response to viral proteins could also cause it. I had self limited ITP after chicken pox as a kid...

Humans are terrible at assessing risk, and this is a good example of it. COVID also is a rare cause of ITP, and *much more likely* to make you clot to death, and kill you in a number of other ways. It’s good we’ve figured this out, it will be easier to recognize and treat!

And immunity from the vaccines, even with this as a possible side effect of AZ and JJ remain wildly safer than infection. This is a no-brainer.