Read on Twitter
ICYMI, @ldtimmerman asked me to write a brief piece about clotting and COVID-19. It was kind of a blast from the past and we really fun to write. It was motivated by reports on @Twitter and case reports describing rampant thrombosis in sick COVID-19 patients
There are also reports like this https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext of strong association between elevated D-Dimer and bad outcomes in COVID-19
So I briefly reviewed the history of the relationship between inflammation and coagulation. I even got to reference my favorite paper on the fascinating evolutionary biology of snake venoms and how they attack various proteins in the coag cascade https://www.sciencedirect.com/science/article/pii/S0041010198001263
I also briefly reviewed PROWESS and APEX trials which were used in medically ill patients
https://www.nejm.org/doi/full/10.1056/NEJM200103083441001 https://www.nejm.org/doi/full/10.1056/NEJMoa1601747
https://www.nejm.org/doi/full/10.1056/NEJM200103083441001 https://www.nejm.org/doi/full/10.1056/NEJMoa1601747
I then review data showing an increase in micro and macrovascular thrombosis in SARS-CoV-1 https://onlinelibrary.wiley.com/doi/full/10.1002/path.1440
And I conclude with a call to explore the potential use of anticoagulants in sick COVID-19 patients. This is a call to do rigorous trials. What would they look like? What patients? What targets? What drugs? What outcomes? Many questions... I have some ideas
And of course I forgot to link to the actual piece https://timmermanreport.com/2020/04/rationale-for-testing-anticoagulants-against-covid19/
And this... https://twitter.com/erictopol/status/1247994939775959041?s=21 https://twitter.com/EricTopol/status/1247994939775959041
Getting all kinds of interesting DMs and emails. Here is one exploring how avian influenza uses a thrombin like protease to replicate in vivo. They then use the direct thrombin inhibitor, argatroban, in mice and see this
https://mbio.asm.org/content/10/6/e02369-19
https://mbio.asm.org/content/10/6/e02369-19
Here is the paper referenced in the LTE from @NEJM describing antiphospholipid antibodies in 3 COVID-19 patients in China. https://www.sciencedirect.com/science/article/pii/S0049017202836861?via%3Dihub
And here is a fantastic recent review on antiphosholipid syndrome https://www.nejm.org/doi/full/10.1056/NEJMra1705454
Interestingly, given the association with autoimmune diseases such as lupus, look at what has been used for treatment
Interestingly, given the association with autoimmune diseases such as lupus, look at what has been used for treatment
This space is moving so fast. I’ll have some updates soon but also here’s a really nice thread from @ScottGottliebMD https://twitter.com/scottgottliebm … https://twitter.com/scottgottliebmd/status/1250069609581031428?s=21 https://twitter.com/scottgottliebmd/status/1250069609581031428
And I’ve already had several conversations with biotech/pharma about spinning up trials here quickly. It’s doable. It has to be done
