title: Functional fibrinogen assay indicates that fibrinogen is critical in correcting abnormal clot strength following trauma.
abstract: Thromboelastography (TEG) is emerging as the standard in the management of acute coagulopathies in injured patients. Although TEG is sensitive in detecting abnormalities in clot strength, one shortcoming is differentiating between fibrinogen and platelet contributions to clot integrity. Current American algorithms suggest platelet transfusion, whereas European guidelines suggest fibrinogen concentrates for correcting low clot strength. Therefore, we hypothesized that a TEG-based functional fibrinogen (FF) assay would assess the contribution of fibrinogen and platelets to clot strength and provide insight to transfusion priorities. Blood samples were obtained from trauma patients on arrival to the emergency department or who were admitted to the surgical intensive care unit (n = 68). Citrated kaolin TEG, FF, and von Clauss fibrinogen levels (plasma-based clinical standard) were measured. Correlations were assessed using linear regression models. In vitro studies were also performed with adding fibrinogen concentrates to blood collected from healthy volunteers (n = 10). Functional fibrinogen and citrated kaolin TEG parameters were measured. Functional fibrinogen strongly correlated with von Clauss fibrinogen levels (R = 0.87) and clot strength (R = 0.80). The mean fibrinogen contribution to clot strength was 30%; however, there was a direct linear relationship with fibrinogen level and percent fibrinogen contribution to clot strength (R = 0.83). Traditional TEG parameters associated with fibrinogen activity (α angle and kinetic time) had significantly lower correlations with FF (R = 0.70 and 0.35). Furthermore, platelet count had only a moderate correlation to clot strength (R = 0.51). The addition of fibrinogen concentrate in in vitro studies increased clot strength (MA) (60.44 ± 1.48 to 68.12 ± 1.39) and percent fibrinogen contribution to clot strength (23.8% ± 1.8% to 37.7% ± 2.5%). Functional fibrinogen can be performed rapidly with TEG and correlates well with the standard von Clauss fibrinogen assay. Both fibrinogen and platelet contribution of clot strength can be derived from FF. Moreover, FF had a stronger correlation to clot strength, and increased levels were directly associated with increased percent contribution to clot strength. In vitro studies also demonstrated an increase in FF, clot strength, and percent fibrinogen contribution to clot strength with the addition of fibrinogen concentrate. These data suggest that fibrinogen should be addressed early in trauma patients manifesting acute coagulopathy of trauma.
authors.affiliation: Department of Surgery, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Harr
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.forename: Arsen
authors.initials: A
authors.lastname: Ghasabyan
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chin
authors.forename: Angela
authors.initials: A
authors.lastname: Sauaia
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000502:physiology; D001778:Blood Coagulation Disorders / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011446:Prospective Studies; D013916:Thrombelastography / Q000379:methods; D014947:Wounds and Injuries / Q000097:blood / Q000150:complications*
chemical_list: D005340:Fibrinogen