Hemostasis and Thrombosis in Trauma Patients

Hemostasis and thrombosis in trauma patients consist of physiological hemostasis for wound healing and the pathological reaction of disseminated intravascular coagulation (DIC). Whole body trauma, isolated brain injury, and fat embolism syndrome, if extremely severe, can cause DIC and affect a patient's prognosis. Shock-induced hyperfibrinolysis causes DIC with the fibrinolytic phenotype, contributing to oozing-type severe bleeding. If uncontrolled, this phenotype progresses to thrombotic phenotype at the late stage of trauma, followed by microvascular thrombosis, leading to organ dysfunction. Another type of pathological hemostatic change is acute coagulopathy of trauma shock (ACOTS), which gives rise to activated protein C–mediated systemic hypocoagulation, resulting in bleeding. ACOTS occurs only in trauma associated with shock-induced hypoperfusion and there is nothing to suggest DIC in this phenomenon. This review will provide information about the recent advances in hemostasis and thrombosis in trauma and will clarify the pathogeneses of the pathological processes observed in trauma patients.

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Activated Protein C Drives the Hyperfibrinolysis of Acute Traumatic Coagulopathy

Anesthesiology ◽

10.1097/aln.0000000000001428 ◽

2017 ◽

Vol 126 (1) ◽

pp. 115-127 ◽

Cited By ~ 60

Author(s):

Ross A. Davenport ◽

Maria Guerreiro ◽

Daniel Frith ◽

Claire Rourke ◽

Sean Platton ◽

...

Keyword(s):

Murine Model ◽

Protein C ◽

Major Trauma ◽

Activated Protein C ◽

Genetic Mutation ◽

Trauma Patients ◽

Acute Traumatic Coagulopathy ◽

Rotational Thromboelastometry ◽

Level 1 Trauma Center ◽

Traumatic Coagulopathy

Abstract Background Major trauma is a leading cause of morbidity and mortality worldwide with hemorrhage accounting for 40% of deaths. Acute traumatic coagulopathy exacerbates bleeding, but controversy remains over the degree to which inhibition of procoagulant pathways (anticoagulation), fibrinogen loss, and fibrinolysis drive the pathologic process. Through a combination of experimental study in a murine model of trauma hemorrhage and human observation, the authors’ objective was to determine the predominant pathophysiology of acute traumatic coagulopathy. Methods First, a prospective cohort study of 300 trauma patients admitted to a single level 1 trauma center with blood samples collected on arrival was performed. Second, a murine model of acute traumatic coagulopathy with suppressed protein C activation via genetic mutation of thrombomodulin was used. In both studies, analysis for coagulation screen, activated protein C levels, and rotational thromboelastometry (ROTEM) was performed. Results In patients with acute traumatic coagulopathy, the authors have demonstrated elevated activated protein C levels with profound fibrinolytic activity and early depletion of fibrinogen. Procoagulant pathways were only minimally inhibited with preservation of capacity to generate thrombin. Compared to factors V and VIII, proteases that do not undergo activated protein C–mediated cleavage were reduced but maintained within normal levels. In transgenic mice with reduced capacity to activate protein C, both fibrinolysis and fibrinogen depletion were significantly attenuated. Other recognized drivers of coagulopathy were associated with less significant perturbations of coagulation. Conclusions Activated protein C–associated fibrinolysis and fibrinogenolysis, rather than inhibition of procoagulant pathways, predominate in acute traumatic coagulopathy. In combination, these findings suggest a central role for the protein C pathway in acute traumatic coagulopathy and provide new translational opportunities for management of major trauma hemorrhage.

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Activated Protein C in Cutaneous Wound Healing: From Bench to Bedside

International Journal of Molecular Sciences ◽

10.3390/ijms20040903 ◽

2019 ◽

Vol 20 (4) ◽

pp. 903 ◽

Cited By ~ 5

Author(s):

Ruilong Zhao ◽

Haiyan Lin ◽

Lara Bereza-Malcolm ◽

Elizabeth Clarke ◽

Christopher Jackson ◽

...

Keyword(s):

Wound Healing ◽

Clinical Studies ◽

Protein C ◽

Activated Protein C ◽

Epithelial Barrier ◽

Cutaneous Wound Healing ◽

Cutaneous Wound ◽

Beneficial Effects ◽

The Past ◽

Complex Process

Independent of its well-known anticoagulation effects, activated protein C (APC) exhibits pleiotropic cytoprotective properties. These include anti-inflammatory actions, anti-apoptosis, and endothelial and epithelial barrier stabilisation. Such beneficial effects have made APC an attractive target of research in a plethora of physiological and pathophysiological processes. Of note, the past decade or so has seen the emergence of its roles in cutaneous wound healing—a complex process involving inflammation, proliferation and remodelling. This review will highlight APC’s functions and mechanisms, and detail its pre-clinical and clinical studies on cutaneous wound healing.

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Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing

Wound Repair and Regeneration ◽

10.1111/j.1067-1927.2005.00130311.x ◽

2005 ◽

Vol 13 (3) ◽

pp. 284-294 ◽

Cited By ~ 56

Author(s):

Christopher J. Jackson ◽

Meilang Xue ◽

Patrick Thompson ◽

Ross A. Davey ◽

Kaley Whitmont ◽

...

Keyword(s):

Wound Healing ◽

Protein C ◽

Activated Protein C ◽

Cutaneous Wound Healing ◽

Cutaneous Wound

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Analyzing fat embolism syndrome in trauma patients at AIIMS Apex Trauma Center, New Delhi, India

Journal of Emergencies Trauma and Shock ◽

10.4103/0974-2700.83859 ◽

2011 ◽

Vol 4 (3) ◽

pp. 337 ◽

Cited By ~ 6

Author(s):

Nita D′souza ◽

Kamran Farooque ◽

Pramendra Agrawal ◽

Babita Gupta ◽

Chhavi Sawhney ◽

...

Keyword(s):

Trauma Center ◽

Fat Embolism ◽

New Delhi ◽

Trauma Patients ◽

Fat Embolism Syndrome ◽

Embolism Syndrome

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Trauma and major haemorrhage

10.1093/med/9780199696260.003.0011 ◽

2017 ◽

Author(s):

Sheila Adam ◽

Sue Osborne ◽

John Welch

Keyword(s):

Emergency Department ◽

Critical Care Unit ◽

Burn Injury ◽

Specific Area ◽

Fat Embolism ◽

Major Haemorrhage ◽

Initial Assessment ◽

Trauma Patients ◽

Nursing Management ◽

Embolism Syndrome

This chapter discusses the medical and nursing management of trauma patients from their initial assessment in the emergency department to their subsequent management in the critical care unit. Each section of the chapter covers a specific area of trauma and describes its underlying physiology, management, and associated complications. Injuries discussed include spinal, head, chest, cardiovascular, genitourinary, renal, abdominal, pelvic, musculoskeletal, burn injury, hypothermia, and drowning. Major complications, such as fat embolism syndrome, compartment syndrome, and rhabdomyolysis, are described in detail. The chapter also discusses the management of major haemorrhage and the complications of massive blood replacement therapy.

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