87 Evaluating Endothelial Dysfunction in Thermally-injured Patients with syndecan-1, Tissue Factor Pathway Inhibitor, and Thrombomodulin as Predictors of Mortality

2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S57-S58
Author(s):  
John W Keyloun ◽  
Saira Nisar ◽  
Kathleen Brummel-Ziedins ◽  
Maria Bravo ◽  
Matthew Gissell ◽  
...  

Abstract Introduction Endotheliopathy in burn patients is largely uncharacterized. Syndecan-1 (SDC-1), thrombomodulin (TM), and tissue factor pathway inhibitor (TFPI) are components of the vascular endothelial glycocalyx. Proteolytic cleavage of these moieties may yield biomarkers for endothelial damage. The aim of this study is to evaluate endotheliopathy after burn injury by monitoring plasma levels of these biomarkers over time to investigate potential relationship to mortality. Methods Burn injured patients presenting to a regional burn center from 2012 to 2017 were prospectively enrolled. Blood samples were collected at 0, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours from admission. Plasma SDC-1, TM, and TFPI levels were quantified by ELISA. Demographic data and injury characteristics were obtained from the medical chart. Patients with concomitant inhalation injury, trauma, or < 10% total body surface area (TBSA) burns were excluded. Statistical analysis was performed using mixed-effect models with Sidak’s correction for multiple comparisons. Significance was set at p =0.05. Data are presented as mean ± standard deviation. Results A cohort of 22 patients was identified with an average age of 45±14 years, TBSA of 30±15%, with 6 patients who died from their injuries. The deceased group was older (59±13 vs. 40±10 years, p = 0.01), and there was no significant difference in burn size. Mean SDC-1 levels were higher in the deceased group at all time points (p=0.0004) and this difference was significant at hour 12 (106±11 vs. 41±31 ng/mL, p = 0.0002), hour 24 (160±39 vs. 35±20 ng/mL, p = 0.04) and hour 72 (100±3 vs. 35±38 ng/mL, p = 0.01). Mean soluble TM levels were higher in the deceased group after hour 12 (p = 0.04) and there was a trend towards higher TFPI levels after hour 12 in the deceased group. Conclusions Biomarkers are elevated in patients following burn injury who die, when inhalation injury and trauma are excluded. Given equivalent TBSA, older patients appear more sensitive to thermally induced glycocalyx degradation. SDC-1 shows the greatest promise as a prognostic indicator as levels tend to be higher among deceased patients on admission and are significantly higher as early as hour 12. Applicability of Research to Practice Reliable assessment of the patient’s endothelial damage may hold predictive value for clinicians and could assist in clinical decision making. Further research must investigate endotheliopathy in burn patients.

1998 ◽  
Vol 79 (05) ◽  
pp. 919-923 ◽  
Author(s):  
Eriko Morishita ◽  
Takuma Hashimoto ◽  
Hidesaku Asakura ◽  
Masanori Saito ◽  
Masahide Yamazaki ◽  
...  

SummaryTissue factor pathway inhibitor (TFPI) is present in a free-form and in lipoprotein-associated forms in plasma. In this study, the plasma concentrations of total TFPI (tTFPI) and free-form TFPI (fTFPI) were measured in 25 patients with Graves’ disease and 25 age-matched healthy subjects, and the relationship between thyroid state and plasma TFPI was examined. Plasma concentrations (median) of tTFPI and fTFPI in Graves’ patients who were hyperthyroid were significantly increased compared with Graves’patients who were euthyroid (152 ng/ml versus 124 ng/ml, p <0.01 and 41.3 ng/ml versus 20.2 ng/ml, p <0.0001, respectively), and control subjects (152 ng/ml versus 96 ng/ml, p <0.0001 and 41.3 ng/ml versus 18.7 ng/ml, p <0.0001, respectively). There was no significant difference in plasma fTFPI concentrations between the euthyroid group and the control group. Plasma fTFPI concentrations correlated closely with thyroid hormone (T3) levels in the patients (r = 0.559, p <0.005). Serial measurement of individual patients revealed that plasma concentrations of fTFPI and tTFPI were significantly decreased, reaching normal control values upon attainment of euthyroidism. In conclusion, the close correlation between plasma fTFPI and serum thyroid hormone levels suggests that thyroid hormones might influence the synthesis or metabolism of TFPI on the surface of endothelial cells in patients with Graves’ disease. This is the first report concerning high concentrations of plasma fTFPI in patients with hyperthyroidism.


2004 ◽  
Vol 10 (4) ◽  
pp. 379-385 ◽  
Author(s):  
Thyyar M. Ravindranath ◽  
Masakatsu Goto ◽  
Muzaffer Demir ◽  
Mahmut Tobu ◽  
M. Florian Kujawski ◽  
...  

Burn and septic injuries induce profound changes in coagulation status. This study examined the changes in plasma tissue factor pathway inhibitor (TFPI) and thrombin activatable fibrinolytic inhibitor (TAFI) levels in a rat model of burn and septic injuries. Rats underwent 30% TBSA cutaneous scald burn injury and septic insult was induced by caecal ligation and puncture (CLP). CLP was superimposed on burn injury to mimic the clinical model of sepsis complicating burn injury. Rats were pretreated with Cprofloxacin orally to colonize their gut with Enterococcus faecalis. TFPI and TAFI plasma levels were measured using functional activity assay kit with a chromogenic method at 24 and 72 hours following the injuries. TFPI levels decreased significantly at 24 hours in burn, CLP, and burn+CLP groups, followed by incomplete rebound recovery at 72 hours in all three groups. On the other hand, TAFI levels increased significantly at 24- and 72-hour time points in all three groups. These results suggest that burn, septic, and their combined injuries perturb coagulation cascade and thrombotic process toward the procoagulant pathway by impairing fibrinolysis.


2019 ◽  
Author(s):  
Edward A. Bittner ◽  
Connie W. Chaudhary

Anesthetic management of burn-injured patients can be particularly challenging. Burn-injured patients exhibit pathophysiologic changes that can affect nearly all the organs in the body. Challenges the anesthesiologist may encounter when caring for burn patients include difficult airway management, impaired lung function, vascular access issues, hypothermia, pharmacokinetic and pharmacodynamic alterations, and pain management. Other important considerations that could affect the condition of burn patients include blood loss, hypermetabolism, pain control, and temperature management.  Anticipating appropriate precautions can change the clinical outcome of these patients.  Optimal care requires a full understanding of the unique preoperative, intraoperative, and postoperative issues of the burn-injured patient. This review contains 2 figures, 3 tables, and 77 references. Key Words: anesthetic management of acute burns, burn injury, electrical injury, fluid resuscitation, inhalation injury, Parkland formula, pain management


2015 ◽  
Vol 18 (2) ◽  
pp. 207-212 ◽  
Author(s):  
Robert Ślusarz ◽  
Mariola Głowacka ◽  
Monika Biercewicz ◽  
Ewa Barczykowska ◽  
Beata Haor ◽  
...  

Objectives: The aim of the study was to assess the concentrations of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the blood of patients with a postoperative wound after neurosurgery. Method: Participants included 20 adult patients who underwent neurosurgery because of degenerative spine changes. The concentration of TF and TFPI in the patients’ blood serum was measured 3 times: before surgery, during the first 24 hr after surgery, and between the 5th and 7th days after surgery. The control group comprised 20 healthy volunteers similar to the patient group with respect to gender and age. Results: A statistically significant difference was observed between TF concentration at all three measurement time points in the research group and TF concentration in the control group ( p = .018, p = .010, p = .001). A statistically significant difference was found between TFPI concentration at the second time point in the research group and TFPI concentration in the control group ( p = .041). No statistically significant within-subject difference was found between TF concentrations before and after surgery. A statistically significant within-subject difference was found between TFPI concentrations within 24 hr after surgery and 5–7 days after surgery ( p = .004). Conclusion: High perioperative concentrations of TF indicate not only the presence of thrombophilia but also the importance of TF in the wound-healing process. Perioperative changes in TFPI concentrations are related to its compensatory influence on hemostasis in thrombophilic conditions.


2019 ◽  
Vol 40 (3) ◽  
pp. 269-273 ◽  
Author(s):  
Megan A Rech ◽  
Michael J Mosier ◽  
Kevin McConkey ◽  
Susan Zelisko ◽  
Giora Netzer ◽  
...  

Abstract This study examines health outcomes in burn patients with sepsis. We hypothesized that burn patients with sepsis would have an increased odds risk for in-hospital death and longer intensive care unit (ICU) stays. This was a retrospective cohort of consecutive patients admitted to the burn ICU with total BSA (TBSA) ≥10% and/or inhalation injury between January 2008 and March 2015. Overall 407 burn patients were included; the case-rate for sepsis was 39.1% (n = 159); 20.1% (n = 82) patients were septic and 18.9% (n = 77) patients experienced septic shock. Patients with septic shock had the highest mortality rate (13.31% no sepsis vs 3.7% sepsis vs 49.4% septic shock, P &lt; .01). Median 28-day ICU-free days was higher in patients without sepsis (23 days [Interquartile range (IQR) 14–27] no sepsis vs 0 days [IQR 0–10] sepsis vs 0 days [IQR 0–0] septic shock, P &lt; .01). Sepsis (with or without shock) increased odds of in-hospital death (odds ratio 7.04, 95% confidence interval 1.93–25.7) in reference to the no sepsis group. With each incremental Sequential Organ Failure Assessment (SOFA) score or 10% TBSA increase, the odds risk for in-hospital death increased by 56 and 75%, respectively. Our study characterized outcomes in patients with sepsis after severe burn injury. The odds risk for in-hospital death was greater in patients with sepsis, increasing burn severity according to TBSA and SOFA score.


Shock ◽  
2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
John W. Keyloun ◽  
Tuan D. Le ◽  
Anthony E. Pusateri ◽  
Robert L. Ball ◽  
Bonnie C. Carney ◽  
...  

Author(s):  
John W Keyloun ◽  
Tuan D Le ◽  
Kathleen E Brummel-Ziedins ◽  
Melissa M Mclawhorn ◽  
Maria C Bravo ◽  
...  

Abstract Burn injury is associated with endothelial dysfunction and coagulopathy and concomitant inhalation injury increases morbidity and mortality. The aim of this work is to identify associations between inhalation injury (IHI), coagulation homeostasis, vascular endothelium, and clinical outcomes in burn patients. One-hundred and twelve patients presenting to a regional burn center were included in this retrospective cohort study. Whole blood was collected at set intervals from admission through 24 hours and underwent viscoelastic assay with rapid TEG (rTEG). Syndecan-1 (SDC-1) on admission was quantified by ELISA. Patients were grouped by the presence (n=28) or absence (n=84) of concomitant IHI and rTEG parameters, fibrinolytic phenotypes, SDC-1, and clinical outcomes were compared. Of the 112 thermally injured patients, 28 (25%) had IHI. Most patients were male (68.8%) with a median age of 40 (IQR, 29-57) years. Patients with IHI had higher overall mortality (42.68% vs. 8.3%; p&lt;0.0001). rTEG LY30 was lower in patients with IHI at hours 4 and 12 (p&lt;0.05). There was a pattern of increased abnormal fibrinolytic phenotypes among IHI patients. There was a greater proportion of IHI patients with endotheliopathy (SDC-1 &gt; 34 ng/mL) (64.7% vs. 26.4%; p=0.008). There was a pattern of increased mortality among patients with inhalation injury and endotheliopathy (0% vs. 72.7%; p=0.004). Significant differences between patients with and without IHI were found in measures assessing fibrinolytic potential and endotheliopathy. Mortality was associated with abnormal fibrinolysis, endotheliopathy, and inhalation injury. However, the extent to which IHI associated dysfunction is independent of TBSA burn size remains to be elucidated.


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