The role of fibrinogen in trauma-induced coagulopathy

2014 ◽  
Vol 34 (01) ◽  
pp. 29-39 ◽  
Author(s):  
C. J. Schlimp ◽  
H. Schöchl
Keyword(s):  
Major Trauma ◽  
Coagulation Factor ◽  
Repeated Measurements ◽  
Plasma Fibrinogen ◽  
Fibrinogen Concentration ◽  
Trauma Patients ◽  
Trauma Induced Coagulopathy ◽  
Low Concentrations ◽  
Increased Risk

SummaryFibrinogen plays an essential role in clot formation and stability. Importantly it seems to be the most vulnerable coagulation factor, reaching critical levels earlier than the others during the course of severe injury. A variety of causes of fibrinogen depletion in major trauma have been identified, such as blood loss, dilution, consumption, hyperfibrinolysis, hypothermia and acidosis. Low concentrations of fibrinogen are associated with an increased risk of diffuse microvascular bleeding. Therefore, repeated measurements of plasma fibrinogen concentration are strongly recommended in trauma patients with major bleeding. Recent guidelines recommend maintaining plasma fibrinogen concentration at 1.5–2 g/l in coagulopathic patients. It has been shown that early fibrinogen substitution is associated with improved outcome.

scholarly journals Pulmonary embolism occurring early after major trauma

2019 ◽  
Vol 12 (9) ◽  
pp. e228783
Author(s):  
Paschalitsa Serchan ◽  
George Shorten ◽  
Michael Maher ◽  
Stephen P Power
Keyword(s):  
Pulmonary Embolism ◽  
Major Trauma ◽  
Adolescent Female ◽  
Trauma Patients ◽  
Common Cause ◽  
Risk Of Bleeding ◽  
The Third ◽  
Trauma Induced Coagulopathy ◽  
Increased Risk ◽  
Early Occurrence

Pulmonary embolism (PE) secondary to trauma is the third most common cause of death in trauma patients who have survived 24 hours following injury. We describe a case of PE diagnosed within 3 hours of a major trauma in a previously well adolescent female. The early occurrence of PE in this case is at odds with what is generally reported (3–5 days) after major trauma. General consensus is that patients who suffer major trauma move from an initial hypocoaguable state, with increased risk of bleeding, to normocoagulable or hypercoaguable state, with a subsequent increased risk of venothromboembolism. However, Sumislawski et al recently demonstrated that a marginally greater proportion of trauma patients were in fact hypercoaguable rather than hypocoaguable on arrival to hospital and that trauma-induced coagulopathy tended to resolve within 24 hours; such data cause us to re-evaluate when to commence thromboprophylaxis for major trauma patients.

scholarly journals Outcomes of major trauma among patients with chronic kidney disease and receiving dialysis in Nova Scotia: a retrospective analysis

2021 ◽  
Vol 6 (1) ◽  
pp. e000672
Author(s):  
Ryan Pratt ◽  
Mete Erdogan ◽  
Robert Green ◽  
David Clark ◽  
Amanda Vinson ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Nova Scotia ◽  
Kidney Disease ◽  
Hospital Mortality ◽  
Major Trauma ◽  
Injury Severity ◽  
Cox Regression ◽  
Trauma Patients ◽  
Risk Of Death ◽  
Increased Risk

BackgroundThe risk of death and complications after major trauma in patients with chronic kidney disease (CKD) is higher than in the general population, but whether this association holds true among Canadian trauma patients is unknown.ObjectivesTo characterize patients with CKD/receiving dialysis within a regional major trauma cohort and compare their outcomes with patients without CKD.MethodsAll major traumas requiring hospitalization between 2006 and 2017 were identified from a provincial trauma registry in Nova Scotia, Canada. Trauma patients with stage ≥3 CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) or receiving dialysis were identified by cross-referencing two regional databases for nephrology clinics and dialysis treatments. The primary outcome was in-hospital mortality; secondary outcomes included hospital/intensive care unit (ICU) length of stay (LOS) and ventilator-days. Cox regression was used to adjust for the effects of patient characteristics on in-hospital mortality.ResultsIn total, 6237 trauma patients were identified, of whom 4997 lived within the regional nephrology catchment area. CKD/dialysis trauma patients (n=101; 28 on dialysis) were older than patients without CKD (n=4896), with higher rates of hypertension, diabetes, and cardiovascular disease, and had increased risk of in-hospital mortality (31% vs 11%, p<0.001). No differences were observed in injury severity, ICU LOS, or ventilator-days. After adjustment for age, sex, and injury severity, the HR for in-hospital mortality was 1.90 (95% CI 1.33 to 2.70) for CKD/dialysis compared with patients without CKD.ConclusionIndependent of injury severity, patients without CKD/dialysis have significantly increased risk of in-hospital mortality after major trauma.

scholarly journals Advances in the understanding of trauma-induced coagulopathy

Blood ◽  
2016 ◽  
Vol 128 (8) ◽  
pp. 1043-1049 ◽  
Author(s):  
Ronald Chang ◽  
Jessica C. Cardenas ◽  
Charles E. Wade ◽  
John B. Holcomb
Keyword(s):  
Animal Studies ◽  
Causes Of Death ◽  
Endothelial Activation ◽  
The United States ◽  
Trauma Patients ◽  
Platelet Dysfunction ◽  
Intracranial Injury ◽  
Trauma Induced Coagulopathy ◽  
Common Causes

Abstract Ten percent of deaths worldwide are due to trauma, and it is the third most common cause of death in the United States. Despite a profound upregulation in procoagulant mechanisms, one-quarter of trauma patients present with laboratory-based evidence of trauma-induced coagulopathy (TIC), which is associated with poorer outcomes including increased mortality. The most common causes of death after trauma are hemorrhage and traumatic brain injury (TBI). The management of TIC has significant implications in both because many hemorrhagic deaths could be preventable, and TIC is associated with progression of intracranial injury after TBI. This review covers the most recent evidence and advances in our understanding of TIC, including the role of platelet dysfunction, endothelial activation, and fibrinolysis. Trauma induces a plethora of biochemical and physiologic changes, and despite numerous studies reporting differences in coagulation parameters between trauma patients and uninjured controls, it is unclear whether some of these differences may be “normal” after trauma. Comparisons between trauma patients with differing outcomes and use of animal studies have shed some light on this issue, but much of the data continue to be correlative with causative links lacking. In particular, there are little data linking the laboratory-based abnormalities with true clinically evident coagulopathic bleeding. For these reasons, TIC continues to be a significant diagnostic and therapeutic challenge.

scholarly journals Dynamics of Platelet Counts in Major Trauma: The Impact of Haemostatic Resuscitation and Effects of Platelet Transfusion—A Sub-Study of the Randomized Controlled RETIC Trial

2020 ◽  
Vol 9 (8) ◽  
pp. 2420
Author(s):  
Helmuth Tauber ◽  
Nicole Innerhofer ◽  
Daniel von Langen ◽  
Mathias Ströhle ◽  
Dietmar Fries ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Platelet Transfusion ◽  
Major Trauma ◽  
Coagulation Factor ◽  
Trauma Patients ◽  
First Line ◽  
Platelet Counts ◽  
Randomized Controlled ◽  
Coagulation Factor Concentrates ◽  
Haemostatic Resuscitation

Although platelets play a central role in haemostasis, the dynamics of platelet counts during haemostatic resuscitation, the response to platelet transfusion, and effects on clinical outcome are poorly described for trauma patients. As a sub-study of the already published randomized controlled RETIC Study “Reversal of Trauma-induced Coagulopathy using First-line Coagulation Factor Concentrates or Fresh-Frozen Plasma” trial, we here analysed whether the type of first-line haemostatic resuscitation influences the frequency of platelet transfusion and determined the effects of platelet transfusion in coagulopathic patients with major trauma. Patients randomly received first-line plasma (FFP) or coagulation factor concentrates (CFC), mainly fibrinogen concentrate. In both groups, platelets were transfused to maintain platelet counts between 50 and 100 × 109/L. Transfusion rates were significantly higher in the FFP (n = 44) vs. CFC (n = 50) group (FFP 47.7% vs. CFC 26%); p = 0.0335. Logistic regression analysis adjusted for the stratification variables injury severity score (ISS) and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion (odds ratio (OR) 5.79 (1.89 to 20.62), p = 0.0036) and this effect was larger than a 16-point increase in ISS (OR 4.33 (2.17 to 9.74), p = 0.0001). In conclusion, early fibrinogen supplementation exerted a platelet-saving effect while platelet transfusions did not substantially improve platelet count and might contribute to poor clinical outcome.

scholarly journals Effect of Cigarette Smoking on Plasma Fibrinogen and Platelet Count

2012 ◽  
Vol 2 (3) ◽  
pp. 181-184 ◽  
Author(s):  
Rashmi Narayanrao Gitte
Keyword(s):  
Platelet Count ◽  
Cigarette Smoking ◽  
Coagulation Factor ◽  
Plasma Fibrinogen ◽  
Fibrinogen Concentration ◽  
Human Beings ◽  
Healthy Male ◽  
The Mean ◽  
Surrounding Areas ◽  
Two Parameters

Objective: Cigarette smoking is one of the major lifestyle factors influencing the health of human beings. Fibrinogen is the major plasma protein coagulation factor. Higher plasma fibrinogen concentrations are associated with cardiovascular diseases. Material & Methods: One hundred twenty healthy male smokers and one hundred twenty healthy male non-smokers among hospital employees and people from surrounding areas of Narayana Medical College, Nellore (India) were studied. The platelet count was done using Beckman Coulter Automatic Analyzer; AcT 5diffCP.Assay for plasma fibrinogen was performed using turbido-metric immunoassay. Results: The mean plasma fibrinogen concentration for smokers is 3.78 gms/L and for non-smokers 3.02 gms/L. The mean platelet count for smokers is 257325 per mm3 and for non-smokers 215483.3 per mm3. The difference between mean plasma fibrinogen and platelet count of smokers and non-smokers was statistically significant (p<0.0001). Conclusion: Thus we concluded that in smokers plasma fibrinogen concentration and platelet count increase significantly. Regular monitoring of these two parameters in smokers is advised DOI: http://dx.doi.org/10.3126/ajms.v2i3.4261 Asian Journal of Medical Sciences 2 (2011) 181-184  

scholarly journals Overexpression of miR-24 Is Involved in the Formation of Hypocoagulation State after Severe Trauma by Inhibiting the Synthesis of Coagulation Factor X

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lu-Jia Chen ◽  
Lian Yang ◽  
Xing Cheng ◽  
Yin-Kai Xue ◽  
Li-Bo Chen
Keyword(s):  
Negative Correlation ◽  
Major Trauma ◽  
Injury Severity ◽  
Coagulation Factor ◽  
In Vitro Study ◽  
Severe Trauma ◽  
Trauma Patients ◽  
Factor Xii ◽  
Factor X

Background. Dysregulation of microRNAs may contribute to the progression of trauma-induced coagulopathy (TIC). We aimed to explore the biological function that miRNA-24-3p (miR-24) might have in coagulation factor deficiency after major trauma and TIC. Methods. 15 healthy volunteers and 36 severe trauma patients (Injury Severity Score ≥ 16 were enrolled. TIC was determined as the initial international normalized ratio >1.5. The miR-24 expression and concentrations of factor X (FX) and factor XII in plasma were measured. In vitro study was conducted on L02 cell line. Results. The plasma miR-24 expression was significantly elevated by 3.17-fold (P=0.043) in major trauma patients and reduced after 3 days (P<0.01). The expression level was significantly higher in TIC than in non-TIC patients (P=0.040). Multivariate analysis showed that the higher miR-24 expression was associated with TIC. The plasma concentration of FX in TIC patients was significantly lower than in the non-TIC ones (P=0.030) and controls (P<0.01). A negative correlation was observed between miR-24 and FX. miR-24 transduction significantly reduced the FX level in the supernatant of L02 cells (P=0.030). Conclusions. miR-24 was overexpressed in major trauma and TIC patients. The negative correlation of miR-24 with FX suggested the possibility that miR-24 might inhibit the synthesis of FX during TIC.

Relation of plasma fibrinogen concentration changes to human arteriosclerosis

1961 ◽  
Vol 16 (4) ◽  
pp. 660-664 ◽  
Author(s):  
L. O. Pilgeram
Keyword(s):  
Myocardial Infarction ◽  
Anticoagulant Therapy ◽  
Technical Assistance ◽  
Fibrinogen Level ◽  
Test System ◽  
Plasma Fibrinogen ◽  
Fibrinogen Concentration ◽  
Inflammatory Conditions ◽  
Concentration Changes

A 35% increase (P < 0.001) in plasma fibrinogen levels was found in patients who recovered from the trauma of myocardial infarction and had not received anticoagulant therapy for 5 months preceding donation of plasma. The elevated fibrinogen levels are not a consequence of inflammatory conditions or traumatized tissue resulting from clinically overt vascular incidents. The fibrinogen level does not return to normal following a myocardial infarction. Occlusion of beta lipoproteins in the fibrin coagulum did not account for elevated levels of fibrinogen as shown by experiments where a) known quantities of alpha and beta lipoproteins were added to the test system, b) correction was made for the occlusion factor, and c) the increased yield due to this occlusion factor represented only a 3.5% increase in fibrinogen yield for as much as 300% increase in the level of beta lipoproteins. The fibrinogen level not only increases with age but also superimposes upon the arteriosclerotic an increase in addition to that occurring with increasing chronologic age. The role of fibrin in vascular hypertrophy and atheromatous development is emphasized. Possible causes for abnormal levels of fibrinogen are discussed. Note: (With the Technical Assistance of A. C. Schram and D. Mills) Submitted on December 5, 1960

scholarly journals The Potential Role of Coagulation Factor Xa in the Pathophysiology of COVID-19: A Role for Anticoagulants as Multimodal Therapeutic Agents

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e288-e299
Author(s):  
Galit H. Frydman ◽  
Michael B. Streiff ◽  
Jean M. Connors ◽  
Gregory Piazza
Keyword(s):  
Potential Role ◽  
Alveolar Epithelium ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Therapeutic Agents ◽  
Increased Risk ◽  
Potential Therapeutic Role ◽  
Risk Patients ◽  
Multiple Cells

AbstractSARS-CoV-2 infection (COVID-19) results in local and systemic activation of inflammation and coagulation. In this review article, we will discuss the potential role of coagulation factor Xa (FXa) in the pathophysiology of COVID-19. FXa, a serine protease, has been shown to play a role in the cleavage of SARS-CoV-1 spike protein (SP), with the inhibition of FXa resulting in the inhibition of viral infectivity. FX is known to be primarily produced in the liver, but it is also expressed by multiple cells types, including alveolar epithelium, cardiac myocytes, and macrophages. Considering that patients with preexisting conditions, including cardiopulmonary disease, are at an increased risk of severe COVID-19, we discuss the potential role of increased levels of FX in these patients, resulting in a potential increased propensity to have a higher infectious rate and viral load, increased activation of coagulation and inflammation, and development of fibrosis. With these observations in mind, we postulate as to the potential therapeutic role of FXa inhibitors as a prophylactic and therapeutic treatment for high-risk patients with COVID-19.

scholarly journals A Functional Variant of CXCL16 Predisposes to Sepsis and MODS in Traumatic Patients

2020 ◽  
Author(s):  
Jianhui Sun ◽  
Huacai Zhang ◽  
Di Liu ◽  
Li Cui ◽  
Qiang Wang ◽  
...  
Keyword(s):  
Major Trauma ◽  
Southern China ◽  
Eastern China ◽  
Guizhou Province ◽  
Western China ◽  
Morbidity Rate ◽  
Trauma Patients ◽  
Chinese Han ◽  
Increased Risk

Abstract Background: CXC chemokine famliy genes play an important role in inflammatory and immune diseases. CXCL16 affects the occurrence and development of inflammation through leukocyte chemotaxis, leukocyte adhesion and endotoxin clearance. We selected a set of tagSNPs in CXCL16 gene and investigated their clinical relevance in relation to the development of sepsis and MODS in patients with major trauma in three independent Chinese Han populations.Methods: A total of 1,620 major trauma patients were enrolled in this study. Among which, 920 patients came from Chongqing in western China, 350 patients came from Zhejiang province in eastern China and 350 patients came from Guizhou province in southern China. Improved multiplex ligation detection reaction (iMLDR) was used in the genotyping and genetic association study was used to analyze the association between CXCL16 haplotypes and sepsis morbidity rate and higher MOD Scores in three cohorts. Results: CXCL16 T123V181 haplotype was associated with an increased risk for sepsis morbidity rate and higher MOD Scores in three cohorts. In vitro chemotactic experiment showed that T123V181 protein enhanced the chemotaxis of immunocytes. The adhesion ability of THP-1 cells which expressing T123V181 to immunocytes was also stronger than that of the other three haplotypes. T123 and V181 altered the structure of CXCL16 active center, which led to the change of protein function and the change of adhesion and chemotaxis of CXCL16 expressing immunocytes. The structural change might be the cause of the increased incidence of sepsis and higher score of MODS.Conclusions: We demonstrate that CXCL16 genetic variation regulates sepsis morbidity rate and explore a paradigm for the prewarning diagnosis of sepsis tailored by individual genetic information.Trial registration： ClinicalTrials.gov , NCT01713205. Registered 18 October 2012, retrospectively registered.

scholarly journals Liver X Receptor (LXR) Is a Novel and Reversible Regulator of Trauma-Induced Coagulopathy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 2-2
Author(s):  
Peter Einersen ◽  
Sanchayita Mitra ◽  
Reid Selby ◽  
Ernest E. Moore ◽  
Marguerite Kelher ◽  
...  
Keyword(s):  
Plasma Protein ◽  
Conflicts Of Interest ◽  
Protein Profile ◽  
Liver X Receptor ◽  
Coagulation Cascade ◽  
Trauma Patients ◽  
Trauma Induced Coagulopathy ◽  
Increased Risk ◽  
Total Plasma Protein ◽  
Coagulation Proteins

Trauma-induced coagulopathy (TIC) manifests as a bimodal disruption of normal fibrinolysis, where at the two extremes, fibrinolytic shutdown (TICFS) places the patient at increased risk for thromboembolism and post-injury multiple organ failure, and systemic hyperfibrinolysis (TICHF) results in excessive bleeding. Plasma proteomic profiles for 65 trauma patients were used to identify changes in the patient's plasma protein profile stratifying them by risk for TIC. A strong correlation was seen between total plasma protein concentration of individual patients and the concentration of coagulation proteins within that patient, suggesting that trauma-induced coagulation may be affected through a mechanism that controls the efflux of many coagulation proteins into the plasma (Figure 1). Pathway analysis, in addition to elucidating changes in the coagulation cascade, identified several proteins that are known to be regulated by the Liver X receptor/Retinoid X receptor (LXR/RXR), suggesting that LXR/RXR-mediated activity may regulate TIC (p=9.03E-26). Validation experiments in a rat model revealed that fibrinolytic response to an LXR antagonist and/or agonist can be observed in less than 60 minutes (Figure 2). Additionally, we show through reciprocal rescue of fibrinolysis that the TIC phenotypes (TICHF and TICFS) are one continuum and are ultimately co-reversible, where the reduced LXR signaling that causes sequestration of blood factors in the liver leading to excess bleeding or induced LXR signaling that causes excess efflux leading to thrombosis can be reversed through administration of the LXR agonist or antagonist, respectively. Thus, as modulation of LXR shows co-reversibility and rapid response, induction/inhibition of the LXR pathway provides a direct and novel therapeutic intervention in severely injured patients at risk for TIC. Disclosures No relevant conflicts of interest to declare.

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