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Clinical Science Aspects

The Association Between ABO Blood Type and Mortality Among Severely Injured Trauma Patients

Griffin, Russell L.; Jansen, Jan O.; Bosarge, Patrick L.; Marques, Marisa B.; Kerby, Jeffrey D.

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doi: 10.1097/SHK.0000000000001497
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Abstract

INTRODUCTION

Injury accounts for approximately 180,000 deaths in the United States each year, and is the leading cause of death for individuals aged 1 to 44 years (1). The impact of blood group on mortality following injury has received considerable attention, particularly in view of the known association between blood group and von Willebrand Factor (vWF) levels. In general population cohorts, type O blood has been associated with a decreased risk of conditions such as coronary heart disease (2), pancreatic cancer (3), and pulmonary embolism (4). Type O blood is known to have lower vWF levels, due to increased clearance, which is thought to be responsible for protection for many cardiovascular diseases. Among trauma patients, type O is associated with decreased risk of complications such as acute respiratory distress syndrome (ARDS) (5) and acute kidney injury (AKI) (6), although both associations were limited to Caucasian patients with major trauma. A recent study from Japan reported that type O was associated with a 3-fold increase in the risk of mortality compared with all other blood types (7). The authors hypothesized that this association could be the result of lower vWF levels, given its critical role in hemostasis. The objective of the current study is to examine whether blood type is associated with mortality of patients with major trauma, in a different population, based in the United States.

METHODS

Study design

This is a retrospective cohort study of patients admitted to the level I trauma center at the University of Alabama at Birmingham (UAB) hospital in Birmingham, Alabama. UAB serves a seven-county area with a population of approximately 1.1 million residents, and is the quarternary referral center for the State of Alabama. The study was approved by the Institutional Review Board. Patients admitted between 2015 and 2018 were considered for inclusion. Patients without major trauma, defined as an Injury Severity Score (ISS) <16, patients who were dead on arrival, and patients aged <18 years were excluded. For each included patient, data were collected on demographics (i.e., age, race, and sex), and injury and clinical characteristics. Injury characteristics included mechanism, ISS, Glasgow Coma Scale (GCS) score, and the maximum Abbreviated Injury Scale (AIS) score for each body region including the head and neck combined, face, chest, extremities, abdomen and pelvis combined, and spine. Clinical characteristics included the Revised Trauma Score (RTS), patient blood type, Rh type (positive or negative), number of units of packed red blood cells (PRBCs) transfused in the first 24 h following admission, number of days in the intensive care unit, number of days on ventilator support, and hospital length of stay (in days). In addition, patients were classified as to whether they incurred a nosocomial complication including ARDS, AKI, cardiac arrest, deep vein thrombosis, pneumonia, pulmonary embolism, and/or sepsis.

Variable definitions

The exposure of interest for the study was blood type defined as type A, B, AB, or O. The main outcome of interest was all-cause, in-hospital mortality. Injury mechanism was defined as blunt or penetrating. The number of PRBCs was separated into those units that were cross-matched and uncrossmatched. Race was categorized as white, black, and other (i.e., Asian, Native American, Pacific Islander, and anyone noted as having Hispanic ethnicity). The RTS was calculated from the patient's GCS, systolic blood pressure, and respiratory rate (8). Type of emergency transport was defined as air (i.e., fixed or rotary wing aircraft) or ground (i.e., private vehicle, police transport, or emergency medical transport).

Statistical analysis

Demographic, injury, and clinical characteristics were compared among ABO groups using a Pearson chi-square or analysis of variance (or Kruskal–Wallis for nonparametric comparisons of AIS by body region) for categorical and continuous variables, respectively. A Pearson chi-square was used to compare the incidence of nosocomial complications by ABO group. A logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between blood type and mortality. The regression model was adjusted for factors that had a P value of <0.20 in the bivariate analysis; a backwards selection process was subsequently used to create the most parsimonious model. In a secondary analysis, a logistic model using the same covariates in the most parsimonious model for overall mortality was created separately for death caused by traumatic brain injury, exsanguination, and all other causes (i.e., cardiac arrest, multiorgan failure, respiratory failure, causes not fully specified, and unknown causes).

RESULTS

From 2015 to 2018, 3,993 patients met the study inclusion criteria. Of these, 80 (2.0%) were missing blood type data, leaving 3,913 for analysis. Of the latter, 1,386 (34.7%) were blood type A, 506 (12.7%) were type B, 126 (3.2%) were type AB, and 1895 (47.5%) were type O. A total of 509 patients (13.0%) were Rh negative. There was no difference among blood type groups in regards to age or sex; however, based on standardized Pearson residuals, those who were type B were more likely to be black (P < 0.0001) (Table 1). In addition, those who were type B were more likely to have a penetrating injury (P = 0.0071) and have a higher maximum AIS to the head and neck (P = 0.0346), but there were no differences among groups by GCS, ISS, or maximum AIS for other body regions. Those who were types O and A were more likely to be transported by air (P = 0.0022). There was no difference among the groups in regards to any of the clinical parameters or the incidence of any of the nosocomial complications (Fig. 1).

Table 1
Table 1:
Comparison of demographic, injury, and clinical characteristics among ABO blood groups
Fig. 1
Fig. 1:
Comparison of nosocomial complication risk by ABO blood group.

Compared with patients who were blood type O, there was no difference in all-cause mortality for any of the blood types (Table 2), an observation that remained after adjusting for race, head/neck/face AIS, injury mechanism, transfusion of at least one unit of uncrossmatched type O PRBCs, and type of emergency transport. By cause of death, no association was observed for any blood type (compared with type O) for death due to traumatic brain injury. While not statistically significant, a weak decreased association for death to exsanguination was observed for type A (OR 0.64, 95% CI 0.36–1.12) compared with type O patients. No difference in mortality by all other causes was observed by blood type.

Table 2
Table 2:
Associations between ABO blood group and mortality among severe trauma patients by cause of death

DISCUSSION

In the current study, there was no observed difference in all-cause mortality or cause-specific mortality for any of the blood types when compared with type O patients. These findings are in direct contrast to Takayama et al. (7) who reported a near 3-fold increase in mortality for type O blood compared with other blood types. This was an intriguing finding, given that patients with group O blood are known to have lower vWF levels. vWF is essential for subendothelial platelet adhesion and platelet aggregation in vessels in which rapid blood flow results in elevated shear stress. vWF is also the carrier of factor VIII in plasma and protects it from proteolytic degradation, efficiently localizing it at the site of vascular injury. Severe vWF deficiency (known as von Willebrand disease) is responsible for a hemorrhagic diathesis. It is therefore conceivable that blood group O trauma patients could harbor a similar hemorrhagic diathesis, manifesting as an increased risk of death. Although conceptually attractive, our results demonstrate that—at least in our population—this does not appear to be the case.

There are multiple reasons for the difference in the two studies. First, the median maximum AIS for the head region in the Takayama study was 4 (IQR 3–4) for all ABO groups while it was zero for all other body regions, suggesting that the patient population was comprised mostly of patients with severe traumatic brain injuries. The current study population more often included patients with severe injuries to other body regions as evidenced by median AIS scores of 2 and 3 for the chest and extremities. That said, limiting our study population to patients with a head AIS of 3 or greater did not alter our results (data not shown). Second, all but two of the patients in the Takayama study were Rh positive; however, limiting our study population to Rh-positive patients did not alter the results either (data not shown). Another possible explanation could be due to differences in how the logistic model was built between the two studies. While Takayama et al. included age, RTS, and ISS based on clinical importance, we opted to utilize an approach based on statistical significance; however, including only age, RTS, and ISS in our models did not alter the results. The prior study additionally compared type O patients to all other blood types combined, while the current study compared type O to type A, B, and AB individually. Comparing type O patients to all other blood types for the current population again showed no association (OR 1.02, 95% CI 0.83, 1.26), which is not surprising given that a majority of the patients were type O or type A (thus resulting in point estimates of associations being weighted toward the experience of the two groups). Finally, only 19 (0.5%) of the patients in the current study were Asian while all patients in the Takayama study were Japanese; thus, it is possible that the differences in the two studies could be explained by race and ethnicity differences. In addition, another possible reason for differences in the results of the two studies could be due to regional differences in coordination of trauma care. While we cannot comment on the trauma system coordination in the setting of the Takayama study, our trauma system is coordinated by a central communications center located near our trauma center. The communications center utilizes a proprietary software that allows for real-time monitoring of available hospital and prehospital resources to ensure that patients are brought to our trauma center in a timely, efficient manner. Prior research utilizing data from our trauma system reported that the presence of the system (and the trauma communications center), decreased the likelihood of death from exsanguination and brain injury when compared with a time period without the trauma system in place for all-cause trauma (9) and specifically homicides (10).

Our study has strengths and limitations. First, we included a number of Rh-negative patients and a variety of racial groups, increasing the generalizability of the results; additionally, we studied a larger sample compared with the study of Takayama et al., allowing for more efficient measures of association. That said, the study is limited by being from a single-center, and it is possible that the same associations may not be observed for other populations.

Although the possibility of a relationship between blood group and outcome—possibly mediated by von Willebrand factor levels—is intriguing, our results suggest that, among severely injured patients, there is no association between mortality risk and ABO blood type. Given potential regional differences in trauma coordination and care, as well as demographic and genetic differences, additional studies utilizing populations from different geographies are needed to determine whether blood type could be associated with trauma mortality.

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Keywords:

Blood group; death; injury; outcomes; transfusion

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