Hypofibrinogenemia is associated with a high degree of risk in infectious diseases: a post-hoc analysis of post-marketing surveillance of patients with disseminated intravascular coagulation treated with thrombomodulin alfa

Kazuo Kawasugi,Toshimasa Uchiyama,Takayuki Ikezoe,Toshiaki Iba,Naoki Takezako,Noriaki Kawano,Yoshinobu Seki,Goichi Honda,Seiji Madoiwa,Kohji Okamoto,Hideo Wada,Kei Suzuki

doi:10.1186/s12959-021-00264-z

Abstract

BackgroundIn patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has thus remained unclear.MethodsWe analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level < 1.5 g/L.ResultsHypofibrinogenemia 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 higher 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 for infectious disease patients with DIC with hypofibrinogenemia than for those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.ConclusionsHypofibrinogenemia among infectious disease patients with DIC may reflect increased consumption of fibrinogen due to accelerated coagulation reactions, while hypofibrinogenemia among hematological disease patients with DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.

Highlights

Disseminated intravascular coagulation (DIC), which occurs in association with various underlying diseases, such as sepsis, hematological malignancy, solid tumors and aneurysm, is often associated with severe and lifethreatening bleeding or organ failure with [1,2,3]
The diagnostic criteria for disseminated intravascular coagulation (DIC) have been established by the Japanese Ministry of Health and Welfare (JMHW) [6], the International Society of Thrombosis Haemostasis (ISTH) [4], the Japanese Association for Acute Medicine (JAAM) [7] and the Japanese Society of Thrombosis and Hemostasis (JSTH) [8]
The present study examined the frequency of hypofibrinogenemia in infectious and hematological diseases with DIC and suspected DIC, and analyzed the characteristics of hypofibrinogenemia in infectious disease patients with DIC

Summary

Introduction

Disseminated intravascular coagulation (DIC), which occurs in association with various underlying diseases, such as sepsis, hematological malignancy, solid tumors and aneurysm, is often associated with severe and lifethreatening bleeding or organ failure with [1,2,3]. The diagnostic criteria for DIC have been established by the Japanese Ministry of Health and Welfare (JMHW) [6], the International Society of Thrombosis Haemostasis (ISTH) [4], the Japanese Association for Acute Medicine (JAAM) [7] and the Japanese Society of Thrombosis and Hemostasis (JSTH) [8]. Most guidelines show that infectious-type DIC is frequently associated with organ failure, whereas hypofibrinogenemia or bleeding tendency is less common They have recommended the treatment of DIC via treatment of the underlying diseases, along with supportive therapy such as administration of platelet concentrates and fresh frozen plasma [10,11,12,13]. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has remained unclear

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