Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock

Abstract

BACKGROUND:It has been shown that binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients. METHODS:Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes. RESULTS:Thirty-four HS patients were studied: age, 46 (19-89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively.Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion. CONCLUSION:We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation.

Early lyophilized cryoprecipitate enhances the ADAMTS13/VWF ratio to reduce systemic endotheliopathy and lessen lung injury in a mouse multiple-trauma hemorrhage model

“…It is possible that cryoprecipitate infusion itself could have contributed to the lack of mortality benefit. However, a recent study by Zeineddin et al examined organ dysfunction at 72 hours postinjury after using cryoprecipitate products in a mouse model of hemorrhagic shock and showed no adverse effects 26 . The extent of hemoperitoneum following liver injury and total blood removed to reach shock state also did not differ between groups (Table 1).…”

Immediate use cryoprecipitate products provide lasting organ protection in a rodent model of trauma/hemorrhagic shock and prolonged hypotensive resuscitation

“…There have been recent clinical studies demonstrating persistent changes in both syndecan-1 and VWF in hemorrhagic shock patients out to 24 hours, but we are not aware of any preclinical or clinical studies that have examined these parameters thru 72 hours postinjury. 23,24 We were interested in determining if the cryoprecipitate products would provide protection beyond the early postresuscitation phase. There are limited mouse models of hemorrhagic shock that extend beyond the immediate postresuscitation phase.…”

“…While there were significant reductions in gut histopathologic injury and preserved gut syndecan-1 immunostaining as well as reduced lung permeability, there were no persistent differences in indices of lung injury or syndecan-1 immunostaining, nor in liver function, kidney function, or systemic parameters of endothelial injury including syndecan-1 and VWF. There have been recent clinical studies demonstrating persistent changes in both syndecan-1 and VWF in hemorrhagic shock patients out to 24 hours, but we are not aware of any preclinical or clinical studies that have examined these parameters thru 72 hours postinjury 23,24 …”

Injury-induced endotheliopathy: What you need to know

“…Additional recent data show that EoT is a pathophysiologic state that persists over the first 24 hours after injury and remains a significant predictor of poor outcomes throughout this time period. 14 Using innovative proteomics approaches, Krocker et al 15 have shown that EoT is associated with a unique plasma proteome signature enriched in damage-associated molecular patterns (DAMPS), inflammatory mediators, and organ-specific intracellular markers, corroborating clinical evidence linking EoT with organ damage.…”