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Official reprint from UpToDate®

www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Disseminated intravascular coagulation (DIC) during

pregnancy: Clinical findings, etiology, and diagnosis
Author: Michael A Belfort, MBBCH, MD, PhD, D.A. (SA), FRCSC, FRCOG, FACOG
Section Editors: Charles J Lockwood, MD, MHCM, David L Hepner, MD, Lawrence LK Leung, MD, Lynne Uhl, MD
Deputy Editor: Vanessa A Barss, MD, FACOG

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Feb 2023. | This topic last updated: Sep 12, 2022.

INTRODUCTION

Disseminated intravascular coagulation (DIC) is a pathologic disruption of the finely balanced

process of hemostasis. It is characterized by systemic activation of blood coagulation, which
results in generation and deposition of fibrin and formation of microvascular thrombi
(thrombosis) in the small blood vessels throughout the body and activation of plasmin
(fibrinolysis), eventually leading to multiple organ dysfunction. Because widespread clotting
depletes platelets and clotting factors that are needed to control bleeding, excessive bleeding
often occurs.

Any patient with DIC presents a major management challenge, and this challenge is further
complicated when the patient is carrying a fetus at or beyond the limit of viability. For example,
delaying delivery to transfuse a pregnant patient with DIC who is bleeding heavily may not be in
the best interest of a fetus with a category III heart rate tracing, whereas performing an
emergency cesarean delivery on a pregnant patient with DIC may not be in the pregnant
patient's best interest. Even in the setting of fetal demise, labor and vaginal delivery of a
pregnant patient with DIC carries the potential for catastrophic hemorrhage.

This topic will review DIC related to pregnancy, focusing on clinical findings, etiology, and
diagnosis. The management and prognosis of pregnant women with DIC are discussed
separately. (See "Disseminated intravascular coagulation (DIC) during pregnancy: Management
and prognosis".)

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Broader discussions of the pathogenesis, clinical manifestations, diagnosis, and treatment of

DIC can be found elsewhere (see "Evaluation and management of disseminated intravascular
coagulation (DIC) in adults"). Other causes of pregnancy-associated thrombocytopenia and
obstetric hemorrhage are also presented elsewhere. (See "Thrombocytopenia in pregnancy"
and "Evaluation and differential diagnosis of vaginal bleeding before 20 weeks of gestation".)

PREVALENCE

● Pregnancy-associated disseminated intravascular coagulation (DIC) accounts for

approximately 1 to 5 percent of all cases of DIC in resource-abundant countries; this
proportion appears to be higher in resource-limited countries [1].

● The prevalence of pregnancy-associated DIC ranges from 0.03 to 0.35 percent of delivery
hospitalizations in population-based studies [2-4]. A study from the United States reported
prevalence of 12.5 per 10,000 delivery hospitalizations (0.13 percent) [2].

● Although the overall prevalence of pregnancy-associated DIC is low, patients with specific
pregnancy complications, such as placental abruption or amniotic fluid embolism, can be
at very high risk (eg, prevalence >20 percent) [5-7].

PATHOPHYSIOLOGY

Normal pregnancy is a hypercoagulable state [8-18]. Changes include marked increases in most
coagulation factors, decreased endogenous anticoagulation, reduced fibrinolysis, and
increased platelet reactivity. The shift in the balance between the hemostatic and fibrinolytic
systems serves to prevent excessive bleeding during placental separation. (See "Maternal
adaptations to pregnancy: Hematologic changes".)

● Clot formation – The primary driver of clot formation at the site of vascular injury is tissue
factor (TF). TF generated or exposed at the injury site interacts with circulating factor VIIa
to rapidly initiate the clotting cascade via the extrinsic pathway ( figure 1). TF is
produced by numerous cell types including subendothelium, fibroblasts, monocytes, and
decidual cells, and it is present in amniotic fluid. In pregnancy, important sites of injury
resulting in TF generation or exposure are the placental/decidual interface in the setting of
placental separation and necrosing fetoplacental tissue in the setting of retained fetal
demise [19-21]. Exposure to endothelial collagen activates the intrinsic pathway, which
plays a lesser role in development of disseminated intravascular coagulation (DIC). Both

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pathways converge into the common pathway of clot formation. (See "Overview of
hemostasis", section on 'Clotting cascade and propagation of the clot'.)

● Control of clot formation and clot breakdown – As clotting is activated, several

mechanisms to keep clot formation in check also become activated. These include
plasmin, which cleaves fibrin; proteins C and S; antithrombin (AT); and TF pathway
inhibitor [22-25]. (See "Overview of hemostasis", section on 'Control mechanisms and
termination of clotting'.)

Abnormal excessive activation of both of these processes can cause depletion of coagulation
factors (including fibrinogen) and platelets, giving rise to consumptive coagulopathy; increased
production of fibrin degradation products and D-dimers (both of which can interfere with
platelet function and uterine contractility); and depletion of natural anticoagulants [26-28]. This
in turn can result in the microvascular thrombosis and tissue necrosis, endothelial damage,
hemorrhage, and multiorgan failure that characterize DIC ( figure 2). (See "Evaluation and
management of disseminated intravascular coagulation (DIC) in adults", section on
'Pathogenesis'.)

CAUSES

Disseminated intravascular coagulation (DIC) does not occur in isolation. It is a secondary

manifestation of an underlying disorder that has led to uncontrolled activation of clot formation
and breakdown, thus identification and treatment of the underlying cause are critical to
resolution of the hemostatic abnormalities. (See "Disseminated intravascular coagulation (DIC)
during pregnancy: Management and prognosis".)

The type and frequency of pregnancy-related conditions that triggered DIC in a review of 49
cases from a tertiary maternity hospital included [3]:

● Placental abruption – 37 percent (See "Acute placental abruption: Pathophysiology, clinical

features, diagnosis, and consequences" and "Acute placental abruption: Management and
long-term prognosis".)

● Postpartum hemorrhage (PPH) – 29 percent (See "Overview of postpartum hemorrhage".)

● Preeclampsia/eclampsia/HELLP syndrome (hemolysis, elevated liver enzymes, low platelet

count) – 14 percent. These cases were likely complicated by coexistent abruption or liver
failure, as most preeclampsia is associated with thrombocytopenia without changes in
prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen [29].

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(See "Preeclampsia: Clinical features and diagnosis" and "Preeclampsia: Antepartum

management and timing of delivery" and "Eclampsia" and "HELLP syndrome (hemolysis,
elevated liver enzymes, and low platelets)".)

● Acute fatty liver – 8 percent (See "Acute fatty liver of pregnancy".)

● Amniotic fluid embolism – 6 percent (See "Amniotic fluid embolism".)

● Pregnancy-related sepsis – 6 percent (See "Unsafe abortion", section on 'Morbidity and

mortality' and "Pregnancy loss (miscarriage): Clinical presentations, diagnosis, and initial
evaluation", section on 'Septic abortion'.)

There were no cases of prolonged retention of a dead fetus because these cases are generally
identified early and delivered without significant delay in contemporary obstetric practice [30].
(See "Stillbirth: Maternal care".)

DIC may also be caused by conditions that may occur in the nonpregnant population. The most
common events that initiate DIC in the general population are sepsis, trauma, and cancer
( table 1). The possibility of these nonobstetric causes of DIC should be considered in
pregnant patients with DIC, especially when an obvious pregnancy-associated cause is absent
[31,32]. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in
adults", section on 'Causes of DIC'.)

There is some debate about the relationship between severe PPH and DIC. There is evidence
that severe tissue hypoxia in the setting of shock may result in release of tissue factor (TF) from
damaged cells and supraphysiologic activation of coagulation, leading to DIC [33,34]. The
counterargument is that coagulopathy in the setting of PPH is simply due to depletion of
clotting factors and platelets by blood loss; in the absence of plasma, cryoprecipitate, or platelet
transfusions, this results in dilutional coagulopathy. Further research in this area is needed.

CLINICAL FINDINGS

Presentation — Disseminated intravascular coagulation (DIC) typically occurs in the setting of

one of the pregnancy complications described above (see 'Causes' above). It may present in
either of two ways, depending on the underlying etiology, intensity of coagulation activation,
and the deficiency of natural anticoagulation mechanisms:

● Overt DIC – Overt fulminant DIC is the more common scenario in pregnancy. Coagulation
and fibrinolysis are both increased, and both overt bleeding and thrombosis are present.
Patients may present with severe uterine bleeding and/or diffuse oozing of blood from
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skin (eg, at intravenous sites) or mucosa (eg, from a bladder catheter). Importantly, severe
uterine bleeding from abruption may not be seen at presentation if most of the blood is
initially retained in utero behind the placenta (called "concealed abruption").
Intraabdominal bleeding is uncommon but can occur in the setting of hepatic rupture
related to preeclampsia, eclampsia, or HELLP syndrome-associated hepatic disease. Signs
of shock (eg, tachycardia, hypotension, weak peripheral pulses, altered mental status, cool
extremities, narrow pulse pressure [<25 mmHg]) and/or organ dysfunction (eg, acute renal
failure, hepatic dysfunction, acute lung injury, neurologic dysfunction) may be present.
(See "Evaluation and management of disseminated intravascular coagulation (DIC) in
adults", section on 'Clinical manifestations'.)

● Latent and compensated activation of coagulation – In this situation, there is subtle

hemostatic dysfunction and increased thrombotic risk without obvious clinical symptoms
or signs. It is characterized by imbalance between activation and inhibition of the
coagulation system and can be rapidly normalized by removing the procoagulant stimulus
and enhancing the inhibitory mechanisms. This state may become a chronic condition,
which is rare in pregnancy, or may progress to overt DIC. (See "Evaluation and
management of disseminated intravascular coagulation (DIC) in adults", section on 'Acute
versus chronic DIC'.)

Laboratory findings — There is no single laboratory test that is sensitive and specific for DIC.
Laboratory findings generally include abnormal coagulation studies and thrombocytopenia.
These findings need to be interpreted within the context of normal reference values in
pregnancy ( table 2), which are sometimes different from values in nonpregnant women. (See
"Normal reference ranges for laboratory values in pregnancy".)

● Thrombocytopenia – The platelet count is typically mildly to moderately reduced in DIC;

platelet counts below 20,000/microL are uncommon [35].

In normal pregnancy, the mean platelet count is slightly lower than in nonpregnant
patients (ie, gestational thrombocytopenia) but usually remains within the normal range.
Because platelet counts may be within the normal range in the early stages of DIC, the
trend in platelet count should be monitored when DIC is suspected. In a clinical scenario
that includes DIC in the differential diagnosis, a falling platelet count may be a sign of
developing DIC even if the absolute count is in the normal range.

Thrombocytopenia in pregnancy is not specific for DIC; it is observed in several pregnancy-

related disorders. (See "Thrombocytopenia in pregnancy".)

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● Prolongation of the activated partial thromboplastin time (aPTT) and prothrombin

time (PT) – The aPTT and PT are tests that measure the time taken, in vitro, for blood to
form fibrin. The PT/international normalized ratio (INR) evaluates the extrinsic pathway,
and the aPTT measures the time taken to form fibrin via the intrinsic pathway.

Both PT/INR and aPTT are prolonged. In a normal gestation, the aPTT and PT/INR may be
slightly shorter than that in nonpregnant patients due to normal changes in coagulation
factors. This can cause a delay in the recognition of ongoing coagulopathy since
prolongation/increase in the aPTT and PT/INR may not become obvious until the causative
pathology is well advanced [36]. Thus, it is essential to note any prolongation/increase of
the aPTT and PT/INR, even if the starting point is within the normal range and the current
aPTT and PT/INR are still within that normal range. A widening differential between
baseline and repeat tests in either the aPTT or the PT/INR may be indicative of clinical
worsening [37]. (See "Maternal adaptations to pregnancy: Hematologic changes", section
on 'Coagulation and fibrinolysis'.)

The thrombin time (TT) is another coagulation test that measures the final step in the
coagulation cascade (conversion of fibrinogen to fibrin). The TT is not routinely measured
in pregnancy or DIC, but if measured, it tends to follow the same pattern as the aPTT and
PT/INR (ie, it is shorter than normal in normal pregnancy and prolonged in DIC) [38].

● Hypofibrinogenemia – Fibrinogen levels fall in DIC. In a normal pregnancy, the fibrinogen

level is >300 mg/dL in the third trimester, a level that is substantially higher than in
nonpregnant individuals, since fibrinogen is an acute phase reactant [39]. Reduction in the
fibrinogen level from the patient's baseline is concerning even if the absolute level
remains in the normal range, as the fall in fibrinogen in DIC can be a relatively late finding
[40].

In a study of patients with persistent uterine atony, a fibrinogen level <200 mg/dL had a
positive predictive value of 100 percent for progression to severe postpartum
hemorrhage, whereas a level >400 mg/dL had a negative predictive value of 79 percent
[41]. The greatest concern for bleeding generally occurs when the fibrinogen level is <100
mg/dL; this is also the typical level below which the aPTT and PT/INR become
prolonged/increased.

● Increased D-dimer – D-dimer is increased in DIC. In a normal pregnancy, D-dimer is

higher than in nonpregnant individuals [42,43]. In one study of 760 healthy patients with
singleton pregnancies, the D-dimer median value was 316 ng/mL at 24 weeks, gradually
increasing to 668 ng/mL at 40 weeks; the 95th percentiles at 24 and 40 weeks were 704

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ng/mL and 1538 ng/mL, respectively [42]. D-dimer is further increased in DIC, but because
of the higher baseline values in pregnancy, a positive D-dimer test and the absolute D-
dimer value are difficult to interpret.

● Variable white blood cell (WBC) count – The WBC count is increased in pregnancy,
particularly during labor. In DIC, it may be normal, increased, or decreased (eg, due to
sepsis). (See "Maternal adaptations to pregnancy: Hematologic changes", section on
'White blood cells'.)

DIAGNOSTIC EVALUATION

Evaluation for disseminated intravascular coagulation (DIC) may need to occur concurrently
with initial management before the diagnosis is completely established, especially if there is
ongoing hemorrhage, shock, or an abnormal fetal heart rate pattern. (See "Disseminated
intravascular coagulation (DIC) during pregnancy: Management and prognosis", section on
'Initial preparation and assessment of all patients'.)

Many pregnancy-associated causes of DIC are obvious from the history and physical
examination. Because the absence of external bleeding does not exclude overt DIC, any
pregnant patient with features consistent with DIC should be evaluated for abdominal and
retroperitoneal hemorrhage and large vaginal or vulvar hematomas. Pregnant patients who
have been involved in trauma can lose large amounts of blood into the soft tissues (eg,
fractured femur with bleeding into the thigh).

Laboratory testing includes the following:

● Complete blood count (CBC) with platelet count and differential.

● Coagulation studies including prothrombin time (PT) and international normalized ratio
(INR), activated partial thromboplastin time (aPTT), fibrinogen level, and D-dimer.

● Liver biochemical and function tests (alanine aminotransferase, aspartate

aminotransferase, albumin, bilirubin) – Normal results in the setting of coagulopathy
suggests DIC, whereas very abnormal results suggest that at least part of the pathology
leading to the coagulopathy may be liver failure and failure to produce adequate
coagulation factors.

● Thromboelastography (TEG)/Rotational thromboelastometry (ROTEM). This information

provides a global assessment of hemostasis in whole blood that includes contributions of
platelets, fibrinogen, fibrinolysis, and coagulation factors. TEG/ROTEM can be particularly
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useful in diagnosing dilutional coagulopathy [44]. (See "Postpartum hemorrhage: Medical

and minimally invasive management", section on 'Viscoelastic testing'.)

● Blood urea nitrogen and creatinine, as acute kidney injury occurs in 25 to 40 percent of
patients with acute DIC.

● Blood and urine cultures in patients with suspected sepsis. In cases where intrauterine
infection is suspected, aspiration of amniotic fluid culture is appropriate.

Prior to the return of the first set of laboratory studies, a crude clotting time may be performed
using any of a variety of methods [45]. One method is to determine the clotting time of 5 mL of
blood in a red top tube (ie, no additives) at room temperature; if the blood in the tube clots
within 8 to 10 minutes and the clot remains intact, the patient likely has adequate fibrinogen
stores. If the blood in the tube does not clot or an initial clot dissolves, it is likely that the patient
is markedly deficient in key clotting factors. However, such tests are highly subjective,
insensitive, imprecise, and not validated in pregnancy.

Although serial coagulation testing is rarely necessary to diagnose DIC in the obstetric setting
(where DIC is typically fulminant), serial laboratory assessments over a few hours in less
fulminant cases may show progressively prolonged coagulation times, decreasing platelet
counts, increasing values for D-dimer, and falling fibrinogen levels. In challenging cases, this
pattern can help distinguish mild DIC from normal pregnancy-related changes in these
laboratory values.

Serial testing of the CBC, fibrinogen level, and coagulation times are important for guiding
management (eg, coagulation factor replacement). (See "Disseminated intravascular
coagulation (DIC) during pregnancy: Management and prognosis", section on 'Measure blood
loss'.)

DIAGNOSIS

We make the diagnosis of acute disseminated intravascular coagulation (DIC) in a pregnant

patient when the clinical setting is appropriate (eg, placental abruption, amniotic fluid
embolism, acute fatty liver, sepsis) and there is laboratory evidence of thrombocytopenia,
coagulation factor consumption (eg, prolonged prothrombin time and activated partial
thromboplastin time; low fibrinogen), and fibrinolysis (eg, increasing D-dimer), as long as
another etiology for these findings does not become apparent. No single laboratory test is
highly sensitive or specific for the diagnosis.

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Early involvement of a hematology specialist is advised when the cause is not thought to be one
of the more common obstetric causes described above. (See 'Causes' above.) Specific steps to
evaluate the likelihood of DIC and eliminate other possibly life-threatening causes of the
findings, such as thrombotic thrombocytopenic purpura, can then be taken. (See 'Differential
diagnosis' below.)

Scoring systems — Scoring systems for diagnosis of DIC in pregnant patients have been
developed, but are not widely used or well-validated.

● One group adapted the International Society of Thrombosis and Hemostasis (ISTH) DIC
scoring system for diagnosis of overt DIC for use in pregnant patients. The revised system
includes platelet count, prothrombin time (PT) difference (difference between the PT value
of the patient and laboratory control in seconds), and fibrinogen levels [4]. The parameters
are assigned a score of 0, 1 (platelet count <50,000 or 100,001 to 185,000 or fibrinogen
400 to 450 mg/dL), 2 (platelet count 50,000 to 100,000), 5 (for PT difference 0.5 to 1), 6 (for
fibrinogen 300 to 400 mg/dL), 12 (for PT difference 1 to 1.5), or 25 (for PT difference >1.5
or fibrinogen ≤300 mg/dL). In a study of 684 patients with placental abruption, of whom
150 needed blood transfusion and 43 had DIC, a score ≥26 had 88 percent sensitivity and
96 percent specificity to identify those who needed blood and blood product transfusion.

● Pregnancy-specific scoring systems for nonovert DIC have also been developed to predict
patients likely to require blood product transfusion. The parameters include fibrinogen,
antithrombin III, protein C, prothrombin time, platelet count, thrombin-antithrombin (TAT)
complex, and D-dimer [46]. In one study, a score ≥3 had a sensitivity and specificity of 71.4
and 77.9 percent to identify patients at risk for obstetrical hemorrhage requiring blood
product transfusion.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of disseminated intravascular coagulation (DIC) in pregnancy includes

other causes of bleeding, thrombosis, and/or organ damage. In some cases, these conditions
may coexist with DIC or contribute to the pathogenesis of DIC. Treatment of the underlying
cause typically leads to resolution of DIC (see "Disseminated intravascular coagulation (DIC)
during pregnancy: Management and prognosis", section on 'Identify and address the triggering
event'):

● Postpartum hemorrhage (PPH) with dilutional coagulopathy – Severe bleeding from

PPH may result in dilutional coagulopathy.

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Like DIC, there may be reduced levels of coagulation factors that can prolong the
prothrombin time (PT) and activated partial thromboplastin time (aPTT). There may be a
mixed picture with elements of coagulation factor consumption in PPH. There should be
no microangiopathy on blood smear (schistocytes) in PPH with dilutional coagulopathy,
while schistocytes should be evident in fulminant DIC. (See "Overview of postpartum
hemorrhage", section on 'Criteria for diagnosis'.)

● Primary thrombotic microangiopathy – Primary thrombotic microangiopathies such as

thrombocytopenic purpura (TTP) are rare during pregnancy; however, the physiologic
stress of pregnancy may trigger clinical manifestations of hereditary or acquired TTP.
Pregnancy (including the postpartum period) is also a major precipitating factor for
complement-mediated hemolytic uremic syndrome. (See "Thrombotic microangiopathies
(TMAs) with acute kidney injury (AKI) in adults: CM-TMA and ST-HUS", section on
'Pregnancy or postpartum'.)

Like DIC, patients may have Coombs-negative hemolytic anemia with schistocytes on the
blood smear, thrombocytopenia, and organ damage. In contrast to DIC, in TTP, the
coagulation studies typically are normal, and the ADAMTS13 (A disintegrin and
metalloproteinase with thrombospondin-like repeats-13) activity is severely reduced (eg,
activity <10 percent). Mild decreases in ADAMTS13 activity (eg, between 10 and 60 percent)
are often seen in acutely ill pregnant women (eg, preeclampsia, HELLP syndrome) and are
not thought to be pathophysiologically or clinically significant [47]. (See "Diagnosis of
immune TTP" and "Diagnostic approach to suspected TTP, HUS, or other thrombotic
microangiopathy (TMA)".)

● von Willebrand disease (VWD) – VWD is the most common inherited bleeding disorder,
and many pregnant patients with VWD already will be aware of their diagnosis. Pregnancy
is generally well-tolerated in most cases of VWD (in particular type 1, which may be
asymptomatic or associated with mild bleeding symptoms), partly due to the physiologic
increases in von Willebrand factor (VWF) levels. However, VWF levels decline in the
postpartum period, and it is possible for a patient who has not had a prior hemostatic
challenge to have marked postpartum bleeding as the initial manifestation of VWD [48-
50].

Like DIC, some types of severe VWD may be associated with thrombocytopenia and/or
prolongation of the aPTT. Unlike DIC, VWD does not cause prolongation of the PT, a low
fibrinogen level, or elevated D-dimer; and patients with VWD will have low levels of VWF,
VWF activity (ristocetin cofactor activity), and factor VIII. (See "Clinical presentation and
diagnosis of von Willebrand disease".)
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● Antiphospholipid syndrome (APS) – APS is caused by autoantibodies to proteins bound

to anionic phospholipid-protein complexes (the dominant protein target is beta2-
glycoprotein I); it can occur in the setting of systemic lupus erythematosus or
independently.

Like DIC, patients can have thrombosis and elevated D-dimer, and the aPTT is frequently
prolonged. Unlike DIC, in APS, the PT and fibrinogen levels are normal, and bleeding
typically does not occur. Furthermore, the autoantibodies in APS can sometimes cause
prolongation of the aPTT as a laboratory artifact (ie, lupus anticoagulant); they are actually
prothrombotic. (See "Clinical manifestations of antiphospholipid syndrome".)

● Pulmonary embolism (PE) – PE is a leading cause of death in pregnant/postpartum

persons and is often underappreciated due to the wide range of presenting symptoms.

Like DIC, patients with PE may present with shock and elevated D-dimer. Unlike DIC, PE
generally is not associated with bleeding, prolongation of the clotting times, or low
fibrinogen. (See "Diagnosis of pulmonary embolism in pregnancy".)

● Heparin-induced thrombocytopenia (HIT) – HIT is a potentially life-threatening disorder

in which autoantibodies cause activation of platelets in the presence of heparin (ie, the
antibodies are prothrombotic). HIT is extremely rare in pregnancy.

Like DIC, HIT can present with thrombocytopenia, thrombosis, and/or organ damage;
bleeding may be present due to the heparin. Unlike DIC, HIT has a temporal relationship
to heparin exposure; patients with HIT have positive testing for HIT antibodies and do not
have coagulation abnormalities (except for those due to their anticoagulant). (See "Clinical
presentation and diagnosis of heparin-induced thrombocytopenia".)

● Transfusion reaction – Severe transfusion reactions, especially due to ABO

incompatibility, can mimic or cause DIC.

Like DIC, a severe transfusion reaction from ABO mismatch can cause anemia,
thrombocytopenia, oozing from mucocutaneous sites, and bleeding. Unlike DIC,
transfusion reactions have a history of antecedent transfusion and often are associated
with a positive direct antiglobulin (Coombs) test. (See "Approach to the patient with a
suspected acute transfusion reaction", section on 'Acute hemolytic transfusion reaction
(AHTR)'.)

Additional discussion of the differential diagnosis in nonobstetric patients is reviewed

separately. (See "Evaluation and management of disseminated intravascular coagulation (DIC)

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in adults", section on 'Differential diagnosis'.)

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: Obstetric hemorrhage".)

INFORMATION FOR PATIENTS

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
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Here are the patient education articles that are relevant to this topic. We encourage you to print
or e-mail 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

● Pathophysiology – Disseminated intravascular coagulation (DIC) is a secondary

manifestation of an underlying primary cause of uncontrolled activation of coagulation
and fibrinolysis. (See 'Pathophysiology' above.)

● Underlying cause – DIC typically occurs in the setting of one of the following pregnancy
complications:

• Placental abruption
• Preeclampsia with severe features/eclampsia/HELLP syndrome (hemolysis, elevated
liver enzymes, low platelets)
• Amniotic fluid embolism
• Acute fatty liver of pregnancy
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• Septic abortion

Severe postpartum hemorrhage (PPH) by itself usually does not cause consumptive
coagulopathy unless associated with increased release of tissue factor but can lead to a
dilutional coagulopathy. Prolonged retention of a dead fetus over several weeks is now a
rare cause of DIC because these cases are identified early and delivered without
significant delay. (See 'Causes' above.)

● Prevalence – The prevalence of DIC in pregnancy ranges from 0.03 to 0.35 percent in
population-based studies or 12.5 per 10,000 delivery hospitalizations (0.13 percent).
Although the overall prevalence of DIC is low in pregnancy, the frequency of DIC in
patients with specific pregnancy complications, such as amniotic fluid embolism or
placental abruption, can be very high. (See 'Prevalence' above.)

● Diagnosis – The diagnosis of acute DIC in a pregnant patient is made when the clinical
setting is appropriate and there is laboratory evidence of consumptive coagulopathy
characterized by thrombocytopenia, coagulation factor consumption (eg, prolonged
prothrombin time [or international normalized ratio] and activated partial thromboplastin
time; low fibrinogen), and fibrinolysis (eg, increasing D-dimer, thromboelastography
evidence of accelerated fibrinolysis). Bleeding is often present but is not required for
diagnosis. (See 'Clinical findings' above and 'Diagnostic evaluation' above and 'Diagnosis'
above.)

● Differential diagnosis – The differential diagnosis of DIC in pregnancy includes other

causes of bleeding, thrombosis, and/or organ damage, which may coexist with DIC or
contribute to its pathogenesis. These include PPH with dilutional coagulopathy, primary
thrombotic microangiopathy, von Willebrand disease, antiphospholipid syndrome,
pulmonary embolism, heparin-induced thrombocytopenia, and transfusion reaction. (See
'Differential diagnosis' above.)

ACKNOWLEDGMENT

The UpToDate editorial staff acknowledges Kirk D Ramin, MD, and Susan Ramin, MD, who
contributed to earlier versions of this topic review.

Use of UpToDate is subject to the Terms of Use.

REFERENCES

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GRAPHICS

Coagulation cascade overview

This schematic shows a revised version of the coagulation cascade

that emphasizes the importance of pathways for hemostasis in vivo.
Coagulation factors are shown as Roman numerals. Only the
activated forms (with the suffix "a") are shown in this diagram for
simplicity. Thrombin is activated factor II (factor IIa); unactivated
factor II is prothrombin.

Tissue factor exposed at a wound interacts with factor VIIa and

initiates clotting by two pathways:
(1) – Activation of factor X to factor Xa (the extrinsic ten-ase
complex).
(2) – Conversion of factor IX to factor IXa, which activates factor X
to factor Xa (the intrinsic ten-ase complex).

Pathways 1 and 2 are equally important.

In a third pathway (3), thrombin also activates factor XI to factor XIa,

which can lead to further generation of factor IXa; it serves as an
amplification pathway required during severe hemostatic
challenges.

Graphic 90873 Version 11.0

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Pathogenesis of disseminated intravascular coagulation

Text in blue refers to pathophysiologic processes; text in green denotes

associated laboratory abnormalities. Refer to UpToDate topics on disseminated
intravascular coagulation for additional details.

NET: neutrophil extracellular trap; PT: prothrombin time; aPTT: activated partial
thromboplastin time; FDPs: fibrin degradation products; dsDNA: double-
stranded DNA; MAHA: microangiopathic hemolytic anemia.

Graphic 98047 Version 3.0

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Major causes of disseminated intravascular coagulation (DIC)

Events that can initiate DIC

Septicemia - Gram negative and Gram positive

Crush injury or complicated surgery

Severe head injury

Cancer procoagulant (Trousseau syndrome)

Acute leukemia, especially promyelocytic

Complications of pregnancy

Amniotic fluid embolism

Abruptio placentae

HELLP syndrome

Eclampsia and severe preeclampsia

Septic abortion

Amphetamine overdose

Giant hemangioma (Kasabach-Merritt syndrome)

Abdominal aortic aneurysm

Peritoneovenous shunt

Acute hemolytic transfusion reaction (ABO incompatibility)

Snake and viper venoms

Liver disease

Fulminant hepatic failure

Reperfusion after liver transplantation

Heat stroke

Burns

Purpura fulminans

Events that can complicate and propagate DIC

Shock

Complement pathway activation

Refer to UpToDate for further information.

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DIC: disseminated intravascular coagulation.

Graphic 58104 Version 4.0

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Range of normal results for coagulation tests in pregnancy

Normal (reference) range

Test
First trimester Second trimester Third trimester

Prothrombin time 9.7 to 13.5 9.5 to 13.4 9.6 to 12.9

(seconds)

Activated partial 23.0 to 38.9 22.9 to 38.1 22.6 to 35.0

thromboplastin
time (seconds)

Platelet count (x10 9 /L) 174 to 391 155 to 409 146 to 429

Fibrinogen (mg/dL) 244 to 510 291 to 538 301 to 696

D-dimer 0.05 to 0.95 0.32 to 1.29 0.13 to 1.7

(micrograms/mL)

Data from: Abbassi-Ghanavati M, Greer LG. Reference Table of Normal Laboratory Values in Uncomplicated Pregnancies. In:
Cunningham FG, Leveno KJ, Bloom S, Hauth JC, Rouse DJ, Spong CY. Williams Obstetrics, 23rd Edition. New York: McGraw-Hill,
2010.

Graphic 89013 Version 3.0

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Contributor Disclosures
Michael A Belfort, MBBCH, MD, PhD, D.A. (SA), FRCSC, FRCOG, FACOG Equity Ownership/Stock Options:
Glenveigh Medical [Preeclampsia]. Patent Holder: Clinical Innovations [Postpartum hemorrhage]. All of the
relevant financial relationships listed have been mitigated. Charles J Lockwood, MD, MHCM No relevant
financial relationship(s) with ineligible companies to disclose. David L Hepner,
MD Grant/Research/Clinical Trial Support: Pharmacosmos [ERAS-driven Elective Surgery].
Consultant/Advisory Boards: Pharmacosmos [IV Iron-Associated Hypophosphatemia ]. All of the relevant
financial relationships listed have been mitigated. Lawrence LK Leung, MD No relevant financial
relationship(s) with ineligible companies to disclose. Lynne Uhl, MD Grant/Research/Clinical Trial Support:
NHLBI [Myocardial infarction and transfusion]. Consultant/Advisory Boards: Abbott [Transfusion Medicine
educational services];Grifols Diagnostic Solutions Inc [Blood bank educational services]. All of the relevant
financial relationships listed have been mitigated. Vanessa A Barss, MD, FACOG No relevant financial
relationship(s) with ineligible companies to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.

Conflict of interest policy

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