Microfluidic transection injury and high shear thrombus formation demonstrate increased hemostatic efficacy of cold-stored platelets and in vitro resuscitation in induced coagulopathy models

Emily P Mihalko^1,2*Refael Munitz²Devin Dishong²Skye Clayton²Susan M. Shea^1,2,3

• ¹Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
• ²Trauma and Transfusion Medicine Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
• ³Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

Hemostatic resuscitation is an essential aspect of treating traumatic bleeding. Trauma-induced coagulopathy is a multifactorial disorder that can lead to increase transfusion requirements. However, little is known about the interplay of coagulopathies and stored blood products used for hemostatic resuscitation, which themselves acquire dysfunction in the form of a storage lesion. Physiologically relevant models can aid in the study of trauma and hemostatic resuscitation, incorporating important aspects such as biological surfaces and flow regimes that mimic injury. This study aims to evaluate the platelet product contribution under varying storage conditions to hemostasis in coagulopathic states. This study utilized microfluidic platforms of high shear, a flow regime relevant to injury, including a stenotic straight channel and a severe transected vessel injury device. Apheresis platelet products were collected from healthy volunteers, stored at room temperature (RT) or cold-stored (CS) (1-6 °C), and tested for product cell count and intrinsic product function in a high shear stenotic microfluidic device through storage days (D2, D5, D7 for RT and D2, D5, D7, D14, D21 for CS). Hemostatic resuscitation efficacy of products was assessed with induced coagulopathy models of dilution and thrombocytopenia. In vitro hemostatic resuscitation was assessed in both the stenotic straight channel for kinetic platelet contributions and a transected vessel injury device with endpoints of blood loss and clot composition. CS had conserved inherent product function regardless of declining platelet counts through storage D7. When mixed with coagulopathic blood, D2 RT did not show hemostatic benefit in a dilutional coagulopathy model. However, both D2 RT and CS showed a hemostatic benefit in the thrombocytopenia model. CS (D5 and D7) also showed enhanced ability to recruit recipient platelets in the thrombocytopenia model compared to RT. Overall, this study highlights disparate responses with product storage day and temperature, indicating the need to further evaluate hemostatic resuscitation efficacy under flow in pathologically relevant models to guide transfusion practice.