Following injury the otherwise healthy individual has a natural ability to clot off bleeding. The higher the vessel pressure, the harder it is for the bleeding to stop, since the fluid essentially “pushes” the clot out and consequently the bleeding resumes. In another words, it is reasonable to think that hypotension facilitates coagulation. Attempts to normalize blood pressure in case of uncontrolled bleeding as in victims of penetrating trauma may result in increased blood loss and worsen outcomes [10]. Another issue with aggressive fluid resuscitation is the potential for hypothermia if fluids that are stored at room temperature are used. If these fluids are not warmed prior to infusion, this can result in a significant drop in core body temperature. As exposed in Fig. 3.1, hypothermia is associated with many problems including bleeding disorder, organ failure, and hypotension and is one of the three components in the “lethal triad,” condition that must be feared and soon corrected by all trauma specialists [5–8].

It is important to remember that permissive hypotension is a temporizing measure to improve outcomes until the source of bleeding is controlled. There are consequences associated with prolonged permissive hypotension (>90 min) that must be taken into account. Prolonged permissive hypotension can lead to aggravated post-injury coagulopathy, ischemic damage secondary to poor tissue perfusion including the brain, mitochondrial dysfunction, and lactic acidosis. Permissive hypotension is currently contraindicated in the presence of traumatic brain injury suspicion.

No published evidence exists to support the strategy of permissive or controlled hypotension, although its usefulness has not been entirely ruled out either. Few would argue against replacing lost intravascular volume in patients with controlled or self-limiting hemorrhage. In patients with uncontrolled hemorrhage, particularly in the context of penetrating torso trauma, a strategy of permissive hypotension, together with expert resuscitation and rapid control of hemorrhage, might be more appropriate. It is conceivable that permissive hypotension is more applicable to the management of penetrating trauma, which is often characterized by the presence of major vascular injuries, than to blunt injuries.

Despite the lack of evidence, guideline recommendations for clinical practice point towards judicious administration of intravenous fluids. In recognition of the unique challenges posed by combat casualties, permissive hypotension has been incorporated into military medical doctrine and used widely during the recent war conflicts [4].

Massive bleeding patients demand a massive transfusion protocol (MTP). The traditional definition of massive transfusion is 20 units red blood cells (RBCs) in 24 h, which corresponds to approximately 1 blood volume in a 70 kg patient. A commonly used definition in the trauma literature is >10 units RBCs in 24 h. Both of these definitions are reasonable for publications, but are not practical in an ongoing resuscitation. Other definitions are loss of 0.5 blood volume within 3 h, use of 50 units of blood components in 24 h, and use of 6 units RBCs in 12 h. From a practical standpoint, requirement for >4 RBC units in 1 h with ongoing need for transfusion or blood loss >150 ml/min with hemodynamic instability and need for transfusion are reasonable definitions in the setting of a MTP situation.

Once MTP is initiated, the target is to achieve a close ratio resuscitation with 1:1:1 of fresh frozen plasma (FFP), platelets (Plts), and packed red blood cells (PRBCs). The rationale behind early and sustained administration of FFP involves the replacement of fibrinogen and clotting factors [15]. In mathematical studies, Hirshberg et al. noted that resuscitation with more than 5 units of PRBCs will lead to a dilutional coagulopathy and that the ideal manner to correct for this coagulopathy would be to add FFP to PRBC in a 2:3 FFP:PRBC ratio [16]. Another study by Ho et al. noted that once excessive deficiency of factors has developed, 1–1.5 units of FFP must be given for every unit of PRBCs transfused [17].

It should be emphasized FFP replacement alone does not address the coagulopathy seen in trauma patients with severe hemorrhage. A quantitative and qualitative platelet dysfunction has been shown to play a role as well in the mechanism of coagulation [18]. Although not as extensively as FFP, platelet replacement as a part of transfusion protocols has been studied to determine the most effective ratio of platelets to PRBC. Hirshberg et al. suggest a ratio of platelet:PRBC of 8:10 is effective in preventing dilution of platelets below the hemostatic threshold [16]. It should be noted, however, that both studies were theoretical models and did not take into account factors such as hypothermia, acidosis, thrombocytopenia, or ACoTS. These mathematical models for FFP and platelets set forth by Hirschberg and Ho have helped modify ratios used for MTPs throughout the world [13, 19].

Approximately 3–5 % of civilian adult trauma patients receive massive transfusion. Early identification of patients requiring MTP has been evaluated by assigning a value of 0 or 1 to the following four parameters: penetrating mechanism, positive FAST for fluid (focused assessment sonography in trauma), arrival blood pressure <90 mmHg, and arrival pulse >120 bpm. A score of 2 or more is considered positive [20–23]. The score is 75 % sensitive and 85 % specific. FAST examination identifies whether there is free fluid within the peritoneum, which could indicate organ rupture and internal bleeding. Patients receiving uncross-matched red cells in the emergency department are three times more likely to receive massive transfusion.

Recombinant factor VIIa use in trauma emerged because of the additional necessity of correcting ACoTS. Researches suggested that a pharmacological adjunct would be useful to treatment of ACoTS and this could play an important outcome role.

Recombinant activated factor VII (rFVIIa) is a hemostatic agent originally developed to treat hemophilia, FVII deficiency, and Glanzmann thrombasthenia patients refractory to platelet transfusion. The activation of platelets at the site of injury is the reason for a localized action of rFVIIa, as it causes clotting at the site of bleeding. The dose ranges from 60 to 200 g/kg; however, prospective randomized controlled clinical trials using different doses of rFVIIa are needed to explore the potential efficacy of lower doses in traumatic coagulopathy to reduce cost and adverse effects, such as thromboembolic complications [24]. The efficacy and safety of rFVIIa as an adjunct therapy for bleeding control in patients with severe blunt and penetrating trauma were evaluated in a parallel randomized, placebo-controlled, double-blind clinical trial [25]. The authors compared three doses of rFVIIa (doses of 200, 100, and 100 μg/kg) with three doses of placebo in addition to standard treatment in patients who received 6 units of RBCs within a 4-h period. In blunt trauma (143 patients), RBC transfusion was significantly reduced with rFVIIa compared to placebo, and the need for massive transfusion (defined as 20 units of RBCs) was reduced (14 % vs. 33 %, respectively). In penetrating trauma (134 patients), there was no reduction in mortality and complications or reduction of PRBCs transfused in patients receiving rFVIIa. Adverse effects, including thromboembolic events (a total of 12, six in each group), were distributed equally between the groups. The authors concluded that rFVIIa is safe within the investigated dose and may be a promising adjunct to existing therapy in trauma [25]. The effects of liberally administering rFVIIa in hemorrhaging trauma patients are unknown because its procoagulant effect must be balanced against a real risk of thromboembolic events. At present, the use of rFVIIa in correcting coagulopathy from trauma is off-label and has not been approved by the Food and Drug Administration [26].

Fibrinogen deficiency develops earlier than deficiency of other clotting factors. Fibrinogen is, therefore, an obvious target for replacement with either cryoprecipitate—which contains fibrinogen, factor VIII, factor XIII, and von Willebrand factor—or fibrinogen concentrate. Updated guidelines recommend giving either product if plasma fibrinogen levels fall below 1.0 g/l. Concerns about patient exposure to a large number of donors and the associated risk of blood borne virus transmission limit the use of cryoprecipitate to situations where conventional treatment has failed [5, 27].

Clot breakdown (fibrinolysis) is a normal response to surgery and trauma in order to maintain vascular patency and can become exaggerated (hyperfibrinolysis) in some cases. The antifibrinolytic drug tranexamic acid (TXA), a lysine analogue, interferes with the binding of plasminogen to fibrin, which is necessary for plasmin activation. Fibrinolysis consists of activated plamin cleaving fibrin. Antifibrinolytic drugs can prevent clot breakdown and thus reduce blood loss in trauma [28, 29]. TXA has recently been shown to reduce deaths in a large population of trauma patients. In 2011, the CRASH-2 investigators published an exploratory analysis of the previous trial that specifically evaluated the effect of tranexamic acid on death due to bleeding subdivided by time from treatment to injury. The results showed that earlier treatment with tranexamic acid is more effective in reducing the risk of death due to bleeding. Patients that received tranexamic acid within 1 h of injury had a death rate due to bleeding of 5.3 % versus 7.7 % for placebo (RR 0.79, CI 0.64–0.97; p < 0.0001). Similarly, patients that received treatment between 1 and 3 h from injury also had a significantly lower risk of death due to bleeding. However, patients receiving tranexamic acid >3 h from injury had a significantly increased risk of death compared to placebo, 4.4 % versus 3.1 %, respectively (RR 1.44, CI 1.12–1.84; p = 0.004) [28].