Disseminated Intravascular

Coagulation
(DIC)

Dimas Bayu
Tutik Harjianti
A. Fachruddin Benyamin
Div of Hematology & Med Oncology - Dept of Int Medicine
Medical Faculty , Hasanuddin University
 Outline

1 Introduction
2 Ethio-Pathogenesis
3 Clinical Manifestation
4 Diagnostic Criteria
5 Treatment

4 Summary
I. Introduction
NORMAL HEMOSTASIS

Normal hemostasis :

Maintains blood in a fluid

State and produces a local
hemostatic plug at sites of
vascular injury
 HEMOSTASIS

I. Primary Hemostasis
- Blood vessel contraction
- Platelet Plug Formation
II. Secondary Hemostasis
- Activation of Clotting Cascade
- Deposition & Stabilization of Fibrin
III. Tertiary Hemostasis
- Dissolution of Fibrin Clot
- Dependent on Plasminogen Activation
 Hemostasis

Consist of :
1. Vascular & endothelium
2. Platelet
3. Coagulation
4. Anticlotting Mechanisms
5. Fibrinolytic System
6. Fibrinolytic Inhibitors
1. Vasoconstriction
2. Platelet activation
3. Haemostatic plug
Platelet activation

Fibrinogen
4. Coagulation
5. Stable clot formation
6. Clot dissolution
 DIC

A clinicopathologic
syndrome in which
widespread A syndrome associated
intravascular with many underlying
coagulation is induced conditions &
by procoagulants that manifested as
are introduced into or microvascular
produced in the blood thrombosis, tissue
secondary to 1 or more hypoxia,& organ damage
underlying
condition(s)
Disseminated Intravascular Coagulation

1. common features :
§  a triggering stimulus
§  tissue damage
•  microvascular thrombosis & occlusion
§  failure of perfusion of vital organs
§  depletion of hemostatic factors
2. common sequelae
§  damage to brain, kidneys & lungs
§  abnormal bleeding
§  death
 SYSTEMIC ACTIVATION
OF COAGULATION

Intravascular deposition Depletion of platelets &

of fibrin coagulation factors

Thrombosis of small & Bleeding

midsize vessels

1
Organ failure DEATH
Why DIC can be occured ?

Overstimulation of coagulation
è suppresion of control mechanism
è DIC.
Important Clue :

§  The presence of thrombin circulating

in bloodline.
__________________________________
Normally : thrombin can only be found
in area of lesion (where the coagulation
process is still running)
II. ETIO-PATHOGENESIS
 Cause of DIC

1. Systemic §  Sepsis

inflammatory ( any
microorgansim )
response, leading to §  Trauma
activation of ( polytrauma,
cytokine neurotrauma,
fat embolism )

§  Cancer ( Both

solid &
2. Release or exposure hematology
of procoagulant tumor )
material into the §  Obstetric
bloodstream problems
§  Vascular
abnormality
 Cause of DIC (2)

3. Less common cause

§  severe hepatic failure
§  Snake bites
§  Transfusion reactions
§  Transplant rejection
§  Deficiency of protein C & protein S
Pathophysiology of DIC

1
1 Activation of Blood Coagulation

1
2 Suppression of Anticoag Pathway

3 Impaired Fibrinolysis

4 Cytokines release & activation

 NORMAL HAEMOSTASIS

Endothelial d
Intravascular Haemostatic
clot formation mechanisms
TF
TF
TF
Cytokines

amage
TF TF

Activated
Monocyte
monocyte
Activation of monocytes

SYSTEMIC INFLAMMATION
 III. Clinical
Manifestation
 Clinical Manifestations of DIC

Ischemic
Findings ORGAN ISCHEMIC HEMOR.
are earliest!
Skin Pur. Fulminans Petechiae
Gangrene Echymosis
Acral cyanosis Oozing
CNS Delirium/Coma Intracranial
Infarcts bleeding
Renal Oliguria/Azotemia Hematuria
Cortical Necrosis
Cardiovascular Myocardial Dysfxn
Pulmonary Dyspnea/Hypoxia Hemorrhagic Bleeding is the
Infarct lung Most obvious
GI Ulcers, Infarcts Massive clinical finding
Endocrine Adrenal infarcts hemorrhage.
 Clinical Features

1.  Acute DIC

•  Develops rapidly over

a period of hours
•  Presents w/ sudden
bleeding from
multiple sites
•  Treated as a medical
emergency
 Clinical Features

2. Chronic DIC

•  Develops over a period

of months
•  May be subclinical
•  Eventually evolves into
an acute DIC pattern
Clinical Manifestations of DIC
Purpura Fulminans
IV. DIAGNOSTIC CRITERIA
 Diagnosis of DIC

Presence of disease associated

with DIC
Appropriate clinical setting
§  Clinical evidence of thrombosis,
hemorrhage or both.
Laboratory studies
§  no single test is accurate
§  serial test are more helpful than
single test
Scoring system for overt DIC

Underlying disorder known to be YES NO

associated with overt DIC
continue stop
§  Platelet count
§  (>100=0, <100=1, <50=2) ..............................
§  Soluble fibrin/D-dimer
§  (normal=0, é=2, éé=3) .............................
§  Prolongation of PT
§  (<3s=0, 3-6s=1, >6s=2) ................................
§  Fibrinogen
§  (>1g/l=0, <1g/l=1) ..........................................

§  Calculate sum ........................................

Scoring system for overt DIC
- Example -
Underlying disorder known to be YES NO
associated with overt DIC
Polytrauma cont st
inue op
§  Platelet count 85 1
§  (>100=0, <100=1, <50=2) ..............................
§  Soluble fibrin/D-dimer
8 3
§  (normal=0, é=2, éé=3) .................................
§  Prolongation of PT
§  (<3s=0, 3-6s=1, >6s=2) ................................. +3 1
§  Fibrinogen
§  2,2
(>1g/l=0, <1g/l=1) ............................................. 0

§  Calculate sum ............................................ 5

Scoring system for overt DIC

§  If the calculated score is

§  ≥5 : compatible with overt DIC
repeat scoring daily
§  <5: suggestive (not affirmative)
for
non-overt DIC repeat next 1-2 days.
 Laboratory Tests Used in DIC

§  D-dimer* §  Thrombin time

§  Antithrombin III* §  Fibrinogen
§  F. 1+2* §  Prothrombin time
§  Fibrinopeptide A* §  Activated PTT
§  Platelet factor 4* §  Protamine test
§  Fibrin §  Reptilase time
Degradation Prod §  Coagulation
§  Platelet count factor levels
§  Protamine test
*Most reliable test
 Laboratory diagnosis

§  Thrombocytopenia
§  plat count <100,000 or rapidly
declining
§  Prolonged clotting times (PT, APTT)
§  Presence of Fibrin degradation
products or positive D-dimer
§  Low levels of coagulation inhibitors
§  AT III, protein C
§  Low levels of coagulation factors
§  Factors V,VIII,X,XIII
§  Fibrinogen levels not useful
diagnostically
Differential Diagnosis

§  Severe liver failure

§  Vitamin K deficiency
§  Liver disease
§  Thrombotic thrombocytopenic
purpura
§  Congenital abnormalities of
fibrinogen
§  HELLP syndrome
V. TREATMENT of DIC
 Treatment of DIC

§  Stop the triggering process

§  The only proven treatment!
§  Supportive therapy
§  No specific treatments
§  Plasma & platelet substitution therapy
§  Anticoagulants
§  Physiologic coagulation inhibitors
 Plasma therapy

§  Indications
§  Active bleeding
§  Patient requiring invasive
procedures
§  Patient at high risk for
bleeding complications
§  Fresh frozen plasma(FFP):
§  provides clotting factors,
fibrinogen, inhibitors &
platelets in balanced
amounts.
§  Usual dose is 10-15 ml/kg
 Platelet therapy

§  Indications
§  Active bleeding
§  Patient requiring
invasive procedures
§  Patient at high risk
for bleeding
complications
§  Platelets
§  dose 1 unit/10kg
 Blood

§  Replaced as needed to maintain

adequate oxygen delivery.
§  Blood loss due to bleeding
§  RBC destruction (hemolysis)
Coagulation Inhibitor Therapy

§  Antithrombin III

§  Protein C concentrate
§  Tissue Factor Pathway Inhibitor
(TFPI)
§  Heparin
 Heparin

§  Use is very controversial. Data is mixed.

§  May be indicated in patients with clinical
evidence of fibrin deposition or
significant thrombosis.
§  Generally contraindicated in patients
with significant bleeding and CNS insults.
§  Dosing and route of administration
varies.
§  Requires normal levels of ATIII.
Summary

§  DIC : syndrome characterized by

systemic intravascular coagulation.
§  Initial event : coagulation
§  The extent of intravascular thrombosis
has the greatest impact on morbidity &
mortality
§  Important link between inflammation &
coagulation.
§  Morbidity & mortality remain high.
§  The only proven treatment is reversal or control
of the underlying cause.
6. Vessel wall with activated endothelium
(colour-enhanced scanning electron micrograph)
This scanning electron micrograph shows how the endothelium has reacted to
compression and damage during surgery. The endothelial cells are activated
and the clotting cascade has started. The formation of thrombin is the pivotal
step in fibrin formation and thrombus development.
 Pathophysiology of DIC…..

1. Activation of Blood Coagulation

§  Tissue factor/factor VIIa mediated thrombin
generation via the extrinsic pathway
•  complex activates factor IX & X
§  TF
•  Endothelial cells
•  Monocytes
•  Extravascular: - Lung
- Kidney
- Epithelial cells
 Pathophysiology of DIC….

2. Suppression of Physiologic Anticoagulant

Pathways
§  reduced antithrombin III levels
§  reduced activity of the protein C-protein S
system
§  Insufficient regulation of tissue factor activity
by tissue factor pathway inhibitor (TFPI)
•  inhibits TF/FVIIa/Fxa complex activity
 Pathophysiology of DIC…..

3. Impaired Fibrinolysis
§  relatively suppressed at time of maximal activation of
coagulation due to increased plasminogen activator
inhibitor type 1

4. Cytokines
§  IL-6, and IL-1 mediates coagulation activation in DIC
§  TNF-α
•  mediates dysregulation of physiologic anticoagulant
pathways and fibrinolysis
•  modulates IL-6 activity
§  IL-10 may modulate the activation of coagulation