By cross-linking fibrin, intravenously injected factor XIII–inspired hemostatic polymers stabilize clots and reduce bleeding in a rat model of trauma and fluid resuscitation.

Our understanding of the events taking place within the blood following severe injury with hemorrhagic shock is quickly evolving. Traditional concepts have given way to a detailed and nuanced understanding of coagulopathy, bleeding, and shock at the cellular and biochemical levels. In doing so, the tremendous complexity of events taking place within the blood have been illuminated and present an additional challenge. In this review, we seek to understand shock, endotheliopathy, and coagulopathy not as isolated events, but rather as the result of changes taking place within a single dynamic organ system. This review will highlight the key linkages existing between blood and endothelium and how these processes are perturbed by hemorrhagic shock to produce a syndrome that we call “hemorrhagic blood failure.” From this perspective, it may be regarded that the blood organ system fails in providing its vital functions predictably after injury. We review how accumulation of oxygen debt during shock leads to endotheliopathy and coagulopathy, and how current transfusion strategies may impact the syndrome of hemorrhagic blood failure.

Platelets contract forcefully after their activation, contributing to the strength and stability of platelet aggregates and fibrin clots during blood coagulation. Viscoelastic approaches can be used to assess platelet-induced clot strengthening, but they require thrombin and fibrin generation and are unable to measure platelet forces directly. Here, we report a rapid, microfluidic approach for measuring the contractile force of platelet aggregates for the detection of platelet dysfunction. We find that platelet forces are significantly reduced when blood samples are treated with inhibitors of myosin, GPIb-IX-V, integrin α_IIbβ_3, P2Y₁₂, or thromboxane generation. Clinically, we find that platelet forces are measurably lower in cardiology patients taking aspirin. We also find that measuring platelet forces can identify Emergency Department trauma patients who subsequently require blood transfusions. Together, these findings indicate that microfluidic quantification of platelet forces may be a rapid and useful approach for monitoring both antiplatelet therapy and traumatic bleeding risk.