Abstract
BackgroundA 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.MethodsWe 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.ResultsAntithrombotic 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).ConclusionsSeptic 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 registrationClinicalTrials.gov, NCT03065751. Retrospectively registered on 28 February 2017.
Highlights
A dysbalanced coagulation system is part of the pathological host response to infection in sepsis
We investigated in patients with early and severe septic shock the effect of a single therapeutic plasma exchange (TPE) against fresh frozen plasma (FFP) on key factors regulating coagulation
Both changes are characteristic for the presence of thrombotic microangiopathy (TMA) with ongoing hemolysis as a consequence of low ADAMTS13 activity
Summary
A dysbalanced coagulation system is part of the pathological host response to infection in sepsis. Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection; if hypotension is refractory to volume resuscitation and serum lactate is elevated, it is termed septic shock [1]. The overwhelming host response consisting of cytokine release, attraction of inflammatory cells, and global endothelial activation is the key driver of morbidity and mortality [3]. Endothelial dysfunction leads to systemic aggregation of platelets in virtually all microvascular beds with consecutive consumption of coagulation factors. This situation is well known as disseminated intravascular coagulation (DIC) resulting in widespread clotting of the microvasculature system and progressive multi-organ failure [4]. The only ever approved “specific sepsis therapeuticum” was an activated protein C preparation (Xigris®) [9], before it was later removed from the market due to a large-scale negative follow-up study [10]
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