Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial

Abstract

BACKGROUND:Thoracic aorta dissection is an acute critical condition associated with shock-induced endotheliopathy, coagulopathy, massive bleeding, and significant morbidity and mortality. Our aim was to compare the effect of coagulation support with solvent/detergent-treated pooled plasma (OctaplasLG) versus standard fresh frozen plasma (FFP) on glycocalyx and endothelial injury, bleeding, and transfusion requirements.METHODS:Investigator-initiated, single-center, blinded, randomized clinical pilot trial of adult patients undergoing emergency surgery for thoracic aorta dissection. Patients were randomized to receive OctaplasLG or standard FFP as coagulation factor replacement related to bleeding. The primary outcome was glycocalyx and endothelial injury. Other outcomes included bleeding, transfusions and prohemostatics at 24 hours, organ failure, length of stay in the intensive care unit and in the hospital, safety, and mortality at 30 and 90 days.RESULTS:Fifty-seven patients were included to obtain 44 evaluable on the primary outcome. The OctaplasLG group displayed significantly reduced damage to the endothelial glycocalyx (syndecan-1) and reduced endothelial tight junction injury (sVE-cadherin) compared to standard FFP. In the OctaplasLG group compared to the standard FFP, days on ventilator (1 day [interquartile range, 0–1] vs 2 days [1–3]; P = .013), bleeding during surgery (2150 [1600–3087] vs 2750 [2130–6875]; P = .046), 24-hour total transfusion and platelet transfusion volume (3975 mL [2640–6828 mL] vs 6220 mL [4210–10,245 mL]; P = .040, and 1400 mL [1050–2625 mL] vs 2450 mL [1400–3500 mL]; P = .027), and goal-directed use of prohemostatics (7/23 [30.4%] vs 13/21 [61.9%]; P = .036) were all significantly lower. Among the 57 patients randomized, 30-day mortality was 20.7% (6/29) in the OctaplasLG group and 25% (7/28) in the standard FFP group (P = .760). No safety concern was raised.CONCLUSIONS:In this randomized, clinical pilot trial of patients undergoing emergency surgery for thoracic aorta dissections, we found that OctaplasLG reduced glycocalyx and endothelial injury, reduced bleeding, transfusions, use of prohemostatics, and time on ventilator after surgery compared to standard FFP. An adequately powered multicenter trial is warranted to confirm the clinical importance of the findings.

Traumaassoziierte Koagulopathie: Pathophysiologie und Therapie

“…Nachdem die Gabe von Plasma zur Volumentherapie des schweren hämorrhagischen Schocks verpönt war, wird derzeit als der am besten geeignete Volumenersatz Plasma, insbesondere im präklinischen Kontext, erneut kontrovers diskutiert. Die akute Hypovolämie durch Blutung führt u. a. zu einer Endotheliopathie, die auf der Schädigung der Glykokalyx basiert [9].…”

“…das Endothel für Zellbotenstoffe und Immunzellen durchgängig [4,8]. Ein entscheidender zusätzlicher Faktor dürfte hierbei der Verlust der Integrität der Glykokalyx sein [9]. An Traumapatienten konnte gezeigt werden, dass ein erhöhter Syndecan-1-Spiegel als Zeichen einer Degradation der Glykokalyx mit einer erhöhten Mortalität vergesellschaftet ist.…”

Proceedings of the Food and Drug Administration public workshop on pathogen reduction technologies for blood safety 2018 (Commentary, p. 3026)

“…Older versions of S/D plasma were associated with hyperfibrinolysis and bleeding; however, changes to the manufacturing process have mitigated the risk of these adverse events . In several studies conducted with the current version of Octaplas, no additional risk of these or other adverse events was identified . No clinically relevant differences in efficacy were identified; however, most of these studies were small and may not have been powered to show significant differences …”

Pathogen reduced plasma products: a clinical practice scientific review from the AABB

“…During the 20‐year interval, there were seven randomized controlled trials evaluating the safety and efficacy of S/D plasma versus various comparators (see Table ): three in liver transplant/liver disease patients, two in open heart surgery, one in thoracic aortic dissections, and one in healthy volunteers . Two additional reports were excluded: one described a subset of patients included in another trial and one studied a product that is no longer manufactured and was withdrawn from US and Canadian markets in the 2000s .…”

“…Synopsis: Fifteen observational trials and seven RCTs were used to evaluate the safety of S/D plasma. No study reported an increase in AE in S/D plasma compared to conventional plasma and most reported a decrease.…”