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Metabolic alkalosis is a frequent nding in patients who required massive trans­fusion due to the metabolism of the citrate preservative in blood products into

The term “damage control resuscitation” or “hemostatic resuscitation” has thus come to refer to a strategy of transfusing FFP and platelets at ratios approximating the ratios found in whole blood [41–44]. Animal studies have demonstrated that “1:1” FFP: RBC transfusion ratios result in decreased systemic inammation, improved platelet function, and attenuated organ injury when compared to “1:2” FFP:RBC transfusion ratio [45, 46]. Interestingly, damage control resuscitation has been associated with higher rates of successful non-operative management of severe blunt liver injuries [47].

The PROMMTT (prospective, observational, multicenter, major trauma transfu­sion) study was conducted at 10 U.S. Level 1 trauma centers and demonstrated decreased 6-h mortality in patients receiving FFP:RBC ratios of 1:1 or greater com­pared to those receiving less than 1:2 [53]. Subsequent to the PROMMTT study, the PROPPR (pragmatic, randomized optimal platelet and plasma ratios) trial random­ized massively bleeding patients to receive FFP:platelets:RBC in 1:1:1 ratio or 1:1:2. This trial did not show improvement in 24-h or 30-day all-cause mortality associated with the higher ratio transfusion strategy, but demonstrated better clinical hemostasis (a secondary outcome) in the high ratio group. Importantly, patients receiving higher volumes of FFP and platelets did not experience higher rates of 23 pre-specied complications, including ARDS, multiorgan failure, and infectious complications [54]. At present, the PROPPR trial represents the highest quality evi­dence on the topic of transfusion ratios in severely injured patients requiring mas­sive transfusion. Yet many questions remain, for example, it is not known whether the same purported benets of “balanced” blood component transfusion extend to non-trauma populations. Similarly, while much attention has been focused on the risk/benets of plasma ratios, much remains unknown regarding platelet transfusion [40, 55, 56]. Recent evidence suggests that platelet transfusions are associated with lung injury, even in the setting of “hemostatic resuscitation” [57]. Finally, it must be acknowledged that the PROPPR trial was a negative trial that failed to prove supe­riority of 1:1:1 transfusion over 1:1:2 for its primary endpoint. An optimal transfu­sion ratio for all patients may not exist, and within a single patient, the optimal transfusion ratio may vary over time as the disease course evolves.

The accumulated evidence may be summarized as: for patients requiring massive transfusion, balanced ratio blood product resuscitation should be initiated as early as possible. For transfusions not meeting the threshold denitions for “massive,” however, the transfusion of plasma is wasteful at best and harmful at worst. The conundrum facing the clinician at the outset is the accurate prediction of volume of transfusion that will be required in the bleeding patient [86]. Clinical gestalt has been demonstrated to be insufciently accurate [109] and therefore, multiple pre­dictive scoring systems have been developed (Table11.5), including TASH (trauma- associated severe hemorrhage) score [110], PWH (Prince of Wales Hospital/Rainer) score [111], Vandromme score [112], ABC (assessment of blood consumption)

score [113], Schreiber score [114], MTS (massive transfusion score) [115, 116], traumatic bleeding severity score (TBSS) [117], and Larsen score [118], among others [119, 120]. Some scores have been independently externally validated while others have not. As with all clinical prediction/decision rules, the more accurate the score, the more input variables it requires and the less likely the bedside clinician will use it; contrarily, the simpler the score, the less accurate are its predictions. Some scores require specialized imaging (e.g., to visualize intra-abdominal uid) while others require laboratory testing (e.g., INR). At this time, no single score has been universally adopted for clinical use.

However, there have been two major criticisms of the CRASH-2 trial: (1) the majority of subjects were enrolled from developing or middle-income countries without mature massive transfusion protocols; and (2) only half of the enrolled sub­jects (50.4 and 51.3%) actually received blood transfusion. To address the former criticism, the military application of tranexamic acid in trauma emergency resusci­tation (MATTERs) study was performed, which conrmed the benet of TXA administration (with or without cryoprecipitate) in terms of coagulopathy measures and survival [157, 158].

In terms of clot durability, hyperbrinolysis and brinolytic shutdown represent two opposite ends of the spectrum, with the former representing a fragile clot and

Of more concern, however, is that TXA has been implicated in the development of later brinolytic shutdown (LY30≤0.8%) and worse outcomes [166].

At this time, TXA is conditionally recommended [135] with two caveats: (1) if TXA is to be given, it should be given only within 3h of injury; (2) in centers with access to viscoelastic testing, TXA administration should be given only to patients with evidence of hyperbrinolysis and should be avoided in those with evidence of brinolytic shutdown or physiologic brinolysis [167]. Additional research is clearly needed to better dene optimal patient selection.

Intraoperatively, PBM programs focus on the minimization of intraoperative blood loss—this not only incorporates surgical techniques designed to reduce hemorrhage,