Time to interventionThe delay selleckchem Imatinib Mesylate to thaw and initiate FFP transfusion leads to another important limitation: timing to initiate and reach the high FFP:RBC ratio. Early formula-driven resusci-tation proposes that FFP should be initiated early, ideally with the first RBC unit at the start of resuscitation [52,53]. Considering that even laboratory-guided resuscitation eventually results in a high FFP:RBC ratio, a critical difference in formula-driven resuscitation is the early implementation of a high ratio. No studies to date have reported on transfusing pre-thawed FFP along with the first RBC units or on the time to reach the 1:1 ratio. Snyder and colleagues stated that the median time to the first RBC was 18 minutes from arrival, while the first FFP was transfused more than 1 hour later [57].

The commonly used definition of massive bleeding as transfusions over 24 hours ignores the fact that 80% of all massive transfusions occur within the first 6 hours of hospitalization, at which point either bleeding reduces substantially or the patient dies [59]. A multicentre study involving 16 trauma centres, 452 massively bleeding trauma patients and transfusion rates within 6 hours of hospitalization (rate <1:4, rate of 1:4 to 1:1 and rate ��1:1) concluded that early high FFP:RBC and platelet:RBC ratios improved survival [19]. Despite limitations, including significant differences in the baseline Glasgow coma scale and therefore the severity of head injuries between groups, the study provides better evidence that reaching high FFP:platelet:RBC ratios within the first hours of admission is associated with mortality reduction.

Missing data, co-interventions and heterogeneityData on timing to initiate FFP transfusions, on timing to reach the 1:1 ratio and on transfusions during the first 6 hours are equally missing in the studies supporting early formula-driven haemostatic resuscitation and in existing guidelines, limiting comparisons between the different strategies.Spinella and colleagues reported in 708 military patients transfused with ��1 units RBC that FFP transfusion was associated with increased survival (odds ratio = 1.17, 95% confidence interval = 1.06 to 1.29; P = 0.002) [12]. Missing data on the International Normalized Ratio, not measured in one-half of the patients, and heterogeneity with nonsurviving patients being significantly more coagulopathic than that for surviving patients, International Normalized Ratio 2.

06 versus 1.4 (P < 0.001) on admission, however, challenge their conclusion.Aggressive and early FFP transfusion is part of damage control resuscitation, which also proposes crystalloid restriction, rFVIIa and other interventions. A small Batimastat study on 40 combat casualties resuscitated with a package containing whole blood, rFVIIa, crystalloid restriction and a high FFP:RBC ratio illustrates the complexity of analysing multiple co-interventions [52].