Disseminated intravascular coagulation in infants and children

Authors: Wendy Wong, MD, Bertil Glader, MD, PhD

Section Editor: Donald H Mahoney, Jr, MD
Deputy Editor: Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Dec 2018. | This topic last updated: Feb 27, 2018.

INTRODUCTION — Disseminated intravascular coagulation (DIC) is an acquired syndrome

characterized by hemorrhage and microvascular thrombosis. Endothelial tissue damage
from a variety of underlying disorders (eg, sepsis, trauma, and malignancy) activates the
coagulation cascade, which promotes fibrin production and deposition, and consumption of
clotting factors. The subsequent consumption of coagulation factors and platelets,
inhibition of natural anticoagulants and fibrinolysis, and fibrin deposition result in the
clinical picture of DIC of a bleeding diathesis accompanied by microvascular thrombosis
that often leads to end organ damage (figure 1 and figure 2).

The etiology, clinical manifestations, diagnosis, and treatment of DIC in infants and children
will be reviewed here. DIC in adults is discussed separately. (See "Clinical features,
diagnosis, and treatment of disseminated intravascular coagulation in adults".)

PATHOGENESIS — The following is a summary of the pathogenesis of disseminated

intravascular coagulation (DIC). A more complete discussion is found elsewhere. (See
"Clinical features, diagnosis, and treatment of disseminated intravascular coagulation in
adults", section on 'Pathogenesis'.)

DIC is a secondary process caused by the systemic activation of the coagulation system by
tissue damage from a variety of underlying diseases (eg, sepsis, trauma, and malignancies)
[1]. The activation of the intravascular coagulation system initiates the following processes
(figure 1):

● Exposure of blood to procoagulants – Tissue damage from the initiating primary

disease releases procoagulants into the bloodstream.

● Formation of fibrin in the circulation – Tissue procoagulants activate hemostasis

primarily through the interaction of tissue factor and Factor VII, which promotes fibrin
formation and deposition within the microcirculation.

● Fibrinolysis – Fibrin formation activates the fibrinolysis pathway, which produces

plasmin that cleaves fibrinogen and fibrin, thereby generating fibrin degradation
 products (FDPs). FDPs interfere with fibrin polymerization and impair platelet
aggregation.

● Depletion of clotting factors and platelets – Ongoing activation of the coagulation

system and fibrin deposition consume clotting factors and platelets.

● End-organ damage – Deposition of fibrin into the microcirculation of organs results in

tissue ischemia and damage.

● Hemolysis – Intravascular fibrin strands cause mechanical shearing of red blood cells
resulting in microangiopathic hemolytic anemia (picture 1).

ETIOLOGY — Disseminated intravascular coagulation (DIC) occurs in a variety of clinical

conditions (table 1). In older infants and children, the major causes of DIC include sepsis,
trauma, and malignancies. In the neonate, DIC is caused primarily by sepsis and perinatal
complications (eg, birth asphyxia).

Older infants and children — The following discussion is a summary of the causes of DIC in
older infants and children, which are similar to those seen in adults. The pathogenesis of
each of these etiologies is discussed in greater detail elsewhere. (See "Clinical features,
diagnosis, and treatment of disseminated intravascular coagulation in adults", section on
'Causes of DIC'.)

Sepsis — Sepsis is the most common cause of DIC in older infants and children. DIC was
classically recognized as a complication of endothelial damage produced by
meningococcemia. Viral, rickettsial, fungal, parasitic, and other bacterial infections are also
associated with DIC (table 1). (See "Clinical manifestations of meningococcal infection",
section on 'Disseminated intravascular coagulation'.)

Trauma and tissue injury — In children, DIC potentially is a serious complication of any
major trauma or tissue injury. These include crush injury, massive burns, extensive surgery,
severe hypothermia, heat exhaustion, and shock. In all these cases, release of tissue
enzymes and phospholipids from damaged tissue into the systemic circulation triggers
activation of the coagulation system. Brain tissue is a potent thromboplastin and patients
who sustain severe brain injury are especially at risk for DIC.

Malignancy — In children with leukemia, laboratory abnormalities in the clotting system

are common [2,3]. DIC is rare in children with acute lymphocytic leukemia, although it has
been reported in patients with the uncommon t(17;19) translocation [4]. Patients with acute
promyelocytic leukemia can present with acute hemorrhage due to DIC. In these patients,
granules within the blast cells contain procoagulants that directly trigger the coagulation
system [5]. (See "Overview of the complications of acute myeloid leukemia".)
Children with malignancies are often leukopenic and may develop DIC secondary to sepsis.

Miscellaneous — Other causes of DIC in children include:

● Acute hemolytic transfusion reactions — Release of adenosine diphosphate and

phospholipids from the hemolyzed red cell activate platelet and the coagulation
system respectively.

● Kasabach Merritt (KM) syndrome — Patients with kaposiform hemangioendothelioma,

an aggressive form of giant hemangioma, can develop KM syndrome, a localized form
of DIC. The large hemangioma consumes fibrinogen and platelets resulting in
thrombocytopenia and consumptive coagulopathy. (See "Extracorpuscular non-immune
hemolytic anemia: Fragmentation hemolysis and hypersplenism", section on 'Kasabach
Merritt syndrome'.)

● Snake and spider bites — The venom of some snakes and spiders (eg, rattlesnakes and
Russell's viper) can directly activate the coagulation system and lead to DIC.

● Liver disease — DIC may be seen in patients with acute or chronic hepatocellular
disease including Reye's syndrome [6].

Neonates — Newborn infants, particularly preterm infants, are vulnerable to DIC because

the anticoagulants (antithrombin and protein C) are normally low at this age [7-10]. The
main causes of DIC include sepsis, birth asphyxia, respiratory distress syndrome (RDS), and
necrotizing enterocolitis (NEC) [11].

Sepsis — Neonatal viral infections (eg, rubella, herpes, cytomegalovirus, and enterovirus),

systemic candidiasis, and bacterial sepsis (eg, Group B streptococcus and gram-negative
organisms) are causes of neonatal DIC. Perinatal acquired infections (eg, TORCH
infections) are also associated with DIC.

Perinatal conditions — Perinatal conditions associated with DIC include complications

from pregnancy and delivery that lead to birth asphyxia, and diseases linked to prematurity
[12].

● Obstetric complications — Obstetric complications resulting in fetal anoxia/birth

asphyxia may cause neonatal DIC. These include abruptio placentae, preeclampsia,
eclampsia, and fetal distress during labor.

● Conditions associated with prematurity — DIC is associated with necrotizing

enterocolitis (NEC) and respiratory distress syndrome (RDS), both of which are seen
more frequently in premature infants. In patients with NEC, ischemic bowel tissue
releases tissue factor, which activates the coagulation system. Patients with severe
RDS are also at risk for DIC presumably due to tissue damage from hypoxia. Autopsy
 studies in preterm infants with RDS have demonstrated fibrin deposition not only in the
lungs but also the liver and kidney [13]. (See "Neonatal necrotizing enterocolitis:
Clinical features and diagnosis".)

● Miscellaneous — Rare causes of neonatal DIC include hypothermia and massive

hemolysis, such as seen in Rh incompatibility.

Congenital disorders — Congenital homozygous deficiency of protein C and S can

present in the neonatal period with DIC and purpura fulminans, while neonates who have
large hemangiomas can develop Kasabach Merritt syndrome. (See "Pathogenesis, clinical
features, and diagnosis of thrombosis in the newborn", section on 'Purpura fulminans' and
"Extracorpuscular non-immune hemolytic anemia: Fragmentation hemolysis and
hypersplenism", section on 'Kasabach Merritt syndrome'.)

CLINICAL MANIFESTATIONS — Although the clinical spectrum and causes of disseminated

intravascular coagulation (DIC) are variable in infants and children, the pathophysiology is
the same, with an overwhelmed hemostatic system that is unable to compensate for the
ongoing consumption of clotting factors and platelets. In these patients, clinical bleeding
and microthrombosis occur, and coagulation tests are often abnormal.

Clinical findings vary depending on the severity of DIC. In mild cases, bleeding may only be
noted at venipuncture sites, but in more severe cases there may be extensive hemorrhage
and thrombosis with end-organ damage to the kidney, liver, lung, extremities, and central
nervous system. Hemorrhage is the most common presentation followed by skin
manifestations of purpura and acral gangrene (purpura fulminans).

In neonates, the most common sites of bleeding are the gastrointestinal tract and
venipuncture sites [14]. In severe cases, intrapulmonary and intraventricular hemorrhages
occur. Risk factors for DIC in neonates include prematurity, low birth weight, and low Apgar
scores [12].

LABORATORY FINDINGS — Laboratory findings in DIC are classified based upon the

pathologic process:

● Consumption of coagulation factors and platelets

● Increased fibrin formation

● Increased fibrinolysis

The range of laboratory abnormalities seen in DIC are described in the following sections.
Not all affected patients have all of these abnormalities. Performing a comprehensive
evaluation that includes all of these tests is generally not necessary to make the diagnosis.
In our practice, the initial evaluation includes the following tests (see 'Laboratory evaluation'
below):

● Complete blood count (CBC)

● Prothrombin time (PT)

● Activated partial thromboplastin time (aPTT)

● D-dimer level

● Fibrinogen level

Consumption — Tests that show consumption of clotting factors and platelets include the
following (figure 2):

● Platelet count — Thrombocytopenia (platelet count <100,000/microL) usually is present

in patients with DIC. On the peripheral smear, platelets are large, suggesting a
destructive process (picture 1).

● PT — The PT is prolonged in 50 to 75 percent of cases [15]. A prolonged PT reflects a

reduction in the activity of the extrinsic and common coagulation pathways.

● aPTT — The aPTT is prolonged in 50 to 60 percent of cases [15]. A prolonged aPTT

reflects a reduction in the activity of the intrinsic and common coagulation pathways.

● Factor V and VIII levels — Both Factor V (common coagulation pathway) and factor VIII
(intrinsic pathway) are decreased (figure 2).

Some patients with DIC will have a normal PT and aPTT as noted above. This may be due to
circulating activated clotting factors such as thrombin and factor Xa [15].

Fibrin formation — Studies indicative of fibrin formation include:

● Fibrinogen — When the fibrinogen concentration is low, it is consistent with a diagnosis

of DIC due to its consumption in the formation of fibrin. However, fibrinogen is not a
sensitive test for DIC because it is also an acute phase reactant. When the
concentration is normal, it may represent a significant decrease in a patient whose
fibrinogen level should be higher because of the inflammation from his or her
underlying disease.

● Thrombin time — Thrombin time is prolonged when the fibrinogen concentration is low.
FDPs also impair fibrin formation, thereby prolonging the thrombin time.
 ● Microangiopathic hemolytic anemia — Microangiopathic changes on the peripheral
smear are suggestive of DIC and are due to mechanical shearing of red blood cells by
intravascular fibrin strands (picture 1).

Fibrinolysis — DIC is unlikely if there is no evidence of fibrinolysis as indicated by the

following:

● D-dimer — D-dimer is a neoantigen produced when cross-linked fibrin is degraded by

plasmin. It is elevated in 90 percent of patients with DIC and is more specific than fibrin
degradation products (FDPs) [15].

● Fibrin degradation products — FDPs are products of plasmin degradation of fibrinogen

and fibrin [15]. They are present in 85 to 100 percent of patients with DIC. However
FDPs are not a specific test, since they are also present in patients who have systemic
lupus erythematous, necrotizing enterocolitis, thrombotic events from causes other
than DIC, and in some individuals taking oral contraceptives.

Other studies — DIC is also characterized by decreased levels of antithrombin, and protein

C and S, which lead to impairment of the anticoagulant pathway. Despite the decreased
concentration of these anticoagulants, their measurement generally is not helpful in clinical
management.

Other tests for DIC that are not widely available or not routinely used include markers of
procoagulant activation (eg, prothrombin fragment 1.2, fibrinopeptide A and fibrinopeptide
B, and thrombin-antithrombin complexes) and measures of fibrinolysis (eg, elevated levels
of plasmin and plasmin-antiplasmin complex).

Neonates — In neonates, establishing normal values for clotting factors and coagulation
tests have been hampered by:

● Changes in concentration of coagulation factors and coagulation test values with

gestational and postnatal age.

● Difficulties in obtaining adequate control groups of healthy preterm and term infants.

Normal ranges for coagulation tests and concentrations of specific clotting factors have
been reported for full-term infants and preterm infants (>30 weeks gestation) from birth to
six months postnatal age (table 2 and table 3) [9,10]. These values are based upon studies
that included 72 term infants [9], 70 preterm infants born at 34 to 36 weeks gestational age
(GA), and 67 infants born at 30 to 33 weeks GA [10]. In extremely preterm infants (GA <27
weeks), factor V and VIII are higher than vitamin K-dependent clotting factors. The level of
vitamin K-dependent factors also increases with increasing gestational age [16].
When interpreting coagulation tests in neonates, it is imperative to recognize the
differences in the normal values of coagulation tests between the neonatal and adult
patient [7]. As an example, aPTT is normally prolonged in term infants at birth compared to
adults (mean values, 42.9 ± 11.6 versus 33.5 ± 6.8 sec, respectively) [9]. This difference is
even greater in the preterm infant (mean value for infants 30 to 36 weeks gestation, 53.6 ±
26.1) [10]. The aPTT in both preterm and term infants decreases to adult values by six
months of age.

Physiologic levels of factors V, VIII, and fibrinogen in term infants are similar to those in
adults and can serve as diagnostic markers for DIC in this age group [7]. In preterm infants,
fibrinogen concentration is low and D-dimer is commonly present without DIC, limiting their
value in the diagnosis of DIC. In addition, neonates have relatively decreased amounts of
plasma due to their higher hematocrit levels and therefore it is imperative that the correct
anticoagulant to plasma ratio is obtained in the blood specimens to ensure accurate
testing.

DIAGNOSIS — The diagnosis of overt disseminated intravascular coagulation (DIC) is based

on both clinical findings (eg, hemorrhage and microthrombi in a patient with a predisposing
medical condition) and abnormal coagulation studies.

Laboratory evaluation — Although laboratory studies are used to support the diagnosis,

there is no single test that is sensitive or specific enough to assure a definite diagnosis [17].
A reasonable panel of coagulation studies to establish the diagnosis includes:

● Complete blood count

● Prothrombin time (PT)

● Activated partial thromboplastin time

● D-dimer level

● Fibrinogen level

Serial measurements of coagulation parameters are more informative than a single

assessment. As an example, a PT in the upper normal range but considerably longer than
an earlier measurement reflects the consumptive process of DIC and not a normal
hemostatic state. Serial measurements of platelet counts that document a downward trend
are a sensitive but not specific sign for DIC [18].

Adding to the challenge of establishing the diagnosis, every patient with DIC does not have
positive findings consistent with DIC in all laboratory studies. The most helpful tests
clinically are those that indicate the presence of fibrinolysis (eg, D-dimer). As previously
discussed, D-dimer is a more specific test for DIC than fibrin degradation products. The
latex agglutination assay for D-dimer is commonly used and is one of the more reliable
tests.

While not routinely required for the diagnosis, decreased levels of factors V and VIII help
substantiate the diagnosis of DIC. Factor VIII levels can be used to distinguish DIC from
coagulopathy associated with severe liver disease. Factor VIII is not produced by
hepatocytes and thus is often low in DIC and increased or normal in liver disease. (See
"Hemostatic abnormalities in patients with liver disease", section on 'Liver disease versus
DIC'.)

Scoring systems — Various scoring systems have been developed to assist in diagnosing

DIC. These scoring systems have been validated largely in adult patients and there are
limited data available in pediatric patients.

● International Society on Thrombosis and Haemostasis – The International Society on

Thrombosis and Haemostasis (ISTH) scoring system is one of the most widely used
methods. It assesses patients with an underlying medical condition known to be
associated with DIC (table 1) and is based upon readily available global coagulation
tests (platelet count, FDPs, PT, and fibrinogen) (table 4) [19]. Scores are dependent on
the degree of abnormality measured by each test (eg, a platelet count <50,000/microL
is scored higher than <100,000/microL).

● Japanese Association for Acute Medicine – The Japanese Association for Acute
Medicine (JAAM) scoring system for DIC is similar to the ISTH system in that it uses
the same four laboratory parameters (platelet count, FDPs, PT, and fibrinogen) (table 5)
[20,21]. However, the JAAM scoring system places more attention on trends in platelet
counts rather than a single measurement.

Both the ISTH and JAAM scoring systems have been validated in adult patients and have
been found to correlate with mortality and morbidity risk [22-24]. Limited pediatric data
suggest that these scoring systems perform reasonably well in pediatric patients [25-27].
Despite a lack of robust data, these scoring systems are routinely used in the pediatric
intensive care unit setting. There are no available data on the use of DIC scoring systems in
neonates.

Neonates — Similar to older patients, the diagnosis of DIC in the neonate relies on abnormal
global coagulation tests in the appropriate clinical setting [28]. However, it is more difficult
to establish the diagnosis of DIC in these neonates. Testing is limited because the volume
of blood required may be difficult to obtain in the neonate. In addition, the interpretation of
these studies in the neonate is challenging as the hemostatic system is still in a state of
flux at birth with physiologic alterations of coagulation and fibrinolysis. As a result, the
diagnosis of DIC in the neonate may rely more heavily on the patient's clinical
manifestations than on laboratory studies. The recognition of the underlying condition
rather than establishing the diagnosis of DIC is more important as the most important
therapeutic intervention is to treat the underlying disorder. (See 'Neonates' above and
'Treatment' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for disseminated intravascular

coagulation (DIC) is broad and includes other diseases associated with bleeding
symptoms, abnormal coagulation tests, and/or thrombocytopenia. The history, clinical
setting, and laboratory evaluation, usually differentiate DIC from other causes.

● Bleeding symptoms/coagulopathy – Hepatic failure and vitamin K deficiency have

similar clinical findings as those with DIC, but the platelet count is typically normal. The
diagnostic approach to the child presenting with bleeding symptoms is summarized in
the algorithm and reviewed in detail separately (algorithm 1). (See "Approach to the
child with bleeding symptoms".)

● Thrombocytopenia – In children, the main cause of destructive thrombocytopenia is

immune thrombocytopenia (ITP). In contrast to DIC, patients with ITP are typically
otherwise well-appearing and coagulation tests are normal. (See "Immune
thrombocytopenia (ITP) in children: Clinical features and diagnosis".)

Other causes of thrombocytopenia in children are summarized in the table (table 6).
The diagnostic approach to the child presenting with thrombocytopenia is reviewed in
detail separately. (See "Approach to the child with unexplained thrombocytopenia" and
"Causes of thrombocytopenia in children".)

In the neonate, causes of consumptive thrombocytopenia include alloimmune neonatal

thrombocytopenia, maternal idiopathic thrombocytopenia, renal vein thrombosis, and
infections. Causes of thrombocytopenia in neonates are reviewed in detail separately.
(See "Causes of neonatal thrombocytopenia".)

TREATMENT — Disseminated intravascular coagulation (DIC) is a serious complication of

the underlying primary disease. As a result, successful treatment of DIC is dependent on
identifying and treating the underlying cause, thereby removing the triggering factors
implicated in the DIC process. In some cases, successful treatment of the underlying cause
will lead to resolution of DIC. In others, despite vigorous therapy directed towards the
primary disease, coagulation abnormalities persist resulting in significant hemorrhage
and/or thrombosis with organ damage. These patients have a high rate of mortality, and as
a result, commonly receive DIC supportive therapy.

There is no consensus on how supportive therapy should be used due to the paucity of
data. In general, supportive care is divided into component replacement and
anticoagulation therapy. Treatment is individualized based upon a patient's age, severity of
clinical symptoms, underlying primary disorder, and overall clinical status.

Replacement therapy — There have been no randomized controlled trials to study the

efficacy of platelet, fresh frozen plasma (FFP), or cryoprecipitate transfusions in children or
adults with DIC. Nevertheless, the use of these agents seems rational in patients with
significant bleeding due to thrombocytopenia and clotting factor consumption [29].

Our approach for replacement therapy in patients with DIC is as follows:

● Indications – Replacement therapy is indicated in patients with DIC who have clinically
significant bleeding symptoms or who are at high risk for bleeding because of an
impending invasive procedure. Examples of clinically significant bleeding may include
gastrointestinal bleeding (not merely a positive guaiac test), prolonged bleeding from
venipuncture sites, prolonged epistaxis, or prolonged bleeding after suctioning the
endotracheal tube.

● Goals – The aim of replacement therapy is to reduce or stop significant bleeding, not to
normalize laboratory tests (which often is impossible). Reasonable goals for the
judicious use of blood components in the setting of clinically significant bleeding
include maintaining platelet counts >50,000/microL and fibrinogen concentration >100
mg/dL (1 mol/L) [30].

● Choice of replacement products – Clotting factors can be replaced by either FFP or

cryoprecipitate. FFP provides both procoagulant and anticoagulant proteins and is
administered every 12 to 24 hours at a dose of 10 to 15 mL/kg per infusion.
Cryoprecipitate has higher concentrations of factor VIII and fibrinogen, and can be
used to correct hypofibrinogenemia. It is administered every 6 hours as needed at a
dose of 10 mL/kg per infusion. Platelet transfusions are administered with a goal of
maintaining the platelet counts >50,000/microL.

● Repeat transfusions – Repeat transfusions may be necessary. The theoretical concern

of replacement therapy increasing thrombotic risk by "adding fuel to the fire" has not
been demonstrated [15], and should not dissuade the clinician from administering
replacement therapy to control significant bleeding. Clinicians should monitor for
volume overload in patients who receive factor replacement.

Anticoagulation

Heparin — Heparin has a very limited role in the management of DIC. In adults with DIC,
heparin is sometimes used in treatment doses for patients with predominantly thrombotic
manifestations and without bleeding, or in prophylactic doses for critically ill patients
without bleeding [28]. In children, it is our practice to administer heparin only to patients
with life-threatening or symptomatic thrombi (eg, acral ischemia or skin infection) without
clinical bleeding. Heparin is contraindicated in patients with central nervous system (CNS)
injury or liver failure. (See "Clinical features, diagnosis, and treatment of disseminated
intravascular coagulation in adults", section on 'Prevention/treatment of thrombosis'.)

Except for the unusual patients described above, heparin is generally avoided for patients
with DIC because of its potential to exacerbate bleeding, and because there are no
controlled trials that demonstrate a benefit in children or adults with DIC. In the past,
heparin was routinely used in patients with clinically overt thrombosis and potential end-
organ failure, but there is little evidence that its use improved organ dysfunction.

If the clinical decision is made to administer therapeutic doses of heparin, continuous

intravenous (IV) infusion of unfractionated heparin (UFH) is often preferred because it
allows for finely tuned titration and can be quickly turned off should bleeding occur. The
starting dose of UFH should be lower than is typically used for treatment of
thromboembolic disease (we typically start the continuous IV infusion at 5 to 10 units/kg
per hour). For children with DIC, loading doses generally should not be used. Low molecular
weight heparin (LMWH) has been used in adults with DIC but there are no data to assess its
effectiveness in children with DIC. In children, anti-factor Xa levels should be monitored
during treatment with either unfractionated heparin or LMWH. (See "Venous thrombosis
and thromboembolism in children: Treatment, prevention, and outcome", section on
'Unfractionated heparin' and "Venous thrombosis and thromboembolism in children:
Treatment, prevention, and outcome", section on 'Low molecular weight heparin'.)

Anticoagulant restoration — The levels of endogenous anticoagulants (eg, antithrombin

and protein C) are decreased in DIC. It has been suggested that administration of these
anticoagulants may reduce microthrombus formation and improve outcomes in patients
with DIC. However, the available data suggest these interventions are either not effective or
their effectiveness is limited to very select clinical settings.

● Antithrombin – In children, there are minimal data on the use of antithrombin [31]. In
adults, data suggest that antithrombin proved no benefit in patients with severe sepsis
or shock. Antithrombin should not be used until further studies demonstrate that it is
effective and safe. (See "Clinical features, diagnosis, and treatment of disseminated
intravascular coagulation in adults", section on 'Treatment'.)

● Human protein C concentrate – Protein C concentrate is not used routinely in

management of DIC. Its clinical utility is limited to patients who present with purpura
fulminans in the setting of one of the following conditions, which are discussed in
greater detail separately:
 • Neonatal purpura fulminans due to congenital protein C deficiency (see
"Management of thrombosis in the newborn", section on 'Neonatal purpura
fulminans')

• Purpura fulminans due to severe meningococcal infection (see "Treatment and

prevention of meningococcal infection", section on 'Protein C concentrate')

● Activated protein C concentrate – Recombinant activated protein C (aPC, drotrecogin

alfa) is not recommended for treatment of DIC or other coagulation disorders, and is
no longer available. Drotrecogin alfa was voluntarily removed from the world market in
2011. (See "Investigational and ineffective therapies for sepsis", section on 'Ineffective
therapies'.)

● Investigational therapy – Recombinant human soluble thrombomodulin (ART-123), an

agent which inactivates coagulation by binding to thrombin and activating protein C, is
an investigational treatment for DIC [32,33]. A clinical trial in Japanese patients >15
years of age with DIC from infection or malignancy showed promising results in
comparison to heparin therapy [34]. Additional data on safety and efficacy of ART-123
are needed before it can be recommended for treatment of DIC in children. ART-123 is
available only in Japan.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from

selected countries and regions around the world are provided separately. (See "Society
guideline links: Thrombotic diseases in infants and children".)

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"The Basics" and "Beyond the Basics." The Basics patient education pieces are written in
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in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to
print or email these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

● Basics topic (see "Patient education: Disseminated intravascular coagulation (The

Basics)")

SUMMARY AND RECOMMENDATIONS

● Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized
by hemorrhage and microvascular thrombosis. It results from activation of the
coagulation system by a variety of underlying disorders (eg, sepsis, trauma, and
malignancy) (table 1). (See 'Pathogenesis' above and 'Etiology' above.)

● Clinical manifestations vary depending on the ability of the hemostatic system to

compensate for the ongoing depletion of coagulation factors and platelets. In mild
cases, bleeding may only be noted at venipuncture sites, but in more severe cases
there may be extensive hemorrhage and thrombosis with end-organ damage to the
kidney, liver, lung, extremities, and central nervous system. (See 'Clinical
manifestations' above.)

● The diagnosis of DIC is based on both clinical findings (eg, hemorrhage and
microthrombi in a patient with a predisposing medical condition) and abnormal
coagulation studies. No single test confirms the diagnosis. Laboratory values must be
evaluated in aggregate, and serial testing is more informative than single
measurements. Scoring systems have been developed to assist in diagnosing DIC
(table 4 and table 5). When evaluating neonates, it is important to recognize that
neonatal values of laboratory tests used to establish the diagnosis of DIC differ
considerably from adult values (table 2 and table 3). (See 'Diagnosis' above and
'Neonates' above.)

● The differential diagnosis for DIC is broad and includes diseases that present with
bleeding, coagulopathy, and/or thrombocytopenia (algorithm 1 and table 6). The
laboratory evaluation usually differentiates DIC from other causes of bleeding in
children. (See 'Differential diagnosis' above.)

● A major principle in the management of DIC in pediatric patients is treatment of the

underlying primary disease. In patients with clinically significant bleeding, we
recommend the administration of replacement therapy with platelets and/or
coagulation factors (fresh frozen plasma or cryoprecipitate) (Grade 1C). (See
'Treatment' above.)

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