Given the risks, costs, and scarcity of blood and blood components, 8 , 9 understanding transfusion requirements for victims of gun violence is an important public health issue. Such information will allow for optimal emergency preparedness and possibly improved outcomes, especially in urban trauma centers where gun‐related injuries are commonly treated. In the current study, we performed a retrospective cohort analysis to test the hypothesis that victims of gun violence have substantially higher transfusion requirements and blood costs, compared to patients with non–gunshot‐related traumatic injuries.

In the United States, 38,658 deaths and 116,414 injuries were attributed to firearms in 2016 1 ; however, blood transfusion requirements for these patients are poorly understood. Massive transfusion protocols are associated with improved hemostasis and a reduction in hemorrhagic death in adult trauma victims, 2 especially when blood products are administered early after the injury in hemorrhaging patients. 3 , 4 Not surprisingly, increased transfusion requirements are also associated with higher mortality after traumatic injury, 5 , 6 likely because transfusion is strongly associated with injury severity. 7

We performed a multivariable logistic regression to assess the risk‐adjusted impact of several clinical variables on the likelihood of high‐dose transfusion, defined as 10 or more RBC units during the hospitalization. The independent variables entered into the model were GSW versus non‐GSW mechanism of injury, age, sex, injury severity score, 12 type of traumatic injury (penetrating vs. blunt or other), abbreviated injury scale (AIS) 13 for the head, and early versus late time period during the study (pre– or post–January 2012; the time when a massive transfusion protocol was implemented at our institution). Analyses were generated with statistical analysis software (JMP version 12.1.0, SAS Institute). For all analyses, p less than 0.05 (two‐tailed) was considered significant.

Blood utilization (the primary outcome) was assessed by two methods: 1) the percentage of patients requiring transfusion and 2) the average number of units transfused per patient. Each of the four major blood components were analyzed separately, and another analysis was performed combining all blood components together as “any blood product.” One unit of apheresis platelets from a single donor with the equivalent of 5 to 6 whole‐blood–derived platelet units was considered to be 1 unit of platelets. Five pooled units of cryoprecipitate (one dose) was considered to be 1 unit of cryoprecipitate. Our massive transfusion protocol was introduced in January 2012, which for trauma patients includes a container with 6 units of RBCs, 5 units of plasma, and 1 apheresis unit of platelets, delivered to the bedside, while the next (and similar) container is being prepared. Every third container includes 10 pooled units of cryoprecipitate. A supply of thawed plasma (group AB) is maintained to support massive transfusion protocols; however, group A plasma is substituted when this is in short supply.

The GSW and non‐GSW cohorts were compared twice—once for the entire trauma patient population (transfused any blood product or nontransfused), and then again for the subset of trauma patients that required any blood product transfusion. The outcomes assessed were blood utilization for each of the four major blood components (red blood cells [RBCs], platelets, plasma, and cryoprecipitate) and the cost of transfusion. Transfusion costs were assessed by two methods: 1) blood acquisition costs and 2) activity‐based costs (the total cost of transfusion including the overhead costs). Acquisition costs were calculated as $200/RBC unit, $500/apheresis platelet unit, $50/plasma unit, and $250/dose of cryoprecipitate. 10 The activity‐based costs were estimated to be fourfold greater than the acquisition costs, based on the findings reported by Shander and colleagues. 11

After receiving Institutional Review Board approval, we conducted a retrospective cohort study using data submitted to the Maryland State Trauma Registry from January 2005 to June 2017. The study population included all patients brought to the emergency department (ED) at a Level 1 urban trauma center (Johns Hopkins Hospital, Baltimore, Maryland), designated to have traumatic injury. Patients who were dead at the scene or dead on arrival were excluded. For our comparison, we categorized patients based on the type of injury to create two cohorts: 1) gunshot wound (GSW) or 2) all other trauma (non‐GSW). The non‐GSW cohort was further divided into three subgroups: 1) penetrating wounds, 2) blunt trauma, and 3) other or unspecified injuries. The non‐GSW penetrating group most often presented with stab injuries.

Interestingly, the cohort of non‐GSW patients with penetrating injury (most often stab wounds) had a substantially lower mortality (about eightfold) than GSW patients (28 of 956 [2.9%] vs. 653 of 2672 [24.4%]; p < 0.0001), and a transfusion rate that was less than half that of GSW patients (81 of 956 [8.5%] vs. 538 of 2672 [20.1%]; p < 0.0001) (Table 3 ). Transfusion requirements and blood costs were about fourfold lower in the non‐GSW penetrating injury compared to the GSW injury group. Further comparison of the GSW and non‐GSW penetrating injury cohorts is shown in Tables 4 and 5 . These findings show a substantially lower injury severity, decreased requirements for all four major blood components, and decreased blood costs and mortality in the non‐GSW penetrating injury group, illustrating that GSW injuries are far more serious than non‐GSW penetrating injuries, such as stab wounds.

Transfusion rates, mean blood activity‐based cost per patient, and overall mortality were analyzed according to the specific type of injury (Table 3 ). Among the two general injury categories (blunt and penetrating), patients with penetrating trauma were more than five‐fold more likely to receive a transfusion (619 of 3628 [17.1%] vs. 505 of 15,508 [3.3%]; p < 0.0001), and average blood costs in that group were 11‐fold higher than in the blunt‐trauma group. Mortality was significantly greater (13‐fold) among patients with a penetrating injury (681 of 3628 [18.8%]) than in those with blunt trauma (216 of 15,508 [1.4%]; p < 0.0001). GSW injury was more likely to require transfusion and to be fatal than an injury resulting from a motor vehicle accident, a fall, or a blunt‐trauma assault.

Transfusion requirements in GSW versus non‐GSW trauma patients. Requirements for all blood component units combined are shown for the GSW and non‐GSW trauma patients who received at least one transfusion. The two cohorts are compared with the number of transfused units shown on the‐axis, and the percentage of patients shown on the‐axis. GSW patients were more likely than non‐GSW patients to receive high‐dose transfusion (>15 units of all blood components during their hospitalization). All blood product units include RBCs, platelets, plasma and cryoprecipitate. [Color figure can be viewed at wileyonlinelibrary.com

For the transfused subset, the number of blood component units given was compared in the GSW and non‐GSW cohorts for all major blood components combined, and for RBCs, platelets, and plasma individually (Fig. 2 ). It was evident that the GSW patients were more likely to receive high‐dose transfusion (>5 or 10 units of each individual component, and >15 units of all components combined). In addition, GSW‐patients were approximately three times more likely than non‐GSW patients to require transfusion with more than 30 units of all blood components combined (77 of 538 [14.3%] of GSW patients vs. 34 of 798 [4.3%] of non‐GSW patients; p < 0.0001).

Within the subset of transfused trauma patients (right side of Table 2 ), the mean number of units transfused per patient was approximately twofold greater in the GSW cohort relative to the non‐GSW cohort. This difference was evident for all blood components combined and for each of the four major blood components individually. Both mean and median blood product costs per patient were also twofold greater in the GSW cohort. By activity‐based cost, the 538 transfused GSW patients received blood totaling $6,093,800, or an average of $11,327 ± 17,339 per patient, whereas the average blood cost per non‐GSW patient was $5716 ± 12,966. Both ED mortality (68 of 538 [12.6%] vs. 17 of 798 [2.1%]; p < 0.0001) and overall mortality (180 of 538 [33.5%] vs. 102 of 798 [12.8%]; p < 0.0001) were substantially greater in the GSW cohort than in the non‐GSW cohort.

For all trauma patients (left side of Table 2 ), the percentage who required transfusion with any blood product was more than fivefold greater in the GSW than in the non‐GSW cohort. This large difference was evident for each of the four major blood components. The mean number of units per patient was approximately 10‐fold greater in the GSW cohort relative to the non‐GSW cohort; this difference was evident for all blood components combined and for each of the four major blood components individually. Although patients with GSWs comprised only 11.4% of all trauma patients, the cost of blood for these patients was greater than the total blood cost for all the other trauma patients: $1,523,450 versus $1,140,250 by acquisition cost, and $6,093,800 versus $4,561,000 by activity‐based cost. These costs were calculated based on 8905 and 6494 total units of product (RBCs, platelets, plasma, and cryoprecipitate combined), given to the GSW and non‐GSW cohorts, respectively. The mean blood product cost for all GSW patients was approximately 10‐fold greater than that for all non‐GSW patients. Both ED mortality (69 of 2672 [2.6%] vs. 17 of 20,750 [0.08%]; p < 0.0001) and overall mortality (653 of 2672 [24.4%] vs. 352 of 20,750 [1.7%]; p < 0.0001) were substantially greater in the GSW cohort than in the non‐GSW cohort.

Flow chart describing the patient population. The distribution of patients among the gunshot wound (GSW) and non‐GSW cohorts, as well as the penetrating‐ and nonpenetrating‐injury subgroups, are shown in the figure, along with the number of patients in each category requiring any blood product transfusions during the hospitalization. In the “Non‐GSW Patients” category, “Other” injuries included those such as animal bites, hanging, drowning, burn injuries, explosions, or injuries that were unspecified. [Color figure can be viewed at wileyonlinelibrary.com

The distribution of all trauma patients by GSW and non‐GSW cohorts, as well as by penetrating, blunt, and other traumatic injuries, along with the proportion that were transfused any blood product during the hospitalization, are shown in Fig. 1 . Among all trauma patients (transfused or not), the GSW patients were younger, were more likely to be male, and had higher injury severity scores and AIS scores for the head, thorax, and abdomen (Table 1 ) compared to non‐GSW trauma patients. These differences persisted in the subset of transfused trauma patients, except for AIS head score of 5 or above, which was similar in the two groups.

DISCUSSION

The main findings in this study show that, compared to patients with non‐GSW trauma, those with GSW injuries have a much higher blood utilization and blood cost, as well as a higher mortality. GSW patients were approximately five times more likely than non‐GSW trauma patients to require transfusion, and both the number of blood units transfused and blood costs were approximately 10 times greater. The increased blood use was evident for all four major components (RBCs, platelets, plasma, and cryoprecipitate). Blood use, blood cost, and mortality were much greater for patients with GSWs than for patients who had undergone motor vehicle accidents, falls, nonpenetrating assaults, and non‐GSW penetrating (most often stab wound) injuries. Although GSWs represented only one in nine injuries, they accounted for more than one‐half of the transfusions and two‐thirds of the deaths.

Although higher mortality from GSWs compared to other traumatic injuries has been reported,14 transfusion requirements for GSW patients have not been well described or compared to those for patients with other traumatic injuries. What has been reported are predictors of massive transfusion (>10 units of RBCs in 24 hours), such as hypotension and acidosis in patients with GSW injuries to the torso.15 It has also been reported that in hemorrhaging adult trauma victims, transfusion of blood components soon after the injury,3, 4 and in a balanced ratio of “red” and “yellow” products, is associated with improved survival and decreased hemorrhagic deaths.2, 3, 16, 17 In the current study, it is noteworthy that transfusion requirements for all blood components and the likelihood of requiring high‐dose transfusion were greater in the GSW cohort, even when compared to non‐GSW penetrating injuries.

Our findings suggest that Level 1 trauma centers, or any hospital that could potentially admit GSW patients, should be prepared to deliver RBCs, platelets, plasma, and cryoprecipitate in high volumes at short notice to provide optimal care for GSW victims. Massive transfusion protocols designed to deliver balanced ratios of these components save lives in hemorrhaging patients.2, 5, 18 Nevertheless, there is a dose‐related increase in mortality associated with blood transfusion,5, 18 and trauma patients do worse than other massively transfused patients such as those undergoing cardiac or transplant surgery.18 The challenge to hospitals is to have adequate stockpiles of blood components ready for transfusion, including thawed plasma and platelets. Platelets are particularly challenging to keep on hand, as they have the shortest shelf life of all blood components and incur the highest risk and costs. For most hospitals, having such a complete blood product inventory represents a challenge, given what has been described recently as a crisis in the US blood system9 that stems from an overall decline in blood use across the United States,19, 20 and the resulting financial impact on the blood industry. Alternatively, some trauma centers have recently moved toward using low‐titer group O (universal donor) whole blood for resuscitation of patients with traumatic hemorrhage,21, 22 rather than stocking and transfusing each of the individual blood components.

As in our previous studies10, 23 we reported blood costs using two commonly used methods—the acquisition cost and the activity‐based cost. Acquisition cost is simply what the hospital pays to purchase a unit of blood from its blood supplier, for example, hospital payments to the American Red Cross or other suppliers. The true cost of that unit, however, is estimated to be about four times greater than the acquisition cost,11 given the many different steps involved in bringing that blood unit all the way from the donor to the recipient. These extra “overhead” cost estimates are based on those related to RBCs; however, we extrapolated them for the other components using the same fourfold multiplier. It should be noted that the activity‐based cost for plasma has been reported to be eight times greater than acquisition cost,24 suggesting that we may have underestimated total blood component costs. Blood costs are, of course, small compared to the cost of an ED visit or a hospitalization. In 2010, the economic cost of hospitalization for firearm victims in the United States was estimated to be $18 billion per year, and the overall societal cost for care of such victims was estimated to be $174 billion,25 which, when put in perspective, is more than 50% greater than the US Department of Education's budget.25

Recent data revealed that in 2016, 38,658 Americans died from firearm injuries, accounting for 16.7% of all injury‐related deaths.1 In single‐center studies from Level 1 urban trauma hospitals, both Efron and colleagues26 in 2006, and Sauaia coworkers14 in 2016 reported increasing fatality rates for patients with GSWs, with an approximate 25% in‐hospital mortality. Nationwide, mortality rates for hospitalized GSW victims are estimated to be 8.3%27; however, the category of hospitalized patients excludes those who die at the scene, are dead on arrival to the ED, or die in the ED. As expected, GSW to the head is most likely to be fatal, with reports of only a 9% survival rate.28 Interestingly, our reported overall mortality was 24.4% in all GSW victims, but 33.5% in transfused GSW victims, and these values were much higher than the mortality rates for non‐GSW patients. The lethality of GSW injuries has recently increased to the extent that even in Level 1 trauma centers with state‐of‐the‐art medical care, there is still a relatively high mortality, which appears to be related to the increased incidence of GSWs to the head and chest.26 Another consideration that we do not even report here is that GSW survivors often experience morbidity and/or loss of functional capacity, and that mortality represents a small fraction of the overall impact of gun violence.

In our highest‐impact medical journals, multiple recent editorials on the challenges of gun violence prevention have been published,29-33 while the number of original research articles is few. The likely explanation is that research efforts on gun violence lag far behind research on other threats to our health, for example, infectious diseases or cancer. The Omnibus Consolidated Appropriations Act of 1997 placed a moratorium on gun violence research by stating that no federal funds made available to the Centers for Disease Control and Prevention for injury prevention and control studies may be used to advocate or promote gun control.34 The Consolidated Appropriations Act of 2012 put similar constraints on gun violence research throughout the entire US Departments of Health and Human Services, Labor, and Education by prohibiting the use of federal funds for the advocacy or promotion of gun control.35 The National Institutes of Health, however, has funded a limited number of grants since 2013 to investigate violence, including two of nine proposals that specifically address firearms.36 Until federal funds become more available, gun violence research will need to be primarily supported by institutions or foundations.

Our study has several limitations that should be recognized. First, this study reports findings from a single‐center urban trauma center, and therefore the results may not be generalizable to other institutions with different geography, demographics, or resources. Second, as with any retrospective study using registry data, we can only comment on associations rather than causation; however, this should not be relevant to our main objective, which was to quantify blood utilization in GSW victims. Third, we most likely underestimated true GSW mortality rates given that individuals who were “dead at the scene” or “dead on arrival” were excluded. Fourth, our particular population also substantially underrepresents the number of GSW deaths in the United States from suicide, which comprise about 60% of gun‐related deaths.37 Less than 1% of GSWs in our study were attributed to self‐inflicted (suicidal) injuries, likely because of the exclusion of patients who were dead at the scene or on arrival, or the demographics of our local population. Although the introduction of our massive transfusion protocol occurred about halfway through the study time period, which could be considered a limitation, this is unlikely to impact the primary findings in our study, which involved comparison of the GSW to non‐GSW cohorts. Finally, we report blood costs, not overall ED visit or hospitalization costs. We focused primarily on blood costs because overall cost of hospitalization and costs to society for patients with GSWs have been previously reported.25

In conclusion, we report a substantially greater blood use and blood cost for victims of gun violence and, not surprisingly, a greater mortality compared with all other types of traumatic injuries. Based on our findings, hospitals that treat GSW patients need ample supplies of all four major blood components. This alone is a challenging proposition given the scarcity of blood and recent difficulties in the blood industry. In addition, increasing federal funding for gun violence research and support for violence prevention outreach also seem to be prudent given the seriousness and lethality of GSW injuries. If advances to reduce gun violence are recognized, more blood and money would be available to treat patients with other, more manageable and survivable medical conditions.