Trauma-induced coagulopathy and damage control resuscitation

            After finding and correcting the source of “surgical” bleeding, the next major task is to keep the trauma patient in shock from experiencing extensive ongoing “nonsurgical” bleeding.  Several retrospective reviews have demonstrated an incidence of coagulopathy in trauma as 25-30%.  Patients with increased wound severity scores and lower Glasgow Coma Scale (GCS) scores exhibit worse coagulopathy secondary to tissue hypoperfusion and tissue injury.  In 80-100% of patients with a GCS less than 6, some evidence of coagulopathy is seen.  A few different factors are important to consider when attempting to correct a patient’s coagulopathy.  These factors include acidosis and hypothermia (figure 1). 

Acidosis can be seen with tissue hypoperfusion and with subsequent inflammatory and metabolic changes.   Problems with hemostasis are especially noted once the pH is below 7.2. This low pH has been noted to affect the enzyme activity of factor V, VIIa, and X and inhibits thrombin generation.   Hypothermia also can cause bleeding abnormalities through decreased platelet responsiveness and altered enzyme functioning at temperatures below 35^◦ C.  Colder temperatures also cause increased fibrinolysis and decreased thromboxane B2 production, thus resulting in various alterations in the coagulation cascade.  In addition to these disturbances in enzymatic and platelet function, a consumptive coagulopathy also occurs in these trauma cases when platelets and coagulation factors begin to be used.  This further contributes to the picture of trauma-induced coagulopathy (figure 2).

 

 

 

            The question then is how do we correct and avoid these factors which lead to such significant coagulopathy in our severely injured trauma patients.  It is important to start with simple strategies like correcting the hypothermia with rewarming techniques such as covering the patient with heating blankets, giving warmed IV fluids, and considering body cavity lavage.  We must be aware of the base deficit and lactate level in order to correct the metabolic acidosis that is present in these patients.  The base deficit is thought to correlate with the severity of shock and can help guide our resuscitation efforts.  Lactate has also been shown to help in this and may be a predictor of mortality but can take longer to obtain.  In addition to laboratory values, a patient may be deemed coagulopathic by just clinical signs such as generalized nonsurgical bleeding from serosal surfaces, IV access sites, wounds, and skin edges.  While we start our resuscitation with isotonic crystalloids, more emphasis is being placed on the early use of blood products due to the potential adverse effects of crystalloids.  Unlike blood products, crystalloids cannot increase the oxygen carrying capacity in a patient, and they can also cause undesirable consequences such as immune activation, decreased cellular function, worsening hyperchloremic acidosis, and increased fluid extravasation into the lungs and abdomen. 

            Damage control resuscitation involves various components such as fresh frozen plasma (FFP), packed red blood cells (PRBCs), platelets, cryoprecipitate, and factor VIIA.  Depending on the condition of the patient, a massive transfusion protocol (MTP) may be initiated based on certain factors like a systolic blood pressure less than 90mmHg, a base deficit of 4 or less, and attending choice.  At Cook County, this ensures that 6U of PRBCs, 6U of FFP, and 5U of platelets are on their way.  In addition to giving PRBCs, it is important to start infusing these other blood products as quickly as possible in patients who present in hemorrhagic shock.  FFP can help correct the coagulation factors that have been exhausted because it contains fibrinogen and all the pro- and anticoagulant blood proteins.  Different studies have shown lower mortality rates in exsanguinating patients who received early administration of FFP with the optimal ratio of FFP to PRBC of 1 : 1.  This survival benefit of giving increased amounts of FFP is especially true in patients who require multiple units of PRBCs.  While decreased mortality has been shown with a similar dispensation of platelets, their functionality is lost during storage and some data suggests that they have no effect on survival.  While both platelets and FFP are important in damage control resuscitation, we must also be aware of their potential side effects such as acute respiratory distress syndrome (ARDS) and transfusion-related acute lung injury (TRALI).

            Another product to consider giving to patients is cryoprecipitate.  This will help give certain additional plasma factors—fibrinogen, von-Willebrand factor, factors VIII and XIII, and fibronectin.  This should be given in hemorrhaging patients whose fibrinogen level is less than 100 mg/dL.  Interestingly, about one dose of cryoprecipitate provides the same amount of fibrinogen that six units of FFP provide.  Factor VIIA and tranexamic acid (TXA) are other adjunctive treatments to consider in these situations.  The mechanism of action of factor VIIA in trauma patients is not completely understood but it is thought to activate factor X and subsequently the common coagulation pathway.  A few keys to giving this is that it is limited to three doses and it requires the patient’s pH to be greater than 7.2 in order to function properly.  TXA, a derivative of lysine, works well within only the first 3 to 8 hours.  In a randomized, placebo-controlled trial know as CRASH-2, TXA was proven to have some benefit in trauma patients.  It helps to prevent fibrinolysis by competitively inhibiting the conversion of plasminogen to plasmin.  Both cryoprecipitate and TXA should be considered when treating trauma patients with ongoing hemorrhage and coagulopathy. 

            Of course the initial concern in trauma patients who present in hemorrhagic shock is to find what is bleeding and control it surgically.  The next hurdle, as discussed above, is to address the other factors that will contribute to the patient’s coagulopathic state and nonsurgical bleeding.  Finally, one must think about giving blood products and various additional treatments as needed and early on in the resuscitative process. 

Sources:

·         Dr. Kimberly Joseph- “Damage Control Resuscitation” Trauma & Burn Symposium, June 14-15, 2013.

·         Duchesne JC, McSwain NE, Cotton BA, et al.  Damage Control Resuscitation: The New Face of Damage Control.  J Trauma. 2010; 69 (4): 976-990.

·         CRASH-2 trial collaborators.  Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. The Lancet. 2010; 376: 23-32.

 

from Dr. Jennifer Jolley