Disseminated Intravascular Coagulation (DIC)

Definition: -DIC is an acute, or chronic thrombo-hemorrhagic disorder occurring as a result of progressive activation of coagulation pathway beyond physiologic set point secondary to a variety of diseases resulting in failure of all components of hemostasis. Hence the other term for DIC is consumption coagulopathy.

Etiology and Pathogenesis

At the outset, it must be emphasize that DIC is not a primary disease. It is a coagulopathy that occurs in the course of variety of clinical conditions. DIC follows massive or prolonged release of soluble tissue factors & /or endothelial-derived thromboplastin into the circulation with generalized (pathologic) activation of coagulation system. Therefore, DIC results from pathologic activation of the extrinsic &/or intrinsic pathways of coagulation or impairment of clot inhibiting influences by different causes. Two major mechanisms activating the coagulation pathway to cause DIC are: (1) release of tissue factor or thromboplastic substance into the circulation (2) widespread injury to the endothelial cells. 

1. Tissue thromboplastin substance may be derived from a variety of sources such as:

A:  Massive trauma, severe burns & extensive surgery. The major mechanism of DIC is believed to be autoinfusion of thromboplastin from the tissues.

B: Obstetric conditions in which thromboplastin derived from the placenta, dead retained fetus, or amniotic fluid may enter the circulation.

C:  Cancers such as acute promyelocytic leukaemia, adenocarcinoma of the lung in which a variety of thromboplastin substances like mucus are released which directly activate factor X, VII, & proteolytic enzymes.

D:  Gram negative sepsis (an important cause of DIC) in which bacterial endoxins cause increased synthesis, membrane exposure, & release of tissue factor from monocytes. Furthermore, activated monocytes release intereukin-1 (IL-I), TNF-α, both of which:

•  Increase expression of tissue factor in endothelial membrane. 

•  Decrease expression of thrombmodulin which is a potent activator of protein C- an anti-coagulant 

• TNF-α, an extremely important mediator of septic shock, in addition to the above, up regulates the expression  of adhesion molecules on endothelial cells and favour adhesion of leukocytes, with subsequent damage of endothelial cells by free radicals & preformed proteases.

2. Endothelial injury: Widespread endothelial injury may result from:

- Deposition of antigen-antibody complexes as it occurs in systemic lupus erythematosus 

-  Extreme temperature eg. Heat stroke, burns

-  Hypoxia, acidosis, shock

Clinical Course

 The consequences of DIC are two fold. First, there is a widespread deposition of fibrin within the microcirculation. This may lead to ischemia of the more severely affected or more vulnerable organs and hemolytic anemia resulting  from fragmentation of led cells as they squeeze through the narrowed microvasculature (Microangiopathic haemolytic anaemia).

Second, a hemorrhagic diathesis may dominate the clinical picture because of consumption of the coagulation factors and increased fibrinolysis. The onset may be fulminant when caused by endotoxic shock or amniotic fluid embolism or it may be chronic in the case of carcinomatosis or retention of dead fetus. The clinical presentation varies with stage & severity of the syndrome. Overall 50% of patients with DIC are obstetric patients & about 33% of patients have carcinomatosis.

Clinically, patients with DIC may present with extensive skin & mucus membrane bleeding and haemorrhage from multiple sites, usually from surgical incision, vein punctures, or catheter sites. Respiratory symptoms such as dyspnea, cyanosis may occur. They may present with convulsion & coma in the case of CNS bleeding or with acute renal failure with oliguria. Less often, they may present with acrocyanosis, pre-gangrenous changes in the digits, genitalia, & nose areas where blood flow may be markedly decreased. Circulatory failure may appear suddenly & may be progressing. The presentations of acute DIC, as it occurs in case of trauma or obstetric conditions, is dominated by bleeding diathesis.

Laboratory manifestations include thrombocytopenia secondary to platelets aggregation in the thrombus, schistocytes or fragmented RBCs, prolonged PT, PTT, thrombin time & reduced fibrinogen from depleted coagulation proteins. There is also increased fibrin degradation product (FDP) from intense fibrinolysis. The cardinal manifestation of DIC, which correlates most closely with bleeding is plasma fibrinogen level, i.e. low fibrinogen means increased tendency of bleeding. 

References

Bezabeh ,M. ; Tesfaye,A.; Ergicho, B.; Erke, M.; Mengistu, S. and Bedane,A.; Desta, A.(2004). General Pathology. Jimma University, Gondar University Haramaya University, Dedub University.

مواضيع ذات صلة

Acute circulatory failure (cardiogenic shock)

Pulmonary hypertension

Pulmonary thromboembolism

Giant cell (temporal) arteritis

ابيضاض الدم النقوي المزمن Chronic myelocytic leukaemias

Abdominal aortic aneurysm

Infective endocarditis

تليف النقيMyelofibrosis

فقر الدم اللا مصنع ( اللا تنسجي ) Aplastic anemia

Septic shock

Distributive shock

Cardiogenic shock