Neuroimmune

and
Acute Coagulopathy
in Trauma

Topics

Classic neuro-endocrine response

Inflammation in shock after injury

Immune mediator cascades

Acute coagulopathy response

Classic neuroendocrine
response

Classic neuro-endocrine response

Acute Blood Loss

Sensed by carotid body and aortic arch

receptor

Preservation of cerebral
and cardiac perfusion

Peripheral
vasoconstriction
Pain

Reduced fluid
excretion

Hypoxia Acidosis Infection

Cardiac
contractility
Temperature changes

Glucose

Hemorrhage
Carotid body and aortic
arch receptor

Sympathetic vasoconstriction

Changes in vascular wall stretch and

pressure

Capacitance of the circulatory system is

reduced

Atrial
receptor
Afferent vagal fiber

Norepinephrine release from

postganglionic sympathetic
fibers

Immediate activation
of thoracolumbar
sympathetic outflow

Loss of tonic inhibition

of heart rate

The cool extremities

Peripheral
vasoconstriction

Arterial
vasoconstriction

Blood flow to other

tissue decrease
dramatically

Venous
capacitance
decrease

Maintain blood flow to

the heart and brain
until compensation fail

Renal blood flow

90-95%

Accelerated
venous return to
the heart

SBP <50 mmHg

SBP <15 mmHg

Splanchnic
Skin
Skeletal muscle
Mediated by epinephrine
and norepinephrine from
the adrenal medulla and
local sympathetic activity

Activation of Hypothalamic-Pituitary Axis

Multiple endocrine response

Glucagon, growth hormone, cortisol, corticotropin (ACTH)

RAA axis is stimulated vasoconstrictive angiotensin II

Vasopressin released water absorption in the distal tubule

of the kidney

Vasopressin induces splanchnic vasoconstriction

Growth hormone and glucagon promote gluconeogenesis,

lipolysis, glycogenolysis

Multiple endocrine response

Catecholamines inhibit insulin release hyperglycemia

increase blood osmolarity attract fluid into
intravascular

Fluid and salt is retained at the kidney

Inflammation in
shock after injury

Inflammation in shock after injury

Trauma may be considered as an inflammatory disease

Mediators and indicators of inflammatory response are elevated in

severely injured patients

Focused in the wound :

Activation of macrophages

Production of proinflammatory mediators

Focused in the microcirculation :

Activation of blood elements

Activation of the endthelium

Brief review of the immune system

Cell mediated

Neutrophils
Monocytes (macrophages)
NK-cells

Humoral

Cytokines
Complement

Cell mediated

T lymphocytes
B lymphocytes

Humoral

Antibodies

Nonspecific
Immune system

Specific
Immune system

Immune
mediator
cascades

Faster response
Local activation of complement cascade
Local endothelium

Endothelial
Leukocyte
Adhesion
Molecules
Respiratory burst

Anaphylatoxins

Activated
Neutrophil

Aggregation,
margination ,
migration

Oxygen radical & synthesis of proteolytic enzymes

Local release of bradykinin, histamine, prostaglandin

Local phagocytes release messenger molecules

Express
adhesion
molecules

Local vasodilation & increased capillary

permeability from macromolecules
GM-CSF

Activate bone marrow to

produce more
inflammatory cells

Slower response
Monocyte

Attracted to the site of injury

Macrophage

Hypoxia
C3a
Maccrophage activating factor
IL-1 like activity

Phagocytosing

Proinflammatory
Proteolytic enzymes
Oxygen radicals
IL-1
IL-6
Tumor Necrosis Factor

Antiinflammatory
IL-10
Prostaglandin E2

Nitric oxide
Cytotoxic radical

Acute
coagulopathy
response

Acute Coagulopathy in Trauma

a disturbed coagulation system with diffuse microvascular bleeding may

result in a haemorrhage that is no longer localised on the site of injury

This is exacerbated by the adverse immunologic effects of blood

transfusions.

Coagulopathy further worsens outcomes in patients having sustained

traumatic brain injury by an increased potential for progression of the
intracranial haemorrhage and secondary neuronal loss

Tissue trauma and shock with systemic hypoperfusion appear to be the

primary factors responsible for the development of acute traumatic
coagulopathy in the immediate postinjury phase.

As a result of overt activation of the protein C pathway, acute traumatic

coagulopathy is characterised by coagulopathy in conjunction with
hyperfibrinolysis.

This coagulopathy can then be exacerbated by subsequent physical and

physiologic derangements associated with ongoing haemorrhage and
inadequate resuscitation or transfusion therapies.

Aggressive and goaldirected haemostatic resuscitation can thereby

minimise exposure to blood products, reduce costs and improve patients
outcome

Tromboelastogram

Early Platelet Dysfunction

Wohlauer MV, J Am Coll Surg 2012;214:739-46.

Platelet dysfunction is manifest after major trauma and before substantial

fluid or blood administration.

Suggest a potential role for early platelet transfusion in severely injured

patients at risk for postinjury coagulopathy.

ACoTS vs DIC-fibrinolytic phenotype

Two concepts have been proposed for the hemostatic changes occurring
early after trauma. Disseminated intravascular coagulation (DIC) with the
fibrinolytic phenotype is characterized by activation of the coagulation
pathways, insufficient anticoagulant mechanisms and increased
fibrinolysis. Coagulopathy of trauma and acute coagulopathy of traumashock (COT/ACOTS) occurs as a result of increased activation of the
thrombomodulin and protein C pathways, leading to the suppression of
coagulation and activation of fibrinolysis. Despite the differences between
these two conditions, independent consideration of COT/ACOTS from DIC
with the fibrinolytic phenotype is probably incorrect. Robust diagnostic
criteria based on its pathophysiology are required to establish COT/ACOTS
as a new independent disease concept.

ACoTS vs DIC-fibrinolytic phenotype

Confusion between two concepts may be based on studies of trauma

lacking the following: (i) a clear distinction of the properties of blood
between the inside and outside of vessels, (ii) a clear distinction between
physiologic and pathologic hemostatic changes, (iii) attention to the time
courses of the changes in hemostatic parameters, (iv) unification of the
study population, and (v) recognition that massive bleeding is not
synonymous with coagulation disorders.