Approach to DIC

APPROACH TO DIC
-WILLIAMS HEMATOLOGY -8th EDITION

WHAT IS DIC
When procoagulants are produced or introduced into the blood &
overcome the anticoagulant mechanisms of coagulation, intravascular
thrombin is generated systemically, which can lead to disseminated
intravascular coagulation (DIC).
The clinical manifestations of intravascular coagulation include
(1) multiorgan dysfunction caused by microthrombi;
(2) bleeding caused by consumption of platelets, fibrinogen, and other
coagulation factors; and
(3) secondary fibrinolysis

IMPAIRMENT OF NATURAL
ANTICOAGULATION IN DIC

TRIGGERS
Exposure of blood to tissue factor(Factor 7)is the most common trigger
This event can occur when mononuclear cell/endothelial cells are
induced to generate/express tissue factor during the systemic
inflammatory response syndrome (e.g., Gram-negative and Gram-
positive infections, fungemia, burns, severe trauma),
or
when contact is established between blood and tissue factor
constitutively present on membranes of cells foreign to blood (e.g.,
malignant, placental, brain, adventitial cells, or traumatized tissues).

PATHOGENESIS
Tissue Factor exposure.
IL-6 Generation
TNF alpha Generation
Endothelial Perturbation(Sine Qua non)
Tissue Factor +Thrombin
Microvascular Thrombi

Typical Blood Parameters
Parameter Inference
Platelet Count Decreased
Plasma Fibrinogen Decreased (150-400mg/dL)
Fibrin Degradation Product Elevated
D-Dimer Elevated(<0.5ug/ml)
Factor V Decreased(25-60%)
Factor VIII Decreased(<50%)
Prothrombin Time Prolonged
aPTT Prolonged

CONDITIONS THAT PREDISPOSE DIC
Added Together constitutes 2/3rd of all cases

SPECIFIC UNDERLYING DISORDER
1.INFECTIOUS DISEASES
most common cause of DIC.
Predisposing Factors-immunocompromised hosts,asplenic patients and
newborns
infections aggravate bleeding & thrombosis by directly inducing
thrombocytopenia, hepatic dysfunction & shock associated with
diminished blood flow in the microcirculation.
Clinically overt DIC may occur in 30 to 50 percent of patients with
Gram-negative sepsis.

1.INFECTIOUS DISEASES
a)group A streptococcus toxic shock syndrome
b)meningococcemia-Waterhouse-fridrichsen syndrome
c)Staph aureus bacteremia-Renal cortical & dermal necrosis
d) Pseudomonas aeruginosa,
e)E. coli and
f)Proteus vulgaris

2.SOLID TUMOURS
tumor cells express different procoagulant molecules including tissue
factor which forms a complex with factor VII- activate factors IX and X,
and
a cancer procoagulant, a cysteine protease with factor X activating
properties
Interactions of P- and L-selectins with mucin from mucinous
adenocarcinoma induce formation of platelet microthrombi & probably
is a third mechanism of cancer-related thrombosis

2.SOLID TUMOURS
Patients with solid tumors are vulnerable to risk factors & additional triggers
of DIC that aggravate thromboembolism & bleeding.
Risk factors include advanced age, stage of the disease & use of
chemotherapy or antiestrogen therapy.
Triggers include septicemia, immobilization & involvement of liver by
metastases that impede the function of the liver in controlling DIC.
Microangiopathic hemolytic anemia frequently is induced by DIC in patients
with malignancies and is particularly severe in patients with widespread
intravascular metastases of mucin-secreting adenocarcinomas

3.Leukemias
In patients with acute promyelocytic leukemia (APL) DIC is present in
more than 90 percent of patients at the time of diagnosis or after
initiation of remission induction
APL cells express TF & the cancer procoagulant that can initiate
coagulation,they release IL-1Beta and TNF-Alpha which downregulate
endothelial thrombomodulin, thereby compromising the protein
C anticoagulant pathway
All-trans-retinoic acid used for induction & maintenance therapy
inhibits in vitro and in vivo deleterious effect of APL cells

4.TRAUMA
Extensive exposure of TF to circulation & hemorrhagic shock probably are
most immediate triggers of DIC in such instances
the changes in cytokine levels are virtually identical in trauma patients and
septic patients
DIC can be aggravated in patients with severe trauma who require massive
blood replacement because stored blood components are diluted and do not
contain sufficient amounts of viable platelets and factors V and VIII.
The time interval between trauma and medical intervention correlates with
the development and magnitude of DIC. Experience during wars proved that
fast evacuation and prompt medical care reduce the risk of DIC

5.BRAIN INJURY
injury exposes the abundant TF of brain to blood
Specimens of contused brain obtained during autopsy, revealed
microthrombi in arterioles and venules
Bleeding in patients with DIC that is related to brain injury can be
managed by replacement therapy

6.BURNS
Tissue factor exposed to blood at sites of burned tissue, the systemic
inflammatory response syndrome induced by burns & the common
presence of superimposed infections all triggers DIC
vascular microthrombi in biopsies of undamaged skin have been
described in patients with extensive burns
the extent of protein C and AT deficiencies correlates with a poor
outcome

7.LIVER DISEASES
Very wide derangements of hemostasis occur in patients with severe
liver disease and during liver transplantation.
a)natural anticoagulants (protein C, protein S, and AT)
b)Components of the fibrinolytic system (plasminogen, TAFI, and alpha
2-antiplasmin) are reduced
c) capacity of the liver to clear the circulation of activated factors IX, X,
and XI and of t-PA is decreased
d) thrombocytopenia is common as a result of hypersplenism and
decreased production of thrombopoietin by the liver

7.LIVER DISEASES
A hypothesis states that patients with liver disease usually do not present
with DIC but are extremely sensitive to the various triggers of DIC because of
their impeded capacity to clear procoagulants and to synthesize essential
components of the coagulation, inhibitory, and fibrinolytic systems
a hemostatic profile should be examined at frequent intervals so as to detect
any dynamic changes that may be helpful in recognizing DIC
Sensitive assays that reflect thrombin generation (TAT complex &
prothrombin fragments) or concomitant thrombin & plasmin generation (D-
dimer), as well as finding a decreased level of factor VIII may help establish
the diagnosis of DIC in a patient with liver disease

8.HEATSTROKE
Body temperature to higher than 42°C
Extensive hemorrhage, unclottable blood & venous engorgement were
found as early as 1838 in postmortem examinations of patients who died of
heat stroke
possible triggers of DIC in patients with heat stroke include endothelial cell
damage and TF released from heat-damaged tissues.
There was a marked correlation between the extent of inflammation and
coagulation activation and the clinical severity of the heat stroke
Prompt cooling and support of vital functions have substantially reduced the
high mortality as commonly observed in recent studies

9.SNAKEBITES
Viperidae family produce venoms that have a wide range of activities affecting hemostasis.
Venoms of these snakes contain enzymes or peptides that exert the following activities:
1) thrombin-like activity,
2) activation of prothrombin even in absence of calcium ions Echis carinatus
3) activation of factors X and V (Russell viper)
4) fibrinogenolytic activity (Agkistrodon acutus)
5) induction of thrombocytopenia by platelet aggregation
6) inhibition of platelet aggregation by the low molecular weight arginine-glycine-
aspartic acid containing peptides
7) activation of protein C; and
8) causing damage to endothelial cells, leading to bleeding, tissue ischemia & edema

9.SNAKEBITES
Interestingly victims of snake bites rarely experience excessive bleeding
or thromboembolism, in spite of the serious derangements in
hemostatic tests & findings that are sometimes consistent with DIC
treatment consists of immediate immobilization, administration of
antivenom and fluids & other general measures to preserve vital
functions
Local incisions, cooling & application of tourniquet should be avoided

10.HEMANGIOMAS
In 1940, Kasabach and Merritt described the association between giant
hemangioma and a bleeding tendency occurring mainly in infants.
Microangiopathic hemolytic anemia & laboratory signs of DIC & fibrinolysis
are demonstrated in patients with giant hemangiomas
Spontaneous mild to moderate bleeding manifestations have been observed,
but severe bleeding generally occurs only after surgery or trauma.
Accelerated growth of these hemangiomas in infants is associated with
augmented consumption of hemostatic factors, and can be effectively
treated with glucocorticoids

11.AORTIC ANEURYSM
An association between aortic aneurysm and DIC is well documented
The initiation of localized and generalized intravascular coagulation can
be ascribed to activation of the TF pathway by the abundant amounts
of TF present in atherosclerotic plaques
Clinical and laboratory signs of DIC should be carefully sought in
patients with an aortic aneurysm because bleeding may seriously
complicate surgical repair of the aneurysm

12.DIC DURING PREGNANCY
Pregnancy predisposes patients to DIC for at least four reasons
1) pregnancy itself is a hypercoagulable state manifested by evidence of
low-grade thrombin generation, with elevated levels of fibrin monomer
complexes and fibrinopeptide A
2) during labor leakage of tissue factor from placental tissue into the
maternal circulation causes a hypercoagulable state
3) pregnancy is associated with reduced fibrinolytic activity because of
increased plasma levels of PAI-1 &
4) pregnancy is associated with a decline in the plasma level of protein S.

DIC may be difficult to diagnose during pregnancy because of the high
initial levels of coagulation factors such as fibrinogen, factor VIII, and
factor VII

a)ABRUPTIO PLACENTAE
Risk-Hypertension,elderly Multipara
large amounts of TF into the blood circulation from the damaged placenta and
uterus
the degree of placental separation correlates with the extent of DIC, suggesting
that leakage of thromboplastin-like material from the placental system is
responsible for the occurrence of DIC
Rapid volume replenishment and evacuation of the uterus is the treatment of
choice with cryoprecipitate, fresh-frozen plasma, and platelets if bleeding +
However, in the absence of severe bleeding, administration of blood components
may not be necessary because depleted coagulation factors increase rapidly
following delivery

b)AMNIOTIC FLUID EMBOLISM
The trigger of DIC probably is TF present in amniotic fluid
The mechanical obstruction of pulmonary blood vessels by fetal debris, meconium & other
particulate matter in amniotic fluid enhances local fibrin–platelet thrombus formation &
fibrinolysis
The extensive occlusion of pulmonary arteries & SIRS provoke sudden dyspnea, cyanosis,
acute cor pulmonale, left ventricular dysfunction, shock & convulsions with bleeding in
minutes to hours
The best modality for decreasing mortality lies in early termination of parturition in
patients at high risk & prevention of hypertonic & tetanic uterine contractions during labor
If DIC has set in -immediate termination of pregnancy under pulmonary and cardiovascular
support is essential

c)ECLAMPSIA & PREECLAMPSIA
Thrombocytopenia and widespread deposition of fibrin in blood vessels
observed in fatal cases were interpreted as evidence of DIC triggered by
placental TF exposure to the circulation.
in a large series of patients, a good correlation was noted between the
clinical severity and abnormalities in platelet counts and fibrin
degradation products
Despite these observations administration of heparin to patients with
preeclampsia and eclampsia has not resulted in convincing benefits

d)HELLP SYNDROME
What actually triggers DIC in these cases is not known but has been
related to endothelial dysfunction
supportive care, careful periodic monitoring & blood component
replacement therapy
With few exceptions immediate delivery is indicated
HELLP syndrome tends to recur in subsequent gestations

e)DEAD FETUS SYNDROME
Several weeks after intrauterine fetal death, approximately one-third of
patients may exhibit laboratory signs of DIC, occasionally accompanied by
bleeding.
TF from the retained dead fetus or placenta slowly enters the maternal
circulation and initiates DIC, which sometimes is accompanied by significant
fibrinolysis.
This complication currently is rarely observed because labor is induced
promptly after the diagnosis of fetal death is made.
However, if labor induction is unavoidably delayed, serial blood coagulation
tests should be performed.

f)ACUTE FATTY LIVER
Rare disorder that occurs during the third trimester of pregnancy.
One predominant mutation (G1528C) accounts for 65 to 90 percent of
cases with the deficiency of LCAD in fetus which contributes this illness
in 15-20%
The typical histologic feature is microvesicular fatty infiltration of liver.
Exceedingly low levels of AT and other laboratory signs of DIC were
seen

END ORGAN DAMAGE

MORTALITY
Both DIC & its underlying disorders contribute to high mortality rate.
Mortality correlates independently with the extent of organ
dysfunction,the degree of hemostatic failure & increasing age.
Mortality rates in major series of patients with DIC ranged from 31 to
86 percent

BLOOD COMPONENT THERAPY
However, plasma or platelet substitution therapy should not be instituted on
the basis of laboratory results alone; it is indicated only in patients with
active bleeding and in those requiring an invasive procedure or are at risk for
bleeding complications
The threshold platelet count that should prompt transfusion is patient and
disease specific.
Cryoprecipitate can be used to rapidly raise fibrinogen & factor VIII levels,
particularly when bleeding is part of the DIC & fibrinogen level is less than 1
g/L.
Cryoprecipitate has at least four to five times the mass of fibrinogen per
milliliter of infusate compared to fresh-frozen plasma.
Fresh-frozen plasma contains fibrinogen in sufficient amounts for treatment
of patients with mild to moderate hypofibrinogemia

RESTORATION OF PHYSIOLOGICAL
ANTICOAGULANT PATHWAYS
Because the levels of the physiologic anticoagulants are reduced in patients
with DIC,restoration of these inhibitors may be a rational approach
Because a decreased function of the protein C system contributes to the
pathogenesis of DIC therapy by an APC concentrate was predicted to be
beneficial.A dose-ranging controlled trial using continuous infusion of
recombinant human APC disclosed that a dose of 24 mcg/kg per hour was
optimal, judged by a decrease of D-dimer level in plasma
patients who manifested "overt DIC" benefited more from the therapy with
APC than did patients without overt DIC.
Recombinant human APC has been licensed in most countries for treatment
of patients with severe sepsis involving two or more organ failures

HEPARIN IN DIC
Administration of heparin is beneficial in some categories of chronic
DIC such as metastatic carcinomas, purpura fulminans & aortic
aneurysm (prior to resection).
Heparin administration may be helpful in patients with acute DIC when
intensive blood component replacement fails to improve excessive
bleeding or when thrombosis threatens to cause irreversible tissue
injury (e.g., acute cortical necrosis of the kidney or digital gangrene).
In patients with chronic DIC because of metastatic carcinoma or aortic
aneurysm, continuous infusion of heparin 500 to 750 U/h without a
bolus injection may be sufficient

HEPARIN IN DIC
If no response is obtained within 24 hours, escalating dosages can be
used.
In hyperacute DIC cases, such as mismatched transfusion, amniotic
fluid embolism, septic abortion, and purpura fulminans, intravenous
bolus injection of 5000 to 10,000 U heparin may be given
simultaneously with replacement therapy with blood products.
Some experts would not administer a bolus dose of heparin even under
these circumstances.
Continuous infusion of 500 to 1000 U/h heparin may be necessary to
maintain the benefit until the underlying disease responds to
treatment

INHIBITORS OF FIBRINOLYSIS
Patients with DIC should not be treated with antifibrinolytic agents such as
∑-aminocaproic acid or tranexamic acid because these drugs block
fibrinolysis that preserves tissue perfusion in patients with DIC except in very
few occasions like
APL, giant hemangioma, heat stroke, amniotic fluid embolism, some forms of
liver disease, and metastatic carcinoma of the prostate provided
1) the patient is bleeding profusely and has not responded to replacement
therapy and
2) excessive fibrinogenolysis is observed
In such circumstances, use of antifibrinolytic agents should be preceded by
replacement of depleted blood components and continuous heparin infusion

TARGETS OF RESUSCITATION
pH-7.35-7.45
SBP-80-100mmhg MAP-60mmhg
Hb-7-9g
Platelets 20,000-30,000
INR<1.5
aPTT<42 Secs
Core Temperature>35C
Base Deficit<3
Lactate <2mEq/L

MASSIVE TRANSFUSION PROTOCOL
Studies show improved survival using Higher ratio of FFP to RBC
transfusion.
The ideal ratio of RBC:FFP/cryo:Platelets=1:1:1/2:1:1
-INDIAN JOURNAL OF ANAESTHESIA sept-oct 2015

Approach to DIC

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Approach to DIC

Similar to Approach to DIC (20)

More from ikramdr01

More from ikramdr01 (20)

Recently uploaded

Recently uploaded (20)

Approach to DIC