Abstract Number: OC 11.4
Meeting: ISTH 2022 Congress
Background: Major trauma haemorrhage is associated with an early increase in activated Protein C (aPC). Consumption of PAI-1 by aPC and loss of inhibitory control over tissue plasminogen activator (tPA) are key to the hyperfibrinolytic response in Acute Traumatic Coagulopathy (ATC). Resuscitation with balanced transfusion primarily supports coagulation rather than directly targeting the mediators of ATC. We wished to characterise the relationship between aPC, fibrinolytic response and clinical outcome during transfusion to understand the potential therapeutic value of aPC pathway modulation.
Aims: Determine the relative importance of dynamic aPC levels during major trauma haemorrhage on fibrinolytic markers and outcome.
Methods: Prospective cohort study of trauma patients admitted to a level 1 trauma centre who received 4+ red blood cells (RBC) units with elevated aPC (>3ng/ml) on admission. Samples were collected after transfusion of 4, 8 and 12 RBC units for aPC and fibrinolytic markers assay. Patients were stratified into DECREASING aPC (decreasing during resuscitation) vs INCREASE/HIGH aPC (increasing or persistently elevated during resuscitation).
Results: Thirty-seven patients were analysed and 58% had INCREASING/HIGH aPC during the bleeding period. This subgroup were more injured than DECREASING aPC patients (Injury Severity Score: 41 vs 25, p=0.03) but had similar shock severity (base deficit 10.8 vs 7.85mEq/L, p=0.165). Mortality was significantly higher in INCREASING/HIGH aPC (67% vs 25%) despite comparable RBC:FFP transfusion ratios.
Plasmin-Antiplasmin levels mirrored aPC levels during bleeding (Pearson r=0.773, p= < 0.001) whilst PAI-1 was inversely associated with aPC (F-test=4.478 p=0.0032). Both groups had similar thrombin generation and an overall decline in fibrinogen during MHP resuscitation.
Conclusion(s): Persistently elevated aPC despite balanced MHP transfusion was associated with increased mortality. Direct modulation of aPC (to mitigate PAI-1 neutralisation) may represent a targeted intervention to treat ATC for improving patient outcomes.
To cite this abstract in AMA style:Thaventhiran A, Brohi K, Davenport R. Dynamic changes in activated protein C during major haemorrhage protocol and associated fibrinolytic response [abstract]. https://abstracts.isth.org/abstract/dynamic-changes-in-activated-protein-c-during-major-haemorrhage-protocol-and-associated-fibrinolytic-response/. Accessed September 29, 2023.
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