Disseminated Intravascular

Coagulation

Atiya A. Hajjaj
 Introduction
Generalized activation of the
coagulation system followed
by marked activation of the
fibrinolytic system.
Systemic rather than localized
activation of coagulation.
 As fibrin is formed, several clotting
proteins and naturally occurring
inhibitors and platelets are consumed
faster than they are synthesized
(consumption coagulopathy).
As a result of consumption of coagulation
factors and platelets and the formation of
fibrin degradation products (FDP), the
patient often bleeds at the same time
that disseminated clotting is occurring.
 Incidence
~ 1 in 1000 hospitalized patients.
~ 20% of the cases are
asymptomatic and suspected only
on the basis of laboratory data.
It can occur at any age, although it
is more often seen in the very
young and the elderly.
 Etiology
A number of diverse disease states can trigger
the DIC syndrome; they often involve the
introduction of tissue factor (TF) into the
blood stream, resulting in the initiation of fibrin
formation.
The coagulation cascade may be activated in
various ways:
By the release of TF from damaged tissues,
monocytes or macrophages.
By damage to endothelial cells.
By abnormal activators of coagulation.
 The most prevalent etiologic factor
was infection, but in another study,
more than 50% of cases were
obstetric patients.
A Japanese study found that in a
hospital population, 45% of DIC cases
were associated with malignancy.
Snakebite.
Rare in heatstroke, autoimmune
disorders, and hemolytic anemias.
 The most common of which are infections,
particularly those associated with
septicemia. The trigger mechanism of
infections is likely cytokines (IL-1, IL-6,
and/or tumor necrosis factor TNF)
released into the tissues by the
inflammatory response, which activate
endothelial cells. Resting endothelium
does not express TF, but endothelial
cells or monocytes activated by
inflammatory cytokines or injured by
endotoxin express TF activity.
 Complications of pregnancy likely cause DIC
because amniotic fluid acts as a
thromboplastin to activate fibrin formation
pathways.
With massive tissue or blood cell injury, it is
thought that TF-like substances, such as fat
and phospholipids, enter the circulation and
activate coagulation. (e.g. head trauma).
The trigger mechanism of malignant cells is a
variation of tissue injury. Some malignant cells
express a TF-like substance, and others
have been shown to produce a cysteine
protease capable of directly activating F-X.
 Classification
Acute DIC (DeCompensated)
It happened rapidly, the coagulopathy
is dominant and major symptoms are
bleeding and shock, mainly seen in
severe infection, amniotic fluid
embolism.
Chronic DIC (Compensated)
it happened slowly and last several
weeks, thrombosis and clotting may
predominate mainly seen in cancer.
 Pathophysiology
DIC results in generalized or systemic
activation.
After the initiating event has occurred,
thrombin is formed within the circulation.
The circulating thrombin acts on its substrates
as they circulate Fibrin.
This unregulated generation of thrombin results
in consumption of fibrinogen; factors V, VIII,
and XIII (the natural substrates of thrombin);
and depletion of prothrombin .
 Thrombin is a potent agonist of
platelets inducing platelet activation and
aggregation.
Thrombin also binds to receptors on
endothelial cells, inducing endothelial
release of tissue plasminogen activator
(tPA), which in the presence of the newly
formed fibrin activates plasminogen to
plasmin and triggers an aggressive
secondary fibrinolysis.
As plasmin is generated, plasminogen
becomes depleted.
 The coagulation inhibitors antithrombin
(AT), heparin cofactor II (HC II), and
thrombomodulin (TM), normally effective
in regulating the localized generation of
thrombin, are overwhelmed in DIC.
Deficiencies of AT, protein C (PC), and
protein S (PS).
IL-1 and TNF (elevated in sepsis)
decrease TM expression on
endothelium, resulting in decreased
activation of the PC/PS inhibitory
mechanism.
 Plasma levels of fibrinopeptides A and B
(FPA and FPB) and D-dimer are elevated
because of the actions of thrombin on
fibrinogen and of plasmin on fibrin.
FDPs interfere with fibrin formation and
platelet function, contributing to the bleeding
tendency.
All of these events can result in bleeding as the
clotting mechanism is activated and
procoagulant components become depleted.
 Clinical Aspects of DIC
The symptoms seen in patients with DIC result
from the presence and activation of thrombin,
plasmin, platelets, endothelium, and proteolytic
inhibitors within the bloodstream and vary from
patient to patient because of the complex
interactions between these components.
Bleeding
Thrombosis
In addition, the intensity and duration can result
in either an acute or chronic clinical course.
 Patients with acute disease tend to manifest
hemorrhagic symptoms whereas in those with
chronic disease thrombosis is more likely to
predominate.
Acute DIC
80 90 % of DIC patients.
Sudden onset of severe bleeding.
Chronic DIC
1020% of patients.
The stimulus that triggers clotting is weaker, and the
natural homeostatic mechanisms are sufficient to
replace depleted hemostatic components.
 Bleeding manifestations include:
Hematuria
Gastrointestinal and respiratory tract
bleeding
Intracranial bleeding
Epistaxis
Spontaneous bruising and
petechiae.
 At the same time, small strands of fibrin
(microclots) form inside blood vessels and
obstruct the microvasculature. Because blood
vessels are occluded, tissue anoxia and
microinfarcts in various organs can occur.
Renal failure
Coma
Liver failure
Respiratory failure
Skin necrosis
Gangrene
Venous thromboembolism.
 Shock is a common feature and can
be either a cause or an effect of DIC.
The association of shock with DIC is
complex and not well understood.
Shock is likely induced because
cytokine generation and products of
the kinin and complement systems
cause increased vascular
permeability and hypotension.
The mortality rate of DIC is 5060%.
 Laboratory Data
Platelet
Fibrinogen
Thrombin time
High levels of fibrin degradation products such
as D-dimers are found in serum and urine.
The PT and PTT (in the acute syndromes).
In many patients there is a hemolytic anemia
(microangiopathic)
Schistocytes.
Schistocytes
 Treatment
Treat the underlying cause.
Bleeding
FFP
Platelet concentrates
Cryoprecipitate (fibrinogen).
Transfusion (RBCs).
Thrombosis
Heparin or antiplatelet drugs.
Antithrombin concentrates or recombinant
activated human protein C may be used to inhibit
DIC in severe cases with sepsis (there is reduced
activated protein C (APC) in severe sepsis).
Avoid fibrinolytic inhibitors.