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Deep venous valves are frequent sites of deep venous thrombosis initiation. However, the possible contribution of the valvular sinus endothelium has received little attention in studies of thrombosis risk. We hypothesized that the endothelium of valve sinus differs from that of vein lumen with up-regulation of anticoagulant and down-regulation of procoagulant activities in response to the local environment. In pursuit of this hypothesis, we quantified endothelial protein C receptor (EPCR), thrombomodulin (TM), and von Willebrand factor (VWF) by immunofluorescence in great saphenous veins harvested at cardiac bypass surgery. We found significantly increased expression of EPCR and TM in the valvular sinus endothelium as opposed to the vein lumenal endothelium, and the opposite pattern with VWF (paired t test for TM and EPCR, each P < .001; for VWF, P ‫؍‬ .01). These data support our hypothesis and suggest that variation in valvular sinus thromboresistance may be an important factor in venous thrombogenesis. (Blood. 2009; 114:1276-1279) IntroductionDirect evidence from autopsy studies and phlebography, as well as circumstantial evidence such as the correlation between frequency of deep venous thrombosis and the number of valves in individuals, have established the venous valvular sinus as a frequent location of thrombosis initiation. [1][2][3][4] This phenomenon has been attributed to stasis, one of the components of Virchow triad. In the 1960s, contrast media was shown to linger in valve sinuses an average of 27 minutes postvenography. 5 Valvular sinus stasis has also been associated with hypoxia and increased hematocrit, 6 as well as preventing the efflux of activated clotting factors and influx of clotting factor inhibitors, constituting a potentially hypercoagulable microenvironment, another component of Virchow triad. Stasis alone, however, is not a sufficient explanation for the propensity of thrombi to form in deep venous valve sinuses because, for example, prolonged periods of stasis associated with sleep are not associated with thrombus formation. Accordingly, there must be other factors interacting with stasis in the generation of venous valvular thrombi.In recent years, attention has been focused on the importance of endothelial heterogeneity in different vascular beds. 7,8 Venous endothelium manifests multiple distinct phenotypes in different organs such as the kidney and liver. Gene expression microarray studies have shown that endothelial cells from macro-versus microvascular beds, from arteries versus veins, and from different organs have distinctly different and characteristic gene expression profiles. 9 In response to local changes in flow, shear stress, or oxygenation, endothelial cells often adapt by increasing or decreasing expression of critical cell-surface and cytoplasmic proteins. 10 Thus, we hypothesized that valvular sinus endothelium would maintain a thromboresistant phenotype with the expression of the anticoagulant proteins thrombomodulin (TM) and endothelial protein C receptor (EPCR) u...

As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (eg, cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have been issued regarding scene investigative protocol, and there is a paucity of publications characterizing COVID-19 postmortem gross and histologic findings. A case of sudden unexpected death due to COVID-19 is presented as a means of illustrating common autopsy findings, as well as diagnostic and biosafety considerations. We also review and summarize the current COVID-19 literature in an effort to provide practical evidence-based biosafety guidance for medical examiner-coroner offices encountering COVID-19 at autopsy.