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Coagulation
Galila Zaher
MRCPath 2005
Definition
“DIC is an acquired syndrome
characterized by the intravascular
activation of coagulation with loss of
localization arising from different causes.
It can originate from and cause damage
to the microvasculature, which if
sufficiently severe, can produce organ
dysfunction.”
Scientific Subcommittee on DIC of ISTH, July , 2001
Disseminated Intravascular
Coagulation (DIC)
Is not a disease, but a complication of various disorders
Conditions with activation of coagulation factors
DIC should always be considered in critically ill
Widespread
Platelets Consumption
microvascular thrombosis
coagulation factors and
inhibitors Consumption.
Platelet count
(> 100 = 0, < 100 = 1, < 50 = 2)
Soluble fibrin/D-dimer
(no increase = 0), ↑ moderate increase: =2, ↑ ↑ strong
increase = 3
Prolongation of PT
(<3 sec = 0; >3 -6 sec =1; >6 sec = 2)
Fibrinogen level
(> 1.0 g/l = 0; < 1.0 g/l = 1)
Calculate score
Calculated Score
Patient scores is >5: compatible with overt DIC,
(decompensated hemostasis) repeat scoring daily
Patient scores is <5: suggestive (not affirmative)
for non-overt DIC, repeat next 1-2 days
Taylor, Thromb Haemostas 2001;86:1327-1330
Algorithm for Diagnostic Sequence for Determining Non-
overt DICK Non-overt DIC
1. Risk assessment:
Does the patient have an underlying disorder known to be associated with DIC? If yes:
proceed
2. General criteria
Platelet count >100 x 109/L = <100 x 109/L Rising = -1 Stable = Falling = Score
0 =1 0 1
PT prolongation <3s >3s Falling = -1 Stable = Rising = 1
0
Soluble fibrin or Normal Raised Falling = -1 Stable = Rising = 1
FDPs 0
3. Specific criteria
Antithrombin Normal = - Low = 1
1
Protein C Normal = - Low = 1
1
TAT complexes Normal = - High = 1
1
4. Calculate score
General Treatment
Pro-inflammatory
cytokines
IL-6 TNF-α
Inhibition of Depression of
TF- physiological fibrinolysis
activation of anticoagulant due to high
coagulation pathways levels of PAI-1.
Enhanced Impaired
fibrin fibrin
formation removal
Microvascular
thrombosis
Practice Points
DIC is not a disease entity on itself but is always
associated to an underlying disease.
There is no single laboratory test with adequate accuracy
to establish the presence or absence of DIC.
Most laboratory tests for DIC have a relatively high
sensitivity but a low specificity
A combination of tests may guide the clinician towards a
confirmation or rejection of a diagnosis of DIC, for
example following the recently established guidelines of
the International Society of Thrombosis and Hemostasis.
Inflammation causing loss of homeostasis of the RES/MV organ. Significant injury of the endothelium occurring as a result of candidate injury
states has the potential for causing significant perturbation of the RES/MV organ in an activation sequence, summarized here. The left side
indicates the anatomic site for the on-going acceleration of the inflammatory and hemostatic processes indicated in the flow diagram, an implies a
semblance of the sequence itself. In many, if not most, instances, however, these events are occurring in parallel. Indeed, in the case of
acceleration to overt DIC, these processes are not only occurring in parallel, but in fact are being recapitulated at diffuse and distal anatomic sites
throughout the body. Specific steps of this activation process are discussed in the text. For example, bacterial lipopolysaccharide, vascular injury
(e.g. abruptio placenta), etc. PAI-I plasminogen activator.
Scoring system for DIC
YES NO
Underlying disorder known to be associated with DIC Continu Stop
e
• Platelet count
- (> 100 = 0, < 100 = 1, < 50 = 2)…………………..
• Soluble fibrin/D-dimer
- (normal = 0), ↑ =2, ↑ ↑ = 3)……………………….
• Prolongation of PT
- (< 3s = 0, 3-6s = 1, > 6 = 2)……………………….
• Fibrinogen
- (> 1g/1 = 0, < 1g/1 = 1)…………………………...
• Calculate score
Dr Galila Zaher
Consultant Haematologist
MRCPath
Normal Homeostasis
IL1-B TNF
Microvascular thrombosis
Inflammatory cells
IL-B TNF
TF-VIIa TPI
IIIIa TM-IIa
Fibrinolysis Va,VIIIaVi,VIIIi
Clinical conditions associated
with DIC
Sepsis/severe infection .
Trauma .
Organ destruction .
Malignance.
Obstetrical calamities.
Vascular abnormalities.
Server hepatic failure.
Severe immunologic reactions.
Recreational drugs
Transplant rejection
DIC
An acquired syndrome characterized by:
The intravascular activation of
coagulation.
Activated platelets (PL) for thrombin
formation
Consumption of pro-coagulant factors&
natural anticoagulant.
Widespread fibrin deposition .
Impaired fibrinolysis (PAI-1).
Micro vascular occlusion.
DIC
Earlier management.
Battery of tests .
Serial testing.
Inevitable delay.
Diagnostic scoring criteria for DIC
General criteria:
Platelets count <100.
PT prolongation >3s.
FDPs raised.
Specific criteria:
Anti-thrombin.
Protein C.
TAT complex.
If >5 compatible with overt DIC ,if <5reapet scoring
daily :suggestive of non overt DIC.
BIOLOGIC MARKERS TO MEASURE
NON-OVERT DIC
Platelet activation.
Single. .i
Sensitive . .ii
Specific. .iii
Simple. .iv
( Downey et al).
Transmittance Waveform in DIC
Diagnosis .
Sensitivity 97.6%
PPV 74% .
APC concentrate .
Heparin.
Anti-thrombin concentrates .
TFPI.
rNAPc2.
rIL-10 .
APC concentrate
Endotoxemia(T-TM).
Depression of PC system .
Enhance the pro-coagulant state.
In sepsis reduce MR .
24 g/kg/h for 96 h.
The first intervention shown to be
effective in reducing mortality in
sepsis.
Anti-thrombin concentrates
Activation of coagulation
FDPs depend on fibrin generation
and clearance.
High predictive value of PAI-1
multi-organ failure .
A high level of soluble fibrin is an
early indicator.
D-dimer an indicator of fibrin
formation.