Disseminated Intravascular Coagulation (DIC)

Disseminated Intravascular Coagulation Definition

Disseminated intravascular coagulation (DIC) is a rare life threatening bleeding disorder. This condition is characterized by a defective clotting mechanism. DIC causes thrombosis (excessive clotting) or hemorrhage (bleeding) throughout the body. The clotting cells or platelets cluster to form small clumps in the blood vessels. These clumps can clog small blood vessels throughout the body. This may cause damage to organs and may lead to widespread internal and external bleeding. In some cases, both blood clotting and bleeding occur simultaneously. Therefore DIC leads to organ failure, shock, and death.

DIC is not a disease in itself but a complication arising from the progression of other diseases. The process of blood coagulation starts with the production and deposition of a protein called fibrin. Other coagulation proteins and platelets soon join in to make the condition more severe. Various conditions that can result in DIC may include the following :

  • Severe infections or sepsis
  • Brain and spinal cord injuries
  • Organ damage
  • Cancer
  • Rheumatologic diseases (like lupus, adult stills disease)
  • Pregnancy and delivery complications
  • Blood circulation abnormalities
  • Liver failure
  • Toxicity developed during transfusions or transplant rejections
  • Heat stroke and high body temperature

Sepsis (inflammation in response to bacteria, viruses or fungi) is most commonly associated with DIC.

Disseminated Intravascular Coagulation Types

DIC can be of two types:

  • Acute DIC develops upon sudden exposure of blood to substances that promote coagulation (pro-coagulants). In acute DIC, the body’s compensatory mechanisms fail and this leads to hemorrhage and organ failure.
  • Chronic DIC develops by continuous or intermittent exposure to such substances.

Disseminated Intravascular Coagulation Incidence

DIC occurs in 30 to 50% of sepsis patients and in 1% of hospitalized patients. DIC disappears if the underlying conditions are treated properly and in time. Left untreated, severe DIC can increase the mortality rate significantly.

Disseminated Intravascular Coagulation Pathophysiology

DIC progresses in four phases:

  • Some proteins or tissue factors promote excessive production of a protein called thrombin. Thrombin promotes clumping of platelets and also activates other proteins involved in coagulation.
  • Thrombin changes the inactive form of fibrin (fibrinogen) to its active, insoluble form.
  • Anti-coagulation mechanisms in the body become dysfunctional due to excess of thrombin.
  • Inflammation ensues.

In the normal state, thrombin is inhibited by antithrombin III. In DIC, however, levels of antithrombin III decrease due to various reasons. In addition, the body’s capacity to remove extra fibrin becomes defective.

Disseminated Intravascular Coagulation Symptoms

Symptoms of DIC vary depending on the underlying conditions. The non-specific symptoms may include the following:

  • Bleeding of gums and gastrointestinal (GI) tract
  • Kidney and/or liver dysfunction with jaundice
  • Respiratory failure, breathlessness, coughing up of blood
  • Shock
  • Neurological symptoms such as nerve pain, dullness and coma.

Disseminated Intravascular Coagulation Complications

DIC can result in death. DIC may also lead to other complications like:

  • Sudden kidney failure
  • Change in mental status
  • Respiratory failure
  • Liver dysfunction
  • Severe clotting or bleeding
  • Accumulation of blood between heart muscles, between chest wall and lungs, and in the brain
  • Gangrene and loss of fingers
  • Shock

Disseminated Intravascular Coagulation Causes

DIC can develop in two ways:

  • Inflammation throughout the body can activate the coagulation process as is seen in sepsis or major trauma.
  • Release of pro-coagulants into the blood can lead to DIC as is seen in cancer, in pregnancy or during delivery.

Cancers and pregnancy/delivery related complications can lead to both acute and chronic DIC.

Other causes can be categorized according to acute or chronic DIC.

Acute Disseminated Intravascular Coagulation

  • Bacterial, viral, fungal, or parasitic infections
  • Traumas with burns, automobile accidents or snake bite
  • Blood transfusions
  • Liver diseases or failure
  • Use of prosthetics or shunts

Chronic Disseminated Intravascular Coagulation

  • Premature breakdown of red blood cells
  • Rheumatoid arthritis
  • Raynaud disease
  • Heart attack
  • Inflammation in ulcerative colitis, sarcoidosis, Crohn disease
  • Clots in blood vessels, vascular tumor as is seen with giant hemangioma
  • Kidney transplant rejection
  • Hemolytic uremic syndrome

Disseminated Intravascular Coagulation Diagnosis

DIC can be difficult to diagnose. Various blood tests that help in diagnosis may include:

  • D-dimer test measures fibrin levels.
  • Prothrombin time (PT/INR) test measures the time taken for blood to clot.
  • Fibrinogen test measures blood fibrinogen levels.
  • Complete blood count (CBC) determines the number of red and white blood cells.
  • An abnormal and damaged blood smear may be indicative of DIC.

Disseminated Intravascular Coagulation Treatment

Treatment focuses on treating the underlying disease. By doing so, DIC resolves on its own. The aims of treatment are to reduce complications and to bring down the risk of death.

  • Platelet and coagulation factor replacements are frequently recommended in patients with active bleeding and for those with bleeding complications.
  • Heparin is reserved for chronic DIC cases that show excess fibrin accumulation in the absence of much bleeding.
  • A factor called activated protein C (APC) is beneficial in sepsis patients.
  • Administration of blood components and coagulation factors.
  • Platelet transfusion is recommended for patients with severe platelet deficiency.
  • Coagulation factors administration may be risky and is done with great caution. Fresh frozen plasma (FFP) is administered in patients with coagulation defects.
  • Administration of vitamin K is considered in cases of vitamin K deficiency.
  • Low molecular weight heparin (LMWH) formulations, like  enoxaparin, are used for treating chronic DIC cases.
  • Administration of anti-thrombin may help restore the functions of the anti-coagulation pathways.
  • Administration of activated protein C decreases the risk of death and organ failure in patients with sepsis.
  • Recombinant thrombomodulin is given to blood cancer patients with severe sepsis.

DIC Medication

  • Heparin supports anti-thrombin III action and prevents conversion of fibrinogen to fibrin. It also prevents the reformation of the clot after it is broken down.
  • Anti-thrombin III inactivates thrombin, plasmin, and other factors to inhibit coagulation.
  • Recombinant Human Activated Protein C (APC) inhibits clotting factors
  • Blood components (platelet concentrates, washed packed red blood cells) correct abnormal blood parameters.
  • Washed packed RBCs are recommended for individuals with transfusion reactions.
  • Cryoprecipitate or fibrinogen concentrates are recommended in rare cases of fibrinogen deficiency.
  • Anti-fibrinolytic agents (like aminocaproic acid and tanexamic acid) are generally given to cancer patients. The use of aminocaproic acid carries the risk of blood clot formation. These clots are difficult to break down.

References :