PB0196 - Hemostatic capacity of lyophilized cryoprecipitate in a microfluidic model of hyperfibrinolysis

Sunday, June 23, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Katelin C. Rahn, BS

PhD Candidate
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States

Co-Author(s)

Emily Mihalko

Research Scientist
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
KM

Kestrel Merritt

Research Technician
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
JK

Jack Killinger

Research Technician
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
SC

Skye Clayton

Clinical Research Coordinator
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
NR

Nicholas Rocchio-Giordano

Phlebotomist
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
PS

Philip Spinella

Co-Director
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States
Susan Shea

Assistant Professor
Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh
Pittsburgh, Pennsylvania, United States

Background: Fibrinogen supplementation improves outcomes in traumatic bleeding, post-partum hemorrhage, cardiac surgery, and liver transplants. Cryoprecipitate, a potential fibrinogen source, offers logistical benefits with lyophilization for long-term storage and immediate availability in pre-hospital and in-hospital resuscitation. The hemostatic capacity of these products hasn't been assessed in flow-based assays with biologic surfaces.

Aims: This study aims to evaluate cryoprecipitate (Cryo) and lyophilized cryoprecipitate (Lyo-Cryo) and the ability of these adjuncts to resuscitate ex vivo induced hyperfibrinolytic coagulopathy in a microfluidic model.

Methods: Fresh Frozen Plasma units were cold precipitated, pooled, and stored frozen or lyophilized, resulting in Cryo or Lyo-Cryo, respectively. Protein and biochemical properties were measured(n=12). For microfluidic studies, healthy human blood(n=3) was incubated with anti-CD41 and 50μg/mL exogeneous fluorescent fibrinogen and mixed with 75ng/mL tissue plasminogen activator to induce a hyperfibrinolytic phenotype, along with non-coagulopathic controls(n=3). Coagulopathic samples were mixed (5:1) with Cryo, Lyo-Cryo, or lactated ringer’s (LR) crystalloid-only resuscitation control. Samples were assessed via stenotic flow chamber at arterial wall shear rates(3500s-1). Kinetic parameters, occlusion time, and clot composition were measured.

Results: Lyo-Cryo versus Cryo was not different in traditional coagulation metrics including prothrombin time, Factors VIII and XIII, but had elevated fibrinogen. The subset of Cryo and Lyo-Cryo products used for microfluidics had 1512±320mg/dl and 1880±190mg/dl fibrinogen. Mixed with hyperfibrinolytic blood, LR samples did not achieve an occlusive clot. Cryo and Lyo-Cryo mixed samples reached occlusion at 783±389s and 1040±277s respectively, comparable to healthy controls (774±376s). Surface area and mean fluorescence intensity of platelet deposition during clot formation was highest with Cryo mixing (Figure1). Cryo and Lyo-Cryo mixing exhibited differing clot structures, with denser fibrinogen distribution compared to LR (Figure2).

Conclusion(s): Lyophilized blood products provide logistic advantages but may have reduced hemostatic capacity. Clinical studies are needed to determine if more immediate availability can offset reduced hemostatic function for hyperfibrinolytic conditions.