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The Natural History and Effect of Resuscitation Ratio on Coagulation After Trauma: A Prospective Cohort Study

Kutcher, Matthew E. MD; Kornblith, Lucy Z. MD; Vilardi, Ryan F. BS; Redick, Brittney J. BA; Nelson, Mary F. RN, MPA; Cohen, Mitchell Jay MD

doi: 10.1097/SLA.0000000000000366
Original Articles

Objective: To investigate the natural history of coagulation factor perturbation after injury and identify longitudinal differences in clotting factor repletion by red blood cell:fresh frozen plasma (RBC:FFP) transfusion ratio.

Background: Hemostatic transfusion ratios of RBC to FFP approaching 1:1 are associated with a survival advantage in traumatic hemorrhage, even in patients with normal coagulation studies.

Methods: Plasma was prospectively collected from 336 trauma patients during their intensive care unit stay for up to 72 hours from February, 2005, to October, 2011. Standard coagulation studies as well as pro- and anticoagulant clotting factors were measured. RBC:FFP transfusion ratios were calculated at 6 hours after arrival and dichotomized into “low ratio” (RBC:FFP ≤ 1.5:1) and “high ratio” (RBC:FFP > 1.5:1) groups.

Results: Factor-level measurements from 193 nontransfused patients provide an early natural history of clotting factor-level changes after injury. In comparison, 143 transfused patients had more severe injury, prolonged prothrombin time and partial thromboplastin time (PTT), and lower levels of both pro- and anticoagulants up to 24 hours. PTT was prolonged up to 12 hours and only returned to admission baseline at 48 hours in “high ratio” patients versus correction by 6 hours in “low ratio” patients. Better repletion of factors V, VIII, and IX was seen longitudinally, and both unadjusted and injury-adjusted survival was significantly improved in “low ratio” versus “high ratio” groups.

Conclusions: Resuscitation with a “low ratio” of RBC:FFP leads to earlier correction of coagulopathy, and earlier and prolonged repletion of some but not all procoagulant factors. This prospective evidence suggests hemostatic resuscitation as an interim standard of care for transfusion in critically injured patients pending the results of ongoing randomized study.

In traumatic hemorrhage, “low ratio” transfusion with ratios of red blood cell:fresh frozen plasma approaching 1:1 leads to more effective repletion of specific coagulation factor deficits and improved injury-adjusted survival. These data provide prospectively collected evidence suggesting that low-ratio transfusion may have both coagulation-dependent and independent mechanisms accounting for improved survival after trauma.

From the Department of Surgery, San Francisco General Hospital, San Francisco, CA; and the University of California at San Francisco, San Francisco, CA.

Reprints: Mitchell Jay Cohen, MD, Department of Surgery, Ward 3A, San Francisco General Hospital, 1001 Potrero Avenue, Room 3C-38, San Francisco, CA 94110. E-mail:

M.E.K. and L.Z.K. contributed equally.

Disclosure: Supported by NIH GM-085689 (M.J.C.), NIH T32 GM-08258-20 (M.E.K.), and NIH T32 GM-008258-25 (L.Z.K.). The authors declare no conflicts of interest.

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