OC 69.5 - The Use of a Microfluidic Transection Model to Evaluate Coagulopathies and Hemostatic Resuscitation in Trauma

Background: Bleeding secondary to trauma is a leading cause of death worldwide. Hemostatic resuscitation is an essential aspect of treating traumatic bleeding.

Aims: This study aims to evaluate platelet product contribution to hemostasis in a microfluidic model of vessel transection.

Methods: Heparinized blood (n=36) and apheresis platelet units (PLT)(n=16) were collected from healthy volunteer donors. The inherent function of PLT was tested in a straight channel microfluidic device. To model transection, platelets were labelled with fluorescent anti-CD41. Blood was combined with saline (2:3v/v) to induce dilutional coagulopathy(dWB)(n=8), or thrombocytopenia(tWB)(n=28) was induced. Samples were perfused by constant pressure simulating an arterial bleed. Outflow mass quantified blood loss and immunofluorescent images were captured. Coagulopathies were mixed with 4 PLT volumetric equivalent. Products at d2, 5, 7 storage at room temperature(RT) plus d14 and 21 for cold storage(CS) were evaluated. Paired t-tests were conducted for coagulopathy blood loss, unpaired t-tests for inherent product function, and one-way analysis of variance for mixing studies.

Results: In the transection model, dWB resulted in 2.883+/-1.032g blood loss versus paired control 1.174+/-0.510g (p=0.0024), while tWB resulted in 1.540+/-0.374g versus 1.340+/-0.485g(p=0.0183)(Fig1A-B). Clots that formed had high platelet content(Fig1C). RT-2d PLT did not reduce dWB blood loss(Fig1D-E). Inherent hemostatic evaluation of CS versus RT PLT showed significantly reduced occlusion time at d7(Fig2A-B). Representative images from mixing studies in the transection model illustrate predominant inclusion of product platelets versus recipient(Fig2C), although recipient platelets are recruited(Fig2D). Neither RT nor CS products reduced blood loss compared to tWB(Fig2E-F). Regardless of storage temperature, d2 products had significantly lower blood loss compared to later storage days(p=0.0017)(Figure 2G-H).

Conclusion(s): This study establishes a transection model capable of quantifying blood loss. While platelet product mixing did not reduce blood loss, disparate responses with product storage day were observed, indicating the need to further evaluate hemostatic function under flow in a pathologically-relevant model.