The term disseminated intravascular coagulation implies systemic coagulation within the blood vessels, contrasted to normal blood coagulation that takes place extravascularly and locally. As mentioned, the clinical picture known as DIC involves not only coagulation but also fibrinolysis, and is not always systemic. Consequently, several authors have advocated the use of more descriptive terms, such as defibrination syndrome, consumption coagulopathy, or intravascular coagulation with fibrinolysis. Nevertheless, DIC remains the most commonly used name for the condition.

Thrombin has many roles in hemostasis (Chapter 36). All of the roles are involved in the pathogenesis of DIC. The first function is removal of fibrinopeptides A and B from fibrinogen, forming fibrin monomers. Some monomers polymerize. Others circulate as soluble fibrin monomers. The fibrinopeptides circulate in the bloodstream, too, and are removed from the circulation by the macrophage system. Within the plasma the fibrinogen level decreases and the level of fibrinopeptides, especially A, increases.

A second action of thrombin is activation of factors V and VIII, which are consumed as they function in the cascade of fibrin formation. In DIC they are used at a faster rate than they can be synthesized, and the plasma levels decrease. Additionally, thrombin activates factor XIII that is also consumed. As thrombin is formed, the plasma level of its inactive precursor, prothrombin, decreases. The presence of thrombin may decrease the function of liver macrophages in removing activated factors and particles, allowing them to remain for a longer time in the circulation. Finally, thrombin may contribute to thrombocytopenia by activating platelets and inducing platelet aggregation. Thrombocytopenia is a universal finding in DIC.¹ In addition to decreased factors of fibrin formation, the activity of the natural controls, antithrombin and the protein C-protein S system, are reduced.

Plasmin is formed within the circulation as plasminogen is activated by tissue activators and by prekallikrein. Consequently, plasma levels of plasminogen decrease. Plasmin digests both fibrin and fibrinogen, resulting in circulating fibrin (fibrinogen) degradation products (FDP). FDPs act as anticoagulants by forming soluble complexes with fibrin monomers, which prevents them from polymerizing. They also adhere to platelet surfaces and cause decreased platelet function. Fibrinogen levels are further reduced because circulating plasmin digests it. Plasmin also attacks other proteins, including factors V, VIII, IX, and XI.² When plasmin digests cross-linked fibrin, D-dimers are formed and circulate. Within time PAI-1 levels have been shown to increase, and this results in impaired fibrinolysis.

Reference

1. Baglin T. Disseminated intravascular coagulation: diagnosis and treatment. BMJ. 1996; 312:683-687.
2. Roberts HR, Hoffman M. Hemophilia and related conditions–inherited deficiencies of prothrombin (factor II), factor V, and factors VII to XII. In: Beutler E, Lichtman MA, Coller BS, Kipps TJ, eds. William's Hematology. 5^th ed. New York, NY: McGraw-Hill; 1995: 1413-1439.