Disseminated Intravascular Coagulation (DIC)

Disseminated Intravascular Coagulation (DIC) as the name suggested is characterized by disseminated (wide-spread) intravascular coagulation (clots within blood vessels).  DIC is an unfortunate complication that can result from several different illnesses or conditions.  DIC is detrimental as it leads to the production of microvascular thrombi that lodge and obstruct blood vessels throughout the body causing ischemia and hypoxia, potentially leading to multi-organ failure.  To make matters worse, the depletion of platelets and clotting factors that occur due to excessive clotting, makes an individual susceptible to life-threatening bleeding (internal or external hemorrhaging). As one can imagine, having both a clotting problem and a bleeding problem at the same time is challenging to treat.

DIC can develop quickly or slowly.  Acute DIC develops when there is sudden rise in procoagulants (e.g., Tissue Factor, TF, a transmembrane glycoprotein activated on the surface of endothelial cells, macrophages and mast cells in response to vascular damage).  Chronic DIC more often occurs when progressive damage is occurring, (e.g., as a result of a growing tumor).

Hemostasis involves 3 steps: a vascular spasm, platelet plug formation, and coagulation.  The third step, coagulation, involves extrinsic and intrinsic pathways, both of which are enzymatic cascades that lead to the activation of Factor X (Prothrombin Activator).  The extrinsic pathway includes: Tissue Factor, clotting factors, and Ca⁺⁺.  The intrinsic pathway includes: Platelet Activating Factor (PAF), clotting factors, and Ca⁺⁺.  Once Prothrombin Activator is activated, it catalyzes the conversion of prothrombin (inactive state) into thrombin (active state).  Thrombin is an enzyme that catalyzes the conversion of fibrinogen (soluble, non-sticky plasma protein) into fibrin (insoluble protein that binds to endothelial cells and platelets and can form clots).

Pathogenesis – DIC

DIC occurs as a result of disordered regulation of blood coagulation, characterized by an imbalance of procoagulation (pro-hemostasis) and anticoagulation (fibrinolysis) components.  It has been found that extensive cellular damage due to sepsis, trauma or burns etc. induces a strong inflammatory response.  The resulting high levels of pro-inflammatory cytokines coupled with blood vessel injury leads to high levels of hemostasis (clotting) pathways being stimulated.  This leads to high levels of the enzyme thrombin converting the soluble, globular, inactive fibrinogen plasma protein into the ropy insoluble fibrin protein that is then deposited within blood vessels narrowing the lumen and impeding blood flow.

Thrombin activation is normally held in check by anticoagulant factors (e.g., antithrombin and Protein C).  In the case of DIC, pro-inflammatory cytokines have been found to impair activation and/or production of antithrombin and Protein C, which leads to more thrombin, more fibrin and more clotting, exacerbating the conditions in DIC.

As mentioned, inappropriately high levels of activated thrombin leads to the activation of fibrin (from fibrinogen) and intravascular deposition of fibrin.  Increased stimulation of hemostasis pathways also leads to high levels of platelet activation which then become sticky and clot together.  Impaired or inadequate fibrin degradation and removal contributes to the problem.  Platelet and fibrin clots travel and lodge in blood vessels forming micro- and macro-thrombi throughout the body causing ischemia and hypoxia to multiple organs.

To make things worse, the sudden dissolution of clots can cause reperfusion injuries, which further induces inflammation and procoagulation conditions leading to more thrombosis (clotting).  Extensive thrombosis leads to a depletion of platelets and clotting factors, making one very susceptible to bleeding.

In the case of sepsis-induced DIC, septic shock can develop at the same time, leading to systemic vasodilation and hypotension.  During septic shock, poor perfusion of organs often results in hypermetabolism, with increases in anaerobic cellular respiration, protein catabolism, and metabolic acidosis.  Dangerously low blood pressure leads to reflexive tachycardia, while low oxygen delivery, tissue hypoxia, and low serum pH contribute to the development of tachypnea.

Risk Factors – DIC

Risk factors are often those that have involved significant cellular damage and destruction and have triggered strong immune and inflammatory responses.  Examples include:  trauma, cancers, blood transfusion rejections, severe infections (e.g., sepsis), heat stroke, hyperthermia, snake bites, obstetric complications, major surgery, and burns.  Sepsis is thought to account for approximately 30-50% of DIC cases, with 45% of DIC cases due to trauma, burns or major surgery.

Signs and Symptoms – DIC

DIC is accompanied by clinical manifestations of the initial condition (e.g., sepsis, trauma, burns, cancer, etc.) that led to DIC occurring.

Signs and symptoms of DIC may include evidence of micro-bleeds such as: petechiae (tiny red spots of bleeding less than 4mm in size), purpura (blood spots or skin hemorrhages approximately 4-10mm in size), ecchymosis (i.e. bruises or skin bleeds larger than 1cm).

Purpura fulminans can also occur and is more serious than a purpura rash in that purpura fulminans begins as blood-spotted skin but develops into spots of skin necrosis leaving dark coloured raised blisters that may become infected.

Bleeding is often detected in the gingivae and gastrointestinal system.  External bleeds may also be present at sites of open trauma, or surgical incision sites.

Signs and symptoms of dysfunction (or failure) of the renal, hepatic, respiratory, cardiovascular, and/or central nervous system may occur.  These can be monitored by function tests of the kidney, liver, lungs, heart, brain and nervous system.

Signs and symptoms include signs of thromboembolism and/or internal bleeding.

Diagnostic Tests – DIC

DIC is confirmed by measuring serum levels of procoagulant and anticoagulant factors, platelet counts, and concentrations of fibrinogen and fibrin degradation products. Thrombocytopenia (low platelet numbers) and high levels of fibrin degradation products will likely be present.  Long clotting times are also indicative of DIC.

Treatment – DIC

Treatment of the underlying cause (e.g., sepsis, trauma, burns, obstetric emergencies, cancer, snake bites, etc.) is of utmost importance.

Treatment of hypovolemia may be required.

At times blood transfusions (e.g., packed red blood cells and/or platelets) may be required.  Plasmapheresis is sometimes recommended.

In patients with active bleeding and thrombocytopenia, platelet transfusions may be considered.  Additional administration of coagulation factors (including vitamin K) may also be advisable depending on clotting times and the risk for bleeding and/or thrombosis (clotting).

In some cases, it has been found that early treatment with heparin can be effective as it is both an anti-thrombin and an anti-inflammatory which reduces the formation of clots (and depletion of reservoir platelets).  However, heparin should be used cautiously and is contraindicated in cases of anticoagulating DIC patients.

Experimental treatment with the anticoagulant Protein C protease (which degrades clotting factors required for thrombin activation) has not been found to be very successful in reducing thrombosis.  Antifibrinolytics pose a risk for the development of complications which include myocardial infarction and renal artery thrombosis.

Summary:

• DIC (disseminated intravascular coagulation) is an abnormal clotting disorder.
• It can occur due to trauma, infection, or other major body problems.
• Excessive clotting in the bloodstream can lead to capillary blockage and tissue hypoxia.
• Platelets are consumed in forming useless clots, leading to bleeding issues.
• Diagnosis involves measuring coagulant and anticoagulant factors in the blood.
• Treatment involves addressing the underlying condition and may include heparin or transfusions.
• DIC can lead to organ failure and is considered a medical emergency.