Abstract
Background
Hypofibrinogenaemia is a common complication of multiple trauma with severe traumatic brain injury (Abbreviated Injury Scale score of the head ≥4; body ≥3). In Japan, neither fibrinogen concentrate nor cryoprecipitate is permitted to treat acquired hypofibrinogenaemia with the purpose of rapidly restoring a haemostatic level of fibrinogen. The aim of this study was to investigate transfusion usage and mortality in patients with multiple trauma and severe traumatic brain injury who were given a cryoprecipitate prepared in-house, comparing those administered the product early or later.
Material and methods
We prepared and produced cryoprecipitate from fresh-frozen plasma beginning in March 2013. We performed a retrospective cohort study of patients admitted to our single tertiary medical centre with severe multiple trauma with traumatic brain injury from March 2013 to June 2018, sorting them into those given the cryoprecipitate infusion within 90 minutes of admission (Early group) and those given it more than 90 minutes after admission (Late group). Clinical outcomes were compared between the two groups using chi-square or Fisher’s exact tests and the Wilcoxon test as appropriate.
Results
There were 26 and 16 patients in the Early and Late groups, respectively. The 24-hour mortality tended to be lower in the Early group than in the Late group (8 vs 13%, respectively). The patients were more severely anaemic and thrombocytopenic after haemostatic therapy in the Late group than in the Early group. Transfusion usage in the Early group was lower than that in the Late group (red blood cells: 7±1 units vs 17±3 units, p<0.05; fresh-frozen plasma: 9±1 units vs 16±3 units, p<0.05; platelet concentrate: 3±1 units vs 15±4 units, p<0.05, respectively).
Discussion
Early administration of an in-house cryoprecipitate may reduce transfusion usage in patients with multiple trauma with severe traumatic brain injury.
Keywords: multiple trauma, resuscitation, mortality, hypofibrinogenaemia
INTRODUCTION
Despite the high usage rate of fresh-frozen plasma (FFP) to correct acquired hypofibrinogenaemia due to massive bleeding in various conditions, including trauma and post-partum haemorrhage, neither fibrinogen concentrate nor cryoprecipitate is permitted in Japan. Cryoprecipitate contains a high concentration of fibrinogen, clotting factor VIII (FVIII), clotting factor XIII (FXIII), von Willebrand factor, and fibronectin, among other substances1,2. In contrast to FFP, cryoprecipitate and fibrinogen concentrate can, theoretically, immediately restore the normal level of fibrinogen in patients with acquired hypofibrinogenaemia3. The accepted indications for the administration of cryoprecipitate include, but are not limited to, hypofibrinogenaemia, t-plasminogen activator-related life-threatening haemorrhage, and massive transfusion (>10 units of red blood cells [RBC] in 24 hours with continued bleeding)4. Nascimetro et al. also reported that cryoprecipitate is commonly used to restore fibrinogen levels in patients with acquired coagulopathy, such as in those with haemorrhage from trauma, cardiac surgery, liver transplantation, or obstetric conditions5. Coagulopathy complicated with massive bleeding may indicate a poor prognosis. Although the optimal transfusion strategy to treat acute hypofibrinogenaemia after severe multiple trauma has been extensively investigated6–10, no transfusion guidelines for the administration of cryoprecipitate or fibrinogen concentrate have been established in Japan. Moreover, cryoprecipitate is neither produced nor supplied by the Japanese Red Cross Society. We, therefore, produced cryoprecipitate in our hospital using a method described by the Japan Society of Transfusion Medicine and Cell Therapy11. In this study, we aimed to evaluate the effects of transfusing our in-house cryoprecipitate in patients with severe multiple trauma. Moreover, given that early administration of fibrinogen concentrates or cryoprecipitate has been reported to be beneficial for patients with severe multiple trauma12–14, we also aimed to examine the effects of early administration of the in-house cryoprecipitate in patients with multiple trauma with severe traumatic brain injury (TBI).
MATERIALS AND METHODS
Study setting
This retrospective cohort study was performed in a tertiary medical centre located in the eastern part of metropolitan Tokyo, Japan. In our 24-bed Intensive Care Unit, patients are managed by full-time physicians, including surgeons and intensivists.
We reviewed a retrospectively maintained database of all transfused patients with multiple trauma with severe TBI, defined as having an Abbreviated Injury Scale (AIS) score of the head ≥4 and body ≥3, who were admitted to our institution from March 2013 to June 2018. Patients who were younger than 10 years old, had cardio-pulmonary arrest at admission, or were transferred from other hospitals were excluded.
In our tertiary emergency medical centre, we routinely perform blood tests immediately after a patient’s arrival and throughout the treatment of haemostasis in patients with severe trauma. Computed tomography (CT) of the whole body was performed as soon as possible during stabilisation of the respiratory and circulatory systems. Based on the circulatory state, Glasgow Coma Scale, and CT findings, senior emergency physicians determined the haemostatic and transfusion strategies.
Blood components were transfused based on reference guidelines issued by the Ministry of Health, Labour, and Welfare in Japan15, and transfusion for massive bleeding was performed based on the guidelines on trauma16–18. In principle, three packs of cryoprecipitate were transfused for adult patients with hypofibrinogenaemia or for those receiving massive blood transfusions (≥10 units of RBC), although the decision was ultimately left to the attending physician’s discretion.
Data collection
The following data were collected: medical history; age; sex; vital signs on admission, such as systolic blood pressure, heart rate, and body temperature, Glasgow Coma Scale score, Injury Severity Score, and probability of survival based on the trauma and injury severity score (TRISS); laboratory values obtained on admission and after treatment (in principle, after early haemostatic treatment); units transfused in 24 hours and during hospitalisation; and outcome. The duration of hospitalisation, time spent in the Intensive Care Unit, duration of ventilation, modified Rankin scale score, and 24-hour mortality were the parameters used to assess outcomes.
To evaluate the effectiveness of early transfusion of in-house cryoprecipitate, we divided the eligible patients into two groups: those given the in-house cryoprecipitate within 90 minutes of admission (Early group) and those given the transfusion more than 90 minutes after admission (Late group). We set the threshold of 90 minutes on the basis of a report by Curry et al.13. The typical treatment course of each group was as follows: the Early group was administered cryoprecipitate immediately after prompt resuscitation and CT evaluation, while the Late group was administered the product after surgical intervention, massive fluid infusion, and RBC/FFP transfusion.
In-house cryoprecipitate and blood products
Blood products, such as RBC solutions, FFP, and platelet concentrates, were supplied by the Japan Red Cross Society (Tokyo, Japan). The RBC solutions (one unit: 140 mL; two units: 280 mL) and FFP (one unit: 120 mL, two units: 240 mL) were produced from donated whole blood, while the platelet concentrates and 480-mL FFP were obtained via apheresis from donors.
Because cryoprecipitate is not supplied by the Japan Red Cross Society, it was prepared and produced by the staff of our Department of Transfusion Medicine using a modified method, as previously described11. Briefly, one pack of cryoprecipitate was prepared from type AB RhD-positive FFP (480 mL) by collecting the precipitate formed during controlled thawing at 4 °C for 24 hours and re-suspending it in 30–50 mL of plasma. Cryoprecipitate can be stored for up to 1 year at a temperature of −20 °C or below. At least 20 packs of cryoprecipitate are always ready for use in our hospital. A pack of cryoprecipitate can be thawed within 9 minutes using a recirculating water-bath thawing system at 37 °C (FF-40; Kawasumi Laboratories Inc., Oita, Japan). A pack of 240-mL FFP can be thawed within 13 minutes19. Although production methods may vary in different facilities, the products have relatively similar features1. The fibrinogen level in the in-house cryoprecipitate (n=6) was 1,992±515 mg/dL.
Statistical analysis
Data are expressed as group means ± standard errors of the mean. All statistical calculations were performed using JMP version 8.0 software (SAS Institute Inc., Cary, NC, USA). We tested for differences in baseline characteristics between patients in the Early and Late groups using the chi-square or Fisher’s exact test for categorical data and the Wilcoxon test for continuous data. A p-value <0.05 was considered statistically significant.
Ethical approval
This study was approved by the institutional review board of the Tokyo Metropolitan Bokutoh Hospital. Informed consent for blood product transfusion, including cryoprecipitate, was obtained from the patients.
RESULTS
Clinical features and outcomes of patients with multiple trauma with severe traumatic brain injury.
From March 2013 to June 2018, 42 patients met the inclusion criteria. The mean time from the trauma scene to arrival at hospital was 33 minutes, and all patients were transferred without fluid infusion. The Early and Late groups comprised 26 and 16 patients, respectively. In the Early group, cryoprecipitate was administered subsequently to early resuscitation and CT evaluation, and as one of the first components of massive transfusion. In contrast, in the Late group, cryoprecipitate was administered during the course of massive transfusions and often during surgical interventions. The demographic characteristics, clinical features and outcomes of these two groups are summarised in Table I. There were no significant differences in demographic characteristics, clinical features, or injury severity between the two groups. Moreover, there was no significant difference in haemostatic treatments; however, the number of angiographic interventions in the Early group tended to be higher than that in the Late group (35 vs 13%; respectively) (Table I).
Table I.
Clinical characteristics and outcomes of the study population
| Early cryoprecipitate group (N=26) | Late cryoprecipitate group (N=16) | |
|---|---|---|
| Age | 58 (5) | 61 (4) |
| Sex (male/female, % of males) | 17/9 (65%) | 12/4 (75%) |
| Vital signs and scores on admission | ||
| Systolic blood pressure (mmHg) | 135 (11) | 115 (9) |
| Heart rate (beats/minute) | 102 (5) | 103 (6) |
| Temperature (°C) | 35.8 (0.2) | 36.1 (0.2) |
| Glasgow Coma Scale score | 7.4 (0.8) | 7.8 (1.1) |
| Injury Severity Score | 38 (2) | 40 (2) |
| AIS score of the head | 4.5 (0.1) | 4.6 (0.1) |
| Probability of survival | 0.46 (0.06) | 0.43 (0.08) |
| Interventions | ||
| Surgery (n, %) | 15, 58% | 13, 81% |
| Angiography (n, %) | 9, 35% | 2, 13% |
| None (n, %) | 2, 8% | 1, 6% |
Data are presented as the mean with standard errors in parentheses.
AIS: abbreviated injury scale.
Laboratory findings on admission and after treatment
Laboratory findings on admission and after treatment are shown in Table II. The results of haematological and clotting tests on admission were not significantly different between the two groups. Haemoglobin levels and platelet counts after angiographic or surgical treatment for haemostasis were significantly higher in the Early group than in the Late group (Table II).
Table II.
Laboratories values of the study population
| On admission | After treatment | |||
|---|---|---|---|---|
| Early cryoprecipitate group (N=26) | Late cryoprecipitate group (N=16) | Early cryoprecipitate group (N=24#) | Late cryoprecipitate group (N=15#) | |
| Haematology | ||||
| Haemoglobin (g/dL) | 11.7 (0.4) | 12.9 (0.5) | 10.1 (0.3)* | 8.7 (1.7) |
| Platelet count (×104/μL) | 21.3 (1.4) | 19.8 (1.5) | 13.4 (1.2)* | 7.3 (0.9) |
| Clotting activity | ||||
| % prothrombin time (%) | 80 (5) | 75 (6) | 69 (5) | 59 (5) |
| aPTT (sec) | 32.0 (2.0) | 32.7 (3.8) | 37.0 (4.1) | 42.0 (6.2) |
| fibrinogen (mg/dL) | 233 (20) | 189 (25) | 211 (16) | 179 (25) |
| FDP (μg/dL) | 422 (124) | 509 (158) | 240 (54) | 157 (36) |
Data are presented as the mean with standard errors in parentheses.
with missing values due to death.
p<0.05 vs values in the Late cryoprecipitate group.
aPTT: activated partial thromboplastin time; FDP: fibrinogen degradation products.
Transfusion volume and clinical outcome
The volume of transfused units of RBC, FFP, platelet concentrate, and albumin administered during the first 24 hours was significantly lower in the Early group than in the Late group (Table III). Moreover, the volume of transfused RBC units and FFP during hospitalisation was significantly lower in the Early group than in the Late group.
Table III.
Transfusion usage and clinical outcome in the study population
| Early cryoprecipitate group (N=26) | Late cryoprecipitate group (N=16) | |
|---|---|---|
| 24-hour transfusion, or infusion | ||
| Red blood cells (U) | 7 (1)* | 17 (3) |
| Fresh-frozen plasma (U) | 9 (1)* | 16 (3) |
| Platelet concentrates (U) | 3 (1)* | 15 (4) |
| Platelet concentrates (n, %) | 7, 27% | 10, 63% |
| Cryoprecipitate (pack) | 3.6 (0.2) | 3.1 (0.2) |
| 5% albumin product (bottles) | 0.2 (0.1)* | 1.4 (0.7) |
| 5% albumin product (n, %) | 3, 12% | 7, 44% |
| Tranexamic acid (n, %) | 25, 96% | 12, 75% |
| Total transfusions | ||
| Red blood cells (U) | 9 (1)* | 23 (5) |
| Fresh-frozen plasma (U) | 9 (1)* | 17 (4) |
| Clinical outcome | ||
| ICU stay (days) | 12 (2) | 12 (2) |
| Duration of ventilation (days) | 9 (2) | 7 (2) |
| Duration of hospitalisation (days) | 41 (6) | 46 (8) |
| 24-hour mortality (%) | 2/26 (8%) | 2/16 (13% |
| Mortality at discharge (%) | 8/26 (31%) | 4/16 (25%) |
| Modified Rankin scale <4 n, % | 8, 31% | 2, 13% |
Data are presented as the mean with standard errors in parentheses.
p<0.05 vs values in the Late cryoprecipitate group.
ICU: Intensive Care Unit.
Although there was not a significant difference in clinical outcomes between the Early and Late groups (Table III), the 24-hour mortality (8 vs 13%, respectively) and the number of patients with a modified Rankin scale <4 (31 vs 13%, respectively) tended to be better in the Early group than in the Late group. Mortality at discharge was not different between the two groups (31 vs 25%, respectively); however, it was better than the estimated probability of survival of each group (Table I).
DISCUSSION
To our knowledge, this is the first paper reporting that in-house cryoprecipitate may be beneficial for treating patients with multiple trauma with severe TBI.
We previously reported that in-house cryoprecipitate significantly reduced post-partum haemorrhage and transfusion usage as compared to standard treatment without in-house cryoprecipitate in a Japanese study20. However, in the early analysis of severe trauma patients, there was no difference in the number of blood transfusions or better prognoses resulting from the administration of in-house cryoprecipitate. Then, as a control group of patients for the cryoprecipitate treatment, we reviewed the data of patients who were admitted to our institution from January 2011 to February 2013, and extracted the data regarding patients with multiple trauma with severe TBI (AIS of head ≥4; body ≥3) who were treated with more than 2 units of FFP within 24 hours after arrival in hospital (historical FFP group). Twenty patients were eligible, and their 24-hour and discharge mortality rates were 35% (7/20 died) and 55% (11/20 died), respectively. Both mortalities rates were higher than those in the current study (Table I). We speculated that FFP transfusions alone did not correct the coagulopathy in patients with severe multiple trauma, resulting in the observed higher mortality. Similarly, Kahn et al. reported that FFP alone did not improve trauma-induced coagulopathy21. Meanwhile, we have not yet reported on the difference in transfusion usage between the historical FFP group (24-hour RBC: 10±2 units, 24-hour FFP: 12±2 units) and the in-house cryoprecipitate groups (Table III). Although the apparent lack of effectiveness on transfusion usage might be a result of survivorship bias, we also speculated that the timing of the administration of cryoprecipitate would be an important factor. We, therefore, examined the effects of the timing of in-house administration of cryoprecipitate on transfusion usage and mortality in this study. We found that blood transfusion usage was lower in the patients treated early with cryoprecipitate transfusion. In this study, we evaluated patients with multiple trauma with severe TBI, who were at very high risk of developing severe coagulopathy. By excluding mildly to moderately injured patients and those with isolated TBI, we were able to analyse the data of patients who needed massive blood transfusions by standard treatment methods. Although the haematological parameters of patients on arrival at the hospital did not appear to be seriously deranged in spite of the high Injury Severity Score, these parameters were evaluated before the patients had received fluid infusions. Previous studies have reported worse coagulopathy data on admission, because pre-hospital fluid strategies vary between countries and hospital systems22–23.
In this study, the patients were classified into two groups according to a threshold time of 90 minutes from admission to administration of cryoprecipitate, in accordance with the report by Curry et al.13. These authors reported that the administration of cryoprecipitate within 90 minutes of arriving in hospital was feasible. Although the appropriateness of this threshold remains unclear, almost all patients in the Early group of our study were administered cryoprecipitate prior to surgical intervention and in the early stages of haemostatic resuscitation. The present study showed that this approach may correct haemostatic conditions early, stop bleeding promptly, and lead to a reduction in transfusion requirements. Moreover, it might improve the outcomes of patients with severe trauma13,24. The mortality rate of patients with concomitant TBI and haemorrhagic shock has been reported to be 51.6%25. In our study, the discharge mortality rate was 29% (12/42 patients died), indicating that in-house cryoprecipitate might be effective for treating patients with multiple trauma with severe TBI. Early haemostasis and haemodynamic stabilisation may prevent secondary brain injuries in patients with concomitant traumatic brain and torso injury. The 24-hour mortality rate in the Early group tended to be lower than that in the Late group. However, the reason for the discrepancy between mortality rates and transfusion usage remains unclear. Early use of in-house cryoprecipitate might lessen coagulopathy in its acute phase, resulting in reduced transfusion usage and acute-phase mortality. On the other hand, we expected improvements in neurological and performance status at discharge, as well as improved mortality. According to our data, the percentage of patients with a modified Rankin scale <4 tended to be higher in the Early group than in the Late group (31 vs 13%, respectively). Given that 15% of the patients (3/20 patients) in the historical FFP group had a modified Rankin scale score <4, late transfusion of an in-house cryoprecipitate did not improve the rate of transfusion usage or neurological outcomes.
While fibrinogen concentrate is known to be beneficial for treating hypofibrinogenaemia after massive bleeding26, it does not reduce transfusion usage in patients with severe trauma8,14. Three packs of in-house cryoprecipitate might be capable of supplying approximately 2 g of fibrinogen, since each pack contains 1,992±515 mg/dL of fibrinogen. Because of factors other than fibrinogen, more than 3 g of fibrinogen (three vials of fibrinogen concentrate) may be necessary to stop bleeding. Cryoprecipitate contains FXIII, FVIII, von Willebrand factor, and fibrinogen. Binding of FXIII with endogenous anti-plasmin reveals the anti-fibrinolytic action and fibrin polymerisation of cryoprecipitate27. Severe isolated TBI has been reported to reveal hyperfibrinolysis28. Moreover, reductions in the activity of FXIII, FII, and FX have been reported in patients with severe multiple trauma with hyperfibrinolysis29. Cryoprecipitate might, therefore, correct the decreased level of FXIII in haemorrhagic circumstances. We also speculated that concentrated FVIII and von Willebrand factor in cryoprecipitate might be involved in improving the outcome of patients with severe multiple trauma. Reductions in FV and FVIII activity have been reported to be associated with mortality following trauma29. Furthermore, it was recently found that blood type O was associated with high mortality in severe trauma patients30, with results also indicating that von Willebrand factor might be involved in the outcome of trauma patients.
Given these benefits, the Japanese Red Cross is expected to supply cryoprecipitate to Japanese hospitals, similarly to that provided by blood centres in the United States and Europe.
We acknowledge several limitations of this study. First, this was a retrospective cohort study and was, therefore, prone to the biases associated with this research design. Second, the sample size was small, and the statistical power was low. Differences in some analyses did not reach statistical significance. Further research with a larger sample size is, therefore, warranted.
CONCLUSIONS
The early transfusion of our in-house cryoprecipitate might reduce blood transfusion usage in patients with multiple trauma with severe TBI.
ACKNOWLEDGEMENTS
The Authors thank the staff of the Clinical Laboratory in Tokyo Metropolitan Bokutoh Hospital for their cooperation and efforts with the cryoprecipitate transfusions.
Footnotes
AUTHORSHIP CONTRIBUTIONS
KS designed the research study. HF performed the study and wrote the paper. SN analysed the data.
The Authors declare no conflicts of interest.
REFERENCES
- 1.Callum JL, Karkouti K, Lin Y. Cryoprecipitate: the current state of knowledge. Transfus Med Rev. 2009;23:177–88. doi: 10.1016/j.tmrv.2009.03.001. [DOI] [PubMed] [Google Scholar]
- 2.Freedman M, Rock G. Analysis of products of cryoprecipitation: RiCoF is deficient in cryosupernatant plasma. Transfus Apher Sci. 2010;43:179–82. doi: 10.1016/j.transci.2010.07.004. [DOI] [PubMed] [Google Scholar]
- 3.Collins PW, Solomon C, Sutor K, et al. Theoretical modelling of fibrinogen supplementation with therapeutic plasma, cryoprecipitate, or fibrinogen concentrate. Br J Anaesth. 2014;113:585–95. doi: 10.1093/bja/aeu086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Pantanowitz L, Kruskall MS, Uhl L. Cryoprecipitate. Patterns of use. Am J Clin Pathol. 2003;119:874–81. doi: 10.1309/56MQ-VQAQ-G8YU-90X9. [DOI] [PubMed] [Google Scholar]
- 5.Nascimetro B, Goodnough LT, Levy JH. Cryoprecipitate therapy. Br J Anaesth. 2014;113:922–34. doi: 10.1093/bja/aeu158. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Chang R, Cardenas JC, Wade CE, Holcomb JB. Advances in the understanding of trauma-induced coagulopathy. Blood. 2016;128:1043–9. doi: 10.1182/blood-2016-01-636423. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Nascimetro B, Rizoli S, Rubenfeld G, et al. Cryoprecipitate transfusion: assessing appropriateness and dosing in trauma. Trans Med. 2011;21:394–401. doi: 10.1111/j.1365-3148.2011.01098.x. [DOI] [PubMed] [Google Scholar]
- 8.Winearls J, Campbell D, Hurn C, et al. Fibrinogen in traumatic haemorrhage: a narrative review. Injury. 2017;48:230–42. doi: 10.1016/j.injury.2016.12.012. [DOI] [PubMed] [Google Scholar]
- 9.Levy JH, Goodnough LT. How I use fibrinogen replacement therapy in acquired bleeding. Blood. 2015;125:1387–93. doi: 10.1182/blood-2014-08-552000. [DOI] [PubMed] [Google Scholar]
- 10.Ketchum L, Hess JR, Hippala S. Indications for early fresh frozen plasma, cryoprecipitate, and platelet transfusion in trauma. J Trauma. 2006;60:S51–8. doi: 10.1097/01.ta.0000199432.88847.0c. [DOI] [PubMed] [Google Scholar]
- 11.Ohishi K, Matsumoto T, Tanaka Y, et al. [Protocol for the in-house production of cryoprecipitate]. Jpn J Transfus Cell Ther. 2016;62:664–72. [In Japanese.] [Google Scholar]
- 12.Curry N, Foley C, Wong H, et al. Early fibrinogen concentrate therapy for major haemorrhage I trauma (E-FIT 1): results from a UK multi-centre, randomised double blind, placebo-controlled pilot study. Crit Care. 2018;22:164. doi: 10.1186/s13054-018-2086-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Curry N, Rourke C, Davenport R, et al. Early cryoprecipitate for major haemorrhage in trauma: a randomised controlled feasibility trial. Br J Anaesth. 2015;115:76–83. doi: 10.1093/bja/aev134. [DOI] [PubMed] [Google Scholar]
- 14.Inokuchi K, Sawano M, Yamamoto K, et al. Early administration of fibrinogen concentrate improves the short-term outcomes of severe pelvic fracture patients. Acute Med Surg. 2017;4:271–7. doi: 10.1002/ams2.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. [Accessed on 31/03/2018]. Available at: http://www.mhlw.go.jp/new-info/kobetu/iyaku/kenketsugo/5tekisei3b.html. [In Japanese.]
- 16.Rossaint R, Bouillon B, Cerny V, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. 2016;20:100. doi: 10.1186/s13054-016-1265-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Spahn DR, Bouillon B, Cerny V, et al. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Crit Care. 2013;17:R76. doi: 10.1186/cc12685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Spahn DR, Cerny V, Coats TJ, et al. Management of bleeding following major trauma: a European guideline. Crit Care. 2017;11:R17. doi: 10.1186/cc5686. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. [Accessed on 30/03/2018]. Available at: http://www.kawasumi.jp/product_b_14.html. [In Japanese].
- 20.Nishimura S, Takada Y, Ohtake C, et al. [Effects of cryoprecipitate on clinical outcome of obstetric haemorrhage]. Jpn J Transfus Cell Ther. 2017;63:23–9. [In Japanese.] [Google Scholar]
- 21.Kahn S, Davenport R, Raza I, et al. Damage control resuscitation using blood component therapy in standard doses has a limited effect on coagulopathy during trauma haemorrhage. Int Care Med. 2015;41:239–47. doi: 10.1007/s00134-014-3584-1. [DOI] [PubMed] [Google Scholar]
- 22.Rourke C, Curry N, Khan S, et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J Thromb Haemost. 2012;10:1342–51. doi: 10.1111/j.1538-7836.2012.04752.x. [DOI] [PubMed] [Google Scholar]
- 23.McQuilten ZK, Bailey M, Cameron PA, et al. Fibrinogen concentration and use of fibrinogen supplementation with cryoprecipitate in patients with critical bleeding receiving massive transfusion: a bi-national cohort study. Br J Haematol. 2017;179:131–41. doi: 10.1111/bjh.14804. [DOI] [PubMed] [Google Scholar]
- 24.Stanworth SJ, Davenport R, Curry N, et al. Mortality from trauma haemorrhage and opportunities for improvement in transfusion practice. Br J Surg. 2016;103:357–65. doi: 10.1002/bjs.10052. [DOI] [PubMed] [Google Scholar]
- 25.Galvagno SM, Fox EE, Appana SN, et al. Outcomes of after concomitant traumatic brain injury and hemorrhagic shock: a secondary analysis from the Pragmatic Randomized Optimal Platelets and Plasma Ratios trial. J Trauma Acute Care Surg. 2017;83:668–74. doi: 10.1097/TA.0000000000001584. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Cushing MM, Fitzgerald MM, Harris RM, et al. Influence of cryoprecipitate, factor XIII, and fibrinogen concentrate on hyper-fibrinolysis. Transfusion. 2017;57:2502–10. doi: 10.1111/trf.14259. [DOI] [PubMed] [Google Scholar]
- 27.Banerjee A, Sillimen CC, Moore EE, et al. Systemic hyperfibirinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma. J Trauma Acute Care Surg. 2018;84:929–38. doi: 10.1097/TA.0000000000001878. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Laroche M, Kutcher ME, Huang MC, et al. Coagulopathy after traumatic brain injury. Neurosurg. 2012;70:1334–45. doi: 10.1227/NEU.0b013e31824d179b. [DOI] [PubMed] [Google Scholar]
- 29.Kunitake RC, Howard BM, Kornblith LZ, et al. Individual clotting factor contributions to mortality following trauma. J Trauma Acute Care Surg. 2017;82:302–8. doi: 10.1097/TA.0000000000001313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Takayama W, Endo A, Koguchi H, et al. The impact of blood type O on mortality of severe trauma patients: a retrospective observational study. Crit Care. 2018;22:100. doi: 10.1186/s13054-018-2022-0. [DOI] [PMC free article] [PubMed] [Google Scholar]