Ex Vivo Recapitulation of Trauma-Induced Coagulopathy and Preliminary Assessment of Trauma Patient Platelet Function Under Flow Using Microfluidic Technology

摘要

Background: Relevant to trauma induced coagulopathy (TIC) diagnostics, microfluidic assays allow controlled hemodynamics for testing of platelet and coagulation function using whole blood.Methods: Hemodilution or hyperfibrinolysis was studied under flow with modified healthy whole blood. Furthermore, platelet function was also measured using whole blood from trauma patients admitted to a Level 1 Trauma center. Platelet deposition was measured with PPACK-inhibited blood perfused over collagen surfaces at a wall shear rate of 200 s-1, while platelet/fibrin deposition was measured with corn trypsin inhibitor (CTI)-treated blood perfused over TF/collagen.Results: In hemodilution studies, PPACK-treated blood displayed almost no platelet deposition when diluted to 10% Hct with saline, platelet poor plasma (PPP), or platelet rich plasma (PRP). Using similar dilutions, platelet/fibrin deposition was essentially absent for CTI-treated blood perfused over TF/collagen. To mimic hyperfibrinolysis during trauma, exogenous tPA (50 nM) was added to blood prior to perfusion over TF/collagen. At both venous and arterial flows, the generation and subsequent lysis of fibrin was detectable within 6 min, with lysis blocked by addition of the plasmin inhibitor, [epsilon]-aminocaproic acid. Microfluidic assay of PPACK-inhibited whole blood from trauma patients revealed striking defects in collagen response and secondary platelet aggregation in 14 of 21 patients, while platelet hyperfunction was detected in 3 of 20 patients.Conclusions: Rapid microfluidic detection of (i) hemodilution-dependent impairment of clotting, (ii) clot instability due to lysis, (iii) blockade of fibrinolysis, or (iv) platelet dysfunction during trauma may provide novel diagnostic opportunities to predict TIC risk.Level of Evidence: Level IVStudy type: Diagnostic Test