Understanding Coagulation and Inflammation in Burns

Trauma injury is the leading cause of death in people 1-44 years old in the US. Burn injury is a particularly debilitating form of trauma. In the U.S. the incidence of burn injury is estimated to be greater than 2 million cases per year. Burns account for ~ 300,000 deaths worldwide every year. In 1996, the cost of caring for burn patients in the U.S. was estimated at $573 million per year.

Notably, 20-40% of trauma deaths that occur after hospital admission involve massive bleeding. Hemorrhage is the second most common cause of early in-hospital mortality accounting for a large portion of trauma deaths that occur within the first 24 hours. Resuscitation has dramatically changed over the last decade or so. Nowadays, we are substituting the normal saline and the other resuscitating fluids with blood products. This early administration of blood products during resuscitation is referred to as damage control resuscitation (DCR). The goal of DCR is to prevent and immediately correct trauma associated coagulopathy. DCR was initially practiced in the military where a balanced ratio of FFP:platelets:RBCs of 1:1:1 was employed. DCR has resulted in improved outcomes in both the military as well as civilian trauma setting as compared to previous resuscitation patterns. Despite the early use of a 1:1:1 ratio, a 1:1:2 ratio also became commonly used. Thus, the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) study was done to investigate the best ratio of products to use during resuscitation. The PROPPR study found no differences in mortality between the 1:1:1 and the 1:1:2 groups at 24 hours or at 30 days. Additionally, there was no difference in complications between the two groups. Notably, exsanguination was significantly decreased in the 1:1:1 group and more patients in the 1:1:1 group reached hemostasis. The Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study showed that early transfusion (within minutes of arriving at hospital) was associated with improved 6-hour survival. Furthermore, patients with increased plasma to RBC ratios (>1:2) were found to have improved 30-day survival as compared to patients who received lower plasma to RBC ratios (<1:2). Notably, 1-day and 30-day survival were found to be increased when patients received higher ratios of platelets to RBCs. Delayed but balanced transfusion ratios did not have the same protective effect as receiving plasma early.

To date there have been few studies on the effects of hemorrhage during burn and soft tissue excision and optimal blood product resuscitation. It is unclear whether DCR is optimal in burn patients. Moreover, it is unknown exactly what is happening in burn patients with respect to coagulation, platelet function, and microparticles (MPs). Patients with burns and soft tissue injuries typically have considerable bleeding during surgeries. Intraoperative blood loss is estimated at 9.2% of blood volume for every 1% of total body surface area (TBSA) burn excised in adults. In children undergoing burn excision, blood loss is estimated as 2% of blood volume for every 1% TBSA excised in extremities and trunk and 5% of blood volume for each 1% TBSA excised for the face. Moreover, early complete excision and grafting of major burns has been shown to decrease transfusions, infections, and mortality in children. Interestingly, many burn surgeons anecdotally report that their burn patients develop microvascular bleeding during the surgery. This phenomenon may be indicative of development of coagulopathy.

There have been several prospective studies looking at perioperative coagulation status in burn patients. These studies show that the coagulation proteins (FV, FVIII, FIX, and fibrinogen) decrease during surgery. Notably, in most cases, the factor levels were still within "normal" reference ranges. FVIII and fibrinogen are acute phase reactants and were elevated in the burn patients preoperatively. These studies were performed before the adoption of DCR. Additionally, several studies have shown that antithrombin, protein S, and protein C (the natural anticoagulants) levels decrease in burn injuries. A recent study by Palmieri et al. looked at compared a transfusion ratio of 1:1 RBCs:FFP to 4:1 RBCs:FFP in children with >20% TBSA burns. In their study of 16 children, they found a trend toward increased length of stay (LOS), peak PELOD score (measure of organ dysfunction), increased time to wound healing, and increased infection rates in the 4:1 group; however, the differences were not statistically significant. Notably, they found that the 1: 1 ratio was safe in the burn patients and that the 1:1 ratio was also less expensive ($26,635 versus $34,485). A recent study by Pidcoke et al. showed that current blood product resuscitation during burn and soft tissue excision is not hemostatic. Thus, the effect of using a balanced resuscitation ratio of blood products including platelets in burn patients has not been well studied.

In general, platelet dysfunction is believed to play a role in the development of trauma associated coagulopathy (TAC). The effect of burns on patients' platelets count and activity is unknown. Upon hospital admission, burn patients typically have normal platelet counts. By days 3-5, the patients' platelet counts usually drop, especially in burns of large TBSA. In severe burn patients, platelet mediators, such as platelet factor 4 (PF4) and thromboxane B2 (TxB2), have been found to be elevated. This is thought to be attributable to platelet activation and consumption. Thus, further investigation of the effect of burns on platelets will offer further insight into the transfusion needs of burn patients.