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61. Disseminated intravascular coagulation (DIC)

Disseminated intravascular coagulation (DIC) is what occurs when something causes an uncontrolled activation of coagulation and fibrinolysis. It’s characterised by the presence of both thrombosis and haemorrhage simultaneously, and it may cause organ failures or even death. It does not occur by itself, but is rather a result of another severe disorder.

Following the uncontrolled activation of coagulation that leads to the formation of microthrombi everywhere in the body, clotting factors and platelets are used up (“consumed”). Now that the level of clotting factors and platelets is much lower than normal, the body is in a hypocoagulable state, and so widespread haemorrhage occurs.

Etiology

DIC can occur secondarily to many disorders, but the most common are:

  • Sepsis
  • Malignancy
  • Trauma
  • Obstetrical complications
  • Transfusion reactions

Pathomechanism

DIC can occur due to the activation of either of the two different pathways of the coagulation cascade:

  • The intrinsic pathway of coagulation
  • The extrinsic pathway of coagulation

The intrinsic pathway is activated if there is widespread endothelial damage or toxins which activate factor XII. This can occur due to:

  • Circulatory shock
  • Hypothermia or heat shock
  • Sepsis
  • Haemolytic-uraemic syndrome

Endothelial damage or toxins activate factor XII, which in turn activates:

  • The intrinsic pathway of coagulation
  • The kallikrein-kinin system, especially bradykinin, which causes vasodilation and hypotension
  • Fibrinolysis by activating plasminogen and plasmin.

In the intrinsic pathway, hypotension and fibrinolysis will occur early.

The extrinsic pathway is activated when there is widespread release of tissue factor into the circulation, which may occur due to:

  • Tissue damage
    • Burns, frost-bite
    • Head trauma
    • Polytrauma (like in car crash)
  • Pregnancy complications (amniotic fluid embolism, abnormal separation of placenta)
  • Cancer
  • Heat stroke
  • Acute pancreatitis

The widespread tissue damage releases thromboplastin, a protein stored in tissues. Thromboplastin is released into the circulation, which activates factor VII, the first factor in the extrinsic pathway of coagulation.

In the extrinsic pathway, hypotension and fibrinolysis will appear late.

DIC has three phases:

  • The thrombotic phase is characterised by widespread microthrombi formation in the capillaries, which impairs the tissue circulation by creating sludge-like circulation in the capillaries. This also consumes most of the platelets and clotting factors.
  • The consumption coagulopathy phase is characterised by widespread bleeding similar to a bleeding disorder, because the platelets and clotting factors are depleted.
  • The fibrinolytic phase occurs simultaneously as the previous phases. The fibrinolytic system is activated by the formation of microthrombi. Plasmin cleaves fibrin and fibrin degradation products into other products like D-dimers. These D-dimers impair further clotting.

Organ damage may occur due to reduced perfusion due to microthrombosis, due to thrombosis, and/or due to bleeding.

Consequences

Consequences of DIC include:

  • Circulatory shock (or aggravation of the shock if already present)
  • Severe bleeding
  • Organ failure of any organ (acute kidney injury, acute liver failure, acute respiratory distress syndrome, CNS dysfunction, etc.)
  • Multi organ dysfunction syndrome (MODS)
  • Death

Patients may spontaneously start to bleed in the skin or mucosal surfaces (petechiae, ecchymoses) or at the site of IV catheters, or into body cavities.

DIC may also cause:

  • Sheehan’s syndrome, where there is a pituitary necrosis caused by blood loss during and after child birth
  • Waterhouse-Friderichsens’s syndrome, where there is apoplexy (severe bleeding) in adrenal glands, causing adrenal insufficiency and death.

Treatment

Treatment involves treating the underlying condition as well as transfusions of fresh frozen plasma and platelets to replenish clotting factors and platelets.

Chronic DIC

Yes, DIC can be chronic in certain cases, especially in cancer patients. The formation of microthrombi isn’t fulminant and fast but slow and moderate. Spontaneous bleeding and fever doesn’t occur, but the impaired capillary flow still causes cyanosis of the distal parts of the body (fingers, nose, genitalia), a condition called acrocyanosis.

Primary activation of fibrinolytic system

Excessive primary activation of the fibrinolytic system causes a state of hypocoagulability, a clinical picture which is similar to DIC (except no thrombosis). It may lead to severe bleeding and haemorrhagic shock.

The job of the fibrinolytic system is to break down clots when they’re no longer needed and to prevent clots from growing too large. The most important components are urokinase and plasmin. Urokinase converts plasminogen into plasmin, which will then lyse fibrin clots.

It can be caused by:

  • Prostate tumors (they can secrete urokinase)
  • Urogenital inflammation
  • Liver cirrhosis
  • Heat stroke
  • Snake venom

Overactivation of the fibrinolytic system means that no clots will be formed because fibrin is immediately degraded into fibrin degradation products. These degradations products (like D-dimer) suppress further blood clotting as well. The consequence is than any small bleeding, such as a venepuncture or catheter can cause severe bleeding and hypovolaemic shock.