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Optimising diagnosis and treatment of coagulopathy in severely injured trauma
patients
Balvers, K.
Publication date
2016
Document Version
Final published version
Link to publication
Citation for published version (APA):
Balvers, K. (2016). Optimising diagnosis and treatment of coagulopathy in severely injured
trauma patients.
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K. Balvers, S. van Dieren, K. Baksaas-Aasen, C. Gaarder, K. Brohi, S. Eaglestone, S. Stanworth, P.I. Johansson, S.R. Ostrowski, J. Stensballe, M. Maegele, J.C. Goslings, N.P. Juffermans, TACTIC partners
Submitted
THERAPEUTIC STRATEGIES ASSOCIATED WITH IMPROVED
OUTCOMES IN BLEEDING TRAUMA PATIENTS
ABSTRACT
Introduction: The effect of a combined approach of balanced transfusion ratios, pro-coagulant and anti-fibrinolytic therapies on trauma-induced exsanguination is not known. The aim of this study was to investigate the effect of transfusion ratios, tranexamic acid (TXA) and products containing fibrinogen on outcome of bleeding trauma patients.
Methods: A prospective multicentre observational study was performed in 6 Level-1 trauma centres. Trauma patients who received at least 4 red blood cells (RBCs) were analysed (n=385) and divided into groups with low (<1:1) or high (≥1:1) ratios of plasma and platelets (PLTs) to RBCs, receiving TXA and fibrinogen products (fibrinogen concentrates or cryoprecipitate) or not. Logistic regression models were performed to assess the effect of transfusion strategies on the outcomes ‘alive and free of massive transfusion’ (≥10 RBCs in 24 hours) and early ‘normalization of coagulopathy’ (INR ≤1.2).
Results: A high PLT:RBC ratio and TXA were independently associated with an increased number of patients alive and free of massive transfusion (OR 2.8, 95% CI 1.3-6.0, p<0.01 and OR 2.2, 95% CI 1.0-4.9, p=0.04 resp.) A trend was observed for patients receiving a high ratio of plasma to RBCs (OR 2.0, 95% CI 1.0-3.9, p=0.052). Ratio, TXA and fibrinogen products were not associated with correction of coagulopathy.
Conclusion: A high PLT:RBC ratio and TXA are associated with a decreased need of massive transfusion and an increased survival in bleeding trauma patients. No effect on the early correction of coagulopathy, as defined by prolonged INR, was seen for transfusion ratio, TXA and fibrinogen products.
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INTRODUCTION
Traumatic injury is responsible for an increasing number of deaths globally. Haemorrhage after trauma is one of the main causes of death1. Trauma-induced coagulopathy
(TIC) aggravates blood loss and increases mortality2-4. Mostly based on observational
studies, resuscitation treatment of massive haemorrhage has shifted towards earlier administration of higher doses of plasma and platelets (PLT) to red blood cells (RBC)5-10.
The recent PROPPR trial compared the effect of transfusion of plasma, PLTs and RBCs in a 1:1:1 with a 1:1:2 ratio in a randomized trial design. The 1:1:1 approach did not reduce 28-days mortality, which was the primary outcome, but was associated with a reduction in early exsanguination7.
In addition to the ratio of blood products, pro-coagulant therapy such as fibrinogen containing products and anti-fibrinolytic therapy such as tranexamic acid (TXA) are increasingly being used during trauma resuscitation. TXA and fibrinogen products, like fibrinogen concentrates and cryoprecipitate, improve clot firmness and reduce clot breakdown. In this context, some trials, mostly from Europe, have reported that fibrinogen products and TXA are associated with reduced transfusion requirements and a decreased risk of death from haemorrhage11-18. However, across the globe, large
variation in transfusion strategies exists. Studies in hospitals in the United States suggest that TXA and fibrinogen products are given to a minority of patients6, 19, whereas in
European hospitals, TXA and fibrinogen products are widely used and are integrated in European guidelines20. Until now, no studies have reported the effect of a balanced
transfusion ratio in combination with the administration of TXA and fibrinogen products on TIC and mortality. Therefore, the aim of this study was to investigate the effect of transfusion ratios, TXA and fibrinogen products on the number of patients requiring massive transfusions (≥10 RBCs in 24 hours) and overall survival in bleeding trauma patients in a combined model. The second aim was to evaluate which transfusion strategy was associated with correction of TIC, as measured by an elevated INR.
METHODS
A prospective multicentre observational study, the Activation of Coagulation and Inflammation in Trauma (ACIT) study (United Kingdom Clinical Research Network Study Portfolio, ID: 5637) was conducted in 6 European level-1 trauma centres including London, Oslo, Copenhagen, Oxford, Cologne and Amsterdam, which are members of the International Trauma Research Network (INTRN)21. Of the ACIT patients recruited
between January 2008 and April 2015, all adult trauma patients who received at least 4 RBCs or more in 24 hours, were analysed. ACIT exclusion criteria included patients
who received >2 L intravenous fluids pre-hospital, who arrived >2 hours after injury in the Emergency Department (ED), who were transferred from other hospitals, who had burns covering >5% of the total body surface area, who had a known bleeding diathesis, who were taking anticoagulant medications other than aspirin (<650mg/day) or who declined to give informed consent, were excluded. Written informed consent was obtained from each patient or next of kin. This study was performed after approval by the local ethics committees and according to the declaration of Helsinki.
TRANSFUSION STRATEGY
Issuing of blood products, TXA and fibrinogen products by the blood bank was performed through locally implemented massive transfusion protocols (MTP) in all centres. The MTP was activated in most centres by physicians for patients with a systolic blood pressure <90 mmHg with an inadequate response to fluid administration and suspicion of ongoing bleeding. The applied ratio of blood products between hospitals ranged from 1:1:2 to 1:1:1. Oxford, Oslo and Amsterdam also used Octaplas®. Cryoprecipitate was
used in London, Oxford and Copenhagen, whereas Amsterdam, Oslo and Cologne used fibrinogen concentrates. The trigger for fibrinogen administration differed between centres from a fibrinogen level ≤1.0 g/L to a fibrinogen level ≤1.5 g/L or was based on visco-elastic testing. TXA was a principal component in the MTPs of all hospitals. In London, Oxford, Oslo and Amsterdam, transfusion of blood products was monitored by conventional coagulation tests. In Copenhagen and Cologne, transfusion was guided by visco-elastic tests.
DATA COLLECTION
Research personnel screened and enrolled patients. The following data were collected prospectively in a centralized database: data on hospital, patient demographics, time of injury, mechanism (blunt or penetrating), comorbidities, vital signs and laboratory tests up to 24 hours post-injury, injury severity classified using the Abbreviated Injury Scale Score (AIS) and Injury Severity Score (ISS), requirement of surgical procedures, 24-hours mortality, total fluids (crystalloids, colloids, hypertonic saline), blood products (plasma, PLTs and RBCs), TXA, fibrinogen concentrates and cryoprecipitate administered within 24 hours.
To determine the effect of the transfusion strategy on the outcome, the following transfusion strategies were compared; high (≥1:1) and low (<1:1) ratios of plasma and PLTs to RBCs, the administration of TXA (yes/no) and fibrinogen products (fibrinogen concentrates and cryoprecipitate) (yes/no) within 24 hours. The number of PLT units was
9
corrected for the number of pooled donors.
The outcome of interest was the incidence of patients alive and free of massive transfusion within 24 hours. Massive transfusion was defined as the administration of ≥10 RBCs within 24 hours. Correction of TIC was defined as an INR ≤1.2 within 24 hours post injury. Of note, correction of coagulopathy was determined only in those patients who were still alive after 24 hours.
STATISTICS
In order to handle the problem of missing values, multiple imputation was performed, with the exception of missing outcome variables and variables with more than 50% missing. The mean predictive value was used to impute ten different datasets. The distribution of the original data was used to define constraints. Data were tested for distribution before multiple imputation. Skewed distribution of the original data was corrected with square root terms and log transformations. To test for differences in patient characteristics between the ratio, TXA and fibrinogen product groups, linear and logistic regression analyses were used. Furthermore, univariate logistic regression analyses were used to define possible confounders for the primary and secondary outcomes. Variables tested for a possible confounding effect were: age, gender, trauma mechanism, ISS, vital signs and laboratory tests in the ED, fluid administration, number of blood products transfused in 24 hours, surgical procedure and severe chest, limb or head injury (Appendix Table 1 and 2). Variables with a p-value of <0.20 were determined as having a relevant confounding effect and were included in the multivariable logistic regression models. Only those variables with a significant association with the primary and secondary outcomes after backward selection were included in the final multivariable logistic regression models. Subsequently, in a multilevel mixed effect logistic regression model, patients were clustered within each hospital. Multiple imputation was performed in R (an environment for statistical computing, R version 3.1.2 with R studio 0.98), further statistical analyses in SPSS version 21 (IBM, Chicago, IL, USA). A p-value <0.05 was considered to be statistically significant.
RESULTS
In total, 385 bleeding patients were included. The majority of the patients was male, suffered from blunt injury and was severely injured with a mean ISS of 31. Of the 385 bleeding patients, 216 patients (56%) received high plasma to RBC ratios and 150 patients (39%) received high PLT to RBC ratios. Additionally, 126 patients (34%) received TXA and 138 patients (36%) received fibrinogen products. Patients were coagulopathic with a mean initial INR of 1.3 and received a mean of 10 RBCs within 24 hours.
TABLE 1:
Characteristics of patients transfused with high ratios of plasma or PL
Ts to RBCs, TXA or fibrinogen pr
oducts
Plasma:RBC≥ 1:1 OR/B (95% CI)
(n=216) PL T:RBC ≥1:1 OR/B (95% CI) (n=150) TXA OR/B (95% CI) (n=126) Fibrinogen prod -ucts OR/B (95% CI) (n=138) Age, years -4 (-8 -(-1))* -1 (-5-3) -4 (-8 -0) -4 (-8-0) Gender , male 2.8 (0.9-2.1) 0.3 (0.8-2.1) 1.0 (2.0-3.5) 0.3 (0.8-2.1)
Trauma mechanism, blunt
0.3 (0.8-2.3) 0.1 (0.6-1.9) 0.7 (1.1-3.3)* 0.0 (0.6-1.8) ISS 1 (-2-3) 2 (-1-4) 3 (0-6) 4 (-1-7)* SBP , mmHg -3 (-11-4) 0 (-7-7) -8 (-16-0) -8 (-15-0)* Heart rate, bpm 4 (-3-10) -3 (-9-4) 7 (0-14)* 17 (11-24)* GCS -8 (-2-0) 0 (-1-1) -1 (-2-0) -1.0 (-2-0) Hb, g/dL -1.6 (-0.6-0.3) -0.1 (-0.6-0.3) 0.6 (0.1-1.1)* -0.2 (-0.7-0.3) Platelet count, x10^9/L 5 (-10-20) -18 (-33-(-3)* 4 (-11-20) -17 (-32-(-2)* INR -0.27 (-0.18-0.12) 0.04 (-0.12-0.19) -0.09 (-0.25-0.08) 0.10 (-0.02-0.18) Fibrinogen, g/L -0.2 (-0.5-0.0) -0.1 (-0.3-0.2) -0.2 (-0.5-0.1) -0.5 (-0.7-(-0.2))* BE, mEqL -2.7 (-1.7-1.1) -0.3 (-1.1-1.8) -1.5 (-3.0-0.0)* -3.7 (-5.1-(-2.3))* Blood pr oducts transfused in 24 hr , units 6 (2-10)* 14 (9-18)* 4 (0-9) 11 (7-16)*
Patients alive and fr
ee of massive transfusion -0.1 (0.6-1.3) -1.7 (0.1-0.3) 0.2 (1.0-1.6) -0.4 (0.4-1.2) V
ital signs and laboratory tests on Emergency Department. Data ar
e given as odds ratios (OR) or r
egr
ession coef
ficients
(B) and the confidence intervals, *p-value <0.05. ISS= injury severity scor
e, SBP= systolic blood pr
essur
e, GCS= Glasgow
9
FIGURE 1:
Comparison of the number of blood pr
oducts transfused between high and low plasma and PL
Ts to RBC ratios at dif
fer
ent time points. Black lines
repr
esent a high ratio (≥1:1), gr
ey lines r
epr
Patients receiving higher ratios of plasma and PLTs to RBCs did not differ in patient characteristics from those receiving lower ratios (Table 1). The transfusion ratio of plasma and PLTs to RBCs over time is illustrated in Figure 1. Between time of arrival in the ED and transfusion of 4 RBCs, mainly RBCs were given, while plasma and PLT transfusion lagged behind. After the time point of receiving 4 RBC units, in general a balanced transfusion ratio was obtained. More blood products were transfused in the high plasma and PLT to RBC groups compared with the groups with low plasma (p<0.01) and PLT ratios (p<0.01).
The characteristics of patients who received TXA and fibrinogen products and those who had not, are also shown in Table 1. Data about TXA administration were missing in 16 patients (4%). Patients receiving TXA or fibrinogen products were more acidotic, coagulopathic and were more severely injured. Patients in whom fibrinogen products were administered received significantly more blood products after 24 hours. Patients in the TXA and fibrinogen product groups suffered more from shock.
The mean total dose of TXA was 1.1 g, the mean total dose of fibrinogen was 3.8 g and the mean total dose of cryoprecipitate was 3 units. Plasma fibrinogen level did not differ between patients administered fibrinogen products and those who did not (Figure 2). Also, no difference was observed in the plasma fibrinogen level before and after fibrinogen administration.
FIGURE 2: Level of fibrinogen at different time points; comparison between patients receiving fibrinogen products and not receiving fibrinogen products. Data are expressed by the median and the interquartile ranges.
9
Alive and free of massive transfusion
The primary outcome alive and free of massive transfusion was obtained in 60% of all included patients and varied between 49% and 65% in the different transfusion groups. In the univariate analysis, factors associated with survival are shown in supplemental Table 1. After adjustment for significant confounders in a multivariable multilevel logistic regression model, a high ratio of PLTs to RBCs and the administration of TXA were both independently associated with an increase of the number of patients alive and free of massive transfusion with an odds ratio (OR) of 2.2 (95% CI 1.0-4.9, p=0.04) and 2.8 (95% CI 1.3-6.0, p<0.01), respectively (Table 2). A trend was observed towards a reduced number of patients requiring massive transfusions and a higher overall survival in patients receiving a high ratio of plasma to RBCs (OR 2.0, 95% CI 1.0-3.9, p=0.052). Administration of fibrinogen containing products was not associated with an increase in the number of patients alive and free of massive transfusion.
Correction of TIC
Of the 385 patients, 60 patients were excluded because they deceased within 24 hours post injury. Additionally, INR after 24 hour was not available in 85 patients. Correction of coagulopathy within 24 hours was therefore achieved in 65% of the remaining 240 patients. The unadjusted response of the INR to transfusion strategy at different time points, is illustrated in the Appendix Figure 1. Although patients were more coagulopathic at admission, no differences in INR during transfusion and after 24 hours were observed between patients transfused with high or low ratios of plasma to RBC. Patients transfused with a high ratio of PLTs to RBCs had significantly prolonged INR compared to patients receiving a low ratio of PLTs to RBCs, whereas the INR was significantly decreased in patients receiving TXA and fibrinogen products compared to patients who did not after 24 hours. However, patient characteristics differed largely
TABLE 2: Multivariable logistic regression analysis for alive and free of massive transfusion <24 hr
OR (95% CI) p-value
Heart Rate, bpm 1.01 (1.00-1.02) 0.04 BE mEqL 1.09 (1.03-1.16) <0.01 AIS head ≥3 0.40 (0.22-0.75) <0.01 Total amount of blood products,units 0.81 (0.77-0.86) <0.01 High ratio of plasma to RBCs 1.98 (0.99-3.93) 0.05 High ratio of PLTs to RBCs 2.23 (1.02-4.85) 0.04
TXA 2.84 (1.34-6.00) <0.01
Fibrinogen products 1.46 (0.60-3.55) 0.41 *Patients were clustered within each hospital
between different transfusion strategy groups. After adjustment for confounders in the multilevel multivariable logistic regression model, no significant association was observed between the administration of blood products, TXA and fibrinogen products and an improved coagulation profile (Table 3).
DISCUSSION
This study suggests that both high ratios of PLTs to RBCs and the administration of TXA are independently associated with an increased number of patients alive and free of massive transfusion in bleeding trauma patients. No significant effect of blood product ratio, TXA and fibrinogen products on the correction of coagulopathy as defined by prolonged INR was observed. To our knowledge, this is the first prospective observational study in which the combined effect of a balanced transfusion ratio, TXA and fibrinogen products on outcome is reported.
In this study we found that transfusion of a high ratio of PLTs to RBCs was significantly associated with an increased overall survival and a reduction in the number of patients receiving massive transfusions within 24 hours. In line with this, studies from the military as well as from the civilian setting have suggested that a high PLTs to RBC ratio is beneficial8, 22. In these retrospective studies, a decrease in early mortality of
approximately 10-20% was reported in patients receiving high PLT:RBC ratios compared to patient receiving low PLT:RBC ratios. The finding that high PLT ratios are potentially associated with a beneficial outcome, is also in line with the PROPPR randomized controlled trial, which compared the use of plasma, PLTs and RBCs in a 1:1:1 ratio with a 1:1:2 ratio7. More patients in the 1:1:1 group achieved haemostasis and fewer patients
experienced a haemorrhagic death. However, it is not possible to conclude whether this beneficial effect on haemostasis and survival is a result of a high PLT or plasma to RBC ratio, as the combined effect of PLTs and plasma was evaluated in the PROPPR trial.
TABLE 3: Multivariable logistic regression analysis for correction coagulopathy <24 hr
OR (95% CI) p-value
Age 1.03 (1.01-1.05) <0.01
Fluids per 100 ml in 24 hours 0.98 (0.97-0.99) <0.01 High ratio of plasma to RBCs 0.89 (0.45-1.78) 0.74 High ratio of PLTs to RBCs 0.63 (0.32-1.26) 0.19
TXA 1.64 (0.82-3.29) 0.17
Fibrinogen products 1.61 (0.74-3.54) 0.23 *Patients were clustered within each hospital
9
We found a less strong effect of transfusion of high plasma to RBCs ratio on outcome. No significant association, but only a trend, was found between a high plasma to RBC ratio and improved survival. This is in apparent contrast with the PROPPR trial. There may be several explanations. The PROPPR trial investigated the effect of a balanced transfusion ratio, whereas we investigated the combined effect of blood product ratio, TXA and fibrinogen products. In the PROPPR trial, TXA and fibrinogen containing products were given to a minority of patients, whereas in this study 54% of the patients received either TXA or fibrinogen products. We hypothesize that the effect of TXA partly outweighs the benefit of an increased plasma to RBC ratio. In line with this, TXA had a strong effect on survival in this study, even though patients in the TXA group were more severely ill, as demonstrated by a higher heart rate and base excess level at baseline. Alternatively, differences between the studies may be due to differences in outcome parameters and sample sizes. We have combined haemostasis and mortality in the primary outcome “alive and free of massive transfusion” because transfusion strategy is in the first place targeted on bleeding control and secondly on decreasing mortality. Previous studies have determined these outcome measures separately5-8, 10.
Administration of TXA was associated with increased survival of patients alive and free of massive transfusion. These findings are in accordance with the CRASH-II trial, which showed that TXA was able to reduce the risk of death from traumatic bleeding when TXA was administered within 3 hours post injury17.
Somewhat surprisingly, no effect of fibrinogen products on outcome was found, even though the mean fibrinogen level in these bleeding patients was below 2 g/L. An explanation may be that the level of fibrinogen did not increase over time in patients administered fibrinogen products compared to patients who did not receive any fibrinogen products in addition to plasma. This may indicate that the dose of fibrinogen substitution may have been too low to have an effect and that higher dosages are required to achieve a therapeutic effect. This hypothesis is in accordance with the guidelines in which amounts of 4-8 g are recommended for severe bleeding patients23.
Whether fibrinogen products are beneficial in a setting in which balanced resuscitation is practiced, requires a randomized trial with a sufficient dose.
Limitations of this study are that we included patients who were administered with at least 4 units of RBCs, whereas the majority of the previous studies examined transfusion strategies in massively transfused patients (≥10 RBCs within 24 hours) or transfused patients (≥1 RBC transfused), which hampers the comparability of this study. However, we have chosen to use the definition of at least 4 RBCs transfused in order to include patients with a relevant bleeding but with a possibility that an optimal transfusion
strategy might also prevent patients from massive transfusion. Furthermore, prolonged INR was used to define coagulopathy which has not been validated for monitoring coagulopathy24-27. The INR represents a part of the coagulation profile and is not able
to visualize the complete coagulation process, including clot formation, clot firmness and clot breakdown. However, although the INR as predictor for coagulopathy has not been validated, it is generally used as reference for the definition of trauma-induced coagulopathy. Furthermore, INR is frequently used in clinical practice and is a good prognosticator of outcome in massive haemorrhage28-30. Moreover, adverse events such
as thromboembolism or organ failure were not recorded in this study, limiting a risk-benefit analysis of any transfusion strategy. This study also has strengths. We combined all transfusion strategies into one model, which is a better reflection of the fact that all treatment interventions interact with outcome.
CONCLUSION
High PLT to RBC ratio and TXA are associated with an increased number of patients alive and free of massive transfusion. Blood product ratio, TXA and fibrinogen products did not correct coagulopathy as defined by prolonged INR. Fibrinogen products did not affect outcome, however under-dosing may have influenced the outcome. These findings may offer guidance for designing a randomized controlled trial, in which the effect of the addition of TXA and fibrinogen products to a balanced resuscitation is investigated.
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APPENDIX
TABLE 1: Univariable logistic regression analysis for alive and free of massive transfusion <24 hr
OR Upper limit Lower limit p-value
Age, years 1.00 0.99 1.01 0.60
Gender, male 1.28 0.81 2.01 0.29
Trauma Mechanism, Penetrating 1.41 0.81 2.47 0.23 Injury Severity Score 0.96 0.95 0.98 <0.01 Heart Rate, bpm 1.01 1.00 1.01 0.06 Systolic Blood Pressure, mmHg 1.01 1.00 1.01 0.05
GCS 1.07 1.02 1.13 <0.01
Haemoglobin, g/dL 1.29 1.17 1.43 <0.01 Platelet count, x109 1.01 1.01 1.01 <0.01 Fibrinogen, g/L 1.64 1.19 2.26 <0.01
BE, mEql 1.13 1.09 1.18 <0.01
Fluid administration per 100 ml 1.00 1.00 1.01 0.88
Procedure No 0.63 0.37 1.08 0.09
Procedure DCS 0.91 0.56 1.48 0.71 Procedure Coiling 1.53 0.66 3.58 0.61 Procedure Coiling + Surgery 3.10 1.03 9.33 0.31 Total amount blood products, units 0.85 0.82 0.88 <0.01 AIS head ≥3 0.53 0.35 0.81 <0.01
AIS chest ≥3 0.72 0.48 1.10 0.13
AIS limb ≥3 0.86 0.57 1.29 0.45
Hospital 0.88 0.77 1.02 0.09
High ratio of plasma to RBCs 0.89 0.59 1.35 0.57 High ratio of PLTs to RBCs 0.48 0.32 0.74 <0.01
TXA, yes 1.52 0.97 2.37 <0.07
Fibrinogen products, yes 2.30 1.29 4.12 <0.01 *Vital signs and laboratory tests on Emergency Department
9
TABLE 2: Univariable logistic regression analysis for correction coagulopathy <24 hr
OR Upper limit Lower limit p-value
Age, years 1.02 1.10 1.04 <0.01
Gender, male 0.95 0.52 1.73 0.86
Trauma Mechanism, Penetrating 0.75 0.35 1.60 0.45 Injury Severity Score 1.00 0.98 1.03 0.71 Heart Rate, bpm 1.01 1.00 1.01 0.33 Systolic Blood Pressure, mmHg 1.01 0.99 1.01 0.90
GCS 0.98 0.91 1.04 0.47
Haemoglobin, g/dL 1.07 0.93 1.22 0.36 Platelet count, x109 1.00 1.00 1.01 0.27 Fibrinogen, g/L 1.07 0.72 1.58 0.75
BE, mEql 1.01 0.97 1.05 0.69
Fluid administration per 100 ml 0.99 0.98 1.00 0.01
Procedure No 0.63 0.30 1.32 0.22
Procedure DCS 0.81 0.92 1.73 0.81
Procedure Coiling - - -
-Procedure Coiling + Surgery - - - -Total amount blood products 0.98 0.96 0.99 0.01
AIS head ≥3 1.30 0.75 2.24 0.36
AIS chest ≥ 3 1.34 0.78 2.31 0.29
AIS limb ≥3 1.07 0.63 1.83 0.81
Hospital 0.68 0.56 0.82 <0.01
High ratio of plasma to RBCs 0.71 0.41 1.23 0.23 High ratio of PLTs to RBCs 0.42 0.24 0.72 <0.01
TXA, yes 2.06 1.14 3.73 0.02
Fibrinogen Products, yes 0.74 0.43 1.30 0.30 *Vital signs and laboratory tests on Emergency Department
FIGURE 1: Response of the INR to transfusion practice in bleeding trauma patients at different time points. Data are expressed by the median and interquartile ranges. A significant difference between the two groups is illustrated by a (*).
A B
