Coagulation: 14 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Managing sepsis and septic shock in an endothelial glycocalyx-friendly way: from the viewpoint of surviving sepsis campaign guidelines
This narrative review examines how the endothelial glycocalyx — the gel-like carbohydrate layer lining blood vessels — is degraded in sepsis and how standard sepsis treatments may either protect or further injure it. The authors map recommendations in the Surviving Sepsis Campaign Guidelines 2021 (fluid strategy, albumin use, catecholamine limitation, corticosteroids, glycemic control, anticoagulants) onto the available evidence for glycocalyx preservation. They note that no current guideline recommendation is explicitly aimed at glycocalyx protection and call for this to be addressed in future sepsis research and guidelines.
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Published paper
Sidestream dark field video microscopy demonstrates shelf-stable blood products preserve the endothelial glycocalyx in a canine hemorrhagic shock model
Six anesthetized dogs underwent induced hemorrhagic shock and were each resuscitated with five different fluid or blood-product strategies in a crossover design, with the endothelial glycocalyx assessed by sidestream dark field video microscopy (perfused boundary region, PBR). Crystalloid plus hydroxyethyl starch resuscitation was associated with increased PBR (indicating glycocalyx degradation), whereas chilled whole blood, plasma plus packed red cells, and shelf-stable products (freeze-dried plasma with a hemoglobin-based oxygen carrier, with or without lyophilized platelets) did not show significant PBR change from baseline.
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Published paper
Effect of acute heparin administration on glycocalyx thickness and endothelial function in healthy younger adults
In this single-arm pilot study, 19 healthy young adults received one intravenous bolus of unfractionated heparin (5,000 U) and were reassessed 30 minutes later. Neither sublingual glycocalyx thickness (perfused boundary region by GlycoCheck), circulating syndecan-1 and heparan sulfate, nor brachial artery flow-mediated dilation changed. The authors conclude that acute heparin is not a usable way to experimentally degrade the glycocalyx in healthy humans.
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Published paper
Sidestream dark field imaging and biomarker evaluation reveal minimal significant changes to the microcirculation and glycocalyx in a canine hemorrhagic shock model
Eight anesthetized purpose-bred dogs underwent pressure-targeted hemorrhagic shock followed by fresh whole blood retransfusion, with sublingual sidestream dark field (GlycoCheck) imaging and plasma glycocalyx biomarkers measured at five time points. Despite marked drops in mean arterial pressure and cardiac output during shock, the perfused boundary region and microcirculatory variables did not change significantly, and only heparan sulfate showed a significant change (a decrease) over time.
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Published paper
Microvascular rarefaction in patients with cerebrovascular events
This prospective observational study used sublingual sidestream darkfield videomicroscopy to assess microcirculation in 21 patients within 24 hours of an acute stroke or transient ischemic attack, with repeat measurements on day 3 and after one week, compared with age- and sex-matched healthy controls. Patients showed substantially lower capillary density than controls, and the perfused boundary region (an inverse marker of glycocalyx thickness) correlated strongly with red blood cell filling of capillaries. The authors conclude that cerebrovascular events are accompanied by measurable systemic microvascular changes detectable under the tongue.
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Published paper
Relationship of the main indicators of systemic COVID-associated endotheliopathy with the morphofunctional state and hemodynamics of the retina and chorioid in the acute period of the disease
Russian researchers compared retinal and choroidal imaging (OCT) with sublingual microvascular glycocalyx measurements (GlycoCheck PBR) in 44 people convalescing from moderate or severe COVID-19 and 18 healthy volunteers. Patients showed thicker choroids and wider peripapillary retinal vessels in proportion to disease severity, and these ocular changes correlated with inflammatory/coagulation blood markers and with glycocalyx indices. The authors interpret this as indirect evidence linking post-COVID retinal microangiopathy to systemic endotheliopathy.
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Published paper
Vascular Endothelial Glycocalyx Damage in COVID-19
This narrative review, which includes a small structured literature search, argues that damage to the vascular endothelial glycocalyx is a common mechanism linking COVID-19 risk factors (hypertension, diabetes, obesity, smoking, cardiovascular disease) to severe outcomes such as ARDS, DIC, and microvascular thrombosis. The author proposes a new concept, 'systemic inflammation-reactive microvascular endotheliopathy' (SIRME), defined by inflammation, thrombogenic endothelial damage with increased permeability, and organ injury, with shed glycocalyx fragments or bilateral ground-glass lung shadows marking progression. Of six eligible clinical reports identified, all showed elevated circulating glycocalyx components in severe COVID-19.
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Published paper
Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C)
This single-center case report describes two critically ill children with MIS-C in whom endothelial glycocalyx damage was documented using plasma syndecan-1 and sublingual video microscopy (GlycoCheck) alongside a marked systemic inflammatory response. Both children had abnormal perfused boundary region (PBR) values and reduced capillary density compared with a postoperative control child, and PBR normalized (1.68 and 1.54 microns) before transfer out of intensive care after immunoglobulin and methylprednisolone treatment plus supportive care. The authors argue that microcirculatory and glycocalyx involvement may partly explain shock, capillary leak, and prothrombotic features in MIS-C.
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Published paper
Microvascular dysfunction in COVID-19: the MYSTIC study
This prospective, multi-center cross-sectional study used sublingual sidestream dark-field video microscopy (GlycoCheck) plus blood biomarkers to characterize microvascular and endothelial glycocalyx changes in 23 hospitalized COVID-19 patients versus 15 healthy controls. Patients showed marked loss of small capillaries, slower red blood cell velocity, and evidence of glycocalyx damage, most pronounced in those on mechanical ventilation. Higher perfused boundary region (thinner glycocalyx) and lower ADAMTS13 were associated with 60-day in-hospital mortality.
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Published paper
Immediate effects of whole blood donation on the endothelial surface layer and glycocalyx shedding
Researchers measured the sublingual microcirculation and blood markers of glycocalyx shedding in healthy volunteers immediately before and after donating 500 mL of whole blood. Using sidestream dark-field imaging with GlycoCheck software, they found no significant immediate change in the perfused boundary region (PBR) or red blood cell filling percentage. Plasma heparan sulfate and hyaluronan fell slightly while syndecan-1 was unchanged, suggesting the endothelial surface layer remains structurally stable after a standard donation.
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Published paper
Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source
This case-control study compared 90 patients who had an embolic stroke of undetermined source with 90 controls carrying similar cardiovascular risk factors. ESUS patients had thinner endothelial glycocalyx (higher sublingual perfused boundary region), stiffer arteries (higher pulse wave velocity), more oxidative stress, and impaired left atrial function. Glycocalyx damage correlated with arterial stiffness, which in turn related to left atrial reservoir strain.
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Published paper
Derangement of the endothelial glycocalyx in sepsis
This narrative review describes the structure and functions of the endothelial glycocalyx and how it is degraded during sepsis. It covers glycocalyx roles in leukocyte adhesion, anticoagulation, vascular permeability and mechanosensing, methods of assessment (circulating syndecan-1, heparan sulfate, hyaluronan; electron and intravital microscopy; sidestream dark-field imaging with automated PBR analysis), and candidate protective strategies. The authors conclude that no treatment has yet been proven clinically effective and that links between glycocalyx damage, sepsis severity and DIC remain inadequately defined.
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Published paper
Effect of acute hypernatremia induced by hypertonic saline administration on endothelial glycocalyx in rabbits.
In 20 rabbits, acute hypernatremia was induced with intravenous 10% NaCl and the sublingual and brain microcirculation were imaged with sidestream dark-field video microscopy before and 20 minutes after infusion. The perfused boundary region (PBR), an index of red blood cell penetration into the endothelial glycocalyx, increased slightly in the sublingual area, while blood syndecan-1 did not change. The authors interpret this as compression or charge alteration of the glycocalyx from transient hypervolemia rather than true shedding.
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Published paper
Effects of ultrapure hemodialysis and low molecular weight heparin on the endothelial surface layer
In 20 hemodialysis patients, researchers measured the endothelial surface layer during dialysis sessions using sidestream dark-field imaging (perfused boundary region, PBR) and plasma markers of glycocalyx shedding, varying whether low molecular weight heparin was given at the start of dialysis or 120 minutes in. Plasma syndecan-1 rose significantly during hemodialysis, with the increase appearing to follow heparin administration, while PBR did not change measurably.
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