Fibrinogen and platelet contributions to clot formation: implications for trauma resuscitation and thromboprophylaxis.
BACKGROUND
Thromboelastography (TEG) is used to diagnose perturbations in clot formation and lysis that are characteristic of acute traumatic coagulopathy. With novel functional fibrinogen (FF) TEG, fibrin- and platelet-based contributions to clot formation can be elucidated to tailor resuscitation and thromboprophylaxis. We sought to describe the longitudinal contributions of fibrinogen and platelets to clot strength after injury, hypothesizing that low levels of FF and a low contribution of fibrinogen to clot strength on admission would be associated with coagulopathy, increased transfusion requirements, and worse outcomes.


METHODS
A total of 603 longitudinal plasma samples were prospectively collected from 251 critically injured patients at a single Level 1 trauma center from 0 hour to 120 hours. TEG maximal amplitude (MA), FF MA, FF levels, von Clauss fibrinogen, and standard coagulation measures were performed in parallel. Percentage contributions of FF (%MA(FF)) and platelets (%MA(platelets)) were calculated as each MA divided by overall kaolin TEG MA.


RESULTS
Coagulopathic patients (international normalized ratio ≥ 1.3) had significantly lower admission %MA(FF) than noncoagulopathic patients (24.7% vs. 31.2%, p < 0.05). Patients requiring plasma transfusion had a significantly lower admission %MA(FF) (26.6% vs. 30.6%, p < 0.05). Higher admission %MA(FF) was predictive of reduced mortality (hazard ratio, 0.815, p < 0.001). %MA(platelets) was higher than %MA(FF) at all time points, decreased over time, and stabilized at 72 hours (69.4% at 0 hour, 56.2% at 72 hours). In contrast, %MA(FF) increased over time and stabilized at 72 hours (30.6% at 0 hour, 43.8% at 72 hours).


CONCLUSIONS
FF TEG affords differentiation of fibrin- versus platelet-based clot dynamics. Coagulopathy and plasma transfusion were associated with a lower %MA(FF). Despite this importance of fibrinogen, platelets had a greater contribution to clot strength at all time points after injury. This suggests that attention to these relative contributions should guide resuscitation and thromboprophylaxis and that antiplatelet therapy may be of underrecognized importance to thromboprophylaxis after trauma.


METHODS
Prognostic study, level III.
From the Department of Surgery, San Francisco General Hospital, University of California, San Francisco, San Francisco, California.
Lucy Z
LZ
Kornblith
Matthew E
ME
Kutcher
Brittney J
BJ
Redick
Carolyn S
CS
Calfee
Ryan F
RF
Vilardi
Mitchell Jay
MJ
Cohen
D000328:Adult; D001778:Blood Coagulation Disorders / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D001780:Blood Coagulation Tests; D016913:Blood Component Transfusion / Q000379:methods; D001792:Blood Platelets / Q000502:physiology; D005260:Female; D063285:Fibrin Clot Lysis Time; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D015601:Injury Severity Score; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012151:Resuscitation / Q000379:methods*; D018570:Risk Assessment; D012494:Sampling Studies; D015996:Survival Rate; D013916:Thrombelastography / Q000379:methods*; D013918:Thrombin Time; D013927:Thrombosis / Q000517:prevention & control*; D014193:Trauma Centers; D014947:Wounds and Injuries / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D055815:Young Adult
D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen