Impact of Antithrombin Activity Levels Following Recombinant Antithrombin Gamma Therapy in Patients with Sepsis-Induced Disseminated Intravascular Coagulation

Abstract

Recombinant antithrombin gamma (rAT) is reported as an effective drug for patients with disseminated intravascular coagulation (DIC) in Japan. As the appropriate dose and targeted AT activity remain unknown, this study aimed to determine these aspects for sepsis-induced DIC. Thirty-one patients with septic shock and DIC with AT levels <70% were treated with rAT between May 2018 and December 2020. The recovery rates from DIC were 32.2% and 63.3% on day 3 and 5 post administration, respectively. Recovery and survival rates were significantly higher in patients who achieved AT activity ≥70% or 80% on day 3 post administration. Receiver operating characteristic curve analysis revealed that the cutoff values of post-treatment AT activity on day 3 for 28-day survival and 5-day recovery from DIC were 79.5% and 81.5%, respectively. Patients who did not achieve AT activity ≥80% on day 3 presented a lower base level of AT activity and lower dose supplementation. Our results suggest that targeted AT activity should be at least 70%, and ideally 80%, and sufficient doses to maintain this activity are required to achieve better outcomes.

The antithrombin activity recovery after substitution therapy is associated with improved 28-day mortality in patients with sepsis-associated disseminated intravascular coagulation

“…Third, along with vascular injury, circulating antithrombin can leak out rapidly from the intravascular space with increased capillary permeability [ 16 ]. These and other factors are involved in the decreased antithrombin activity in sepsis-associated DIC, and the mean activity at the baseline was below 50% in this study which was consistent with the reports from others [ 11 , 17 ].…”

“…Therefore, we assume that outcomes are not determined by the mentioned factors but are also affected by the achieved antithrombin activity after antithrombin substitution. The observation that higher post-treatment antithrombin activity is associated with better survival was repeatedly reported [ 11 , 17 , 20 ], and it suggested the idea of aiming the target activity-oriented dose settings. Although the current study results cannot alone support this concept or provide the target dose.…”

“…Previous studies have demonstrated that antithrombin activity after three consecutive days of antithrombin substitution estimated the morbidity and mortality in sepsis-associated DIC [ 10 ]. Akahoshi et al [ 11 ] reported the survival rates of septic DIC were significantly higher in patients who achieved post-treatment antithrombin activity of more than 70% or 80%. However, these studies have examined the relationship between antithrombin activity and mortality using receiver operating characteristic (ROC) curve analysis and compared the mortality rates above and below cutoff values.…”

Effects of combination therapy of antithrombin and thrombomodulin for sepsis-associated disseminated intravascular coagulation: a systematic review and meta-analysis

“…AT in plasma inhibits thrombin and several other serine protease coagulate factors, and it exerts antiplatelet effects via stimulating prostacyclin production by using vascular endothelial cells [ 4 , 5 ]. Further, AT administration has been suggested to protect vascular endothelial cells [ 6 ], thereby potentially improving the prognosis [ 7 ].…”

Risk stratification utilizing sequential organ failure assessment (SOFA) score, antithrombin activity, and demographic data in sepsis-associated disseminated intravascular coagulation (DIC)

“…Antithrombin is the most abundant and essential natural anticoagulant, inhibiting multiple coagulation factors, particularly thrombin and factor Xa 10 . A number of studies have revealed an association between reduced antithrombin levels and an increased risk of morbidity and mortality 8 , 11 , 12 . In addition, antithrombin activity has served as a marker of disease severity in DIC 13 .…”