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. 2020 Mar 2;24(1):71.
doi: 10.1186/s13054-020-2799-5.

Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock

Klaus Stahl  1 , Julius J Schmidt  2 , Benjamin Seeliger  3 , Bernhard M W Schmidt  2 , Tobias Welte  3 , Hermann Haller  2 , Marius M Hoeper  3 , Ulrich Budde  4 , Christian Bode  5 , Sascha David  6
Affiliations

Effect of therapeutic plasma exchange on endothelial activation and coagulation-related parameters in septic shock

Klaus Stahl et al. Crit Care. .

Abstract

Background: A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Activation of pro-coagulant pathways and attenuation of anti-coagulant activity ultimately lead to microvascular stasis and consequent organ failure. No treatment approaches specifically targeting this axis are available. We explored the effects of therapeutic plasma exchange (TPE) on microvascular coagulation dysbalance in septic shock.

Methods: We conducted a prospective single-center study enrolling 31 patients with early septic shock (onset < 12 h) requiring high doses of norepinephrine (NE > 0.4 μg/kg/min). Clinical and biochemical data, including measurement of protein C; a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13 (ADAMTS13); and von Willebrand factor antigen (vWF:Ag), were obtained before and after TPE against fresh frozen plasma.

Results: Antithrombotic acting proteins such as antithrombin-III (ATIII) and protein C were markedly reduced in septic patients, but their activity increased after TPE (ATIII, 51% (41-61) vs. 63% (48-70), p = 0.029; protein C, 47% (38-60) vs. 62% (54-69), p = 0.029). Median ADAMTS13 activity was increased by TPE from 27 (21-42) % before to 47 (38-62) % after TPE (p < 0.001). In contrast, vWF:Ag was elevated and could be reduced by TPE (353 (206-492) IU/dL vs. 170 (117-232) IU/dL, p < 0.001). Regression analysis yielded a correlation between ADAMTS13 activity and platelet count (p = 0.001, R2 = 0.316).

Conclusions: Septic shock was associated with activation of pro-coagulant pathways and simultaneous depletion of anti-coagulant factors. TPE partially attenuated this dysbalance by removing pro- and by replacing anti-coagulant factors.

Trial registration: ClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.

Keywords: ADAMTS-13; Extracorporeal treatment; Plasmapheresis; Septic shock; von Willebrand factor.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of study participants. NE, norepinephrine; TPE, therapeutic plasma exchange
Fig. 2
Fig. 2
Effect of TPE on routine coagulation parameters, antithrombin-III, protein C, and D-dimers. Box and whisker blots showing fibrinogen (a), platelet count (b), antithrombin-III activity (c), protein C activity (d), D-dimer concentration (e), and DIC score (f) immediately before and post (=after) TPE. Gray areas highlight the reference range for healthy individuals
Fig. 3
Fig. 3
Effect of TPE on ADAMTS13, vWF:Ag, and vWF:Ag/ADAMTS-13 ratio. Box and whisker blots showing ADAMTS13 activity (a), vWF:Ag (b), and vWF:Ag/ADAMTS13 ratio (c) immediately before start and post (=after) TPE. Gray areas highlight the reference range for healthy individuals
Fig. 4
Fig. 4
Correlation of ADAMTS13 with clinical parameters of disease severity. Box and whisker blots demonstrating SOFA scores (a), NE dose (b), DIC score (c), LDH (d), and platelet count (e) for both patients with profound reduction of ADAMTS13 activity (< 30%) and patients with less severe suppression of ADAMTS13 activity (≥ 30%) at the time of inclusion before TPE treatment. f Non-linear regression of ADAMTS13 activity to platelet count
See this image and copyright information in PMC

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