Disseminated Intravascular Coagulation (DIC) During Pregnancy - Clinical Findings, Etiology, and Diagnosis - UpToDate

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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, Steven Kleinman, MD, Lawrence LK Leung, 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: Apr 2021. | This topic last updated: Apr 29, 2021.
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.
https://www.uptodate.com/contents/disseminated-intravascular-coagulation-dic-during-pregnancy-clinical-findings-etiology-and-diagnosis/print?search=amniotic fluid embolism&source=search_result&selectedTitle=2~50… 1/23

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".)
Broader discussions of the pathogenesis, clinical manifestations, diagnosis, and treatment of DIC can be found elsewhere (see
"Disseminated intravascular coagulation (DIC) in adults: Evaluation and management"). Other causes of pregnancy-associated
thrombocytopenia and obstetric hemorrhage are also presented elsewhere. (See "Thrombocytopenia in pregnancy" and
"Overview of the etiology and evaluation of vaginal bleeding in pregnant women".)
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 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 "Disseminated intravascular coagulation (DIC) in adults: Evaluation and management",
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 "Placental abruption: Pathophysiology, clinical features, diagnosis, and
consequences" and "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]. (See
"Preeclampsia: Clinical features and diagnosis" and "Preeclampsia: Management and prognosis" 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 'Infection' and "Pregnancy loss (miscarriage):
Assessment, counseling, and choice of treatment".)
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
"Disseminated intravascular coagulation (DIC) in adults: Evaluation and management", 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 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 "Disseminated intravascular coagulation (DIC) in adults: Evaluation and management", 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 "Disseminated intravascular coagulation (DIC) in adults: Evaluation and management", 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".)
● 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 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 'Patient
preparation, assessment, and supportive care'.)
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 useful in diagnosing dilutional coagulopathy [44]. (See "Postpartum hemorrhage: Medical
and minimally invasive management", section on 'Thromboelastography and rotational thromboelastometry'.)
● 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.
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.
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 'Definition/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: C-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 "Acquired
TTP: Clinical manifestations and diagnosis" and "Approach to the patient with 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".)
● 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 "Pulmonary embolism in pregnancy: Epidemiology,

pathogenesis, and diagnosis".)
● 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 "Disseminated
intravascular coagulation (DIC) in adults: Evaluation and management", 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 Basics." The Basics patient education
pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a

patient might have about a given condition. These articles are best for patients who want a general overview and who prefer
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These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and
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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
• Septic abortion
Severe postpartum hemorrhage (PPH) by itself usually does not cause consummative DIC 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 editorial staff at UpToDate would like to acknowledge Kirk D Ramin, MD, and Susan Ramin, MD, who contributed to earlier
versions of this topic review.
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 4460 Version 50.0

GRAPHICS
Coagulation cascade overview
This schematic shows a revised version of the coagulation cascade that emphasizes
the importance of pathways for hemostasis in vivo. Tissue factor exposed at a wound
interacts with factor VIIa and initiates clotting by two pathways: (1) activation of factor
X to Xa (ie, the extrinsic ten-ase complex) and (2) conversion of factor IX to IXa, which
activates factor X to Xa (ie, the intrinsic ten-ase complex). Pathways 1 and 2 are equally
important.
In a third pathway (3), thrombin also activates factor XI to XIa, which can lead to
further generation of factor IXa; it serves as an amplification pathway required during
severe hemostatic challenges.
Coagulation factors are shown as Roman numerals. Only the activated forms (with the
suffix "a") are shown in this diagram for simplicity. Thrombin is factor IIa.
Graphic 90873 Version 9.0

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.

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.
DIC: disseminated intravascular coagulation.

Range of normal results for coagulation tests in pregnancy
Normal (reference) range

Test
First trimester Second trimester Third trimester
Prothrombin time (seconds) 9.7 to 13.5 9.5 to 13.4 9.6 to 12.9
Activated partial thromboplastin 23.0 to 38.9 22.9 to 38.1 22.6 to 35.0

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 (micrograms/mL) 0.05 to 0.95 0.32 to 1.29 0.13 to 1.7
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.

Contributor Disclosures
Michael A Belfort, MBBCH, MD, PhD, D.A. (SA), FRCSC, FRCOG, FACOG Equity Ownership/Stock Options: Glenveigh Medical. Patent Holder:
Clinical Innovations [Postpartum hemorrhage]. Charles J Lockwood, MD, MHCM Nothing to disclose David L Hepner, MD Nothing to
disclose Steven Kleinman, MD Consultant/Advisory Boards: Cerus Corp [Pathogen reduction of blood components]; Creative Testing
Solutions (CTS) Medical Advisory Board [Blood donor testing]; Roche Molecular Systems [Blood donor testing]. Lawrence LK Leung,
MD Nothing to disclose Vanessa A Barss, MD, FACOG Nothing 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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20/05/2021 Disseminated intravascular coagulation (DIC) during pregnancy: Clinical ﬁndings, etiology, and diagnosis - UpToDate

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Disseminated intravascular coagulation (DIC) during pregnancy: Clinical

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

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

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

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Laboratory testing includes the following:

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

● Thromboelastography (TEG)/Rotational thromboelastometry (ROTEM). This information provides a global assessment of

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pathogenesis, and diagnosis".)

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SUMMARY AND RECOMMENDATIONS

● Pathophysiology – Disseminated intravascular coagulation (DIC) is a secondary manifestation of an underlying primary

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Coagulation cascade overview

Graphic 90873 Version 9.0

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Pathogenesis of disseminated intravascular coagulation

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

Graphic 98047 Version 3.0

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Major causes of disseminated intravascular coagulation (DIC)

Events that can initiate DIC

Crush injury or complicated surgery

Severe head injury

Cancer procoagulant (Trousseau syndrome)

Acute leukemia, especially promyelocytic

Giant hemangioma (Kasabach-Merritt syndrome)

Abdominal aortic aneurysm

Acute hemolytic transfusion reaction (ABO incompatibility)

Snake and viper venoms

Events that can complicate and propagate DIC

Complement pathway activation

Refer to UpToDate for further information.

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

Prothrombin time (seconds) 9.7 to 13.5 9.5 to 13.4 9.6 to 12.9

Activated partial thromboplastin 23.0 to 38.9 22.9 to 38.1 22.6 to 35.0

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

D-dimer (micrograms/mL) 0.05 to 0.95 0.32 to 1.29 0.13 to 1.7

Graphic 89013 Version 3.0

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