Trauma Induced Dysfibrinogenemia: The von Clauss assay does not accurately measure fibrinogen levels after injury

1. Fibrinogen activity decreases rapidly post injury.

2. Fibrinogen repletion increases quantity but does not improve activity in injured patients.

Trauma patients who sustain severe tissue injury and hemorrhage often receive fibrinogen repletion to avert coagulopathy and achieve hemostasis. However fibrinogen supplementation has not shown a benefit in trauma patients with coagulopathy. The von Clauss functional fibrinogen assay is the primary indication for fibrinogen transfusion. This assay, however infers fibrinogen levels optically via in vitro clot formation time and does not directly measure the quantity or quality of plasma fibrinogen. We hypothesized that the Clauss fibrinogen activity assay does not accurately reflect true fibrinogen levels in severely injured patients. Here we demonstrate normal baseline plasma fibrinogen levels as measured by mass spectrometry despite coagulopathic Clauss values in severely injured patients. This discrepancy is most significant in patients with coagulopathy (INR > 1.3) or with high shock, and persists even following fibrinogen repletion. These data highlight the need to re-evaluate clinical testing of fibrinogen activity and transfusion criteria for the critically injured, and indicate that correcting shock and the oxidative, inflammatory milieu of trauma may be more effective at improving fibrinogen activity. Clinical Trial: NCT01838863.