scholarly journals Effects of Therapeutic Plasma Exchange on the Endothelial Glycocalyx in Septic Shock

2021 ◽  
Author(s):  
Klaus Stahl ◽  
Uta Carola Hillebrand ◽  
Yulia Kiyan ◽  
Benjamin Seeliger ◽  
Julius J. Schmidt ◽  
...  
Keyword(s):  
Septic Shock ◽  
Organ Failure ◽  
Plasma Exchange ◽  
Degradation Products ◽  
Ex Vivo ◽  
Fresh Frozen Plasma ◽  
Therapeutic Plasma Exchange ◽  
Endothelial Glycocalyx ◽  
Shock Onset ◽  
Blood Concentrations

Abstract BackgroundDisruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) against fresh frozen plasma might influence eGC related pathology.MethodsWe enrolled 20 norepinephrine dependent (NE > 0.4μg/kg/min) patients with early septic shock (onset < 12h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products such as heparan-sulfate (HS) and the eGC regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls.ResultsSDF demonstrated a marked decrease in eGC thickness in septic patients compared to healthy individuals (p=0.001). Circulating HS levels were increased more than six-fold compared to controls and decreased significantly following TPE (controls: 16.9 (8-18.6) vs. septic patients before TPE: 105.8 (30.8-143.4) μg/ml, p<0.001; vs. after TPE: 70.7 (36.9-109.5) μg/ml, p<0.001). The Hpa-2 /Hpa-1 ratio was markedly reduced in septic patients before TPE but normalized after TPE (controls: 13.6 (6.2-21.2) vs. septic patients at inclusion: 2.9 (2.1-5.7), p=0.001; vs. septic patients after TPE: 13.2 (11.2-31.8), p<0.001). Ex vivo stimulation of endothelial cells with serum from septic patients induced eGC damage that could be attenuated with serum post TPE.ConclusionsSeptic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency.Trial registrationclinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

scholarly journals Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Klaus Stahl ◽  
Uta Carola Hillebrand ◽  
Yulia Kiyan ◽  
Benjamin Seeliger ◽  
Julius J. Schmidt ◽  
...  
Keyword(s):  
Septic Shock ◽  
Organ Failure ◽  
Plasma Exchange ◽  
Degradation Products ◽  
Ex Vivo ◽  
Fresh Frozen Plasma ◽  
Therapeutic Plasma Exchange ◽  
Endothelial Glycocalyx ◽  
Shock Onset ◽  
Blood Concentrations

Abstract Background Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) using fresh frozen plasma might influence eGC-related pathology by removing injurious mediators of eGC breakdown while at the time replacing eGC protective factors. Methods We enrolled 20 norepinephrine-dependent (NE > 0.4 μg/kg/min) patients with early septic shock (onset < 12 h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products, such as heparan sulfate (HS) and the eGC-regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls. Results SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p = 0.001). Circulating HS levels were increased more than sixfold compared to controls and decreased significantly following TPE [controls: 16.9 (8–18.6) vs. septic patients before TPE: 105.8 (30.8–143.4) μg/ml, p < 0.001; vs. after TPE: 70.7 (36.9–109.5) μg/ml, p < 0.001]. The Hpa-2 /Hpa-1 ratio was reduced in septic patients before TPE but normalized after TPE [controls: 13.6 (6.2–21.2) vs. septic patients at inclusion: 2.9 (2.1–5.7), p = 0.001; vs. septic patients after TPE: 13.2 (11.2–31.8), p < 0.001]. Ex vivo stimulation of endothelial cells with serum from a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE. Conclusions Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

scholarly journals Effects of Therapeutic Plasma Exchange on the Endothelial Glycocalyx in Septic Shock

2021 ◽  
Author(s):  
Klaus Stahl ◽  
Uta Carola Hillebrand ◽  
Yulia Kiyan ◽  
Julius Schmidt ◽  
Benjamin Seeliger ◽  
...  
Keyword(s):  
Septic Shock ◽  
Organ Failure ◽  
Plasma Exchange ◽  
Degradation Products ◽  
Ex Vivo ◽  
Fresh Frozen Plasma ◽  
Therapeutic Plasma Exchange ◽  
Endothelial Glycocalyx ◽  
Shock Onset ◽  
Blood Concentrations

Abstract Background: Disruption of the endothelial glycocalyx (eGC) is observed in septic patients and its injury is associated with multiple-organ failure and inferior outcomes. Besides this biomarker function, increased blood concentrations of shedded eGC constituents might play a mechanistic role in septic organ failure. We hypothesized that therapeutic plasma exchange (TPE) against fresh frozen plasma might influence eGC related pathology.Methods: We enrolled 20 norepinephrine dependent (NE > 0.4mg/kg/min) patients with early septic shock (onset < 12h). Sublingual assessment of the eGC via sublingual sidestream darkfield (SDF) imaging was performed. Plasma eGC degradation products such as heparan-sulfate (HS) and the eGC regulating enzymes, heparanase (Hpa)-1 and Hpa-2, were obtained before and after TPE. A 3D microfluidic flow assay was performed to examine the effect of TPE on eGC ex vivo. Results were compared to healthy controls. Results: SDF demonstrated a decrease in eGC thickness in septic patients compared to healthy individuals (p=0.001). Circulating HS levels were increased more than six-fold compared to controls and decreased significantly following TPE (controls: 16.9 (8-18.6) vs. septic patients before TPE: 105.8 (30.8-143.4) μg/ml, p<0.001; vs. after TPE: 70.7 (36.9-109.5) μg/ml, p<0.001). The Hpa-2 /Hpa-1 ratio was reduced in septic patients before TPE but normalized after TPE (controls: 13.6 (6.2-21.2) vs. septic patients at inclusion: 2.9 (2.1-5.7), p=0.001; vs. septic patients after TPE: 13.2 (11.2-31.8), p<0.001). Ex vivo stimulation of endothelial cells with serum from a septic patient induced eGC damage that could be attenuated with serum from the same patient following TPE.Conclusions: Septic shock results in profound degradation of the eGC and an acquired deficiency of the protective regulator Hpa-2. TPE removed potentially injurious eGC degradation products and partially attenuated Hpa-2 deficiency. Trial registration: clinicaltrials.gov NCT04231994, retrospectively registered 18 January 2020

Effect of Therapeutic Plasma Exchange on Immunoglobulin Deficiency in Early and Severe Septic Shock

2020 ◽  
pp. 088506662096516
Author(s):  
Klaus Stahl ◽  
Rolf Bikker ◽  
Benjamin Seeliger ◽  
Julius J. Schmidt ◽  
Heiko Schenk ◽  
...  
Keyword(s):  
Septic Shock ◽  
Plasma Exchange ◽  
Therapeutic Option ◽  
Fresh Frozen Plasma ◽  
Therapeutic Plasma Exchange ◽  
Shock Onset ◽  
Before And After ◽  
Fresh Frozen ◽  
Immunoglobulin Levels ◽  
Severe Septic Shock

Background: Deficiency of immunoglobulins of the classes IgG, IgG1, IgA and IgM is associated with severity of disease and mortality in sepsis and septic shock. Therapeutic plasma exchange (TPE) with fresh frozen plasma (FFP) has recently gained attention as an adjunctive therapeutic option in early septic shock. We hypothesized that TPE might modulate immunoglobulin deficiencies besides sole elimination of circulating injurious molecules. Methods: We conducted a prospective single center study with TPE in 33 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE > 0.4μg/kg/min). Clinical and biochemical data, including measurement of immunoglobulin subgroups IgG, IgG1, IgM and IgA were obtained before and after TPE. The following immunoglobulin cut-off values were used to analyze subgroups with low immunoglobulin concentrations at baseline (IgG ≤ 6.5, IgG1 ≤ 3, IgM ≤ 1.5 and IgA ≤ 0.35 g/L). Results: At inclusion, median (IQR) SOFA score was 18 (15-20) and NE dose was 0.8 (0.6-1.2) μg/kg/min. The majority of patients demonstrated profound reductions in immunoglobulins levels of all classes. Globally, immunoglobulin levels were not significantly changed after a single TPE session. However, in patients with low baseline immunoglobulin levels a significant increase in all classes was observed (IgG 1.92 (0.96-3) g/L (+41%), IgG1 2.1 (1.46-2.32) g/L (+96%), IgA 0.44 (0.12-0.62) g/L (59%) and IgM 0.18 (0.14-0.34) g/L (+55%), p < 0.001 for comparison to patients above cut-off). Conclusions: The majority of early and severe septic shock patients had reduced immunoglobulin levels and a single TPE could attenuate immunoglobulin deficiencies of all classes. The clinical relevance of this observation has to be investigated in a proper designed trial.

scholarly journals The Therapeutic Efficacy of Adjunct Therapeutic Plasma Exchange for Septic Shock with Multiple Organ Failure: A Single Center Retrospective Review

2020 ◽  
Author(s):  
Philip Keith ◽  
Adam H Wells ◽  
Jeremy Hodges ◽  
Stephen H Fast ◽  
Amber Adams ◽  
...  
Keyword(s):  
Septic Shock ◽  
Mortality Rate ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Plasma Exchange ◽  
Standard Care ◽  
Multiple Organ ◽  
Therapeutic Plasma Exchange ◽  
Adult Patients ◽  
Apache Ii

Abstract Background: Sepsis remains a common condition with high mortality when multiple organ failure develops. The evidence behind therapeutic plasma exchange in this setting is promising but inconclusive. Our study aims to evaluate the efficacy of adjunct therapeutic plasma exchange for septic shock with multiple organ failure compared to standard therapy alone. Methods: A retrospective, observational chart review was performed, evaluating outcomes of patients with catecholamine resistant septic shock and multiple organ failure in Intensive care units at a tertiary care hospital in Winston Salem, North Carolina from August 2015- March 2019. Adult patients with catecholamine resistant septic shock (≥ 2 vasopressors) and evidence of multiple organ failure (lactic acid >2, platelets < 200, and pH < 7.3) were included. Patients who received adjunct TPE were identified and compared to patients who received standard care alone. A propensity score using APACHE II score, SOFA score, and age was used to match patients, resulting in 40 patients in each arm. Results: Mean baseline APACHE II and SOFA scores were 32.5 and 14.3 in TPE patients versus 32.7 and 13.8 in control patients. The 28-day mortality rate was 40% in the TPE group versus 62.5% in the standard care group (p=0.07). The subgroup of patients with pneumonia as the primary diagnosis had a 28-day mortality rate of 47.8% with adjunct TPE compared 81.3% with standard care alone (p = 0.05). Improvements in baseline SOFA scores at 48 hours were greater in the TPE group compared to standard care alone (p= 0.001). Patients receiving adjunct TPE had longer ICU and hospital lengths of stay. Conclusions: Our retrospective, observational study in adult patients with septic shock and multiple organ failure did not show improvement with adjunct TPE except in patients with pneumonia as the primary source of sepsis. Hemodynamics and organ dysfunction did improve with TPE regardless of source. A prospective, randomized clinical trial is needed to investigate TPE in adult sepsis and to identify subgroups that are most likely to benefit.

1423: THERAPEUTIC PLASMA EXCHANGE FOR THROMBOCYTOPENIA-ASSOCIATED MULTIORGAN FAILURE IN SEPTIC SHOCK

2018 ◽  
Vol 46 (1) ◽  
pp. 695-695
Author(s):  
Philip Keith ◽  
Lauren Eyadiel ◽  
Jeremy Hodges ◽  
Karen Sands ◽  
Jared Watkins
Keyword(s):  
Septic Shock ◽  
Plasma Exchange ◽  
Multiorgan Failure ◽  
Therapeutic Plasma Exchange

Therapeutic Plasma Exchange in Neonatal Septic Shock: A Retrospective Cohort Study

2019 ◽  
Vol 37 (09) ◽  
pp. 962-969
Author(s):  
Taylor Sawyer ◽  
Zeenia Billimoria ◽  
Sarah Handley ◽  
Kendra Smith ◽  
Larissa Yalon ◽  
...  
Keyword(s):  
Septic Shock ◽  
Cohort Study ◽  
Plasma Exchange ◽  
Retrospective Cohort Study ◽  
Adjunctive Therapy ◽  
Retrospective Cohort ◽  
Life Support ◽  
Therapeutic Plasma Exchange ◽  
Convenience Sample ◽  
Icu Discharge

Objective This study aimed to examine the use of therapeutic plasma exchange (TPE) as adjunctive therapy in neonatal septic shock. Study Design This retrospective cohort study was performed on a convenience sample of neonates in a quaternary children's hospital between January 2018 and February 2019. Results We identified three neonates with septic shock who received TPE. Two neonates had adenovirus sepsis, and one had group B streptococcal sepsis. All neonates were on extracorporeal life support (ECLS) when TPE was started. The median duration of TPE was 6 days (interquartile range [IQR]: 3–15), with a median of four cycles (IQR: 3–5). Lactate levels decreased significantly after TPE (median before TPE: 5.4 mmol/L [IQR: 2.4–6.1] vs. median after TPE: 1.2 mmol/L [IQR: 1.0–5.8]; p < 0.001). Platelet levels did not change (median before TPE: 73,000/mm3 [IQR: 49,000–100,000] vs. median after TPE: 80,000/mm3 (IQR: 62,000–108,000); p = 0.2). Organ failure indices improved after TPE in two of the three neonates. Hypocalcemia was seen in all cases despite prophylactic calcium infusions. One neonate died, and two survived to ICU discharge. Conclusion TPE can be safely performed in neonates with septic shock. TPE may have a role as an adjunctive therapy in neonates with septic shock requiring ECLS.

Therapeutic Plasma Exchange in Children With Thrombocytopenia-Associated Multiple Organ Failure

2019 ◽  
Vol 47 (3) ◽  
pp. e173-e181 ◽  
Author(s):  
James D. Fortenberry ◽  
Trung Nguyen ◽  
Jocelyn R. Grunwell ◽  
Rajesh K. Aneja ◽  
Derek Wheeler ◽  
...  
Keyword(s):  
Multiple Organ Failure ◽  
Organ Failure ◽  
Plasma Exchange ◽  
Multiple Organ ◽  
Therapeutic Plasma Exchange

Microparticles Are Active Components of Therapeutic Plasma Exchange: Correlation with ADAMTS13 Activity in Patients with Thrombotic Thrombocytopenic Purpura.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 969-969
Author(s):  
Joaquin J. Jimenez ◽  
Wenche Jy ◽  
Lucia M. Mauro ◽  
Katherine M. Lens ◽  
John J. Byrnes ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Total Activity ◽  
Fresh Frozen Plasma ◽  
Therapeutic Plasma Exchange ◽  
Adamts13 Activity ◽  
Active Components ◽  
Parallel Increase ◽  
Fresh Frozen ◽  
Normal Particle ◽  
Inhibitory Antibodies

Abstract INTRODUCTION: Therapeutic plasma exchange (TPE) is a widely accepted therapy for TTP. A leading hypothesis for its benefit is that TPE replenishes ADAMTS13 with fresh frozen plasma (FFP) and removes inhibitory antibodies. We have reported that endothelial microparticles (EMP) positive for ULvWF are elevated in acute TTP, decline with repeated TPE, and can inhibit ADAMTS13. Presence of platelet microparticles (PMP) in FFP has been described. This led us to the hypothesis that the benefit of TPE is partly due to its effect on microparticles (MP). We investigated the effect of TPE on MP and ADAMTS13 in TTP. METHODS: Nine patients were studied longitudinally during an episode of TTP. Blood samples were obtained upon admission and daily pre- and post-TPE. Additionally, the infused and removed plasma were studied. EMP defined by CD31+/CD42b− (EMP31), CD62E+ (EMP62) and CD62E+/vWF+ (EMPVWF); PMP were defined by CD31+/CD42b+ (PMP42) and CD41+ (PMP41), all measured in platelet-poor plasma by flow cytometry; concentrations are in millions / mL. ADAMTS13 activity was assayed by a FRETS-vWF73 method of Kokame et al [Br J Haematol2005; 129:93]. vWF multimers were analyzed following Raines et al [Thromb Res1990; 60:201]. RESULTS: At admission, TTP patients exhibited very low ADAMTS13 levels, 0–10% of controls (ctl), and elevated EMP31 (2.5 ±0.7 vs. 0.35 ±0.09 ctl) and EMP62 (6.3 ±1.9 vs. 0.25 ±0.07 ctl), both p&lt;0.001. After the first TPE, EMP fell significantly, to 1.76 ±0.85 for EMP31 and 3.4 ±1.3 for EMP62, both p&lt;0.02. Similarly, EMPVWF dropped from 3.7 ±1.8 at admission (ctl = 0.28 ±0.20) to 2.6 ±1.0 after the first TPE, p=0.02. In parallel, ADAMTS13 activity slowly increased with each TPE, finally to near normal, 85 ±22% of ctl. These findings suggest a relationship between ADAMTS13 activity and MP counts. The MP fraction isolated from TTP patients had no detectable ADAMTS13 activity. When the MP fraction from TTP patients was incubated with normal particle free plasma (PFP) for 6hr, then centrifuged to remove MP, a significant fraction of activity was lost (25 ±8%, p=0.02), and no activity could be detected in the resuspended MP. Examination of the vWF multimer composition of the MP fraction of TTP patients exhibited enrichment of large vWF. When we assayed FFP for EMP, PMP and ADAMTS13 activity, we found EMP and LMP comparable to controls (EMP31 = 0.4 ±0.25; EMP62 = 0.31 ±0.2). Only PMP were significantly elevated in FFP (PMP42 = 4.4 ±1.8; PMP41 = 9.0 ±3.2). When we compared ADAMTS13 activity in the MP fraction and the PFP of FFP, the MP fraction accounted for 35 ±12% of the total activity. MP from FFP did not exhibit ULvWF. We consistently observed that immediately following each TPE, both EMP31 and EMP62 were reduced by 15–30%, with a parallel increase in both species of PMP of 10–15%. Concomitantly, EMP and PMP profiles in plasma removed through TPE from TTP patients remained comparable to samples obtained prior to the TPE. CONCLUSION: These results suggest that one action of TPE in TTP is to remove EMP which tend to bind and inactivate ADAMTS13. Thus, the basis of TPE is two-fold: infusion of ADAMTS13 by FFP infusion, and reduction of high levels of inhibitors including inhibitory antibodies as well as EMP.

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