Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC)

Illustrations

Blood clot formation

Meningococcemia on the calves

Meningococcemia on the leg

Meningococcemia associated purpura

Blood clots

Alternative Names Consumption coagulopathy

Definition Disseminated intravascular coagulation (DIC) is a serious disorder in which the proteins that control blood clotting are abnormally active.

Causes

Normally, when you are injured, certain proteins are turned on and travel to the injury site to help stop bleeding. However, in persons with DIC, these proteins are abnormally active. Small blood clots form throughout the body. Overtime, the clotting proteins become "used up" and are unavailable during times of real injury.

This disorder can result in clots or, more often, bleeding. Bleeding can be severe.

Risk factors for DIC include:

Blood transfusion reaction

Cancer, including leukemia

Infection in the blood by bacteria or fungus

Pregnancy complications (such as retained placenta after delivery)

Recent surgery or anesthesia

Sepsis

Severe liver disease

Severe tissue injury (as in burns and head injury)

Symptoms Bleeding, possibly from multiple sites in the body

Blood clots

Sudden bruising

Exams and Tests The following tests may be done: Serum fibrinogen - low Prothrombin time (PT) - high

Partial thromboplastin time (PTT) - high

Platelet count

Treatment The goal is to determine and treat the underlying cause of DIC.

Blood clotting factors will be replaced with plasma transfusions. Heparin, a medication used to prevent thrombosis, is sometimes used in combination with replacement therapy.

Outlook (Prognosis)

The underlying disease that causes the disorder will usually predict the probable outcome.

Possible Complications

Severe bleeding

Stroke

Lack of blood flow to arms, legs, or organs

When to Contact a Medical Professional Go to the emergency room or call 911 if you have continued bleeding of unknown cause.

Prevention

Get prompt treatment for conditions known to bring on this disorder.

Disseminated intravascular coagulation

Disseminated intravascular coagulation (DIC), also called consumptive coagulopathy, is a pathological process in the body where the blood starts to coagulate throughout the whole body. This depletes the body of its platelets and coagulation factors, and there is a paradoxically increased risk of hemorrhage. It occurs in critically ill patients, especially those with Gram-negative sepsis (particularly meningococcal sepsis) and acute promyelocytic leukemia.

EtiologyThere are a variety of causes of DIC, all usually causing the release of chemicals into the blood that instigates the coagulation.

Sepsis, particularly with gram-negative bacteria.

Obstetric complications (most common cause), with chemicals from the uterus being released into the blood, or from amniotic fluid embolisms, and eclampsia can be causes. Another obstetric condition which can cause DIC is abruptio placentae.

Tissue trauma such as burns, accidents, surgery or shock.

Liver disease

Incompatible blood transfusion reactions or massive blood transfusion (more than the total circulatory volume)

Cancers, or widespread tissue damage (e.g. burns), or hypersensitivity reactions all can produce the chemicals leading to a DIC.

Acute promyelocytic leukemia

Viral hemorrhagic fevers bring about their frank effects, paradoxically, by causing DIC.

Envenomation by some species of venomous snakes, such as those belonging to the genus Echis (saw-scaled vipers).

DiagnosisAlthough numerous blood tests are often performed on patients prone to DIC, the important measures are: full blood count (especially the platelet count), fibrin degradation products or D-dimer tests (markers of fibrinolysis), bleeding time and fibrinogen levels. Decreased platelets, elevated FDPs or D-dimers, prolonged bleeding time and decreased fibrinogen are markers of DIC.

PathophysiologyUnder homeostatic conditions, the body is maintained in a finely tuned balance of coagulation and fibrinolysis. The activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis. The fibrinolytic system then functions to break down fibrinogen and fibrin. Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots. The breakdown of fibrinogen and fibrin results in polypeptides called fibrin degradation products (FDPs) or fibrin split products (FSPs). In a state of homeostasis, the presence of thrombin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for the breakdown of clots, or fibrinolysis.

In DIC, the processes of coagulation and fibrinolysis lose control, and the result is widespread clotting with resultant bleeding. Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions. One critical mediator of DIC is the release of a transmembrane glycoprotein called tissue factor(TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularly interleukin), tumor necrosis factor, and endotoxin. This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon activation, TF binds with coagulation factors that then trigger both the intrinsic and the extrinsic pathways of coagulation.

Excess circulating thrombin results from the excess activation of the coagulation cascade. The excess thrombin cleaves fibrinogen, which ultimately leaves behind multiple fibrin clots in the circulation. These excess clots trap platelets to become larger clots, which leads to microvascular and macrovascular thrombosis. This lodging of clots in the microcirculation, in the large vessels, and in the organs is what leads to the ischemia, impaired organ perfusion, and end-organ damage that occurs with DIC.

Coagulation inhibitors are also consumed in this process. Decreased inhibitor levels will permit more clotting so that a feedback system develops in which increased clotting leads to more clotting. At the same time, thrombocytopenia occurs because of the entrapment of platelets. Clotting factors are consumed in the development of multiple clots, which contributes to the bleeding seen with DIC.

Simultaneously, excess circulating thrombin assists in the conversion of plasminogen to plasmin, resulting in fibrinolysis. The breakdown of clots results in excess amounts of FDPs, which have powerful anticoagulant properties, contributing to hemorrhage. The excess plasmin also activates the complement and kinin systems. Activation of these systems leads to many of the clinical symptoms that patients experiencing DIC exhibit, such as shock, hypotension, and increased vascular permeability. The acute form of DIC is considered an extreme expression of the intravascular coagulation process with a complete breakdown of the normal homeostatic boundaries. DIC is associated with a poor prognosis and a high mortality rate.

TreatmentThe underlying cause must be treated initially. Anticoagulants are only given when indicated (development of thrombotic renal complications) as patients with DIC are prone to bleeding. Platelets may be transfused if counts are very low, and fresh frozen plasma may be administered.

DIC results in lower fibrinogen (as it has all been converted to fibrin), and this can be tested for in the hospital lab. A more specific test is for "fibrin split products" (FSPs) or "fibrin degradation products" (FDPs) which are produced when fibrin undergoes degradation when blood clots are dissolved by fibrinolysis.

In some situations, infusion with antithrombin may be necessary. A new development is drotrecogin alfa (Xigris), a recombinant activated protein C product. Activated Protein C (APC) deactivates clotting factors V and VIII, and the presumed mechanism of action of drotrecogin is the cessation of the intravascular coagulation. Due to its high cost, it is only used strictly on indication in intensive care patients.[1]The prognosis for those with DIC, depending on its cause, is often grim, leading the initials to be known colloquially as "death is coming".[2