Thread by @GeorgeGoshuamd

1\ Endotheliopathy in COVID-19 Associated Coagulopathy. Where is the field now and where is it moving in its treatment? A thread on behalf of the multidisciplinary work @YaleMedicine published just now @TheLancetHaem.

2\ What is known before our study: DD and fibrinogen are often sky high. Clinically we see thrombosis in 3 forms: macrovascular, microvascular and arterial. The former two at alarming rates in some studies, see below from our late breaking oral #EHA25virtual.

3\ In a beautifully written editorial published alongside our work, @Jme_os and her superb colleagues @RCSI_Irl and @UniversityLeeds summarized the research backdrop that in April led us to characterizing the endotheliopathy in this thrombotic coagulopathy (thank you @Jme_os!).

4\We studied 68 patients (48 in ICU/most intubated and 20 non-ICU all <3L O2) at our single center. Color coded below. Yellow: DD & TAT both increased in non-ICU and further in ICU. DD & TAT significant correlation. High DD source in part augmentation of the coagulation cascade.

5\
Green: Endogenous anticoagulants and fibrinolytic enzyme A2AP largely preserved in both non-ICU and ICU patients. CAC is distinct from DIC.
Blue: PAI-1 universally high in both non-ICU and ICU. Classic fibrinolysis may be inhibited (further characterization ongoing).

6\ VWF and FVIII well above normal in non-ICU and sky high in ICU. This strong signal was a clue we need to drill down into specific biomarkers and we picked soluble P-selectin, soluble thrombomodulin, and soluble CD40 ligand (see expanded figure below).

7\ Significant increases in sP-selectin in ICU (derived from endothelium and activated platelets), sCD40L in patients with COVID (derived from activated platelets), sTM did not reach significance (likely because of sample size) but did correlate with outcomes.

8\ In-hospital mortality was significantly lower among patients with low sTM compared with patients with high sTM among the entire cohort and among ICU patients.

9\ Why does all of this matter? Senior author #AlfredIanLee: "Our study is the first to measure specific markers of endothelial injury in the blood and demonstrate that endotheliopathy is common in COVID-19, especially when patients are critically ill." @YaleCancer @YaleHemOnc

10\ Senior author @hyungjchun:
“Once we have a clearer understanding of the disease mechanisms, we can consider evaluating drugs that target these mechanisms which may already be approved for other indications.” @YaleCardiology @YaleCVRC

medicine.yale.edu/news-article/2…

11\ On behalf of @MattMeiz @BenignHeme @hyungjchun #AlfredIanLee, C-Hong Chang, Hanming Zhang and I: thank you @YaleCancer @YaleCardiology @YalePCCSM @YaleRheumAller1 @Yale_LabMed @YaleHemOnc @ChristinaCPrice @DelaCruzYaleMed @ChrisTormey3 @NataliaNeparid1 @Halene_lab @BarNoffar

12\ Thank you to the entire @TheLancetHaem @TheLancet staff and in particular Drs. Lan-Lan Smith, Emma Cookson, @richardhorton1, Rebecca Cooney, Giulia Vivaldi for helping us share this story with the scientists, healthcare workers, and patients all over the world.

13\ This story is far from over. Check out the great work on platelet activation by Manne et al ashpublications.org/blood/article/… and pay attention to the bleeding complications with great work by Al-Hamkari et al at ashpublications.org/blood/article-….

14\ And of course use the below link for the full manuscript and the editorial by @Jme_os thank you for making these manuscripts open access and free of charge @TheLancetHaem

thelancet.com/coronavirus?dg…

15\ We are #InThisTogether worldwide. Thank you for reading and caring. Reach out to any of us. Thank you to so many not on Twitter who were a key part of this study.

16\ If this Tweetorial was informative please share @Pranay_md @anneliu_md @AnnaGoshua @LaurenPischel @HTRSFellows @RyuJustine @redcell_doc @connors_md @NTConnell @YaleCancer @YaleHemOnc @KaminskiMed @LisaSandersmd @EricTopol @LFiellin @DrRoyHerbstYale @CharlesFuchsMD