Disseminated Intravascular Coagulation

Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout
the body, blocking small blood vessels.[1] Symptoms may include chest pain, shortness of breath, leg
pain, problems speaking, or problems moving parts of the body.[1] As clotting factors and platelets are
used up, bleeding may occur.[1] This may include blood in the urine, blood in the stool, or bleeding
into the skin.[1] Complications may include organ failure.[2]
Relatively common causes include sepsis, surgery, major trauma, cancer, and complications of
pregnancy.[1] Less common causes include snake bites, frostbite, and burns.[1] There are two main
types: acute (rapid onset) and chronic (slow onset).[1] Diagnosis is typically based on blood tests.
[2]
Findings may include low platelets, low fibrinogen, high INR, or high D-dimer.[2]
Treatment is mainly directed towards the underlying condition.[2][3] Other measures may include
giving platelets, cryoprecipitate, or fresh frozen plasma.[2] Evidence to support these treatments,
however, is poor.[2] Heparin may be useful in the slowly developing form.[2] About 1% of people
admitted to hospital are affected by the condition.[4] In those with sepsis, rates are between 20% and
50%.[4] The risk of death among those affected varies from 20 to 50%.[4]
Signs and symptoms[edit]

In 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 cancer. DIC can lead to multiorgan failure and
widespread bleeding.[5]
Causes[edit]
DIC can occur in the following conditions:[5][6][7][8]
 Cancer: solid tumors and blood cancers (particularly acute promyelocytic leukemia)

 Complications of pregnancy: abruptio placentae, pre-eclampsia or eclampsia, amniotic fluid
embolism, retained intrauterine fetal demise, septic abortion, postpartum hemorrhage
 Massive tissue injury: trauma, burn, hyperthermia, rhabdomyolysis, surgery
 Infection: bacterial (Gram-negative or Gram-positive), viral, fungal, or protozoan
 Transfusion reaction: ABO incompatibility
 Allergic or toxic reaction: snake venom
 Hemangioma: Kasabach–Merritt syndrome
 Aortic aneurysm
Liver disease, HELLP syndrome, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome,
and malignant hypertension may mimic DIC but originate via other pathways.[citation needed]
Pathophysiology[edit]
The coagulation cascade of secondary hemostasis.
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 (in the presence of thrombin), which is responsible for the lysis of fibrin
clots. The breakdown of fibrinogen and fibrin results in polypeptides called fibrin degradation
products (FDPs) or fibrin split products (FSPs). 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.[citation needed]
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). TF is present on the surface of many cell
types (including endothelial cells, macrophages, and monocytes) 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 (particularly interleukin 1), tumor necrosis factor,
and endotoxin.[9] 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 (normally present in trace amounts in the blood), 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.[7]
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 (PAI-1), which prevents fibrinolysis.
[10]
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.[citation needed]
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.[citation needed]
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.[citation needed]
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 (SPN) 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.[11] By removing prothrombotic 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 therefore be secondary to increased thrombosis with loss of the mechanical
vascular barrier.[citation needed]
Activation of the intrinsic and extrinsic coagulation pathways causes excess thrombus formation in
the blood vessels. Consumption of coagulation factors due to extensive coagulation in turn causes
bleeding.[citation needed]

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Disseminated intravascular coagulation (DIC) is a condition in which blood clots form throughout

Signs and symptoms[edit]

 Cancer: solid tumors and blood cancers (particularly acute promyelocytic leukemia)

The coagulation cascade of secondary hemostasis.

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