DIC
Dr MB Dhlamini
Department of Molecular
Medicine and Haematology
WITS University
Objectives for the DIC lecture
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Definition of DIC
Describe the pathogenesis of DIC
Discuss mechanisms of acute DIC
Definition of subacute/chronic DIC
Discuss sequelae of activation of coagulation
cascade.
Describe examples of underlying disease and DIC.
Discuss principles of laboratory diagnosis of DIC
Describe management principles of DIC
Disseminated Intravascular
Coagulopathy
Definition:
-Clinicopathological syndrome in which
wide spread intravascular coagulation
is induced by procoagulants that are
introduced /produced in the blood &
overcome the natural anticoagulant
mechanism.
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DIC characterised by:
Systemic intravascular coagulation –
widespread fibrin deposition in circulation
 Results : microvascular dysfunction & organ
failure
 Massive ongoing activation may result in
depletion of platelets & coagulation factors–
bleeding.
 Secondary fibrinolysis
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Clinical Picture - DIC
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Underlying disorder
S yste m ic a ctiva tio n of coa g u la tion
W id esp rea d de p osition
C o nsu m p tion o f P la te le ts
M icro va su lar th rom b o tic o b stru ction
D e cre a sed P late le ts & Co a gu la tio n facto r d e ficie n cy
O R G A N F A IL U RE
B L E E D ING
Pathogenesis of DIC
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Acute DIC : Triggering mechanisms (TMS)
1. Entry of thromboplastins with high
phospholipid concentration into circ.
e.g. a) following extensive tissue
trauma during surgery.
b) Acute Vascular haemolytic episode
(ffg incompatible blood transfusion)
Acute DIC TMS cont’d
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2. Direct activation of Factor X or
Prothrombin(Factor II) by specific
proteolytic enzymes in snake venom.
3. Severe Vascular Endothelial Injury
e.g. gram negative septicaemia
viral/protozoal diseases
extensive burns – exacerbated by
prolonged hypotension, hypoxia,
acidosis
Acute DIC TMS cont’d
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4. Direct platelet activation in
septicaemia and viraemic states or
activation of platelets following:
a) vessel wall endothelial damage
b) thrombin generation by the
coagulation cascade
Subacute/Chronic DIC
Slow activation of haemostatic system
 Spontanteous bruising rather than major
bleeds
 Chronic compensated DIC can continue
for many years – usu. Assoc. with
vascular malformations
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Sequelae of Activation of the
Coagulation Cascade
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Thrombin generation– fibrinogen converted to
fibrin
 Trace amts of thrombin inactivated by
formation of thrombin-antithrombin
complexes ( protective mechanisms)
 If excess thrombin– cleavage of
fibrinopeptide A & B from Aά & Bβ forming
monomers
 Fibrin monomers polymerize to form fibrin clot
Sequelae cont’d
Fibrin strands/platelet aggregates cause
blockage of arterial circ.
 Loose fibrin platelet plugs form a fine
mesh sieve– red cells passing through
distorted & fragmented ---- intravascular
haemolysis
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Sequelae cont’d
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Secondary activation of the fibrinolytic
pathway. ffg fibrin deposition – tPA released
from vascular endothelium converting
plasminogen to plasmin within fibrin clot
 Free plasmin – cleavage of fibrinogen and
lysis of cross linked fibrin
 Breakdown of fibrinogen– formation of
fragments D/E ( via X-Y)
Sequelae cont’d
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Specific lysis of fibrin—formation of specific
FXIII cross linked complexes incl. D-Dimers
Fibrinogen/fibrin breakdown—FDPs or DDimers)
 Free plasmin may also cleave other peptides
e.g.FV, FVIII & 1st component of complement.
Sequelae cont’d
Liver cell synthesis fails to compensate
for their consumption thus decreased
Factors V, VIII, XIII, fibrinogen
 BM megakaryocyte production unable
to maintain normal plt count
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Sequelae cont’d
Combination of :
- coagulation factor deficiency
- thrombocytopenia
- impaired platelet function
- inhibitory action of raised FDPs
= generalised/continued widespread
bleeding
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Underlying Dx
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Bacterial infections
- most common cause
gram negative lipopolysaccharide
gram positive exotoxin
cytokines
Meningococcemia- Purpura on the
calves
Meningococcemia-2
Underlying Dx cont’d
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Other infections
1) Viral e.g. viral haemorrhagic fever
probably via endothelial damage
2) Protozoa e.g. Malaria
Underling Dx cont’d
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Trauma
- frequently associated with
1) release of phospholipid
2) endothelial damage
3) Cytokines also play a role
Underlying Dx cont’d
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Malignancy
- low grade or subacute DIC
- Trigger Tissue Factor: usu. assd with
metastatic
disease e.g. Ca Pancreas, Ca lung,
Ca stomach
- APL : hyperfibrinolysis, TF on
leukaemic cells
Underlying Dx cont’d
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Obstetrics
- implicated in the following
1) Septic abortion
2) Abruptio Placenta
3) Ecalmpsia
4) Placent Praevia
5) Amniotic fluid embolism
Underlying Dx obstetrics cont’d
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Mechanisms
- entrance of cellular elements of the
decidua/placenta with thromboplastin-like
activity into maternal circ.
- meconium and fetal squamous cells from
amniotic fluid into maternal circulation–
activation of coagulation
- IUD – slow progressive DIC– bleeding late
manifestation
Underlying Dx cont’d
Vascular disorders
1) large aortic aneurysms
2) Kasabach-Merrit syndrome
---- result in local activation of coagulation
---- overflow into systemic circ.
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Diagnosis of DIC
-Investigate underlying dx
-Evidence of consumption eg.
Thrombocytopenia,prolonged
INR/PTT,decreased factors
-Evidence of activation of fibrinolytic pathway :
elevated D-Dimer levels and presence of
FDP’s
-Decrease in coagulation inhibitors:
Antithrombin,Protein C&S
Management of DIC
NB: Rx of the underlying disease
 Supportive management eg. Platelets,
FFP’s, cryoprecipitate
 Coagulation inhibitors : Heparin,
Antithrombin and Activated Protein C
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Stroke
Case Studies
38yr male,RVD positive, neutropenic
 Confused, not on warfarin or heparin
 INR 1.08, PTT 34.90s, D-Dimers
1.66mg/l, fibrinogen 3.81g/l
,antithrombin 110% and platelets
182x10^9/l
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Case 2
66yr old female post- NSTEMI, treated
with antibiotics for infection
 INR 2.73, correct. 1.01,PTT 32.6s, DDimers 0.87mg/l, fibrinogen 4.1g/l
,Factor VII 17%, Antithrombin 84% and
Plt 204x10^9/l.
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Case3
52yr female with perforation of the
bowel and sepsis
 INR1.82, correct. 1.33, PTT
65.5s,correct 34.1s, D-Dimers 4.71mg/l,
fibrinogen 1.96g/l, antithrombin 57%
and platelets 35x10^9/l.
 Thrombin ratio 0.78 (within normal
range)
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