Classifying types of disseminated intravascular coagulation: clinical and animal models

Abstract

Disseminated intravascular coagulation (DIC) has a common pathogenesis in terms of persistent widespread activation of coagulation in the presence of underlying disease, but the degree of fibrinolytic activation often differs by DIC type. DIC with suppressed fibrinolysis is a DIC type usually seen in sepsis. Coagulation activation is severe, but fibrinolytic activation is mild. DIC with enhanced fibrinolysis is a DIC type usually seen in acute promyelocytic leukemia (APL). Both coagulation activation and fibrinolytic activation are severe. DIC with balanced fibrinolysis is a DIC type usually seen in solid tumors, with an intermediate pathogenesis between the above two types. In animal DIC models, lipopolysaccharide (LPS)-induced models are similar to suppressed-fibrinolytic-type DIC, whereas tissue factor (TF)-induced models are similar to enhanced fibrinolytic/balanced fibrinolytic DIC. Appropriate diagnosis and treatment may also differ depending on the DIC type.

Keywords: DIC with balanced fibrinolysis; DIC with enhanced fibrinolysis; DIC with suppressed fibrinolysis; Disseminated intravascular coagulation; Tranexamic acid.

Figure 1

Classification of DIC types. Coagulation activation (TAT elevation) is a common feature, but the degree of fibrinolytic activation (PIC elevation) differs depending on the underlying disease. The ‘symptoms’ area in the figure distinguishes organ symptoms and bleeding symptoms. Fibrin degradation product (FDP) is not shown in this figure, but in enhanced fibrinolytic DIC, FDP tends to be elevated more than D-dimer. Because ATRA therapy in APL inhibits annexin II expression in APL cells, the characteristics of enhanced fibrinolytic DIC are lost, with a change to the characteristics of suppressed fibrinolytic DIC. TAT thrombin-antithrombin complex, PIC plasmin-α₂ plasmin complex, DD D-dimer, PAI plasminogen activator inhibitor, APL acute promyelocytic leukemia.

Figure 2

Role of fibrinolysis in DIC. The dotted-line arrows summarize the reaction steps. Even with extensive thrombus, when fibrinolysis is inhibited by the action of PAI, plasmin formation is low, so the thrombi do not easily dissolve, and FDP and D-dimer elevations are mild (for example, DIC in sepsis). On the other hand, when PAI activity is low, plasmin formation increases, the thrombi dissolve more easily, and there are higher elevations of FDP and D-dimer (for example, DIC in APL). FDP and D-dimer are important markers for DIC, but their degree of elevation may not correlate with DIC severity (in particular, the degree of organ dysfunction). t-PA tissue type plasminogen activator, PAI plasminogen activator inhibitor, TF tissue factor, VIIa activated factor VII.

Figure 3

Changes in plasma TAT and PIC in DIC. The horizontal lines show the upper limits of normal. Plasma TAT is elevated in all cases of DIC. However, the degree of plasma PIC elevation differs depending on the underlying disease. The increase in PIC is highest in APL and lowest in sepsis. TAT thrombin-antithrombin complex, PIC plasmin-α₂ plasmin complex, APL acute promyelocytic leukemia, AL acute leukemia except APL, Ca cancer, Sep sepsis.

Figure 4

Variations in active PAI in DIC. The horizontal line shows the upper limits of normal. Plasma active PAI shows the highest elevation in sepsis but is within normal limits in APL. PAI plasminogen activator inhibitor, APL acute promyelocytic leukemia, AL acute leukemia except APL, Ca cancer, Sep sepsis.