Disseminated intravascular coagulation (DIC) is a secondary pathologic process with unbridled systemic activation of the intravascular coagulation system resulting in thrombosis and consumption of both platelets and coagulation factors followed by secondary fibrinolysis.

A consensus definition offered by the International Society of Thrombosis and Haemostasis is: “DIC is an acquired syndrome characterized by the intravascular activation of coagulation with loss of localization arising from different causes. It can originate from and cause damage to the microvasculature, which if sufficiently severe, can produce organ dysfunction.”

It is also known as consumption coagulopathy, defibrination syndrome or consumptive thrombohemorrhagic disorder based on its pathologic findings.

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Hemostasis is maintained by a balance of complex vascular and reticuloendothelial factors. Any exposure of tissue factor initiates coagulation via the factor VIIa pathway leading to thrombin formation. Platelet aggregation and fibrin cross-linking result in a “hemostatic plug.” This coagulation is normally localized to a small area by inhibitors of coagulation, especially antithrombin (AT) and tissue factor pathway inhibitor (TFPI).

Certain clinical conditions (like sepsis, trauma, and obstetric conditions) can lead to an excessive production of thrombin by the following mechanisms:

  • Exposure of tissue factor after extensive injury to the vascular endothelium

  • Release of thromboplastins into the circulation.

  • Cytokine (especially tumor necrosis factor [TNF] or interleukin-6 [IL-6]) or endotoxin-mediated expression of tissue factor by monocytes.

The generation of such large amounts of thrombin can lead to a loss of localization, and its circulation can cause systemic thrombosis tipping the balance in favor of a consumptive state. The circulating thrombin leads to widespread clotting with a resultant microangiopathy causing ischemic effects as well as consumption of platelets, fibrinogen, prothrombin, and coagulation factors.

Secondary fibrinolysis then sets in with generation of plasmin-mediated fibrin-degradation products (FDPs). These further interfere with platelet aggregation and fibrin polymerization leading to diffuse bleeding. As thrombin undergoes rapid activation, its specific inhibitor antithrombin (AT) gets depleted. Similarly, α2-antiplasmin depletion follows the secondary fibrinolysis from plasmin.

Generally, two types are described based on acuity of onset, underlying medical condition, and clinical presentation.

This is generally seen with severe sepsis, trauma, acute promyelocytic leukemia or acute obstetrical emergencies like abruptio placentae. Acute DIC develops when the blood is exposed to a large amount of tissue factor, leading to a significant generation of thrombin. There is rapid systemic activation of the coagulation system and the end result is generally diffuse bleeding with possible hemodynamic instability and microangiopathy with end organ dysfunction as described above.

This is generally seen with advanced malignancies (such as Trousseau’s syndrome), aortic aneurysms, etc., in which the blood is exposed to small or intermittent amounts of tissue factor, leading to localized activation of the coagulation system. Venous and arterial thrombosis predominate as the marrow and liver can maintain adequate platelet counts and coagulation factors respectively, thus preventing an overt consumptive process leading to bleeding.

The following factors determine presence of disseminated intravascular coagulation:

  • Presence of an etiologic condition that is known to precipitate systemic coagulation.

  • Laboratory abnormalities suggesting that the patient has consumption of platelets and coagulation factors.

  • Laboratory abnormalities suggesting that the patient has ongoing fibrinolysis.

The rate of consumption of coagulation factors decides the severity of symptoms, while the underlying systemic illness generally defines whether the patient would manifest with bleeding or thrombosis. Bleeding is more common than thrombosis, especially in acute severe DIC, since the eventual cascade terminates in secondary fibrinolysis with lysis of hemostatic plugs and consumption of factors.

Clinical manifestations include:

  • Laboratory abnormalities without clinically significant symptoms (generally in chronic DIC or very early acute DIC).

  • Bleeding (64%).

  • Thrombosis (7%).

  • Secondary effects including multi-organ failure due to widespread ischemia.

  • Symptoms related to the underlying precipitating disease.

DIC generally leads to diffuse bleeding from recent wounds, surgical incisions, and catheter sites (urinary and vascular). It can cause petechial and ecchymotic lesions in the subcutaneous tissues along with epistaxis and gum bleeding. Occasionally, spontaneous bleeding can be life-threatening when in the gastrointestinal tract, pulmonary system, adrenal glands, or central nervous system. Infarctive necrosis of the microcirculation leading to widespread truncal and extremity ecchymosis seen in sepsis-associated DIC is termed purpura fulminans. Intraoperative DIC (due to trauma, ABO incompatibility reactions, or concurrent sepsis) may be evident only by hematuria or excessive bleeding at the surgical site.

Thrombosis in more frequent in chronic DIC and can be venous or arterial, manifesting as acral cyanosis, digital ischemia or gangrene. In patients with malignancy, especially adenocarcinomas, chronic DIC may present as recurrent thrombophlebitis (Trousseau’s syndrome) and venous thromboses.

Systemic tissue hypoxia due to microthrombosis along with hypoperfusion from bleeding can lead to vital organ dysfunction, especially renal impairment, which is seen in 25-40% of patients. Microthrombi in the afferent arterioles can also cause renal cortical necrosis. Hypoxic hepatic injury or intravascular fibrin deposition resulting in microangiopathic hemolytic anemia (MAHA) can lead to jaundice. Patients may experience myocardial ischemia, delirium or focal neurologic deficits due to prolonged end organ hypoxia.

Etiologic disease symptoms may lead to systemic complications similar to DIC and may confound the picture. Amniotic fluid embolism, sepsis, and trauma can lead to dyspnea and acute respiratory distress syndrome (ARDS). Crush injuries and transfusion reactions can also cause renal failure, while closed head injuries may result in delirium and neurologic deficits.

DIC is thought to be present in up to 1% of hospital admissions. However, the list of etiologies is expansive and the clinical presentations range from isolated laboratory abnormalities to critically ill patients with multi-organ dysfunction. This precludes an accurate assessment of prevalence.

DIC is always secondary to an underlying pathologic disorder that induces an imbalance in the coagulation system. The following common causes of DIC are generally obvious from the clinical symptoms and imaging results.

Classically gram-negative endotoxemia has been implicated with DIC in 30-50% of cases; however, any microorganism (gram-positive organisms, fungi and, rarely, parasites and viruses) is capable of inducing DIC depending on extent of cytotoxin activation (TNF and IL-6).

Apart from release of tissue factor and phospholipids, the associated shock predisposes to accumulation of activated factors which fuels DIC.

Polytrauma/crush injuries

  • Injury to brain tissues including closed head injury.

  • Fat embolism.

  • Frostbite and burns.

  • Pancreatitis, especially when hemorrhagic due to intravascular release of trypsin.

  • Severe hepatic failure.

Some tumors express tissue factor on their surfaces or harbor procoagulant granules:

  • Metastatic solid tumors.

  • Mucinous adenocarcinomas.

  • Lymphoproliferative disorders.

  • Leukemias, especially promyelocytic leukemia.

  • Amniotic fluid embolism.

  • Ectopic pregnancy.

  • Uterine atony.

  • Abruptio placentae.

  • Retained dead fetus.

  • Therapeutic abortion.

  • Kassabach-Merrit phenomenon (giant hemangioma).

  • Vascular aneurysms.

  • Snake venom.

  • Recreational drugs (amphetamines).

  • Hemolytic transfusion reactions.

  • Acute transplant rejection.

  • Vasculitis.

  • Near drowning.

  • Heat stroke.

  • Cardiac arrest.


Severe liver disease can cause elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT) and hypofibrinogenemia due to decreased hepatic synthesis of coagulation factors and proteins, thrombocytopenia from portal hypertension-induced hypersplenism, and elevated fibrin degradation product (FDP) due to decreased clearance. However, the associated hepatic function tests may divert attention to this being of hepatic origin.

Thrombocytopenic thrombotic purpura-hemolytic uremic syndrome (TTP-HUS) induces microangiopathic hemolytic anemia (MAHA) and thrombocytopenia due to a deficiency in ADAMS13 protease, leading to long Von Willebrand factor multimers on the endothelium that bind platelets. In contrast to DIC, patients have a normal PT, aPTT, FDPs and D-dimer levels. A way to remember the difference between DIC and TTP-HUS is that TTP-HUS is not a coagulopathy, and thus PT and aPTT are normal (in DIC, PT and aPTT are elevated).

Hyperfibrinolytic syndrome: Fibrinolysis can be a primary (due to imbalance between the promoters and inhibitors of plasmin) or a secondary phenomenon (due to primary coagulation causing widespread thrombin generation which then triggers endothelial release of plasminogen activator). Hyperfibrinolysis is generally seen in patients with cirrhosis with decreased levels of antiplasmin or those undergoing cardiac bypass or orthotopic liver transplantation with increased levels of tissue plasminogen activator and can cause widespread bleeding. It may be important to differentiate this from DIC due to the potential role of antifibrinolytic agents in its treatment.

HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome can be indistinguishable from DIC, especially since it can precipitate DIC. The presence of hypertension, pre-eclampsia and liver abnormalities may indicate HELLP.

Heparin-induced thrombocytopenia (HIT): HIT is a potentially life-threatening result of antibody formation to platelet factor four (PF4) epitope due to exposure to heparin. Similar to DIC, HIT may manifest with thrombosis and bleeding. However, unlike DIC, HIT is characterized by recent exposure to heparin, positive antibodies to PF4, and normal coagulation factors.


Physical findings depend on the underlying disease process and vary based on a patient’s tendency to bleeding or clot. Careful attention should be given to subtle signs of oozing at incision and catheter sites or nonspecific signs suggestive of venous thrombosis (such as asymmetric leg swelling).

DIC is a clinical diagnosis supported by laboratory data. The International Society for Thrombosis and Hemostasis has developed a scoring system for the diagnosis of DIC. A patient with a DIC triggering disease process, with a decreasing platelet count and abnormal coagulation profile should suggest onset of DIC. Further tests may help hone in on the diagnosis while ruling out the most common mimickers of DIC.

Due to the dynamic nature of DIC, these tests should be performed at the same time to get a snapshot of the coagulation imbalance. However, the diagnosis should not be made from a single observation but from trends in counts over hours or days in the right clinical setting. It is worth noting that treatment directed towards these laboratory abnormalities may stabilize, but this does not alter the course of the disease.

The following panel of tests help diagnose DIC:

  • CBC with peripheral smear.

  • Liver function tests.

  • Prothrombin time (PT) and activated partial thromboplastin time (aPTT).

  • Thrombin time (TT).

  • Fibrin degradation product (FDP) assay and D-dimer.

  • Fibrinogen.


Any degree of thrombocytopenia can be seen in DIC but the count is rarely less than 20,000/μL. Occasionally chronic DIC and those with predominant thrombotic symptoms may present with normal or elevated counts.

Evaluation of the peripheral smear may reveal thrombocytopenia along with schistocytes due to the microangiopathic shearing forces causing RBC damage. This could narrow the differential diagnosis to DIC and TTP-HUS.

Consumption of coagulation factors causes significant elevation of PT, aPTT and TT in approximately two thirds of cases. The circulating FDPs prevent normalization of these values with 1:1 mixing studies.

The few causes of hypofibrinogemia include rare congenital dysfibrinogenemias, liver disease including hepatitis C and DIC. Hence, in the absence of underlying liver disease, a level less than 100 mg/dL is generally indicative of DIC. However, fibrinogen is also an acute phase reactant and patients with cancer, chronic illnesses, pregnancy, etc. may have elevated levels near 500 mg/dL. In such cases, despite a significant drop, data may still show initial normal fibrinogen levels, but due to its half-life of 4 hours, follow-up labs would reveal a declining trend.


An elevated qualitative FDP level indicates secondary fibrinolysis, which is required to diagnose DIC. D-dimer is more sensitive since it is quantitative and measures degradation of clot-specific cross-linked fibrin. However, D-dimer is also non-specifically elevated in patients with thrombosis, acute renal failure, liver failure, cancer, and sepsis. The combination of D-dimer with FDP can be nearly 100% specific for DIC in the right clinical setting. Also, it may be the only laboratory abnormality in some patients with chronic DIC.


A comprehensive metabolic panel can help assess renal function, underlying liver synthetic dysfunction, and evaluate for ongoing hemolysis and underlying acidosis. Hemolysis may be evident in 10-20% patients with DIC.


Platelet counts and fibrinogen levels decrease in proportion to the severity of DIC. However, there are many concurrent factors (complication of liver disease, marrow-suppressing sepsis, and antibiotics) that may affect their values, and it may be difficult to assess the severity of underlying disease separate from that of the DIC it triggered.

As thrombin undergoes rapid activation, its specific inhibitor antithrombin (AT) gets depleted and its level can reflect on the severity and possibly prognosticative outcomes. Similarly α2-antiplasmin depletion follows the secondary fibrinolysis from plasmin. These two levels are rarely utilized and are available at a few tertiary care centers to predict ongoing severe DIC. They tend to normalize within 48 hours of resolution of acute DIC and may also be normal in chronic DIC.


As noted, an elevated D-dimer may be the only abnormality in chronic DIC, which is non-specific in the presence of co-existing systemic illnesses. Some tertiary centers may be able to diagnose chronic DIC with radiolabeled turnover studies of platelets and fibrinogen to suggest increased consumption and a compensated increased production of factors.

Imaging studies have no role in the diagnosis of DIC. However, vascular ultrasounds and computed tomography (CT) imaging may be indicated for symptom-specific evaluation of thrombosis or bleeding.




DIC is a hematologic emergency. It portends a very poor prognosis if the diagnosis is delayed, with mortality in the range of 40-80%. Excessive amounts of time and resources may be spent in correcting laboratory abnormalities, but effective treatment will always require treatment of the underlying condition to resolve the hemostatic imbalance.


Depending on the severity of the underlying illness, the number of organ systems affected, and hemodynamic instability, the patient may need care in an intensive care unit.

The components of treatment are:

  • Treat the underlying disorder.

  • Blood component therapy.

  • Hematologic consultation.

  • Use of heparin.

  • Other therapies: fibrinolytics and activated protein C.


Correcting the inciting event can restore the hemostatic balance within 24-48 hours by allowing the liver and bone marrow to correct the factor and cell deficiencies. This may involve administering antibiotics for sepsis or may involve surgery for dilated aneurysms and retained products of conception.

Promyelocytic leukemia can precipitate DIC since cell lysis releases procoagulant molecules and tissue factor in the circulation. Use of a differentiating agent like all-trans retinoic acid (ATRA) along with chemotherapy at diagnosis can avoid this situation.


There is a tendency to provide aggressive blood components—packed red blood cells (PRBC), platelets, cryoprecipitate, or fresh frozen plasma (FFP)—due to the glaring laboratory abnormalities. However, the coagulopathy in DIC can be short-lived or clinically insignificant and may not require any treatment in a significant proportion of patients. Only patients with clinically significant bleeding or those at a high risk of bleeding merit transfusion support while the underlying illness is treated. Fear of aggravating the coagulopathy by providing exogenous coagulation factors and platelets is unfounded and should not guide clinical decisions.

Indications for platelet transfusion are:

  • Patients with severe thrombocytopenia (<10,000/μL) due to the risk of significant bleeding.

  • Patients with moderate thrombocytopenia (less than 50,000/μL) with severe bleeding. Patients with moderate thrombocytopenia with an increased risk of bleeding, including postoperative patients, patients scheduled for invasive procedures, and patients with major trauma.

Note, transfusions of platelets may not show the expected rise in counts due to concurrent consumption.

Indications for fresh frozen plasma are:

  • Patients with severe bleeding with associated supratherapeutic internal normalized ratio (INR) and aPTT.

  • Patients with purpura fulminans. FFP is a source for protein C, but the half-life of protein is short. Therefore, multiple units of FFP every 6 hours may be required. Protein C concentrate is, therefore, the preferred therapy.

  • Indications for cyroprecipitate are:

Patients with acute DIC with active bleeding to maintain a fibrinogen level greater than 100mg/dL.


This may be appropriate in severe DIC, in critically ill patients, where there is difficulty in controlling the underlying problem, or to seek guidance regarding use of heparin or fibrinolysis inhibitors. Obviously, an oncologic evaluation is required for DIC associated with underlying malignancy.


DIC causes widespread activation of thrombin and hence, potentiating AT could thwart the cascade. Heparin as an AT activator may help decrease the coagulopathy in refractory cases; however, studies have not revealed any benefit of this strategy and the risk of augmenting the bleeding is increased. Therefore, heparin is relatively contraindicated in patients with acute DIC and should only be given in consultation with Hematology. Some guidelines recommend use of heparin in patients with thrombosis, but such recommendations are controversial due to the difficulty in monitoring PTT levels.

Low-dose heparin, without any bolus, may be used in the following settings:

  • Chronic low grade DIC with predominant thrombotic manifestations—Trousseau’s syndrome, digital ischemia, deep vein thromboses (DVTs.)

  • Retained dead fetus prior to induction of labor.

  • Abdominal aortic aneurysm with DIC prior to repair.


  • Platelet counts less than 50,000/μL even with platelet transfusions.

  • Severe intracranial or diffuse gastrointestinal (GI) bleeding.

  • Patients with obstetrical complications, diffuse severe trauma or other conditions with a potential need of emergent surgery.

The heparin is started at a low rate (6-10 U/kg/hour) without bolus and aPTT is targeted to be around 45-50 assuming baseline PTT was close to normal. A stabilizing platelet count and fibrinogen level suggests that the strategy is working. In severe DIC the AT levels may be drastically reduced, precluding a significant effect of heparin. In these cases, FFP or AT concentrates may be needed to boost AT levels to more than 50%.

In Trousseau’s syndrome warfarin has proved to be ineffective and these patients generally require therapeutic dose unfractionated heparin to prevent recurrence of venous thromboembolism (VTE).


Several inhibitors at different nodes in the coagulation pathway have been evaluated without uniform benefit. Epsilon-aminocaproic acid (EACA) infusion in conjunction with heparin (to prevent thrombosis) has been tried for prompt bleeding control. Few trials have shown benefit of activated protein C in cases of DIC associated with sepsis. These therapies remain controversial and should only be considered in consultation with hematology.




DIC is a dynamic condition and hence every 6 hours monitoring of CBC, fibrinogen and coagulation studies are necessary until an improving trend is established.




Since DIC can be a medical emergency, immediate management involves prompt treatment of the underlying disease while supportive care is provided as described above.

Patients should be monitored for decompensation of heart failure if the decision is made for transfusion of multiple units of fresh frozen plasma so as to avoid transfusion-associated volume overload.


It is helpful to give precise sign-out directives on the 6-hourly laboratory data to ensure an improving trend. Transfusion triggers should be explicit, for example “transfuse 10 units of cryoprecipitate for fibrinogen level less than 100 mg/dL”. Also advance directives should be clarified with the patient or next of kin in advance and an emergency contact should be listed on the sign-out.









DIC carries a high inpatient mortality of 40-80% based on the severity of the underlying condition. However, as long as the etiology is recognized and treated promptly, DIC can be reversed before the tissue hypoxia causes permanent damage.






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