Hypofibrinogenemia is Associated With a High Degree of Risk in Infectious and Hematological Diseases: A Post-Hoc Analysis of Post-Marketing Surveillance of Patients With Disseminated Intravascular Coagulation Treated With Thrombomodulin Alfa

Abstract

Introduction In patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value and the relationship between hypofibrinogenemia and the outcomes of infectious DIC has remained unclear.Materials and Methods We analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for with DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level of <1.5 g/L.Results Hypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly high in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower in infectious disease patients with DIC with hypofibrinogenemia than in those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.Conclusion In infectious disease patients with DIC, hypofibrinogenemia may reflect from the increased consumption of fibrinogen due to an accelerated coagulating reaction, while that in hematological disease patients DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with Thrombomodulin Alfa and Antithrombin

“…This unique feature is often complicated by severe organ failure and bleeding that leads to poor outcomes. 22 23 Therefore, although clinical evidence has not been sufficient, anticoagulant therapy was proposed for the treatment of DIC. Another unique aspect of DIC is the wide diversity in its pathophysiology, as well as phenotype, depending on the underlying diseases.…”

“…The prognosis of DIC remains poor, 1 19 25 and decreases in coagulation and anticoagulant factors can predict poor outcomes. 22 23 28 Severe AT deficiency is known to be associated with a high risk of organ failure and death in patients with severe sepsis. 22 29 Together with the activated coagulation, decreased fibrinolysis due to excess production of plasminogen activator inhibitor 1 accelerates the microthrombosis and poor circulation in sepsis.…”

“…22 29 Similarly, hypofibrinogenemia is also helpful to evaluate the severity of sepsis. 23 Hypofibrinogenemia reflects the consumptive coagulopathy that leads to the hemostatic disorder. It is noteworthy that the true fibrinogen level is lower than the measured fibrinogen activity in DIC, since the fibrinogen level is usually measured using a clotting assay despite the presence of a hypercoagulable state.…”

“…Decreased AT levels and hypofibrinogenemia have been shown to independently predict poor outcomes in postmarketing surveillance (PMS). 22 23 In the present study, DIC was classified by AT and fibrinogen levels to examine their usefulness as severity markers. Then, the usefulness of the categorization based on AT and fibrinogen levels to select the target of combination therapy of AT and TM was also evaluated.…”