Disseminated intravascular coagulation (DIC) is an acquired thromboembolic disorder characterized by generalized activation of the clotting pathways, which results in the intravascular formation of fibrin and ultimately thrombotic occlusion of small and midsize vessels, resulting in end-organ damage.

Consumptive coagulopathy

DIC

Defibrination syndrome

About 1% of hospitalized patients may have evidence of DIC. There is no predilection for age or gender. More than 50% of cases are associated with gram-negative sepsis or other septicemic infections, and up to 35% of patients with severe sepsis have DIC.

DIC occurs in both acute and chronic forms and can present with bleeding, thrombosis, or laboratory evidence of clotting cascade activation and fibrinolysis without evident clinical sequelae. Acute DIC is more common and predominantly manifests as bleeding complications. The risk of bleeding increases with worsening thrombocytopenia and is fivefold higher when platelet count is below <50 × 10⁹/liter. Sudden exposure to procoagulants can prompt coagulation cascade activation and platelet consumption, resulting in thrombosis. In contrast, chronic DIC more frequently causes thrombotic complications. The diagnosis of chronic DIC can be challenging, as the PT and PTT are frequently normal. Multiple pathways are involved in DIC pathophysiology ultimately leading to consumptive coagulopathy and thrombosis. These include: (1) Thrombin generation due to release of tissue factor or other procoagulants, (2) suppression of physiologic anticoagulant (e.g., protein C/S or antithrombin insufficiency), (3) impaired fibrinolysis characterized by increased level of plasminogen activator inhibitor type 1 (PAI-1) and fibrin degradation products, and (4) activation of inflammatory pathways.

With DIC, multiple organs may be involved, and clinical presentations may vary. They can include:

• Central nervous system: Altered mental status, transient neurologic deficits
• Cardiovascular: Hypotension, tachycardia
• Respiratory: Hypoxia, dyspnea, localized rales, and acute respiratory distress syndrome
• Gastrointestinal: Intestinal bleeding, bowel infarction
• Genitourinary: Oliguria, anuria, uremia, acidosis, metrorrhagia
• Skin: Wound site bleeding, epistaxis, gingival bleeding, hemorrhagic bullae, petechiae, ecchymosis, purpura, skin necrosis

DIC results from the aberrant and generalized activation of the clotting system, resulting in simultaneous formulation of coagulation and fibrinolysis. As a result of increased thrombus generation in the small and medium vessels, clotting factors and platelets are consumed more rapidly than the synthetic function of the liver and bone marrow, respectively. Diseases associated with DIC are summarized in Box E1. Severe infection is the most common inciting etiology, though an extensive list of other triggers are known, including:

• Infections (e.g., gram-negative sepsis, Rocky Mountain spotted fever, COVID-19, malaria, viral or fungal infection)
• Obstetric complications (e.g., fetal demise, amniotic fluid embolism, toxemia, abruptio placentae, septic abortion, preeclampsia/eclampsia, placenta previa, uterine atony)
• Tissue trauma (e.g., polytrauma, burns, hypothermia rewarming)
• Malignancy (e.g., adenocarcinomas [gastrointestinal, prostate, lung, breast] especially mucin-producing cancers, lymphoproliferative/myeloproliferative; DIC is a hallmark of acute promyelocytic leukemia and a leading cause of mortality)
• Quinine, cocaine-induced rhabdomyolysis
• Liver failure
• Acute pancreatitis
• Transfusion reactions
• Respiratory distress syndrome
• Toxins (snake bites, amphetamine overdose)
• Other: Systemic lupus erythematosus (SLE), vasculitis, aneurysms, polyarteritis, hemangiomas with thrombocytopenia, and consumptive coagulopathy (Kasabach-Merritt syndrome)

• Hepatic necrosis: Normal or elevated factor VIII concentrations
• Vitamin K deficiency: Normal platelet count
• Hemolytic uremic syndrome: Coagulation assays are usually normal
• Thrombotic thrombocytopenic purpura: Low ADAMTS13 activity
• Renal failure, SLE, sickle cell crisis, dysfibrinogenemias
• HELLP syndrome (hemolysis, elevated liver function tests, and low platelets)
• COVID-19 related coagulopathy: Elevated fibrinogen, SARS-CoV-2 PCR positive

The diagnostic workup includes laboratory testing to characterize the coagulopathy and its severity and exclude conditions noted in the differential diagnosis (Tables 1 and 2, Box 2). Additional workup is guided by the clinical scenario and may include distinguishing DIC progression (acute vs. chronic), chief manifestations (thrombotic or hemorrhagic), and extent (localized or systemic).

• Peripheral blood smear generally shows red blood cell fragments (schistocytes) and low platelet counts.
• Coagulation testing: Diagnostic characteristics of DIC are decreased fibrinogen level; thrombocytopenia; and increased prothrombin time (PT), partial thromboplastin time (PTT), thrombin time (TT), fibrin split products, and D-dimer.
• Coagulopathy secondary to DIC must be differentiated from other coagulopathies that result from underproduction of clotting factors, including liver disease or vitamin K deficiency.
  1. Vitamin K deficiency manifests with prolonged PT but normal PTT, TT, platelet, and fibrinogen levels; PTT may be elevated in severe cases.
  2. Patients with liver disease have abnormal PT and PTT; TT and fibrinogen are usually normal unless severe disease is present; platelets are usually normal unless splenomegaly is present.
  3. Factor VIII is not synthesized exclusively by the liver. It can differentiate between DIC, where it is low, and coagulopathy of liver disease, where it is normal or elevated.

Imaging studies are generally not useful. Imaging may be helpful for identifying sequelae of DIC, including chest radiographs to exclude infectious processes in patients with pulmonary symptoms such as dyspnea, cough, or hemoptysis.

• Correcting and eliminating the underlying cause is often sufficient to halt DIC (e.g., antimicrobial therapy for infection, removal of necrotic bowel, evacuation of uterus in obstetric emergencies).
• Patients with bleeding should be given replacement therapy with fresh frozen plasma (FFP) and platelets:
  1. FFP 10 to 15 ml/kg can be given with a goal of normalizing international normalized ratio.
  2. Platelet transfusions are given when platelet count is <10,000 (or higher if major bleeding is present).
  3. Cryoprecipitate 1 U/5 kg is given for low fibrinogen. It also can be given for prevention of bleeding in patients with fibrinogen level <100 mg/dl.
• Patients with extensive thrombosis (e.g., in acute promyelocytic leukemia, purpura fulminans, acral ischemia) require anticoagulation, despite thrombocytopenia and abnormal coagulation parameters. Heparin therapy using unfractionated heparin with lower PTT goal than is used in venous thrombosis may be useful to increase neutralization of thrombin. Low-molecular-weight heparin also may be used in this scenario.
• The mainstays of supportive treatment of DIC are summarized in Box E3.

Mortality rate in severe DIC exceeds 75%. The high mortality rate is often due to the severity of the underlying trigger and complications including acute renal failure, intracerebral bleeding, shock, or cardiac tamponade.

Hematology consultation is recommended in all cases of severe DIC and DIC with hemorrhagic or thrombotic complications.

The treatment of chronic DIC is controversial. Low-dose SC heparin and/or combination antiplatelet agents such as aspirin and dipyridamole may be useful.

Disseminated Intravascular Coagulation (Patient Information)