https://orcid.org/0000-0001-8152-9974
Key Points
Cryoprecipitate improves hemostatic resuscitation of dilutional coagulopathy compared to fibrinogen concentrate in a microfluidic model
Pathogen reduction of cryoprecipitate alters shear-induced activation of von Willebrand factor, reducing platelet engagement under flow
Abstract
Traumatic injury has the highest burden on morbidity and mortality in the United States. Early deaths from trauma are most frequently due to hemorrhage and could be prevented with more timely and efficacious treatments. A hallmark of trauma-induced coagulopathy (TIC) is hypofibrinogenemia, which is treated with fibrinogen concentrates (FibCon) or cryoprecipitate (Cryo). Pathogen reduction (PR) of Cryo (PR-CryoFC) enables extended storage post-thaw at room temperature, permitting immediate availability for bleeding patients. As Cryo contains additional concentrated plasma proteins involved in hemostasis compared to FibCon, we hypothesized Cryo and PR-CryoFC would result in more rapid and effective clot formation. To evaluate the hemostatic capacity of these adjuncts. we simulated TIC (dilution, hyperfibrinolysis) in an ex vivo model and administered Cryo, PR-CryoFC, and FibCon, then performed hemostatic assessment to include viscoelastometry, thrombin generation, and a microfluidic model of vessel injury. Cryo and PR-CryoFC had similar resuscitation capacity in assays without flow (viscoelastometry, thrombin generation), whereas in the dynamic microfluidic model, Cryo had faster VWF-mediated platelet recruitment. There was no difference in intrinsic VWF function between adjuncts in static, non-flowing assays, yet in a flow-dependent vortexing assay, PR reduced VWF cleavage by ADAMTS13, despite equivalent ADATMS13 activity, suggesting impaired biophysical elongation and extension of VWF in PR-CryoFC, resulting in reduced cleavage and platelet binding capacity. Herein, we show ex vivo simulation of coagulopathy and resuscitation differentiated hemostatic function under flow among Cryo, PR-CryoFC, and FibCon. Further exploration of effects of PR on plasma proteins is warranted as well as effects on clinical outcomes.
Author notes
Current Affiliation: Vitalant Research Institute, Denver, CO, USA
Current Affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Current Affiliation: Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
Current Affiliation: Department of Critical Care, University of Pittsburgh, Pittsburgh, PA, USA
Current Affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
Data Sharing Statement
For original data, please contact Dr. Susan Shea (smshea@pitt.edu).
