Symposium on Advances in Hematology

Disseminated Intravascular Coagulation: Current

Concepts
R. Kumar and V. Gupta1

Department of Medical Oncology/Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB,
Canada R3E, OVN
1
Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

ABSTRACT
Disseminated intravascular coagulation (DIC) is an acquired disorder in which normal hemostatic balance is disturbed. There
is excessive thrombin formation leading to fibrin deposition in microcirculation and consequent ischemic organ damage. The
etiology is multifactorial. A number of medical, surgical, oncological and obstetrical conditions can cause DIC. The diagnosis
is essentially clinical supported by laboratory parameters and a scoring system based on these. The mainstay of treatment
is correction of underlying cause and hemostatic support with replacement of coagulation factors. The role of heparin therapy
and other therapeutic options including activated protein C, antithrombin III etc. have also been discussed. [Indian J Pediatr
2008; 75 (7) : 733-738] E-mail : rajatkr@hotmail.com

Key words : Disseminated intravascular coagulation; Clotting factors; Coagulopathy

Disseminated intravascular coagulation (DIC) is an

acquired disorder, which, in its mildest form is an
aberration of laboratory parameters; while in its florid
acute form it gives rise to severe diffuse bleeding with
high mortality rate. DIC occurs when the normal
hemostatic balance is disturbed primarily by excessive
thrombin formation. It is a dynamic process triggered by
a variety of conditions causing activation of the clotting
cascade and generation of excess thrombin within the
vascular system, which in turn leads to deposition of
fibrin in the micro circulation. This definition implies that
microclot formation and consequent ischemic organ
failure and/or a hemorrhagic diathesis may occur. The
diagnosis and treatment of this disorder requires an
understanding of pathophysiology of thrombin
generation, awareness of the disorders which can trigger
DIC, clinical recognition of this condition and PAI - Plasminogen activator inhibitor Type-1
interpretation of laboratory data. Fig. 1. Coagulation Imbalance During Sepsis

PATHOPHYSIOLOGY (FIG. 1)
There are three main processes involved in the
pathogenesis of DIC1:
Initiation of fibrin deposition: Predominance of tissue
Correspondence and Reprint requests : Dr. Rajat Kumar,
Professor, Department of Medical Oncology/Hematology, Cancer
Care Manitoba, Professor, University of Manitoba, Winnipeg, MB,
Canada R3E, OVN. Tel. 204-787-8640
[Received May 27, 2008; Accepted May 27, 2008]
factor dependent (TF) coagulation pathway. The extrinsic
pathway exclusively mediates thrombin generation in
DIC. TF is expressed on monocytes and on endothelial
cells in sepsis. It binds to factor VII and activates it. TF/
factor VIIa complex activates factor X to factor Xa and
initiates the coagulation cascade. Inhibition of TF/factor
VIIa complex in experimental sepsis models showed
complete abrogation of thrombin generation and fibrin
deposition and in vivo studies have confirmed the
endotoxin induced TF expression on circulating
monocytes.

Indian Journal of Pediatrics, Volume 75—July, 2008 733

 R. Kumar and V. Gupta

2. Amplification of fibrin deposition: Defective thrombomodulin. Many of the effects of DIC like
physiological anticoagulation systems. Regulation of hypotension or acute lung injury may be due to the effects
thrombin normally occurs at 3 levels: level of of these cytokines per se.
thrombin and factor Xa by antithrombin (AT), level of
Etiology of DIC (Table 1)
cofactors V and VIII by activated protein C (APC),
level of TF/factor VIIa complex by tissue factor The list of diseases, which can be associated with DIC, is
plasminogen inhibitor (TFPI). extremely large. It is important to remember the main
(a) Thrombin is inactivated by antithrombin (AT) by
Table 1. Diseases Causing Acute or Chronic DIC
forming thrombin-antithrombin (TAT) complexes
which are rapidly cleared from circulation. Moreover, Causes Acute DIC Chronic DIC
thrombomodulin (TM) expressed on endothelial cells
Medical Septicemia / Infections Solid tumors
binds thrombin and inhibits its procoagulant activity.
Fulminant Hepatic failure Liver cirrhosis
During sepsis, the anticoagulant mechanisms are Allergic reactions Allergic reactions
severely compromised. Levels of AT are decreased Transplantation Vasculitis
due to inactivation by elastase released from Heat Stroke Kasabach-Merritt
activated neutrophils, rapid clearance of TAT syndrome
Hypothermia Adult respiratory
decreasing the availability of functional AT and
distress syndrome
decreased hepatic synthesis of AT2. Leukemia Leukemia
Homozygous protein
(b) Thrombin- TM complex activates protein C (PC).
C deficiency
Activated protein C (APC) rapidly dissociates from Snake bites
TM- thrombin complex and inactivates factor Va and Surgical Polytrauma Organ transplantation
factor VIIIa thereby decreasing thrombin generation. Major operations Aortic aneurysm
Free protein S potentiates the inhibitory capacity of Brain injury Vascular tumors
APC. APC also enhances fibrinolysis by Extracorporeal circulation
Thermal injury
neutralization of plasminogen activator inhibitor Fat embolism
type- I (PAI- I). Protein C levels are decreased Cardiac Bypass surgery
secondary to increased consumption, decreased Peritoneovenous shunt
hepatic synthesis, vascular leakage and activation of Obstetrics Amniotic fluid embolism Late gestation
cytokines like tumor necrosis factor (TNF) which and Abruptio placentae HELLP syndrome
Gynaecology Septic abortion Retained dead fetus
down regulate thrombomodulin on endothelial cells
Acute fatty liver
and decrease protein C activation. The anticoagulant Uterine rupture
effect of APC is also decreased secondary to low Toxemia of pregnancy
levels of free protein S which is complexed to plasma Septicemia
C4b binding protein, an acute phase reactant3. Transfusion Acute haemolytic
Medicine transfusion reaction
(c) Tissue factor plasminogen inhibitor (TFPI) levels are Massive Transfusion
moderately decreased in DIC. High doses of TFPI in Artificial surfaces
experimental models have caused complete
inhibition of endotoxin induced coagulation groups of illnesses causing DIC are: infections, obstetrical
activation. complications, malignancy and conditions involving
tissue necrosis such as trauma, ABO incompatible blood
3. Propagation of fibrus deposition: In habitation of transfusion and snakebite.
fibrinolysis due to increase in plasma levels of PAI-I.

As DIC continues, fibrinogen, prothrombin, platelets CLINICAL FEATURES

and other clotting factors are consumed beyond the
capacity of the body to compensate and bleeding ensues.
Role of cytokines
A common pathway for activation of coagulation
pathway in different diseases is the release of various
cytokines. DIC occurs as mediators are released from
macrophages, monocytes and endothelial cells to disturb
coagulation and fibrinolysis. TNF and interleukin- 1 (IL-
1) can cause production of tissue factor by endothelial
cells and monocytes while redicing the expression of
The diagnosis of DIC is mainly clinical. Laboratory tests
provide confirmatory evidence. The relative rates of
formation and breakdown of fibrin determine if the
patient is asymptomatic, having features of bleeding or
thrombosis, or both. Hemorrhage is the commonest
presentation characterized by spontaneous bruising,
muscle oozing, bleeding from venepuncture sites, and
secondary hemorrhage into surgical wounds. Usually
bleeding is associated with varying degrees of shock,
which is often out of proportion to the degree of blood

734 Indian Journal of Pediatrics, Volume 75—July, 2008

 Disseminated Intravascular Coagulation: Current Concepts

loss. Shock is probably due to activation of contact factor (b) Supportive tests: Increased FDPs or increased D-
XII that leads to production of bradykinin, and interaction dimers.
between cytokines like TNF and IL-1. Evidence of major
Fibrin degradation products do not differentiate
organ dysfunction is common, usually involving the
between degradation of cross linked fibrin or fibrinogen.
pulmonary, renal, hepatic and central nervous systems.
They are non specific and are also increased in trauma,
These features are due to a combination of factors, namely
recent surgery, hematoma, inflammatory conditions,
microvascular thrombi, shock and cytokine effects.
venous thromboembolism, hepatic and renal failure. D-
Acute DIC dimer is more specific for fibrin degradation. However,
the levels may be increased after recent surgery or in
This is the most common form of DIC seen in clinical
inflammatory conditions. Serial monitoring of D-dimer
practice. Bleeding manifestations predominate and can be
asays are of value in evaluation of response to therapy.4
normally progressive. In some patients large acral
cyanosis is seen due to thrombic occlusion of dermal No single test is diagnostic of DIC and it is the overall
vessels. clinical picture supported by some investigations, which
should guide the management. Of these tests,
Chronic DIC
thrombocytopenia and hypofibrinogenemia (or a 50%
This occurs from a weak or intermittent activating drop in either value) are the most sensitive in making a
stimulus. The destruction and production of clotting laboratory diagnosis of DIC.
factors and platelets is balanced, so that the DIC is
A scoring system that uses simple laboratory tests has
considered to be compensated. Chronic DIC is most
recently been published by the subcommittee on DIC of
commonly seen in patients with intrauterine fetal death,
the International Society on Thrombosis and Hemostasis
adenocarcinoma and other tumors, giant hemangiomas
(Table 2). The presence of an underlying disorder known
and certain types of vasculitis. Patients may have
to be associated with DIC is pre-requisite for the use of the
recurrent episodes of ecchymosis or mild bleeding and
algorithm. A score of greater than or equal to five is
thrombophlebitis at unusual sites. Trousseau’s sign is a
considered compatible with DIC.5
form of chronic DIC.

TREATMENT
LABORATORY FEATURES

Theoretically, intervention at the various

The number of sophisticated tests, which can be done in
DIC are very large, but most of them are not available to
clinicians working in routine hospital setting. In most
cases a diagnosis of DIC can be made with the following
tests:
(a) Screening tests: Peripheral blood film examination –
showing low platelets and schistocytes, platelet count
– thrombocytopenia, prothrombin time (PT) –
prolonged, activated partial thromboplastin time
(APTT) – prolonged, thrombin time (TT) - prolonged,
fibrinogen levels – low.
pathophysiologic steps involved in the genesis of DIC
should be of benefit, but clinical trials have revealed only
a few measures to be of therapeutic use.
1. Treatment of Underlying Cause and General Care
The disease causing DIC should be vigorously treated to
reverse the process. For example, in case of sepsis,
antibiotics should be started, and if a snake bite is the
precipitating factor, antisnake venom should be initiated.
Tissue perfusion and respiratory function must be
maintained by replacing intravenous fluid and providing

TABLE 2. The Disseminated Intravascular Coagulation Score, Diagnostic Algorithm for the Diagnosis of Overt DIC (ISTH Criteria)

1. Risk assessment. Does the patient have an underlying disorder known to be associated with DIC. If yes, proceed. If no, do not
use this algorithm
2. Order global coagulation tests (platelet count, PT, fibrinogen, soluble fibrin monomers / FDPs
3. Score global coagulation test results
a. Platelet count: (>100,000/cumm=0; 50,000-100,000/cumm=1; 50,000/cumm=2)
b. Elevated fibrin-related marker (eg: soluble fibrin monomers / fibrin degradation products)*: (no increase=0, moderate
increase=2, strong increase=3)
c. Prolonged prothrombin time (<3 sec=0, >3 but<6 sec=1, >6 sec=2)
d. fibrinogen level : (>Ig/L=0, <lg/L=1)
4. Calculate score
5. a. If score >5 : compatible with overt DIC; repeat scoring daily
b. If <5 suggestive (not affirmative) of non-overt DIC; repeat in 1-2 days

* In the prospective validation studies D-dimer assays were used and a value above the upper limit of normal was considered
moderately elevated, whereas a value above 5 times of normal was considered as a strong increase.

Indian Journal of Pediatrics, Volume 75—July, 2008 735

 R. Kumar and V. Gupta

oxygen support to correct hypoxia. Folic acid deficiency TABLE 4. Coagulation Factors and Their Half Life
can develop acutely in the critically ill leading to impaired
Factor Plasma Half life Frequency of
platelet production, and should be supplemented 6 . replacement of FFP/
Coagulopathy may be contributed by vitamin K Factor concentrate
deficiency and 10mg on two consecutive days should be
given. VII 5-6 hr. BD or TID
VIII 8 – 12 hr. BD
2. Hemostatic Support (Replacement Therapy) IX 18 – 24 hr. OD
II (Prothrombin) 65 hr. (2.5 days) OD or less frequent
In patients who have low levels of platelets, fibrinogen I (fibrinogen) 90 hr. (3.5 days) OD or less frequent
and other clotting factors as shown by prolonged PT, V 12 – 15 hr. OD (factor is attached to
APTT, TT, replacement of these factors is useful. platelet membrane)
Although there have been some concerns that this X, XI, XII, XII 36 hr. or more OD
replacement provides ‘fuel to the fire’, there are no clinical
data to support these concerns. Replacement therapy is
not indicated if there is no clinical bleeding and no consumption and whether the DIC is coming under
invasive procedures are planned. If a patient is bleeding control. Replacement can be stopped when there is a rise
or a procedure is required, then an attempt to restore in platelet counts, fibrinogen levels and a fall in FDPs.
hemostatic capacity by replacing platelets and 3. Heparin Therapy
coagulation factors is indicated.6
The use of heparin is theoretically attractive as it should
Measuring the concentration of platelets and stop formation of thrombin and the process of DIC, but in
fibrinogen and assessing the prothrombin time and actual practice this benefit is rarely seen. For a patient
activated partial thromboplastin time are essential for who is actively bleeding, heparin would aggravate the
guiding management. Replacement is monitored by the bleeding before any potential benefits. In most of the
immediate effect after transfusion and a few hours later to typical acute DIC situations (which include 95% or more
determine the need to continue further replacement. of the patients) heparin therapy has not proved to be
The different blood components available are shown in useful and may be harmful. Heparin has been shown to
Table 3 and Table 4. The components commonly used in have a beneficial effect in small, uncontrolled studies of
DIC are: fresh frozen plasma (FFP), cryoprecipitate, patients with disseminated intravascular coagulation, but
platelet concentrates and packed red cells or whole blood. not in controlled clinical trials. There are some limited
The initial dose given in table 3 is a rough guides and indications of heparin therapy:
further doses would vary depending on the degree of (a) Chronic DIC of malignancy (Trousseau’s syndrome)

TABLE 3. Blood Component Therapy

Component Constituents Indication Dose Precautions

Fresh frozen All coagulation
Plasma (FFP) Factors in normal
plasma. 0.7-1.0 U/ml of
factors II, V, VII, VIII,
IX, X, XI, XII, XIII and
2.5 mg/ml fibrinogen
Cryoprecipitate Fibrinogen (150 mg/bag),
Factors VIII (80-120
units/bag), Factor XIII,
vWF
Fresh blood All components of blood
Random donor Platelets : contains at least
Platelets (RDP) 5.5 x 1010 platelets
Single donor Platelets, contains at least
platelets (SDP) 3 x1011 platelets
Treatment of any 15 ml/kg or 1 bag Infuse soon after thawing,
coagulation factors per 10 kg as initial Fluid overload may need
deficiency (prolonged dose (25-30% frusemide, ABO
PT, PPTK), in TTP replacement of compatibility needed
Prolonged PT, PTTK, coagulation factors)
TT
Fibrinogen deficiency or 1 bag per 5 kg will raise
consumption; Factor fibrinogen levels by 70
VIII deficiency mg/dl
(Hemophilia A); VWD;
Factor XIII deficiency
To replace acute blood As indicated Not a good source to replace
loss platelets or coagulation
factors
Thrombocytopenia One unit raises platelet Infuse rapidly, do NOT
counts by 5-10,000/ cu refrigerate prior to
mm. Dose 1 unit/10 kg transfusion
to raise counts by 30,000
to 50,000/cu mm
Thrombocytopenia One collection is Precaution as for RDP
equivalent to
approximately 6 units
of random platelets
(RDP)

736 Indian Journal of Pediatrics, Volume 75—July, 2008

 Disseminated Intravascular Coagulation: Current Concepts
(b) Patients with clinical evidence of fibrin deposition
such as dermal necrosis in purpura fulminans, acral
ischemia or those with venous thromboembolism.
(c) Retained dead fetus with hypofibrinogenemia.
(c) In AML-M3, prior to initiation of chemotherapy.
However, heparin is hardly used nowadays with the
use of ATRA therapy for this leukemia.
(d) Excessive bleeding associated with giant
hemangioma.
(e) When the patient does not demonstrate rise in
platelet count and coagulation factors following
replacement therapy and continues to bleed,
implying ongoing consumption. In this situation
heparin may reduce consumption of clotting factors
by inhibiting thrombin formation, and replacement
therapy would then succeed in stopping the bleeding.
It is important to continue the replacement therapy
along with heparin and monitor the effect of heparin
by repeated platelet counts, fibrinogen levels and PT,
APTT and TT. When prescribed, the dose of heparin
is usually 15 units/Kg/hr by continuous infusion or
300 to 500 units per hour.7 There are no data on dose
response and the coagulopathy makes it extremely
difficult to monitor treatment.
4. New therapeutic strategies
Activated Protein C
Due to the crucial role of APC pathway in the
pathogenesis of sepsis, APC substitution seems to be a
promising treatment. In a phase III clinical trial of
recombinant APC (rAPC) in patients with severe sepsis in
a dose of 24 µg/Kg/h over 96 h, significant reduction in
28 day mortality was seen. However, the incidence of
serious bleeding events was higher in the rAPC group
than the placebo group.8, 9
The drug was used in 188 children (term newborn to
<18 years) in the same dose as the earlier study. 4 day
mortality was 7% and 28 day mortality 13.4% respectively.
It was concluded that no efficacy conclusions were
possible without a placebo group. The most significant
complication was bleeding.10 The guidelines for the use of
activated protein C are available and it is recommended in
patients with severe sepsis and clinical assessment of risk
of death.11, 12
5. Antithrombin (AT III)
The circulating levels of AT are low in DIC, therefore
supplementation should improve the outcome. In a large
double blind placebo controlled multicentre phase III trial
(Kybersept trial) AT was used in a dose of 30,000 IU over
4 days.13 There was no difference in mortality between the
treatment and the placebo group. Moreover, patients
treated with AT had more bleeding complications. It was
speculated that concomitant use of heparin with AT was
responsible for more bleeding complications. Another
Indian Journal of Pediatrics, Volume 75—July, 2008
study evaluated the role of AT without concomitant
heparin in patients with severe sepsis with or without
DIC. It was found that AT significantly reduced the
mortality in patients with DIC.14 However, further studies
are needed to confirm these findings.
6. Tissue factor pathway inhibitor (TFPI)
Since TF/factor VIIa pathway plays a major role in
coagulation activation in sepsis, TFPI substitution seems
to be a reasonable option. It was tested in a phase III trial
in patients with severe sepsis. Tifacogin (TFPI) was given
in a dose of .025mg/kg/hr for 96 hrs.15 There was no effect
on mortality and the risk of bleeding was increased.
Protease inhibitors
Gabexate mesylate is a synthetic inhibitor of serine
proteases, including thrombin and plasmin. It would
therefore seem to be a potentially useful agent for treating
disseminated intravascular coagulation. In a limited
number of patients, the drug (2mg/kg/hr x 7 days) could
not inhibit coagulation or fibrinolysis, improve the DIC
score or reduce mortality in pre or mild DIC.16
7. C1- Inhibitor (C1- Inh)
Activation of factor XIa leads to a thrombin burst,
therefore inhibition of factor XIa by C1 inhibitor might be
beneficial. In a pilot study with limited number C1-
inhibitor patients, C1- Inh was administered to patients
with severe sepsis or septic shock. Organ dysfunction
improved significantly but no effect on mortality was
observed due to small number of patients.
8. Synthetic Inhibitors
Heparin treatment may be ineffective because it requires
antithrombin for anticoagulant activity and this is usually
reduced in DIC. Direct thrombin inhibitors may be more
effective as they do not require antithrombin.
Recombinant hirudin reduces thrombin activity in DIC,
but clinical benefit has not yet been evaluated. Novel
antithrombin III – independent inhibitors of thrombin
such as desirudin and related compounds, might be more
effective than heparin, and experimental studies have had
promising results. However, there have not yet been any
controlled clinical trials of these drugs in patients with
DIC and the relatively high risk of bleeding associated
with the use of these compounds may be the limiting
factor.
Data was collected on 140 patients (M 78, F 62) with
DIC at All India Institute of Medical Sciences, New Delhi.
The age distribution was 0-10 years (5), 11-20 (15), 21-30
(30), 31-40 (25), 41-50 (20), 51-60 (20), >60 (25). Medical
problems (septicemia, pneumonia, renal/liver disease)
were seen in 49% patients whereas oncological conditions
were seen in 25%. Of these, hematological malignancies
(AML, ALL, Lymphoma) were responsible for 16.5% and
others (gliomas, Ca ovary, breast, liver) for 8.5%. Surgical
737
 R. Kumar and V. Gupta

conditions (trauma, major surgery) accounted for 21% monomer and soluble fibrin in disseminated intravascular
and obstetric and gynaecological conditions for 5% cases. coagulation. Semin Thromb Hemost 2001; 27 : 657-666.
5. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M. Towards
The hematological profile was as follows:
definition, clinical and laboratory criteria and a scoring system
Hb 6.0 - 10.5 g/dl for disseminated intravascular coagulation. Thromb Haemost
2001; 86: 1327-1330.
Platelets <150 x 109/L 65 (46.5%) 6. Baglin T. Disseminated intravascular coagulation: diagnosis
150 – 400 x 109/L 75 (53.5%) and treatment. BMJ 1996; 312 : 683-687.
7. Levi M, TenCate H. Disseminated intravascular coagulation.
Prothrombin time increased 140 (100%)
N Engl J Med 1999; 341: 586-592
APTT increased 136 (97.8%) 8. Dhainaut JF, Yan SB, Cariou A, Mira JP. Soluble
TT increased 137 (98%) thrombomodulin, plasma derived unactivated protein C and
recombinanat human activated protein C in sepsis. Crit Care
D dimer increased 140 (100%) Med 2002; 30: 318-324.
9. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF,
Lopez-Rodriguez A et al. Efficacy and safety of recombinant
CONCLUSION human activated protein C for severe sepsis. N Eng J Med
2001; 344 : 699-709.
The pathogenesis of DIC is based on tissue factor 10. Goldstein B, Nadel S, Peter M, Barton R, Machado F, Levy H
mediated initiation of systemic coagulation activation that et al. ENHANCE: results of a global open-level trial of
drotrecogin alfa (activated) in children with severe sepsis.
is insufficiently contained by physiologic anticoagulant Pediatr Crit Care Med 2006; 7: 277-278.
pathways and amplified by impaired endogenous 11. Camporota L, Wyncoll D. Practical aspects of treatment with
fibrinolysis. The etiology is multifactorial and the drotrecogin alfa (activated). Crit Care 2007; 11 suppl 5: S7.
diagnosis is mainly clinical supported by laboratory tests 12. Dellinger RP. Surviving sepsis campaign: International
and scoring algorithms. The mainstay of management is guidelines for management of severe sepsis and septic shock.
Crit Care Med 2008; 36: 1394-1396.
treatment of the underlying condition. The supportive
13. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I et al.
treatment is aimed at replacement of coagulation factors Caring for the critically ill patient. High dose anti-thrombin III
and platelets. There is limited role of anticoagulation and in severe sepsis: a randomized controlled trial. JAMA 2001;
the newer therapies still need more evidence. 286 : 1869-1878.
14. Kienast J, Juers M, Wiedermann CJ, Hoffmann JN, Ostermann
H, Strauss R et al. Treatment effects of high-dose anti
REFERENCES thrombin without concomitant heparin in patients with severe
sepsis with or without disseminated intravascular
coagulation. J Thromb Haemost 2006; 4 : 90-97.
1. Franchini M. Pathophysiology, diagnosis and treatment of 15. Abraham E, Reinhart K, Opal S, Deineyer I, Daig C,
disseminated intravascular coagulation: un update. Clin Lab Rodriguez AL et al. OPTIMIST Trial study group. Efficacy and
2005; 5 : 633-639. safety of tifacogin (recombinant tissue factor pathway
2. Hambleton J, Leung LL, Levi M. Coagulation: consultative inhibitor) in severe sepsis: a randomized controlled trial.
hemostasis. Hematology 2002; 2002 : 335-352. JAMA 2003; 290: 238-237.
3. Zeerleder S, Hack E, Wuillemin WA. Disseminated 16. Nishiyama T, Matsukawa T, Hanaoka K. Is protease inhibitor
intravascular coagulation in sepsis. Chest 2005; 128: 2861-2875 a choice for the treatment of pre or mild disseminated
4. Horan JT, Francis CW. Fibrin degradation products, fibrin intravascular coagulation? Crit Care Med 2000; 27: 657-666.

738 Indian Journal of Pediatrics, Volume 75—July, 2008