Simulating the Impact of Transfusion Products on Clotting Kinetics and Patient Outcome
Authors: Gosselin Andrew , Ahmad Sameer , Toussaint Ashley , Bargoud Christopher , Mathew Shane , Macor Marie , Hanna Joseph , Goswami Julie , Tutwiler Valerie 
Published: December 2024

Introduction: Critically ill trauma patients often receive blood product transfusion upon arrival to the emergency room prior to laboratory workup, based on clinical picture. Common coagulation tests such as prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet count fail to provide real time data to guide treatment. Therefore, there is a need to develop laboratory parameters that reflect how blood products influence coagulation to guide treatment based on a trauma patient's unique hemostatic dysregulations. In this study, we tested plasma clot mechanics, coagulation kinetics, and fibrin structure in platelet poor plasma (PPP) clots of trauma patients. We hypothesize that functional testing of clot formation will provide novel, real time data to guide an individual's response to transfusion after injury.

Methods: PPP was collected from 63 trauma patients after arrival to the emergency department, prior to the use of any resuscitative fluids. Clot mechanics, enzyme concentrations, and fibrin network structure were assessed with rheological, thrombin generation, ELISA and confocal assays. Clinical vital signs and laboratory values at time of arrival were abstracted from electronic medical records. Patients were stratified into those that did and did not receive transfusion, and clinical outcome (survived vs deceased). To understand the impact of transfusion on clot formation and mechanics, a simulated trauma model, mimicking coagulation and fibrinolytic rate, using PPP and whole blood had each product supplemented in similar concentrations as patients received. T-test and one way ANOVA were used to assess differences between groups.

Results: Patients receiving transfusion had similar injury severity scores (27 vs 20, p=0.06), and mortality rates (35% vs 27%, p=0.5) as those who did not. Coagulation tests, PT and aPTT did not detect differences between them. Viscoelastic and clauss testing detected that patients receiving transfusion had reduced clot stiffness, and reduced fibrinogen levels compared to those who did not (p&lt;0.05). Deceased patients who received transfusion had the lowest stiffness and fibrinogen of any group (p&lt;0.05). Deceased patients had increased aPTT, compared to surviving patients, and decreased stiffness, clotting rate and fibrinogen (p&lt;0.05). However, patients who received transfusion, regardless of mortality, received similar units of packed red blood cells (pRBCs) (3.7 vs 2.1), fresh frozen plasma (FFP) (2.2 vs 1.7), platelets (0.5 vs 0.3), crystalloids (0 vs 0) and fibrinogen concentrate (FC) (0.4 vs 1.0). Viscoelastic properties of simulated trauma samples were tested, with maximum stiffness, time to 50% stiffness, and time to 50% lysis, compared between transfusion types. Stiffness was increased with FFP, FC and pRBCS, and decreased by saline. Time to 50% stiffness was not altered by products. Lastly, time to 50% lysis was increased with FFP, decreased with FC, and unaffected by other products.

Conclusions: Viscoelastic testing detected differences between patients who did and did not receive transfusion, which common coagulation tests did not reveal. Differences were detected with viscoelastic testing between survived and deceased patients who received transfusion, indicating the ability of these tests to detect potentially prognostic data, which cannot be seen by common clinical testing. Simulating transfusion in vitro detected the unique changes provided by each product and the ability to use viscoelastic testing as a guide for improving coagulation after trauma. This study highlights the need to detect variation in clot mechanics to provide real-time information to guide resuscitation. Further studies are needed to define why deceased patients were unable to form clots despite transfusion.