Disseminated intravascular coagulation, also known as disseminated intravascular coagulopathy
or less commonly as consumptive coagulopathy, is a pathological process characterized by
the widespread activation of the clotting cascade that results in the formation of blood
clots in the small blood vessels throughout the body.
This leads to compromise of tissue blood flow and can ultimately lead to multiple organ
damage.
In addition, as the coagulation process consumes clotting factors and platelets, normal clotting
is disrupted and severe bleeding can occur from various sites.
DIC does not occur by itself but only as a complicating factor from another underlying
condition, usually in those with a critical illness.
The combination of widespread tissue ischemia and simultaneous bleeding carry an increased
risk of death in addition to that posed by the underlying disease.
DIC can be overt and severe in some cases, but milder and insidious in others.
The diagnosis of DIC depends on the findings of characteristic laboratory tests and clinical
background.
Treatment is mainly geared towards the underlying condition.
Signs and symptoms In people with DIC, the underlying cause usually
leads to symptoms and signs, and DIC is discovered on laboratory testing.
The onset of DIC can be sudden, as in endotoxic shock or amniotic fluid embolism, or it may
be insidious and chronic, as in cases of malignancy.
Overt DIC can further lead to, or precipitate, multiorgan failure and widespread hemorrhage
from various sites.
Causes DIC can occur in the following conditions:
Solid tumors and hematologic malignancies Obstetric complications: abruptio placentae,
pre-eclampsia or eclampsia, amniotic fluid embolism, retained intrauterine fetal demise,
septic abortion Massive tissue injury: severe trauma, burns,
hyperthermia, rhabdomyolysis, extensive surgery Sepsis or severe infection of any kind: bacterial,
viral, fungal, or protozoan infections Transfusion reactions
Severe allergic or toxic reactions Giant hemangiomas
Large aortic aneurysms Liver disease, HELLP syndrome, Thrombotic
thrombocytopenic purpura/Hemolytic uremic syndrome, and malignant hypertension may mimic
DIC but do not occur via the same pathways.
Pathophysiology
Under homeostatic conditions, the body is maintained in a finely tuned balance of coagulation
and fibrinolysis.
The activation of the coagulation cascade yields thrombin that converts fibrinogen to
fibrin; the stable fibrin clot being the final product of hemostasis.
The fibrinolytic system then functions to break down fibrinogen and fibrin.
Activation of the fibrinolytic system generates plasmin, which is responsible for the lysis
of fibrin clots.
The breakdown of fibrinogen and fibrin results in polypeptides called fibrin degradation
products or fibrin split products.
In a state of homeostasis, the presence of plasmin is critical, as it is the central
proteolytic enzyme of coagulation and is also necessary for the breakdown of clots, or fibrinolysis.
In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread
clotting with resultant bleeding.
Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC
is similar in all conditions.
One critical mediator of DIC is the release of a transmembrane glycoprotein called tissue
factor.
TF is present on the surface of many cell types and is not normally in contact with
the general circulation, but is exposed to the circulation after vascular damage.
For example, TF is released in response to exposure to cytokines, tumor necrosis factor,
and endotoxin.
This plays a major role in the development of DIC in septic conditions.
TF is also abundant in tissues of the lungs, brain, and placenta.
This helps to explain why DIC readily develops in patients with extensive trauma.
Upon exposure to blood and platelets, TF binds with activated factor VIIa, forming the extrinsic
tenase complex.
This complex further activates factor IX and X to IXa and Xa, respectively, leading to
the common coagulation pathway and the subsequent formation of thrombin and fibrin.
The release of endotoxin is the mechanism by which Gram-negative sepsis provokes DIC.
In acute promyelocytic leukemia, treatment causes the destruction of leukemic granulocyte
precursors, resulting in the release of large amounts of proteolytic enzymes from their
storage granules, causing microvascular damage.
Other malignancies may enhance the expression of various oncogenes that result in the release
of TF and plasminogen activator inhibitor-1, which prevents fibrinolysis.
Excess circulating thrombin results from the excess activation of the coagulation cascade.
The excess thrombin cleaves fibrinogen, which ultimately leaves behind multiple fibrin clots
in the circulation.
These excess clots trap platelets to become larger clots, which leads to microvascular
and macrovascular thrombosis.
This lodging of clots in the microcirculation, in the large vessels, and in the organs is
what leads to the ischemia, impaired organ perfusion, and end-organ damage that occurs
with DIC.
Coagulation inhibitors are also consumed in this process.
Decreased inhibitor levels will permit more clotting so that a positive feedback loop
develops in which increased clotting leads to more clotting.
At the same time, thrombocytopenia occurs and this has been attributed to the entrapment
and consumption of platelets.
Clotting factors are consumed in the development of multiple clots, which contributes to the
bleeding seen with DIC.
Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to
plasmin, resulting in fibrinolysis.
The breakdown of clots results in an excess of FDPs, which have powerful anticoagulant
properties, contributing to hemorrhage.
The excess plasmin also activates the complement and kinin systems.
Activation of these systems leads to many of the clinical symptoms that patients experiencing
DIC exhibit, such as shock, hypotension, and increased vascular permeability.
The acute form of DIC is considered an extreme expression of the intravascular coagulation
process with a complete breakdown of the normal homeostatic boundaries.
DIC is associated with a poor prognosis and a high mortality rate.
There has been a recent challenge however to the basic assumptions and interpretations
of the pathophysiology of DIC.
A study of sepsis and DIC in animal models has shown that a highly expressed receptor
on the surface of hepatocytes, termed the Ashwell-Morell receptor, is responsible for
thrombocytopenia in bacteremia and sepsis due to Streptococcus pneumoniae and possibly
other pathogens.
The thrombocytopenia observed in SPN sepsis was not due to increased consumption of coagulation
factors such as platelets, but instead was the result of this receptor's activity enabling
hepatocytes to ingest and rapidly clear platelets from circulation.
By removing pro-thrombotic components before they participate in the coagulopathy of DIC,
the Ashwell-Morell receptor lessens the severity of DIC, reducing thrombosis and tissue necrosis,
and promoting survival.
The hemorrhage observed in DIC and among some tissues lacking this receptor may thereby
be secondary to increased thrombosis with loss of the mechanical vascular barrier.
This discovery has possible significant clinical implications in devising new approaches to
reducing the morbidity and mortality of DIC.
Diagnosis The diagnosis of DIC is not made on a single
laboratory value, but rather the constellation of laboratory markers and a consistent history
of an illness known to cause DIC.
Laboratory markers consistent with DIC include: Characteristic history
Prolongation of the prothrombin time and the activated partial thromboplastin time reflect
the underlying consumption and impaired synthesis of the coagulation cascade.
Fibrinogen level has initially thought to be useful in the diagnosis of DIC but because
it is an acute phase reactant, it will be elevated due to the underlying inflammatory
condition.
Therefore, a normal level can occur in over 57% of cases.
A low level, however, is more consistent with the consumptive process of DIC.
A rapidly declining platelet count High levels of fibrin degradation products,
including D-dimer, are found owing to the intense fibrinolytic activity stimulated by
the presence of fibrin in the circulation.
The peripheral blood smear may show fragmented red blood cells due to shear stress from thrombi.
However, this finding is neither sensitive nor specific for DIC
A diagnostic algorithm has been proposed by the International Society of Thrombosis and
Haemostasis.
This algorithm appears to be 91% sensitive and 97% specific for the diagnosis of overt
DIC.
A score of 5 or higher is compatible with DIC and it is recommended that the score is
repeated daily, while a score below 5 is suggestive but not affirmative for DIC and it is recommended
that it is repeated only occasionally: It has been recommended that a scoring system
be used in the diagnosis and management of DIC in terms of improving outcome.
Presence of an underlying disorder known to be associated with DIC
Global coagulation results Platelet count
Fibrin degradation products such as D-Dimer Prolonged prothrombin time
Fibrinogen level
Treatment Treatment of DIC is centered around treating
the underlying condition.
Transfusions of platelets or fresh frozen plasma can be considered in cases of significant
bleeding, or those with a planned invasive procedure.
The target goal of such transfusion depends on the clinical situation.
Cryoprecipitate can be considered in those with a low fibrinogen level.
Treatment of thrombosis with anticoagulants such as heparin is rarely used due to the
risk of bleeding.
Antithrombin and antifibrinolytics are generally not used.
Recombinant human activated protein C was previously recommended in those with severe
sepsis and DIC, but drotrecogin alfa has been shown to confer no benefit and was withdrawn
from the market in 2011.
Recombinant factor VII has been proposed as a "last resort" in those with severe hemorrhage
due to obstetric or other causes, but conclusions about its use are still insufficient.
Prognosis Prognosis varies depending on the underlying
disorder, and the extent of the intravascular thrombosis.
The prognosis for those with DIC, regardless of cause, is often grim: Between 10% and 50%
of patients will die.
DIC with sepsis has a significantly higher rate of death than DIC associated with trauma.
See also Sepsis
Septic shock Blood clotting tests
DIC is discussed in Michael Crichton's 1969 technothriller The Andromeda Strain, and its
movie adaptations.