Here’s an interesting post on comparing SARS-CoV-2 being the Michael Bay Transformer sequel to SARS-1
When you reach the point of ICU you probably have an extended pulmonary intravascular coagulopathy and your chances are not high since you have the prothrombotic phenotypic genetic response to COVID19.
At some point we will have to determinate the inflammatory mediators to determinate the intensity of the inflammatory cascade reaction leading to pulmonary vascular thrombosis by serum testing or genetic testing healthy patients to see if they can be infected without any mortality risk or if they are highly inflammatory responders.https://www.facebook.com/jenniferkastenmd/posts/129795248673422?__tn__=K-R
COVID-19 and blood clots: the evidence, and why it's important for everything from to how to manage a ventilator, to what makes COVID unique. Today we'll look at:
- A new series of autopsies from Italy showing lungs full of clots [resulting in the equivalent of a middle school dance: oxygen on one wall, blood on the other]
- A new clinical term: Pulmonary Intravascular Coagulopathy, which might be the calling card of COVID
- How elevated the clotting risk really is in COVID, and how some patients are basically reverse hemophiliacs
- A paper comparing SARS-1 to our SARS-CoV-2 for clots [the sequel is always worse]
- And lastly: what this means for mechanically ventilated patients, and how it can explain the 'Not Normal ARDS' physiology
ITALIAN AUTOPSIES SHOW LUNGS WHERE BLOOD AND AIR CAN'T MEET
Investigators performed a series of 38 autopsies in Milan and Bergamo (1). The findings reinforced the smaller American series already published: the smallest capillaries are full of fibrin thrombi (clots), which significantly restrict the ability of oxygen to diffuse across into red blood cells- which is the entire purpose of the lungs. If blood and oxygen aren't meeting up, get a new DJ because the party is pretty much a bust.
Of the patients who had an important clotting factor measured, the values were screamingly high: more than 10x the normal range. 33/38 patients showed the fibrin thrombi, which is a much elevated rate over typical ARDS patients. [The picture shows a thrombus from their series, with the virus next door.]
THE CLOTTING IS SO UNIQUE, COVID HAS COINED A NEW TERM: PULMONARY INTRAVASCULAR COAGULOPATHY
Researchers in Ireland observed a 3-fold higher risk of clotting in a series of 83 mainly Caucasian patients, versus the Chinese data (2). (The risk of clotting is related to race: people of African descent are the highest risk, followed by Caucasians, with Asians the least likely (3)). Very importantly: the patients did not develop clots absolutely everywhere (a process called DIC, disseminated intravascular coagulopathy, which occurs in a wide array of critical illnesses). Instead, the deadly coagulation occurs predominantly in the lungs.
Why? They hypothesize that since the ACE-2 receptors are on the lining of blood vessels ("endothelium") as well as in lung cells, the teeming, extra-high viral loads in the lungs spillover into the endothelium and infect it, too. That makes the endothelial cells upset, and kicks off an inflammatory cascade which results in clotting.
ICU PATIENTS MAKE CLOTS EVEN WHEN ON PROPHYLAXIS, AND SOME ARE 'REVERSE HEMOPHILIACS'
It's no news that patients in ICUs are prone to making blood clots. They're in bed and not moving around (DON'T JUDGE, IT'S BEEN A HARD MONTH FOR US ALL), and they're ill, with numerous pro-coagulable factors released in their bloodstream. For that reason, most ICU patients are treated for clots before they can develop (typically, with Low Molecular Weight Heparin).
For COVID, everyone started anti-coagulating after a study in China (4), which showed that 25% of a series of 81 patients developed deep venous thromboses (DVTs), and 40% of those patients died- a rate of clotting which is 2x normal. In France (5) 26 patients were screened for DVTs with ultrasound in: 69% were positive, even though many of them were already on anticoagulation at the low 'preventive' dose. So they stepped up therapy to TREATMENT anti-coagulation, not just prevention and still- they still clotted. 56% developed DVTs, and 6 patients had an even more worrisome pulmonary embolism. In the Netherlands (6) researchers observed a rare phenomenon in COVID-19 patients: heparin resistance, where patients need an ultra-high dose of heparin to prevent clotting. They found that the virus caused the patients to make very high levels of Factor VIII (which is the same Factor many hemophiliacs are missing).
SARS-CoV-2 IS THE MICHAEL BAY OF CLOTTING
Have you ever watched a bloated, meaningless, sequel? Where they took all the good ideas from the original and said "this but more!"? That's the new coronavirus re: clotting. The original SARS definitely caused a similar picture (small clots in the vessels of the lungs, DVTs). About 30% of the patients in the largest series made DVTs, and there were five strokes. Compare that to the French data above (56% on therapy). The data is scantier on MERS, but it seemed to be more garden-variety DIC (7).
VERY INTERESTING, I GUESS, BUT ALSO, WHY IS THIS IMPORTANT?
I see you looking at your watch, trying politely to leave. Congrats! You made it to the end of the post! It's important because it validates all those countless clinical observations that "this isn't normal ARDS." I posted earlier about Dr. Cameron Kyle-Siddell's videos- the "is it like HAPE?" guy- and while no, it's not like HAPE, he was asking good questions. There are some very encouraging early anecdotes of doctors using this information to treat desperately failing patients, patients maxed out on the ventilator, with ANTI-COAGULATION (specifically, tPA) as a a way to open up those capillaries and let oxygen and the blood meet, marry, and diffuse.
1) Luca Carsana, Aurelio Sonzogni, Ahmed Nasr, Roberta Rossi, Alessandro Pellegrinelli, Pietro Zerbi, Roberto Rech, Riccardo Colombo, Spinello Antinori, Mario Corbellino, Massimo Galli, Emanuele Catena, Antonella Tosoni, Andrea Gianatti, Manuela Nebuloni. "Pulmonary post-mortem findings in a large series of COVID-19 cases from Northern Italy." PRE-PRINT on Medrxiv.org.
2) Fogarty H, Townsend L, Ni Cheallaigh C, Bergin C, Martin-Loeches I, Browne P, Bacon CL, Gaule R, Gillett A, Byrne M, Ryan K, O'Connell N, O'Sullivan JM, Conlan N, O' Donnell JS. COVID-19 Coagulopathy in Caucasian patients. Br J Haematol. 2020 Apr 24.
3) White RH, Keenan CR. Effects of race and ethnicity on the incidence of venous thromboembolism. Thromb Res. 2009;123 Suppl 4:S11-7.
4) Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020 Apr 9.
5) Llitjos JF, Leclerc M, Chochois C, Monsallier JM, Ramakers M, Auvray M, Merouani K. High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost. 2020 Apr 22.
6) Beun R, Kusadasi N, Sikma M, Westerink J, Huisman A. Thromboembolic events and apparent heparin resistance in patients infected with SARS-CoV-2. Int J Lab Hematol. 2020 Apr 20.
7) Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020 Apr 9;127:104362.