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Thrombotic Microangiopathy-Like Phenotype in Patients With Infection-Associated Disseminated Intravascular
Naoki Takezako1,2, Fumiyo Komatsu3, Goichi Honda4
1Department of Hematology, National Hospital Organization Disaster Medical Center, Tokyo, Japan.
Despite disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) sharing features of thrombocytopenia, organ dysfunction, and bleeding, the relationship between these two conditions remains unclear. We therefore conducted a post hoc analysis of post-marketing surveillance data from Japan to evaluate the clinical characteristics of 2362 patients with DIC (TMA-like phenotype DIC, n = 217; and non-TMA-like phenotype DIC, n = 2145) who received thrombomodulin alfa (TM-α). TMA-like phenotype DIC was defined as platelet count < 15 × 104/μL, hemoglobin < 10 g/dL and lactate dehydrogenase > 500 IU/L. Approximately 9% of the registered infection-associated cases of DIC were TMA-like phenotype DIC. Patients with TMA-like phenotype were younger and had more renal dysfunction and liver dysfunction than those with non-TMA-like phenotype. Regarding the hemostatic examinations, fibrin/fibrinogen degradation products, D-dimer, and thrombin-antithrombin complex levels were higher in patients with TMA-like phenotype than in those with non-TMA-like phenotype. Patients with TMA-like phenotype had worse resolution of DIC and 28-day survival rates than those with non-TMA-like phenotype; however, the coagulation and fibrinolysis parameters in both groups showed improvement after TM-α administration. These findings describe a clinically severe subgroup of infection-associated DIC and should be interpreted as exploratory given that confirmatory TMA testing was unavailable.
Despite disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) sharing features of thrombocytopenia, organ dysfunction, and bleeding, the relationship between these two conditions remains unclear. We therefore conducted a post hoc analysis of post-marketing surveillance data from Japan to evaluate the clinical characteristics of 2362 patients with DIC (TMA-like phenotype DIC, n = 217; and non-TMA-like phenotype DIC, n = 2145) who received thrombomodulin alfa (TM-α). TMA-like phenotype DIC was defined as platelet count < 15 × 104/μL, hemoglobin < 10 g/dL and lactate dehydrogenase > 500 IU/L. Approximately 9% of the registered infection-associated cases of DIC were TMA-like phenotype DIC. Patients with TMA-like phenotype were younger and had more renal dysfunction and liver dysfunction than those with non-TMA-like phenotype. Regarding the hemostatic examinations, fibrin/fibrinogen degradation products, D-dimer, and thrombin-antithrombin complex levels were higher in patients with TMA-like phenotype than in those with non-TMA-like phenotype. Patients with TMA-like phenotype had worse resolution of DIC and 28-day survival rates than those with non-TMA-like phenotype; however, the coagulation and fibrinolysis parameters in both groups showed improvement after TM-α administration. These findings describe a clinically severe subgroup of infection-associated DIC and should be interpreted as exploratory given that confirmatory TMA testing was unavailable.
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